TEHRAN HEART CENTERthc.tums.ac.ir/UserFiles/File/all page.4.pdf · Primary Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction Morteza Safi, Hassan Rajabi

TEHRAN HEART CENTER

THE

JOURNAL OF TEHRAN

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ABBASALI KARIMI, MD

ASSOCIATE PROFESSOR OF CARDIAC SURGERYTEHRAN UNIVERSITY OF MEDICAL SCIENCES

SEYED HESAMEDDIN ABBASI, MD

TEHRAN HEART CENTERTEHRAN UNIVERSITY OF MEDICAL SCIENCES

Hossien Ahmadi, MD

Tehran Heart Center

Tehran University of Medical Sciences

Shahin Akhondzadeh, PhD

Zohair Yousef Al-halees, MD , FRCSC, FACS

King Faisal Heart Institute

Saudi Arabia

Hooshang Bolooki, MD, FRCS (C), FACS, FCCP

University of Miami, School of Medicine

U. S. A

Yadolah Dodge, PhD

University of Neuchâtel

Switzerland

Ali Dodge–Khatami, MD, PhD

University of Zürich

Switzerland

Iradj Gandjbakhch, MD

Hopital Pitie

France

Omer Isik, MD

Yeditepe University, School of Medicine

Turkey

Sami S. Kabbani, MD

Damascus University Cardiovascular Surgical Center

Syria

Kayvan Kamalvand, MD, FRCP, FACC

William Harvey Hospital

United Kingdom

Jean Marco, MD, FESC

Centre Cardio- Thoracique de Monaco

France

Ali Massumi, MD

Texas Heart Institute

U. S. A

Carlos-A. Mestres, MD

University of Barcelona

Spain

Fred Morady, MD

University of Michigan

U. S. A

Mohammed T. Numan, MD

Hamad Medical Corporation

Qatar

Ahmand S. Omran, MD, FACC, FASE

King Abdulaziz Cardiac Center

Saudi Arabia

Fausto J. Pinto, MD, PhD, FESC, FACC, FASA, FSCAI,FASE

Lisbon University

Portugal

Mehrdad Rezaee, MD, PhD

Stanford University, School of Medicine

U. S. A

Gregory S. Thomas, MD, MPH, FACC, FACP, FASNC

University of California

U. S. A

Lee Samuel Wann, MD

Wisconsin Heart Hospital

U. S. A

Hein J. Wellens, MD

Cardiovascular Research Institute, Maastricht

The Netherlands

Douglas P. Zipes, MD

Indiana University, School of medicine

U. S. A

Roozbeh Psychiatric Hospital


Mohammad Ali Boroumand, MD

Tehran Heart Center

Advisory Board

Kiyomars Abbasi, MD

Tehran Heart Center


Seifollah Abdi, MD

Shaheed Rajaie Cardiovascular Medical Center

Iran University of Medical Sciences

Mohammad Alidoosti, MD

Tehran Heart Center


Alireza Amirzadegan, MD

Tehran Heart Center


Naser Aslanabadi, MD

Shaheed Madani Heart Hospital

Tabriz University of Medical Sciences

Sirous Darabian, MD

Tehran Heart Center


Gholamreza Davoodi, MD

Tehran Heart Center


Ahmad Reza Dehpour, PhD

Department of Pharmacology


Abbasali Karimi, MD

Tehran Heart Center


Davood Kazemi Saleh, MD

Baghiatallah Hospital

Baghiatallah University of Medical Sciences

Majid Maleki, MD



Mehrab Marzban, MD

Tehran Heart Center


Mansor Moghadam, MD

Imam Khomeini Hospital


Sina Moradmand Badie, MD

Amir Alam Hospital


Seyed Mahmood Mirhoseini, MD, DSc, FACC, FAES

Tehran Heart Center


Seyed Rasoul Mirsharifi, MD



Ahmad Mohebi, MD



Mohammad-Hasan Namazi

Shaheed Modarres Hospital

Shaheed beheshti University of Medical Sciences

Ebrahim Nematipour, MD

Tehran Heart Center


Rezayat Parvizi, MD



Masoud Pezeshkian



Hassan Radmehr, MD



Saeed Sadeghian, MD

Tehran Heart Center


Mojtaba Salarifar, MD

Tehran Heart Center


Nizal Sarraf –Zadegan, MD

Isfahan Cardiovascular Research Center

Isfahan University of Medical Sciences

Ahmad Yaminisharif, MD

Tehran Heart Center


Mohammad Reza Zafarghandi, MD

Sina Hospital


Aliakbar Zeinaloo, MD

Children Medical Center’s Hospital



Saeed Davoodi, MD

Tehran Heart Center


Iraj Firoozi, MD



Seyed Khalil Foroozannia, MD

Afshar Haspital

Shaheed Sadoghi University of Medical Sciences

Armen Gasparyan MD, PhD

Yerevan State Medical University

Armenia

Ali Ghaemian, MD

Mazandaran Heart Center

Mazandaran University of Medical Sciences

Namvar Ghasemi Movahedi, MD

Tehran Heart Center


Abbas Ghiasi, MD

Hamid Reza Pour Hosseini, MD

Tehran Heart Center


Hakimeh Sadeghian, MD

Tehran Heart Center


Mohammad Saheb Jam, MD & PT

Tehran Heart Center


Abbas Salehi Omran, MD

Tehran Heart Center


Mahmood Shabestari, MD

Imam Reza Hospital

Mashhad University of Medical Sciences

Shapour Shirani, MD

Tehran Heart Center


Abbas Soleimani, MD

Tehran Heart Center


Seyed Abdolhosein Tabatabaei, MD

Shariati Hospital


Murat Ugurlucan, MD

Department of Cardiac Surgery

Rostock University Medical Faculty

Arezou Zoroufian, MD

Tehran Heart Center


Tehran Heart Center


Seyed Ebrahim Kassaian, MD

Tehran Heart Center


Ali Kazemi Saeed, MD

Tehran Heart Center


Seyed Kianoosh Hoseini

Tehran Heart Center


Mohammad Jafar Hashemi, MD



Elise Langdon- Neuner

The editor of The Write Stuff (The Journal of The

European Medical Writers Association) Austria

Jalil Majd Ardekani, MD

Tehran Heart Center


Fardin Mirbolook, MD

Dr. Heshmat Hospital

Gilan University of Medical Sciences

Mehdi Najafi, MD

Tehran Heart Center


Younes Nozari, MD



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Pedram Amouzadeh

The Journal of Tehran University Heart Center

ContentVolume: 4 Number: 1 Winter 2009


Editorial

Review Article

Original Articles

Case Report

How to "Watch the Sac" after Endovascular Aortic Repair

Mehrab Marzban, Ali Mohammad Haji Zeinali ...................……………………………………..…………………………..………..………………..…...... 1

Assessment of Myocardial Viability: Selection of Patients for Viability Study and Revascularization

Hakimeh Sadeghian, Jalil Majd-Ardakani, Masoumeh Lotfi-Tokaldany ……………………………..…………….…….……….......................................... 5

Left-Sided Angiosarcoma of Heart: A Rare Case

Maryam Moshkani Farahani, Davood Kazemi Saleh, Yahya Dadjoo, Bahram Pishgoo ………………………………………............................................. 49

A Combined Approach to Severe Multi-Organ Atherosclerosis

Mohammad Hasan Namazi, Roxana Sadeghi, Hosein Vakili, Habibollah Saadat, Morteza Safi, Mohammad Reza Motamedi …........................................ 51

Could Mean Platelet Volume Predicts Impaired Reperfusion and In-Hospital Major Adverse Cardiovascular Event in

Patients with Primary Percutaneous Coronary Intervention After ST-Elevation Myocardial Infarction?

Hossein Vakili, Roozbeh Kowsari, Mohammad Hasan Namazi, Mohammad Reza Motamedi, Morteza Safi, Habibollah Saadat, Roxana Sadeghi,

Sanaz Tavakoli.……................................................................................................................................................................................................................. 17

A Hospital-Based Study on Causes Peculiar to Heart Failure

Hamzullah Khan, Hikmatullah Jan, Muhammad Hafizullah ………………………………..………………………………………..................................... 25

Efficacy of Two Streptokinase Formulations in Acute Myocardial Infarction: A Double-Blind Randonized Clinical

Trial

Mojtaba Salarifar, Saeed Sadeghian, Ali Abbasi, Gholamreza Davoodi, Alireza Amirzadegan, Seyed Kianoosh Hosseini, Navid Paydari, Aida Biria,

Parisa Moemeni......................................................................................................................................................................................................................... 29

Relationship between Blood Transfusion and Increased Risk of Atrial Fibrillation after Coronary Artery Bypass

Graft Surgery

Hassan Radmehr, Ali Reza Bakhshandeh, Mehrdad Salehi, Pouran Hajian, Ahmad Reza Nasr ............................................................................................. 35

Impact of Diabetes Mellitus on Peripheral Vascular Disease Concomitant with Coronary Artery Disease

Mehrab Marzban, Mohammadreza Zafarghandi, Mohsen Fadaei Araghi, Abbasali Karimi, Seyed Hossein Ahmadi, Namvar Movahedi, Kyomars

Abbasi, Naghmeh Moshtaghi …………………………..……………………………………...……………......................................................................… 39

Primary Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction

Morteza Safi, Hassan Rajabi Moghadam, Roxana Sadeghi, Habibollah Saadat, Mohammad Hassan Namazi, Hossein Vakili, Seyed Ahmad

Hassantash, Mohammad Reza Motamedi …….…………….……………………………………………................................................................….….… 45

TEHRAN HEART CENTER

The Journal of Tehran University Heart Center 1

TEHRAN HEART CENTER

Editorial

How to "Watch the Sac" after Endovascular

Aortic Repair

Mehrab Marzban, MD*, Ali Mohammad Haji Zeinali, MD

*Corresponding Author: Mehrab Marzban, Assistant Professor of Cardiac Surgery, Tehran University of Medical Sciences, Tehran Heart Center, North

Karegar Street, Tehran, Iran. 1411713138. Tel: +98 21 88029256. Fax: +98 21 88029256. E-mail: [email protected].

Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Introduction

Since its first introduction in clinical practice in 1991, the endovascular repair of the abdominal aortic aneurysm (AAA) has been widely performed and is reported to be an effective alternative to conventional open surgery, especially for patients with medical comorbidities.1-3

The number of patients considered suitable for the endovascular repair of either thoracic or abdominal aortic aneurysm is on the increase currently,4 and this is mainly due to the availability of a newer generation of devices with fewer complications and better applicability. On the other hand, patients are increasingly requesting this procedure as they and also physicians find the minimally invasive nature of the treatment attractive.

Endovascular aneurysm repair (EVAR) is based upon the hypothesis that the exclusion of the AAA sac from arterial pressure will prevent AAA rupture.5 EVAR is, therefore, deemed successful when the device permanently excludes the aneurysm sac from arterial pressure. Endoleaks refer to the persistent perfusion of the aneurysm sac after EVAR and affect 15% to 21% of patients.6-12

The rise in the number of patients treated by endovascular teams and the resultant experience have led to peri-procedural complications and primary anchorage problems with type 1 endoleaks becoming more and more infrequent. Types 1 and 3 endoleaks both give rise to a persistent blood flow into the aneurysm sac at high pressure, causing rapid aneurysm expansion and potential rupture. Type 4 endoleaks are mainly due to the porosity of the graft material in stent-grafts and nowadays are rare with the current devices. Type 2 endoleaks are usually low-pressure leaks into the aneurismal sac secondary to retrograde filling by branching vessels like the lumbar arteries in abdominal aneurysms and most often have a benign course, with only a few of them requiring secondary intervention. Zarins et al. estimated the incidence of Type 2 endoleaks following

EVAR at 10% to 20%.13

Although endoleaks are the major concern in endovascular treatment, there are other potential complications such as graft migration, graft fracture or fatigue, endograft stenosis, and kinking, which may become troublesome.

Because a favorable clinical outcome depends on the reliable detection of such complications, the choice of the right imaging method for follow-up is crucial. However, published data for different methods vary greatly in terms of detection rates.14-19 Follow-up examinations are advised by the European Collaborating Group on Stent-Graft Techniques for Abdominal Aortic Aneurysm Repair (EUROSTAR) at 1, 3, 6, 12, 18, and 24 months and yearly thereafter. Different follow-up protocols are used by different endovascular teams or hospitals, but all of them agree on the crucial role of this surveillance.

What imaging mode should be chosen in the immediate, mid-term and long-term follow-up of patients with an endoprosthesis? Multislice CT scan, magnetic resonance imaging (MRI), duplex ultrasonography (US), sac pressure measurement, and even plain radiography are used for this purpose.

CT scan

In many centers, CT scan is the imaging modality of choice for surveillance, and currently the follow-up protocol recommended by most manufacturers is based upon it. The combination of speed, reproducibility, and spatial and contrast resolution have made this the preferred method of imaging follow-up, despite the associated radiation dose and the potential for nephrotoxicity.20

The clinical performance of CT angiography in aneurysm imaging is well established, with documented utility in both the thoracic and abdominal aortas. The high-resolution data sets allow the reconstruction of thin transverse sections,

2


multiplanar reformatted images, and three-dimensional volumes, all of which can be used to generate highly accurate aneurysm size and volume measurements.Moreover, CT angiography is able to depict endoleaks with a higher sensitivity than is conventional angiography.21,22 It has been shown that volume measurement is more sensitive than diameter to detect any changes which may need secondary intervention.23,24

Helical CT angiography has been widely used in both pre- and post-aortic stent-grafting and has been confirmed to be the preferred modality when compared to conventional angiography. The recent development of multislice CT (MSCT) has further enhanced the applications of CT angiography for aortic stent-grafting. One of the advantages of MSCT angiography over conventional angiography is that the 3D reconstructions, based on the volumetric CT data, provide additional information during the follow-up of aortic stent-grafting. While endovascular repair has been increasingly used in clinical practice, the use of 3D MSCT imaging in endovascular repair continues to play an important role.25

The standard protocol is a triphasic CT, including pre-contrast, arterial, and delayed phases. Endoleaks have variable flow rates; they may, therefore, be detected in different phases of CT scanning. Despite this, Cat scan is known to have its own limitations in the detection of some types of endoleaks as highlighted by the phenomenon of endotension and by the difficulty to visualize type 2 endoleaks with a slow flow. The recommended protocol for long-term follow-up is yearly Cat scan, but what deserves attention is how many Cat scans are needed after an EVAR procedure in young or middle-aged patients given the cumulative radiation dose, cost, patients’ comfort, and dye nephrotoxicity. That is why some investigators believe that a shrinking sac and no evidence of endoleaks one year after EVAR will have negligible risk of late problems and that any problems that do occur can be picked up by the ultrasound determination of the sac size, history taking, and physical examinations alone.

This hypothesis is supported by the fact that the newer generation of endoprostheses has much fewer complications than do the older ones.

Magnetic Resonance Imaging

Gadolinium-enhanced MR angiography is capable of detecting endoleaks, but its performance is dependent on the composition of the stent-graft. Nitinol stents are generally MR-compatible, and stainless steel stents cause extensive artifact that renders the study non-diagnostic. In several studies26-29 on patients with predominantly nitinol stents, MR angiography was at least as sensitive as CT angiography and in some cases demonstrated endoleaks that were not

detected at CT angiography.30

MRI does not have the drawback of radiation exposure and is associated with a lower risk of nephrotoxicity. Consequently, it can be considered a viable alternative to MSCT for the follow-up of patients after EVAR with nitinol stent-grafts.

Duplex ultrasonography

Ultrasonography (US) is frequently used as a screening tool for the detection of AAA by radiologists or vascular surgeons. There are many reports in the literature which show the efficacy of US for the surveillance of patients with endoprosthesis.31,32

There are two sets of complications following endovascular aortic repair: 1) mechanical problems such as graft collapse or kinking and limb occlusion, which can often be detected in routine clinical visits and examinations and sometimes even via plain radiography and 2) endoleaks which can be detected sonographically by an expert and in selected cases.

Although the sensitivity of ultrasound for endoleak identification is highly variable, it can measure the sac size with reasonable accuracy.33-35 The measurements of the aneurysm size obtained with US correlate well with those obtained with CT.36 A meta-analysis studying the detection rate of endoleaks reported a sensitivity of 69% for US in 2005.37 Nevertheless, advances in technology and the accumulated experiences over the recent years have resulted in much higher rates of sensitivity.

US is an inexpensive, safe, and portable mode of imaging; be that as it may, its main disadvantage is the fact that it is operator-dependent, which renders many findings subjective. Another drawback is that US is less useful in some obese patients. In addition, the scanning protocols vary greatly from one institution to another. In spite of these shortcomings, US seems to play an important role in surveillance protocols, not least for young non-obese patients with new endoprostheses and evidence of sac shrinkage in early Cat scans.

Sac Pressure Monitoring

As was mentioned earlier, the "Achilles heel" of the endovascular therapy of AAA is the endoleak, which can beget aneurysm growth and potential risk of rupture. On the other hand, sometimes the sac pressure rises without evident endoleaks; this phenomenon is called "endotension". Whether or not this is due to missed endoleaks or revascularization of the aneurismal sac or other mechanisms is not yet clear.38,39 but it is important inasmuch as it can put the patient at risk of rupture. Therefore, pressure measurement can be utilized to monitor the sac and predict the complications or need for re-intervention.

The primary attempts to measure the pressure were

Mehrab Marzban et al

TEHRAN HEART CENTER


comprised of the direct puncture of the aneurismal sac with a needle40,41 or the insertion of a catheter with a tip sensor during or after EVAR.42 The newer technique is the use of wireless pressure sensors, which enables us to measure the sac pressure via a less invasive technique. There are two types of the sensor: ultrasound-based and radiofrequency-based. The main drawbacks of this monitoring are its inaccuracy and cost. In many centers, it is still an experimental tool; in general, however, it can be considered an adjunctive tool and holds promise for the future.

Radiography

Plain radiography remains a valuable technique for the follow-up of EVAR patients in spite of the availability of multiple sophisticated imaging modalities. Radiographs are still considered by some to be superior to CT scans for demonstrating the conformation of thoracic stent-grafts43

and are important for detecting kinks in abdominal stent-grafts.44 Nonetheless, improvements in multislice CT, along with advances in other imaging tools, may require a reevaluation of the added clinical value of radiographs.

Conclusion

EVAR has gained acceptance as an efficient and minimally invasive therapeutic option for patients with aortic aneurysms, but the main problem is the need for life-time surveillance, which is crucial to detect the major complication of endoprostheses, namely endoleaks.

CT angiography is still the gold standard for follow-up, but MR imaging and contrast-enhanced ultrasonography are adjunctive. Defining a rigid protocol for all patients does not seem to be justified and it should be individualized according to the patient’s age and compliance, cost, type of the stent-graft, anatomy of the aneurysm, and the results of previous imaging.

References

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42. Sonesson B, Dias N, Malina M, Olofsson P, Griffin D, Lindblad B, Ivancev K. Intra-aneurysm pressure measurements in successfully excluded abdominal aortic aneurysm after endovascular repair. J Vasc Surg 2003;37:733-738.

43. Chabbert V, Otal P, Bouchard L, Soula P, Van TT, Kos X, Meites G, Claude C, Joffre F, Rousseau H. Midterm outcomes of thoracic aortic stentgrafts: complications and imaging techniques. J Endovasc Ther 2003;10:494-504.

44. Fearn S, Lawrence-Brown MM, Semmens JB, Hartley D. Follow-up after endovascular aortic aneurysm repair: the plain radiograph has an essential role in surveillance. J Endovasc Ther 2003;10:894-901.

Mehrab Marzban et al


TEHRAN HEART CENTER

Assessment of Myocardial Viability: Selection of

Patients for Viability Study and Revascularization

Hakimeh Sadeghian, MD*, Jalil Majd-Ardakani, MD, Masoumeh Lotfi-Tokaldany, MD


Review Article

Abstract

*Corresponding Author: Hakimeh Sadeghian, Assistant Professor of Cardiology, Echocardiography Department, Tehran Heart Center, North Kargar

Street, Tehran, Iran. 1411713138. Tel: +98 21 88029257. Fax: +98 21 88029256. E-mail: [email protected].

Keywords:

The aim of this article is to review the application of current imaging techniques used for the detection of viable myocardium.

herein are dobutamine stress echocardiography, single photon emission tomography, magnetic resonance imaging, positron

the amount of viable myocardium that could predict a better outcome after revascularization being a challenging issue, the

present article also reviews a variety of cut-off points suggested by different investigators as adequate viable myocardium for

selecting patients for viability study.

Introduction

Viable myocardium can be defined as myocardium that shows severe hypokinesia or akinesia at resting echo which will improve in function after revascularization. Armstrong explained viability as recovery of function (either regional or global) and reduction in symptoms after revascularization.1

The term “viable” describes myocardial cells that are alive. A precise definition of this term is given by Underwood and colleagues,2 who carefully defined that this term, whether applied to a myocyte or to a segment of the myocardium, implies nothing with regard to contractile state. Thus, viable myocardium may contract normally or it may be dysfunctional, depending on other circumstances.The contractile dysfunction of viable myocardium may be seen in two syndromes: myocardial stunning and myocardial hibernation. Myocardial stunning results from a transient coronary occlusion followed by reperfusion and has been defined as reversible myocardial contractile dysfunction

in the presence of normal resting myocardial blood flow.3

Myocardial hibernation refers to chronic ventricular dysfunction associated with severe coronary artery disease with complete or partial recovery of contractile function occurring after revascularization.4 Vanoverschelde et al.5

explained that in a subgroup of patients with non-infarcted collateral-dependent myocardium, immature or insufficiently developed collaterals do not provide adequate flow reserve. Despite nearly normal resting flow and oxygen consumption, these collateral-dependent segments exhibit chronically depressed wall motion and demonstrate marked ultrastructural alterations on morphological analysis. The authors proposed that these alterations are in consequence of repeated episodes of ischemia as opposed to chronic hypoperfusion and represent the flow, metabolic, and morphological correlates of myocardial "hibernation".

The term "ischemic cardiomyopathy" is also used by many investigators to describe the condition of the myocardium damaged by severe coronary artery disease (CAD). This

J Teh Univ Heart Ctr 1 (2009) 5-15

6


term has yet to be defined for clinical use. A report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force defined the term “ischemic cardiomyopathy” as a dilated cardiomyopathy with impaired contractile performance not explained by the extent of CAD or ischemic damage.6 After this definition, many authors referred this term to the state in which CAD accompanies left ventricular (LV) dysfunction. Bart et al.7 found the association of the extent of CAD in a large population with both symptomatic and asymptomatic LV dysfunction. A standardized definition of ischemic cardiomyopathy for use in clinical research was developed by Felker et al.8

By this definition, the presence of ejection fraction (EF) <40% in patients with a history of myocardial infarction or revascularization, >75% stenosis of the left main or proximal left anterior descending artery, or >75% stenosis of two or more epicardial vessels indicates ischemic cardiomyopathy.

Searching for viability in patients with multi-vessel CAD and LV dysfunction is an important issue because more than 50% of dysfunctional segments are viable.9 Although patients with reduced LVEF and multi-vessel CAD have shown improved survival after surgical revascularization, 10-15 suchpatients have increased surgical risk and lower long-term survival rates compared to those with better ventricular function.11 The main goal of a myocardial viability assessment is to identify patients whose symptom and functional capacity may improve after revascularization.

No prognostic benefit of revascularization was found in patients with poor LV function in one study.11 Be that as it may, further trials showed that patients with CAD and LVEF<35% benefit from coronary artery bypass grafting (CABG) if adequate viable myocardial tissue was present. In these patients, the amount of viable myocardium necessary to result in clinically significant improvements in the outcome after revascularization is unknown.

Different methods for viability assessments include: 1) dobutamine stress echocardiography (DSE), 2) nuclear imaging by single photon emission computed tomography (SPECT), 3) magnetic resonance imaging (MRI), 4) positron emission tomography (PET) with F-18 fluorodeoxyglucose (18F-FDG), and 5) tissue Doppler imaging (TDI). Furthermore, the definite presence of viable myocardium is confirmed by the recovery of resting function after revascularization. Although sensitivity and specificity of these techniques have been evaluated by different studies, there is no general agreement regarding the adequate number of viable segments to predict a better outcome after CABG. The following section reviews different available techniques for viability study, followed by the presentation of the results of a comparison between the more frequently used modalities. The subsequent section will focus upon the amount of viable myocardium thought to be adequate for patients with CAD and low EF if they are to benefit from revascularization.

Dobutamine Stress Echocardiography

Assessment of contractile reserve

For the first time Pierfird and colleagues16 described the ability of DSE to detect stunned myocardium and to separate it from irreversibly infarcted myocardium. Among the different proposed imaging techniques, echocardiography enjoys a widespread use and application in any clinical condition. Based on the experimental findings, catecholamine stimulation in ischemic regions can augment myocardial function before ischemia, which occurs as a result of increased myocardial work and blood demand.17 Early studies supported this concept and showed that there is inotropic reserve in many patients with sustained LV dysfunction by administrating epinephrine.18,19 Furtherreports presented low-dose dobutamine to evaluate inotropic response in many patients with acute and chronic ischemia and identify reversible myocardial dysfunction.

Contractility in dysfunctional but viable myocardium increases after the infusion of low-dose dobutamine. There are four defined responses of dysfunctional regions to dobutamine infusion: 1) sustained improvement, 2) improvement at low dose followed by subsequent worsening, 3) progressive worsening of function, and 4) no change. Improvement in segmental wall motion at peak stress by at least one grade (improvement from akinesia to hypokinesia or from hypokinesia to normal motion) compared to the baseline rest study (before dobutamine infusion) is considered the presence of contractile reserve. Although a methodological definition of the presence of contractile reserve and viable myocardium is similar, there is a trend for the use of the term “contractile reserve” instead of viable myocardium in some recent papers. Segments without contractile reserve with inotropes are not always non-viable; they may show viability according to PET or scan or recovery of resting function after revascularization. It has been suggested that contractile reserve is a more appropriate standard than is the recovery of resting function in terms of functional capacity, preventing LV remodeling, and long-term prognosis.20

EF response to Dobutamine

A few studies have examined the relation between viability and changes in LVEF.21,22 Rocchi G et al.23 demonstrated

predictive of >5% increase in EF with radionuclide ventriculography post-operatively in 60% of patients (8±2 months after CABG), whereas an EF improvement <5% at low-dose DSE was predictive of the absence of post-operative functional recovery in 90% of patients. This group

Hakimeh Sadeghian et al

TEHRAN HEART CENTER


had the highest predictive value (80%) for late functional recovery and EF response to dobutamine infusion was superior to segmental wall motion changes in predicting LVEF recovery after CABG.

Baseline echocardiography

Resting echocardiography provides useful information which may guide viability assessment and assist in viability interpretation. Resting wall motion abnormality is commonly used for viability assessment during the first evaluation of patients. LV end diastolic and systolic volumes in resting echocardiography give additional information to predict global functional recovery.

Left ventricular systolic volume

Regardless of the amount of dysfunctional but viable myocardium, the extent of LV remodeling and enlargement also determines the improvement in function following myocardial revascularization. In the study of Schinkel AF et al.,24 the likelihood of recovery of global function decreased proportionally with the increase in end systolic volume,

likelihood of improvement in LVEF post-revascularization.

sensitivity/specificity (68% and 65%, respectively) to predict the absence of global recovery.

Left ventricular end diastolic volume

The echocardiographic study of 59 patients25 before revascularization showed no relationship between resting LV volumes and improvement in global EF (increased EF >5%) after CABG. Although non-significant, approximately 40% of patients with end diastolic volumes <140 ml improved EF by >5%, compared with 70% of patients with volumes of 140-180 ml and 35% of patients with volumes >180 ml. Patients with a very large end diastolic volume (>220 ml) are unlikely to recover significant function.

Nuclear imaging by Single Photon Emission Computed Tomography

This technique evaluates cell membrane integrity andintactness of mitochondria with Thallium-201 (201Tl)or Technetiumm-99 (99mTc) labeled agents to assess viability. Regional perfusion results in the initial uptake of 201Tl, while sustained uptake depends on cell membrane

integrity and myocardial viability.9 Technetiumm-99 sestamibi assesses perfusion and intact mitochondria under resting conditions and provides information on viability. The addition of nitrate before tracer administration enhances viability detection. There are four markers of viability when utilizing nuclear imaging by SPECT using 201Tl and 99mTc: 1) normal perfusion, 2) reversible defect, 3) redistribution in fixed defects, and 4) tracer uptake>50% on rest images.

Both 201Tl and 99mTc regional activities were reported to be similar in segments with reversible as well as irreversible ventricular dysfunction.26,27 The severity of the defect was the most important variable in predicting improvement in revascularization rather than which tracer was used.28

Magnetic Resonance Imaging

Recently used for the detection of viability, MRI has emerged as an important imaging modality for an accurate assessment of regional myocardial function by quantitative wall thickness analysis.29 Using this variable, segments with an end diastolic wall thickness <5.5 mm never show recovery of function after revascularization. By contrast,

improvement in function after revascularization.9

Similar to echocardiography, MRI can use low-dose dobutamine to evaluate contractile reserve. Investigators have explained that an increased systolic wall thickening during dobutamine infusion is an accurate predictor of functional recovery.30,31 A mean sensitivity of 73% and specificity of 83% were reported for dobutamine MRI (DMRI).32

Gotte et al.33 reported that two-dimensional strain analysis by MRI is more accurate than wall thickness analysis in discriminating dysfunctional from functional myocardium and, therefore, it improves the detection of regional differences in function. Two-dimensional strain analysis provides a strong correlation between regional myocardial function and global ventricular function.

Positron emission tomography with F-18

Cardiac FDG (fluorodeoxyglucose) uptake has traditionally been imaged with PET. In the fasting situation, FDG is taken up mainly by ischemic myocardium, whilst the other areas (scar and normal tissue) do not take FDG.34

PET imaging has been extensively studied in the diagnosis of CAD, as well as the determination of prognosis and assessment of myocardial viability in patients known to have CAD.35,36 F-18 fluorodeoxyglucose PET and SPECT assess glucose metabolism,37,38 but PET is more sensitive and specific than is SPECT for detecting viable


8


myocardium.39 In recent years, PET has turned into the gold standard for non-invasive assessment of myocardial viability and allows an accurate detection of CAD by the assessment of myocardial perfusion.5,40 A review of 20 studies41 showed mean specificity and sensitivity of 58% and 93%, and the mean positive and negative predictive values of 71% and 86% for PET in myocardial viability study, respectively.

Tissue Doppler Imaging

TDI measurements allow the reconstruction of strain and strain rate curves and color-coded images. Echocardiographic strain and strain rate imaging is able to assess myocardial function more reliably.42 This technique quantifies myocardial function, such as longitudinal myocardial shortening, and differentiates between active and passive movement of myocardial segments. The assessment of myocardial viability is one of the most important clinical indications for echocardiographic strain and strain rate imaging.43 The augmentation of strain and strain rate with dobutamine is a marker of myocardial viability.44,45

In the study of Hoffman et al.,46 thirty-seven patients with CAD but viable myocardial segments (detected by PET) underwent strain rate imaging during a low-dose dobutamine stress test. Viable myocardium showed higher strain rates than did scar tissue after dobutamine infusion. An increase in the longitudinal strain rate of more than -0.23 S-1 identified viable tissue with a sensitivity of 83% and a specificity of 84%. The role of strain rate imaging at rest in the detection of ischemia and viability study has recently been under evaluation. A study conducted in our institution by Sadeghian et al. showed that strain and strain rate reduced in akinetic non-viable inferobasal compared to normal segments and the range of strain rate in the studied segments did not overlap with that of normal segments.

Comparison between different methods for viability assessment

Dobutamine Stress Echocardiography and Nuclear Imaging

Many studies have paid attention to a comparison between DSE and nuclear imaging by SPECT.47-49 A comparison analysis showed higher specificity, but a lower sensitivity of stress echocardiography for the detection of reversible contractile dysfunction.35 Agreement between the two methods ranges between 60.8% and 72% in these studies.47,48 Discordance between the two methods was observed more frequently in akinetic segments which were viable by 99mTc-sestamibi imaging, but did not show

contractile reserve by DSE.47,49

As already reported by Sadeghian et al., 90% and 59% of akinetic segments were non-viable by DSE and scan (99mTc), respectively. In addition, the figures were 18% and 16% by the two methods in severely hypokinetic segments. Panza et al.49 suggested that the difference in the mechanisms involved in the identification of myocardial viability by the two techniques is responsible for these variations and the cellular processes responsible for a positive inotropic response to adrenergic stimulation require a higher degree of myocyte functional integrity than those responsible for thallium uptake.

A subset of dysfunctional segments; 5.3% and 2% in two studies;48,49 showed contractile reserve by DSE but did not show technetium uptake. Some investigators49 have explained this observation by the error inherent in the comparison of the two techniques, including poor anatomic correspondence of LV segmentation in some patients. Armstrong1 hypothesized thereafter that if infarction involved 15-25% of the thickness of the myocardium and there was hibernation in the remaining thickness, it would show contractile reserve with DSE, but there was less than 50% uptake by scan (considered as non-viable). On the other hand, because the spatial resolution of radionuclide imaging techniques is not sufficient to accurately determine myocardial thickness, non-transmural myocardial infarction cannot be reliably detected on the basis ofscintigraphic anatomy. A study50 reviewed published papers correlating post-revascularization functional recovery following evaluations by myocardial perfusion imaging and stress echocardiography. The mean values of the sensitivity and specificity of the methods are presented in Table1.

DSE 99mTc-SPECT 201Tl-SPECT

Table 1. Accuracy of three most frequently used techniques for myocardial viability study in pooled data reviewed by Bax et al.

DSE, Dobutamine stress echocardiography; Tc, Technetium; Tl, Thallium; SPECT, Single photon emission tomography; PPV, Positive predictive value; NPV, Negative predictive value

Sensitivity

Specificity

PPV

NPV

81%

80%

77%

85%

81%

66%

71%

77%

86%

59%

69%

80%

Dobutamine Stress Echocardiography and Positron

Comparisons between DSE and PET in the evaluation ofviable myocardium in patients undergoing intravenous thrombolysis following acute anterior wall myocardial infarction showed 79% concordance in the affected segments.51 Early recovery of perfusion in the area at risk was associated with a good functional outcome, whereas a high glucose to perfusion ratio suggested jeopardized myocardium that frequently lost viability. The authors51


TEHRAN HEART CENTER


concluded that echocardiography during dobutamine infusion is a promising method to unmask viable myocar-dium in acute myocardial infarction.

Sawada et al.52 reported 19% of the segments with FDG uptake did not exhibit contractile reserve, so the number of viable tissue required determining the presence of metabolic activity was likely to be less than that required for the detection of contractile reserve. In line with their study, Baer et al.53 reported that dobutamine stimulation underestimated the number of segments with preserved FDG uptake. In patients with severe post-ischemic heart failure (mean EF=25%) and New York Heart Association functional

does PET in identifying the recovery of LV dysfunction.21

For DSE, the “specificity” (no evidence of contractile reserve and functional recovery after revascularization) was higher than that for either delayed thallium-201 uptake or F-18 FDG uptake.37,54 Ghesani et al.54 believe that this is not surprising because the end point of all of these studies was functional recovery, and low-dose dobutamine echocardiography specifically evaluates functional improvement. It is yet under question whether other important parameters such as the prevention of ventricular remodeling and the prevention of life-threatening arrhythmias are better predicted by radionuclide or echocardiographic techniques.

Magnetic Resonance Imaging, Dobutamine Stress Echocardiography and Nuclear Imaging

A study by Zamorano et al.55 compared thallium-201 redistribution imaging, cine DMRI, and DSE for the assessment of myocardial viability in a series of patients with ischemic cardiomyopathy undergoing heart transplantation. The patients were evaluated 3 days before transplantation, and the explanted hearts were analyzed to quantify the amount of living cells per segment thereafter. The results showed that DMRI and DSE identified viable segments similarly, but thallium-201 identified more viable myocardial segments. The authors found differences

between three techniques according to the minimum mass of viable cells required to detect myocardial viability.

In a necrotic area of <31%, DSE was found to be 5.5 times more likely to identify a given segment as viable. In turn, when percentage necrosis was >31%, DSE was 7.7 times more likely to classify the segment as non-viable. For MRI, similar to DSE, in a given segment with a necrotic area of <33%, MRI was found to be 5.2 times more likely to identify such segments as viable. In contrast, when the necrotic percentage of the segment was >33%, the probability of this technique to classify this segment as non-viable was 5.5 higher. Finally, the greatest predictive value for thallium redistribution was reached for a percentage of necrotic tissue of 40%, yielding positive and negative likelihood ratios of 2.2 and 3.6, respectively.

Amount of viable myocardium

Patients without myocardial viability not only do not benefit from CABG but also may have worse prognosis after CABG.21 Although there is no general agreement on the number of viable segments which result in improvement in LVEF and survival after revascularization, it differs between 3-8 viable segments in different studies with different modalities (Table 2).56-61

Patients with CAD and severe LV systolic dysfunction

improved survival at a mean follow-up time of 18±10 months after revascularization.59 The authors pointed out that age and LVEF predicted mortality only in patients who were not revascularized. In revascularized patients, the only significant predictor of mortality was the absence of myocardial viability. They found that revascularization did not improve survival in patients without pre-operative myocardial viability (mortality rate of 17%). In addition, their study showed that patients with myocardial viability who underwent medical therapy had a high mortality rate.

Similar to their findings, Bax et al.60 found that patients


* Data are presented as mean ±SDFDG, Fluorodeoxyglucose; PET, Positron emission tomography; DSE, Dobutamine stress echocardiography; 99mTc, Technetiumm-99; SPECT, Single photon emission tomography; EF, Ejection fraction; NYHA FC, New York heart association functional class; MT, Medical treatment; MI, Myocardial infarction

Study End pointsTechnique for viability study

Number of viable Segments

Frequency after revascularization

Frequencyafter MT

Follow-upduration*

Table 2. Studies comparing prognosis of patients undergoing coronary artery revascularization with those receiving medical treatment with regard to different number of viable segments according to different techniques

Pagano et al.

Afridi et al.

Bax et al.

Senior et al.

He ZX et al.

Sadeghian et al.

FDG PET

DSE

DSE

DSE99mTc SPECT

DSE

33±14

18±10

18.7±8.1

21±8.0

23±14

8

14%

6%

17%

3

0

9%

43%

20%

40%

31%

47%

11%

EF improvement

Death

EF and NYHA FC improvement

Death

Death and MI

Death, NYHA FC improvement

10


33%, P<0.01) and NYHA functional class (from 3.2 to 1.6, P<0.01) at three months after revascularization. In patients with <4 viable segments, LVEF and NYHA functional class did not improve. Patients with <4 viable segments had a higher cardiac event rate at long-term (up to two years) follow-up (47% vs. 17%, P<0.05). A cut-off value of 4 viable segments extracted via the receiver operating curve (ROC) analysis in this study, demonstrated an association between a significant improvement in LVEF after revascularization in

Chiming in with these studies, Senior et al.61 reported that

independent variable to predict reduced mortality (by an average of 95%, with a mortality rate of 3%) and improved LVEF compared to cut-off value of 4/12. In contrast, patients with at least 5 viable segments who were treated medically and patients with fewer than 5 viable segments who underwent revascularization had a much higher mortality rate (31% and 50%, respectively).

To evaluate the predictive value of quantitative PET for symptomatic and functional outcome, Pagano and colleagues62

studied 30 patients with significant stenosis in three coronary

and DSE before CABG and resting echocardiography before and six months after surgery. To determine the number of PET and DE viable segments in each patient required to obtain an improvement of >5% points in LVEF, ROC analysis identified 8 segments as the best discriminator for PET (sensitivity=88%, specificity=75%, area under the curve=75%) and 7 segments for DE (sensitivity=47% specificity=91%, area under the curve=0.69). In another study, Pagano et al.21

and LVEF <35%) and viability study by FDG-PET who underwent CABG. They emphasized three independent factors for cardiac event-free survival after a mean

segments, 2) pre-operative LVEF (24% vs. 19%), and 3) patient’s age. The presence of at least 8/16 viable segments by PET was the best predictor for more than 5% increase in LVEF 6 months after CABG.5

In the study conducted by He ZX et al.,57 the myocardium

reversible segments (according to nitrate-augmented Tc-99m sestamibi SPECT). Event-free survival in the patients with myocardial viability was significantly lower in the surgery group compared to the medical group (100% vs. 53%, respectively). In this study, event-free survival was similar between the surgical and medical groups in patients without myocardial viability. The EF of all the patients was <50%, and the mean EF was not different between the two groups.

Clinical end points and myocardial viability

All the currently employed diagnostic techniques for assessing viability are designed as markers of myocardial viability, but none of them is defined as the standard technique.2 Many studies on viability have focused on different clinical end points. The most commonly used clinical characteristics for this purpose include recovery of resting function and improved EF after revascularization.

In a recent study,63 the correlations of echocardiography parameters at stress tests (by dobutamine and dipyridamole) before and resting echocardiograms immediately after the intervention and after 3, 6, and 12 months were evaluated. The results showed that during a 1-year follow-up period after CABG, significant improvement in LV systolic function was observed (LVEF increased, wall motion score index reduced), with major changes occurring over the first 6 months. The strongest relationship was found between the change in the wall motion score index at stress tests and the improvement in the wall motion score index observed after 6 months. The authors concluded that the wall motion score index calculated during stress was identified to have the strongest prognostic value. The mean increase of EF was about 5% and 6% after 6 months and one year, respectively.

Of 180 revascularized segments with severe rest LV dysfunction in the study of Afridi et al.,64 recovery of resting function was seen in 56 (31%) segments late after angioplasty, 80% of which had early recovery. In this study, 34 patients who showed a biphasic response to DSE had the most improvement one and six weeks after percutaneous coronary intervention (PCI). Patients with sustained improvement during DSE had no signification change in wall motion after PCI. In another study,65 the recovery rates of resting function were 18.2% for severely hypokinetic and 15.6% for akinetic segments respectively at a mean of 8 months’ follow-up. Evidence of contractile reserve was demonstrated in 9.4% of the akinetic and 90.9% of the hypokinetic segments.

Zaglavara et al.20 studied the recovery rate of resting function at 6 weeks, 3 months, and 6 months after surgery and showed that recovery rates at 6 weeks, 3 months, and 6 months post-operatively were 21%, 33%, and 45% for resting function (P<0.01), respectively. The authors reported recovery rates of 52% in hypokinetic and 39% in akinetic segments and a significant increase in EF (10%) 6 months after CABG. They pointed out that recovery in resting function and contractile reserve was time dependent and DSE could predict the myocardium that would demonstrate early recovery in contractile reserve with an excellent accuracy.

Two later studies, however, presented different values of recovery rate for hypokinetic and akinetic regions. There are two possible reasons for this difference: firstly, longer follow-up periods in the study of Zaglavara and coworkers;20

and secondly, patients in the study of Sadeghian and colleagues


TEHRAN HEART CENTER


were relatively on the longer waiting lists for CABG.65 It is believed that a delay in revascularization causes myocardial changes to progress to a more advanced stage.66,67

Relationship between coronary artery patency and viability

There is a paucity of data concerning the relationship between the coronary blood flow and myocardial viability. Investigators68 have assessed whether some angiographic variables could be considered as markers of viability after myocardial infarction. They studied 41 patients with previous Q wave infarction and single-vessel CAD by 201TlSPECT and compared viability with angiographic variables, including the degree of patency and collateralization. They found no association between TIMI grade and reversibility. Collateral circulation to occluded arteries was associated with viability, but its absence did not exclude it. Bourdillon et al.69 analyzed coronary artery in 64 patients with CAD and reduced LV function to assess whether coronary patency could help in assessing viability in relation to PET. They reported that segments supplied by patent arteries were more likely to be viable by PET than were segments supplied by occluded arteries (P<0.001). Akinetic segments were more likely to be supplied by occluded arteries (56 vs. 23, 72%). Dyskinetic segments were predominantly non-viable by PET (86%) and were usually supplied by occluded arteries (77%).

In the study of Kumbasar and colleagues,70 forty-seven patients with total occlusion in one coronary artery underwent DSE for viability study; of whom 18 (38.3%) had viable myocardium in the area shed by the totally occluded coronary artery and 29 (61.7%) had non-viable. The incidences of significant coronary collateral circulation to the viable and non-viable areas were 66.7% (12 patients) and 20.7% (6 patients), respectively (P=0.002). In logistic regression analysis between the angiographic data, the only significant coronary collateral circulation (collateral circulation partially fills the epicardial segments of the recipient coronary artery or collateral circulation completely fills the epicardial segments of the recipient coronary artery) was found to be an independent factor for the detection of viable myocardium. The authors concluded that good coronary collaterals had a high sensitivity (75%) and specificity (65.7%) as well as high positive predictive (75%) and negative predictive values (79%).

Some more factors affecting selection of patients for revascularization

With delay in revascularization, myocardial changes may progress to a more advanced stage with a lower likelihood

of functional recovery.66,67 Presence of ischemic mitral valve regurgitation may also influence the patient’s outcome after surgery. It is recommended that in the case of significant ischemic mitral regurgitation, concomitant mitral valve repair be considered.

The extent of scar tissue may assist in the prediction of the recovery of global LV function in patients with CAD and severe LV dysfunction.71 A model developed by PARR-1 study71 suggested that in patients with extensive scar tissue, bypass surgery could be combined with the resection of non-viable scar tissue.

How to select patients for viability study

It is frequently asked which patients should be considered for viability study. The following clinical, angiographical, and echocardiographic findings can be of great help:

Presence of chest pain is a marker of jeopardized myocardium, but the absence of chest pain and only dyspnea as the main symptom in the presence of severe LV dysfunction (LVEF<35%) may warrant viability study.2

Previous studies have demonstrated the effect of poor quality distal run off in the left anterior descending artery and circumflex marginal branch on the operative mortality.72 It is, therefore, advisable that we recommend viability study for patients with poor run off in these territories in the presence of severe LV systolic dysfunction (LVEF<35%).

As was mentioned previously, some studies have revealed the effect of increased left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) in pre-operative resting echo on post-operative global recovery of resting function. Also, Pagano et al. showed that

LVEF had a significant effect on event-free survival after CABG (25% vs. 19%, P=0.02). As a result, it is reasonable to consider viability study for patients with LVEDV>220,25

LVESV>140,24 or EF <20%.21

With respect to the previous findings by DSE, at least 25-40%59,62 (Table 2) of viable myocardium is required for patients to benefit from revascularization; consequently, it can be said that patients with LVEF<35% and maximum


12


of 9.5 (60%) dysfunctional segments warrant viability study. The most important question is which proportion of dysfunctional segments should be akinetic in resting echo to show the physician the necessity of viability evaluation. As is shown in Table 3, different published studies have found the incidence of viability in akinetic segments to be between 9.4 and 45%.73-75 In addition, this figure was reported to be 40-96.6% for hypokinetic segments. Therefore, 55-90.6% of akinetic and 3.4-60% of hypokinetic segments were non-viable, respectively. As a result, it can be hypothesized that if at least 7 akinetic segments are present in patients with EF <35%, viability assessment may be necessary. Larger studies are required to confirm this hypothesis by reviewing and analyzing the results of related studies.

*Each model is named according to the number of segments that myocardium was divided for

AkineticRatio (%)

HypokineticRatio (%)

Mean EF (%)mean±SD Model*

Table 3. Frequency of viable segments in hypokinetic and akinetic segments assessed by DSE in different studies

Pagano et al.

Bax et al.

Bax et al.

Zaglavara et al.

Sadeghian et al.

Panza et al.

Defilippi et al.

Nagueh et al.

Pace et al.

25±7

28±6

28±8

29±8

31±3.7

32±9

36±9

38±14

40±11

16

16

16

16

16

16

16

-

12

67/156 (43)

36/214 (17)

- /629 (37)

38/134 (28)

3/32 (9.4)

76/170 (45)

27/82 (33)

10/40 (25)

64/183 (35)

104/180 (57)

44/108 (41)

- /646 (63)

85/114 (75)

40/44 (90.6)

97/134/ (72)

133/146 (91)

24/59 (41)

-

Conclusions

If patients with multi-vessel CAD and severe LV systolic dysfunction (EF<35%) meet each of the above-mentioned clinical, angiographical, and echocardiographic criteria, viability study is recommended. We would recommend that DSE be utilized as the first step for viability study, because it is widely available, less invasive, and provides additional information about EF, EDV, ESV, and possible valvular abnormalities.

In our institutional experience, if a patient is suitable for revascularization according to DSE, there is no need for further viability evaluations. The patient is recommended for revascularization if DSE findings meet the following

59,60 and 2) >10% increase in EF after low-dose dobutamine infusion compared to baseline.23

Nonetheless, if the patient is unsuitable or is a borderline case for revascularization according to DSE (suitable case: presence of the two foregoing findings; borderline case: presence of one of the two aforesaid findings), we recommend the use of SPECT (either 201Tl or 99mTc mibi) as a more

sensitive modality. If the scan demonstrates adequate viable myocardium; i.e. 15%,57 we recommend revascularization; otherwise, the patient may benefit from medical treatment.

References

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JACC 1996;28:530-535.

2. Underwood SR, Bax JJ, vom Dahl J, Henein MY, Knuuti J, van

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TEHRAN HEART CENTER

Could Mean Platelet Volume Predicts Impaired Reperfusion

and In-Hospital Major Adverse Cardiovascular Event in

Patients with Primary Percutaneous Coronary

Intervention after ST-Elevation Myocardial Infarction?

Hossein Vakili, MD*, Roozbeh Kowsari, MD, Mohammad Hasan Namazi, MD, MohammadReza Motamedi, MD, Morteza Safi, MD, Habibollah Saadat, MD, Roxana Sadeghi, MD,Sanaz Tavakoli, MD

Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Original Article

*Corresponding Author: Hossein Vakili, Associate Professor of Cardiology, Shaheed Beheshti University of Medical Sciences, Modarres Hospital,

Tehran, Iran. Tel: +98 21 22083106. Fax: +98 21 22083106. E-mail: [email protected].

Background: Due to the positive relation between platelet size and platelet reactivity, a high value of the mean platelet

volume (MPV) is an independent risk factor to predict acute myocardial infarction (AMI) and its adverse outcome. Few data

are available to determinate the prognostic value of MPV in ST-elevation myocardial infarction (STEMI) patients treated with

percutaneous coronary intervention (PCI).

The primary purpose of this study was to evaluate the clinical value of MPV to predict impaired reperfusion and in-hospital

major adverse cardiovascular events (MACE) in acute STEMI treated with primary PCI.

Methods: This study included 203 STEMI patients referring for blood sampling before primary PCI to estimate MPV and

MACE.

Results:

Conclusion:

MACE in acute STEMI patients treated with PCI, but also it could be considered a practical way to determine higher-risk

patients.


Received 15 January 2008; Accepted 08 June 2008

Abstract

Keywords:

18


Introduction

Atherosclerosis and its complications such as acute myocardial infarction (AMI) are regarded as one of the most important causes of death in industrial societies.1 Although there are some known risk factors for coronary artery disease such as age, gender, cigarette smoking, hypercholesterolemia, diabetes mellitus, hypertension, and familial history of AMI,1 the detection of some other factors to determine the true risk of acute coronary syndrome seems necessary.1 Since platelets play an important role in forming intra coronary vascular thrombosis, they are considered a principal cause of AMI.

An increase in platelet size is concomitant with a rise in platelet reactivity. In addition, the mean platelet volume (MPV) has a direct relation with the indicators of platelet activity such as glycoprotein Ib and glycoprotein IIb/IIIa receptors.2-9 Previous studies have established that higher amounts of MPV correlate with a poor outcome in AMI patients; nevertheless, only one study has thus far been conducted on the relation between MPV and the outcome of AMI patients treated with primary percutaneous coronary intervention (PCI).10 The present study sought to determine the value of MPV in AMI patients undergoing primary PCI and its relation with impaired reperfusion and in-hospital adverse outcomes.

Methods

This retrospective, descriptive survey conducted from August 2003 to July 2007 included 214 AMI patients undergoing primary PCI in Modarres Hospital, a university teaching hospital in Tehran, Iran. Eleven patients were excluded subsequently due to a lack of file information and emergency status requiring surgical intervention. Consequently, the population of this study consisted of 203 patients.

AMI was defined as patients with typical chest pain lasting more than 30 minutes and concomitant ECG changes

inferior leads) referring within 12 hours from the onset of symptoms. In addition, patients with cardiogenic shock due to AMI within 24 hours from the onset of their symptoms were investigated in this study. The patients were divided into two groups in terms of their MPV: Group 1: MPV<10.2

Major adverse cardiovascular events (MACE), comprising death, cardiogenic shock, MI, cerebrovascular accident (CVA), and mechanical complications leading to urgent revascularization, were investigated in all the patients.

The CBC of all the patients was sampled on admission in test tubes containing ethylenedinitro tetra acetic acid (EDTA)

Hossein Vakili et al

as an anticoagulant substance. The beginning of sampling to the end of sample analysis took less than 2 hours. All the measurements were done using just one Aoutoanalysor-104 Hitachi hematology system. No patient received clopidogrel, heparin, or integrilin before sampling. All the patients underwent coronary angiography in standard projection for different coronary arteries (Siemens Company) using the Judkins 7F and guiding catheter. The thrombolysis in myocardial infarction (TIMI) flow of the infarct-related arteries was determined before and after PCI. Subsequently, corrected TIMI frame count (CTFC) was measured by two cardiologists not aware of the MPV results in order to have a more quantitative study. The TIMI of the involved vessels was determined before and after PCI. CTFC, defined as an impaired reperfusion, was measured to have a more quantitative study. The no-reflow phenomenon was defined as TIMI<3 after PCI in spite of residual stenosis <50%, absence of significant dissection, or visible thrombosis or spasm. Further more, all the patents were checked as regards having any kind of in-hospital MACE.

All the patients received 325 mg ASA and at least 300 mg Plavix before PCI and received 100 u/kg heparin to achieve Active clotting time (ACT)>300 s or 70 u/kg integrilin and heparin to achieve activated clotting time (ACT)=200-250 during the procedure of PCI. All the collected data were analyzed using SPSS 13 software.

Results

This study recruited 203 patients, comprised of 160 (78.8%) men and 43 (21.2%) women, with a mean age of 56±11.2 years. Of the total study population, 95 (46.8%) patients had three-vessel involvement, 59 (29.1%) had small vessel disease, and only 1 (0.5%) had left main coronary artery disease. Stenting was done for 179 (88.2%) cases. Conventional PCI was performed for 13 (6.4%) patients, and the procedure was unsuccessful in 11 (5.4%) patients. For 35 (17.2%) patients, drug-eluting stents; and for 144 (70.9%) patients, non-drug stents were inserted.

A total of 189 (91.6%) patients had a stable hemodynamic,

admission. The mean systolic blood pressure (SBP) of the patients was 119.7±27.04 mmHg, and their mean MPV was 9.55±0.88 ng/dl. The patients were divided into two groups on the basis of their MPV: Group 1: 158 (77.8%) cases with a low MPV (MPV <10.3 ng/dl) and Group 2: 45 (22.2%) cases

In-hospital MACE was detected in 39 (19.2%) cases, comprised of mortality in 15 (7.4%) cases and other in-hospital major events in 24 (11.8%) other cases consisting of 8 (3.9%) cases of MI, 2 (1%) cases of CVA , 12 (5.9%) cases of shock, and 2 (1%) cases of mechanical complications.

The demographic, clinical, and procedural characteristics

TEHRAN HEART CENTER


Could Mean Platelet Volume Predicts Impaired Reperfusion ...

of the patients in the MPV groups are summarized in Table 1. There was no difference between the patients in the high MPV group and low MPV group with respect to having such factors as age, gender, hypercholesterolemia, diabetes mellitus, hypertension, and prior AMI. Although cigarette smoking was slightly more frequent in the low MPV group, the high MPV group had more patients with a higher Killip class on admission and longer time of hospitalization.

In addition, the number of cases with anterior wall MI and left anterior descending coronary artery involvement in the high MPV group was significantly more than that of the low MPV group, as demonstrated by Table 1.

*Data are presented as the mean±SD (P value for Mann-Whitney test) or percentage of patients (P value for chi-square test)MPV, Mean platelet volume; SBP, Systolic blood pressure; MI, Myocardial infarction; Ant, Anterior, IRA, Infarct-related artery; RCA, Right coronary artery; LCx, Left circumflex artery; LAD, Left anterior descending artery; 3VD, Three vessels disease, TIMI, Thrombolysis in myocardial infarction

Low MPV (n=158)

High MPV (n=45)

P value

Table1. Patient’s demographic, clinical, and procedural characteristics in MPV groups*

Male

Age (y)

SBP (mmHg)

Hypertension

Diabetes mellitus

Cigarette smoking

Hyperlipidemia

Prior MI

Ant wall MI

Killip class

I

II

III

IV

IRA (%)

RCA

LCX

LAD

3VD

Base line

TIMI Flow 0/1

Integrilin

Duration of

hospitalization (d)

0.85

0.12

0.29

0.95

0.13

0.06

0.90

0.45

0.02

<0.01

0.54

0.06

<0.01

0.05

0.34

0.02

0.18

0.43

0.95

0.01

79.1

55.27±10.6

120.98±24.7

31.6

20.3

51.3

36.7

11.4

60.8

91.2

4.4

0

4.4

27.2

8.9

63.9

44.3

81.1

10.8

6.52± 3.12

77.8

58.67±13.29

115.22±33.84

31.1

31.1

35.6

37.8

15.6

80

68.9

6.7

2.2

22.2

13.3

4.4

82.3

55.6

86.7

11.1

9.91±5.23

The mean MPV in the group of patients with the no-reflow phenomenon (11 cases: 5.4%) was 9.98±1.08 ng/dl and in the group without it was 9.35±0.87 ng/dl; there was no significant difference in the mean MPV between these two groups (P=0.17). Nonetheless, the frequency of the no-reflow phenomenon in the high MPV group was significantly higher than that of the low MPV group (P<0.0001, 17.8 % vs. 1.9%).

After adjustment for basic characteristics, MPV remained a strong independent factor to predict the no-reflow phenomenon (Odds Ratio [OR]=2.263, 95% Confidence Interval [CI]=1.47 to 5.97; P<0.002), which indicated that the no-reflow group was 3 times more likely to have

The prognostic significance of MPV to cause the no-reflow phenomenon with a cut-off value of 10.3 ng/dl was determined via the receiver operating characteristics (ROC). The area under the ROC curve showed that the prognostic significance of MPV for the no-reflow phenomenon was 83% (95% CI=.76 to .91). Also, an MPV of 10.3 ng/dl had a sensitivity of 60.1% and specificity of 83.9% to cause the no-reflow phenomenon (Figure 1) (ROC curve).

Figure 1. Sensitivity and specificity of mean platelet volume (MPV) to

predict the no-reflow phenomenon

This study showed that 143 (70.4%) patients had TIMI=0, 25 (12.3%) had TIMI=1, 26 (12.8%) had TIMI=2, and 9 (4.4%) had TIMI=3 before PCI. Additionally, 11 (5.4%) patients had TIMI=0, 7 (3.4%) had TIMI=1, 28 (13.8%) had TIMI=2, and 157 (77.3%) had TIMI=3 after PCI.

Ignoring the amount of MPV, diabetes mellitus was not a risk for the no-reflow phenomenon (P=0.72, 22.9% vs. 18.2%). Also, the prevalence of multi-vessel disease had no significant difference between the group of patients with the no-reflow phenomenon and the group without it (OR=0.72, 95 % CI=0.213 to 2.44; P=0.6).

There was a significant difference between the mean

with CTFC<40 (P=0.001, 10.9±0.92 vs. 9.45±0.85). The

MPV group was significantly more than that of the low MPV group (P<0.0001, 7.8% vs. 37.5%), and also the mean CTFC in the high MPV group was more than that of the low MPV group (P<0.0001, 33.98±18.8 vs. 22.05±9.84). After adjust-ment for basic characteristics, a high MPV was corroborated

univariate and multivariate analyses (Table 2 & Figure 2).

20

The Journal of Tehran University Heart Center Hossein Vakili et al

*Adjusted for age, gender, systolic blood pressure, hypertension, diabetes, hyperlipidemia, smoking, previous myocardial infarction, anterior wall

baseline TIMI flow grade 0/1 and stent utilizationMPV, Mean platelet volume; TIFC, Thrombolysis in myocardial infarction frame count; MACE, Major adverse cardiovascular events

Unadjusted OR (CI: 95%)

Adjusted OR*

(CI: 95%)P value P value

No Reflow

MACE

0.002

0.003

0.004

2.96

(1.47-5.97)

2.16

(1.32-3.55)

2.82

(1.64-4.85)

2.96

(1.47-5.97)

2.09

(1.29-3.39)

2.49

(1.34-4.61)

0.002

0.002

0.001

Figure 2. The correlation between corrected thrombolysis in myocardial infarction frame count (CTFC) and Mean platelet volume (MPV) TIMI, Thrombolysis in myocardial infarction

% (P=0.004, 9.33±0.89 ng/dl vs. 9.88±0.99 ng/dl). Also, the

was more than that of the low MPV group (P=0.001, 12% ng/dl vs. 33.3%); however, there was a negligible relation between the decrease in EF and the increase in CTFC as a negative correlation index (r=0.19, P<0.009) (Figure 3).

Figure 3. The correlation between Corrected TIMI Frame Count (CTFC) and patients’ ejection fractionTIMI, Thrombolysis in myocardial infarction; EF, Ejection fraction

TIMI, Thrombolysis in myocardial infarction; CTFC, Corrected TIMI frame count; MACE, Major adverse cardiovascular events; MI, Myocardial infarction

CTFC<40 P value TIMI=3 P value

Table 3. The correlation between TIMI, Corrected TIMI Frame Count (CTFC); and MACE, mortality, shock and MI

MACE

Mortality

Shock

MI

12(7.6%)

5(3.2%)

4(2.6%)

7(4.5%)

12(26.1%)

10(27.7%)

8(17.4%)

1(2.2%)

0.0010

<0.0001

<0.0001

0.4800

13(8.1%)

5(3.1%)

4(2.5%)

7(4.4%)

0.0100

<0.0001

<0.0001

0.5600

6(25%)

6(25%)

4(16.7%)

0

The mean MPV in the group with mortality was significantly higher than that of the group without mortality (P<0.0001, 9.49±0.86 ng/dl vs. 10.41±0.81ng/dl). Also, there was a significant difference between the mean MPV between the group of patients with in-hospital MACE and the group without in-hospital MACE (P<0.0001, 10.29±0.95 ng/dl vs. 9.46±0.83 ng/dl).

The mean MPV in the group of patients referring with shock was significantly higher than that of the group without shock (P=0.001, 9.5±0.86 ng/dl vs. 10.39±0.92 ng/dl). In addition, the frequency of shock in the high MPV group was more than that of the low MPV group (P<0.0001, 20.5% vs. 1.5%).

The frequency of the recurrence of MI in the high MPV group was higher than that of the low MPV group (P<0.0001, 11.4% vs. 1.9%).

After adjustment for basic characteristics, MPV remained a strong independent predictor to cause in-hospital MACE in patients with STEMI after primary PCI (OR=2.49, 95% CI=1.34 to 4.61; P=0.004) (Table 2).

Discussion

This study recruited 203 patients with a mean age of 56±11.2 years, which was five years less than the mean age of the patients in the Huczek study10 but was approximately similar to the mean age of the patients in other studies on MPV.11 In addition, 78.8% of our patients were men; this percentage was similar to that in other studies on the relation between MPV and acute coronary syndrome insofar as men accounted for 70-80% of their study populations.10-14

The present study compared the demographic, clinical, and procedural factors between high MPV and low MPV patients and found no significant differences between these two groups. This finding was similar to that in another study conducted specifically on the correlation between the risk factors of acute coronary syndrome patients and MPV. The Kilicli-Camur study demonstrated that apart from such known risk factors as age, cigarette smoking, diabetes mellitus, and hypertension, a high MPV was an independent risk factor for acute coronary syndrome and patients’ survival.11 Unlike the present study, in the Huczek study on the relation between MPV and demographic characteristics

TEHRAN HEART CENTER



of patients with primary PCI, the frequency of hypertension, as a risk factor, in the high MPV group was lower than that in the low MPV group.10 This difference is probably due to the fact that patients in the said study were older than our subjects.

Chiming in with the Huczek study, the odds ratio of vessel involvements in our study had no significant difference between the high and low MPV groups. Be that as it may, compared with the Huczeck study, we observed a higher rate of anterior wall MI and left anterior descending artery involvement in our high MPV group.10 There is no logical explanation to justify the high value of MPV as an independent risk factor for anterior wall MI.

The use of different methods for the detection of the no-reflow phenomenon has led to a different prevalence for it in various studies. The no-reflow prevalence with a

obstruction has been reported to be approximately 12-15%.12-14 The no-reflow prevalence with a perfusion grade method has been reported at 29%15 and with contrast echocardiography at 34-39%.16,17

a poor patient outcome such as increased mortality, 30-day mortality, in-hospital MACE, and left ventricular remodeling as well as MI recurrence and heart failure.18-23 The rate of the no-reflow phenomenon was 5.4% in our study, which was less than that in other studies; e.g. 10.8% in the Huczeck study.10 This difference may be because the other studies chose older patients, more patients with killip IV class, more patients with a low EF on admission, and higher-risk patients with a positive past history of MI. Furthermore, unlike the present study, PCI procedures were conducted on graft vessels in other studies.

We found that a high value of MPV was an independent hematological marker for the easier detection of patients

consequently in-hospital MACE might happen after primary PCI.

According to what previous studies have proved, platelet size has a positive relation with platelet reactivity and its aggregation. Also, a higher value of MPV predisposes patients to acute coronary syndrome and in-hospital MACE after acute coronary syndrome.24-30

We showed that the respective sensitivity and specificity of MPV with a cut-off value of 10.3 to cause the no-reflow phenomenon was 60.1% and 83.9%, while in the Huczeck study, the sensitivity and specificity of MPV with the same cut-off point were 61.9% and 74.3%, respectively.10

Although in the present study, a high value of MPV, regardless of adjustment for basic characteristics, was an

correlation test showed a lower correlation index between MPV and CTFC in this study than that in the Huczeck study (P<0.0001, r=0.698 vs. P<.0.0001, r=0.329). These

differences were related to our smaller study population. Moreover in the Huczech study, CTFC=100 was defined conventionally as TIMI=0.1 after PCI; however, this study only chose cases whose CTFC was possible to calculate.10

We demonstrated that a measurement of MPV could be

higher-risk patients for in-hospital MACE. Martin et al. showed that a higher value of MPV, up to six months after MI, was accompanied by an increase in the risk of MI recurrence and 2-year mortality.31 In addition, Huzceck et al. measured MPV on admission and reported that a high MPV was an independent risk factor for 6 months’ MACE.10 In our group of patients with mortality, any type of in-hospital MACE and cardiogenic shock had a higher mean MPV by comparison with the other group with none of those complications. With respect to hospital MI, there was no significant difference in mean MPV between the two groups; however, the frequency of MI, like other causes of mortality and shock, was far higher in the high MPV group. As a result, after the multivariate analysis and adjustment for basic factors, a high MPV remained an independent risk factor for in-hospital MACE. This finding is acceptable inasmuch as MPV is a risk factor for the no-reflow

whose study showed a direct relation between in-hospital mortality and a high MPV on admission, support our findings.32

We showed that mortality and in-hospital MACE rate were 1.36 times more for every 10 frames of increase in CTFC.

a negligible relation between a decrease in EF and increase in CTFC with r=0.19 as a negative correlation index. It may have been in consequence of the fact that we neither utilized a quantitative index to determine EF and nor did we employ a more sensitive index for the left ventricular function. As was

was higher than that of the low MPV group, which indicated that the left ventricular function could strongly predict the long-term mortality of patients with MI.

Limitations of study

Whereas numerous similar studies have used Absiximab during PCI, we made use of integrilin. However, only 22 out of the 203 patients in our study received integrilin, which is much fewer than the subjects in other studies. Therefore, the findings are not suitable for comparison or generalization. On the other hand, because the patients’ characteristics for the prescription of integrilin and the specified protocol were not determined beforehand, the

22

The Journal of Tehran University Heart Center Hossein Vakili et al

results which had no significant differences in different groups of MPV, CTFC, and MACE were not discussable.

Unlike the Huczeck study, we made no intervention on graft vessels. Another weak point in the present study is that time constraints, a lack of facilities for long-term follow-up, and the intention to augment the reliability of the results prompted us to only report in-hospital mortality, compared with several studies on MPV, which had followed 6-month mortality of patients.

Although, EDTA, an anticoagulant of complete blood count samples, can raise the size of the platelet, it was not considered a disturbance in our study because if measurement is done within 60 to120 minutes after sampling, volume change will be about 3.4%;32,33 and if it is done over a 30-minute period after sampling, the rate of increase will be less than 0.5 ng/dl.34

Like other studies, heterotypic platelets were not excluded in our study due to the need for flow-cytometry, which is not only expensive and time consuming but also requires special devices, to which we had no access.

Conclusion

Admission MPV in AMI patients is a strong and independent factor to show impaired reperfusion and its related mortality. Also, MPV measurement is a simple and feasible way to detect high-risk patients requiring different approaches and treatments.

Acknowledgments

This study was approved and supported by Shaheed Beheshti University of Medical Sciences.

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2. Endler G, Klimesch A, Sunder-Plassmann H. Mean Platelet

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3. Van der Loo B, Martin JF. A role for changes in platelet production

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5. Jakubowski JA, Thompson CB, Vaillancourt R, Valeri CR, Deykin

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7. Tschoepe D, Rosen P, Kaufmann L. Evidence for abnormal platelet

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8. Giles H, Smith REA, Martin JF. Platelet glycoprotein IIb/IIIa and

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9. Cameron HP, Ibbotson RM, Carson PHM. Platelet size in

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10. Huczek Z, Kochman J, Filipiak K, Horszczaruk G, Grabowski M.

Mean platelet volume on admission predicts impaired reperfusion and

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284-290.

11. Kiliçli-Çamur N, Demirtunç R, Konuralp C, Eskiser A, Baºaran Y.

Could mean platelet volume be a predictive marker for acute

myocardial infarction? Med SCI Monit 2005;11:387-392.

12. Morishima I, Sone T, Okumura K. Angiographic no-reflow

phenomenon as a predictor of adverse long-term outcome in patients

treated with percutaneous transluminal coronary angioplasty for first

acute myocardial infarction. J Am Coll Cardiol 2000;36:1202-1209.

13. Piana R, Paik GY, Moscucci M. Incidence and treatment of “no

reflow” after percutaneous coronary intervention. Circulation 1994;89:

2514-2518.

14. Dibra A, Mehilli J, Dirschinger J. Thrombolysis in myocardial

infarction myocardial perfusion grade in angiography correlates with

myocardial salvage in patients with acute myocardial infarction treated

with stenting or thrombolysis. J Am Coll Cardiol 2003;41:925-929.

15. Ito H, Okamura A, Iwakura K. Myocardial perfusion patterns related

to thrombolysis in myocardial infarction perfusion grades after coronary

angioplasty in patients with acute anterior wall myocardial infarction.

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16. Tarantini G, Cacciavillani L, Corbetti F. Duration of ischemia is a

major determinant of transmurality and severe microvascular obstruction

after primary angioplasty: a study performed with contrast-enhanced

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17. Hearse DJ, Bolli R. Reperfusion induced injury: manifestations,

mechanisms, and clinical relevance. Cardiovasc Res 1992;26:101-108.

18. Baks T, van Geuns RJ, Biagini E. Effects of primary angioplasty

for acute myocardial infarction on early and late infarct size and left

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20. Kawamoto T, Yoshida K, Akasaka T. Can coronary blood flow

velocity pattern after primary percutaneous transluminal coronary

angiography predict recovery of regional left ventricular function in

patients with an acute myocardial infarction? Circulation 1999;100:

339-345.

21. Haager PK, Christott P, Heussen N. Prediction of clinical outcome

after mechanical revascularization in acute myocardial infarction by

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532-538.

22. De Luc G, van’t Hof AW, de Boer MJ. Impaired myocardial

perfusion is a major explanation of the poor outcome observed in

patients undergoing primary angioplasty for ST-segment-elevation

myocardial infarction and signs of heart failure. Circulation

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23. Berger PB, Ellis SG, Holmes Jr. Relationship between delay in

performing direct coronary angioplasty and early clinical outcomes in

patients with acute myocardial infarction: results from the global use

of strategies to open occluded arteries in acute coronary syndromes

(GUSTO-IIb) trial. Circulation 1999;109:958-961

24. Endler G, Klimesch A, Sunder-Plassmann H. Mean platelet

volume is an independent risk factor for myocardial infarction but not

for coronary artery disease. Br J Haematol 2002;117:399-404.

25. Jakubowski JA, Adler B, Thompson CB. In fluence of plate let

volume on the ability of prostacyclin to inhibit platelet aggregation and

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distribution and their sensitivity to agonist in patients with

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outcome after myocardial infarction. Lancet 1991;338:1409-1411.

32. Pabon P, Nieto F, Morinigo JL. The effect of mean platelet

volume on the short-term prognosis of acute myocardial infarction.

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the mean platelet volume in elderly patients with risk factors for

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volume. Am J Hematol 1984;16:161-170.


TEHRAN HEART CENTER

A Hospital-Based Study on Causes Peculiar

to Heart Failure

Hamzullah Khan, MBBS, MPH*, Hikmatullah Jan, FCPS, Muhammad Hafizullah, FRCP

Department of Cardiology, Postgraduate Medical Institute, Lady Reading Hospital, Peshawar, Pakistan.

Original Article

*Corresponding Author: Hamzullah Khan, Department of Cardiology, Postgraduate Medical Institute, Lady Reading Hospital, Peshawar, Pakistan.

Postal code: 25120. Tel & Fax: +92 345 9283415. Email: [email protected].

Background: We sought to determine the frequency of the risk factors for congestive cardiac failure (CCF) in a tertiary

care hospital in Peshawar, Pakistan.

Methods: This retrospective, observational study was conducted in the department of cardiology, Postgraduate Medical

Institute, Lady Reading Hospital Peshawar, from March 2005 to September 2007. Relevant information regarding the risk

factors of CCF was recorded on questionnaires, devised in accordance with the objectives of the study.

Results:

ranged from 6 years to 82 years with a mean age of 48.5 years and a mode of age of 45 years. The distribution of the

Conclusion: Ischemic heart disease, hypertension, cardiomyopathy, valvular heart disease, and congenital heart disease

were the major contributors to CCF in our patients.


Received 14 July 2008; Accepted 24 December 2008

Abstract

Keywords:

Introduction

Congestive heart failure, also referred to as congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood through the body.1 It is not to be confused with “cessation of heartbeat”, which is known as asystole, or with cardiac arrest, which is the cessation of normal cardiac function with subsequent hemodynamic

collapse leading to death. Because not all patients have volume overload at the time of initial or subsequent evaluation, the term “heart failure” is preferred over the older term “congestive heart failure”.2 CCF is often undiagnosed due to a lack of a universally agreed definition and difficulties in diagnosis, particularly when the condition is considered “mild”. Even with the best therapy, CCF is associated with an annual mortality of 10%.3

The symptoms depend largely on the side of the heart which is failing predominantly. Given that the left side of the heart pumps the blood from the lungs to the organs,

26

The Journal of Tehran University Heart Center Hamzullah Khan et al

failure to do so leads to the congestion of the lung veins and symptoms that reflect this, as well as a reduced supply of blood to the tissues. The predominant respiratory symptom is shortness of breath on exertion (or in severe cases at rest) and easy fatigability.4 Echocardiography is commonly used to support a clinical diagnosis of CCF. This modality uses ultrasound to determine the stroke volume (SV), which is the amount of blood that exits the ventricles with each beat; the end-diastolic volume (EDV), which is the total amount of blood at the end of diastole; and the SV in proportion to the EDV, which is a value known as the ejection fraction (EF). Normally, EF should be between 50% and 70%; however, in systolic heart failure, it drops below 40% ( Smith A, Aylward P, Campbell T. Therapeutic Guidelines: Cardiovascular, 4th edition. 2003). No system of diagnostic criteria has hitherto been agreed upon as the gold standard for CCF. Commonly used systems are the Framingham criteria5 (derived from the Framingham Heart Study), the Boston criteria,6 and the Duke criteria.7 Functional classification is generally done in accordance with the New York Heart Association Functional Classification.8

The American Heart Association has reported the following causes of CCF:9

Causes of left-sided CCF: hypertension (high blood pressure), aortic and mitral valve disease, and aortic coarctation

Causes of right-sided CCF: pulmonary hypertension (e.g. due to chronic lung disease), pulmonary valve disease, and tricuspid valve disease

Causes that may affect both sides: ischemic heart disease (due to insufficient vascular supply, usually as a result of coronary artery disease); this may be chronic or secondary to acute myocardial infarction (a heart attack), chronic arrhythmias (e.g. atrial fibrillation), cardiomyopathy of any cause, cardiac fibrosis, chronic severe anemia, and thyroid diseases (hyperthyroidism and hypothyroidism)

The present study was designed to determine the frequency of the risk factors for CCF in a tertiary care hospital in Peshawar, Pakistan.

Methods

This retrospective, observational study was conducted in the department of cardiology, Postgraduate Medical Institute, Lady Reading Hospital Peshawar (PGMI/LRH), from March 2005 to September 2007.

This study randomly included 1019 patients, consisting of 583 (57.12%) men and 436 (42.78%) women, with an established diagnosis of CCF based upon clinical findings and relevant investigations. All the data were hospital-based, and only patients admitted with CCF in the cardiology unit of PGMI/LRH were recruited. It may be deserving of note

that this teaching hospital, located in a north-west frontier province of Pakistan, is the only cardiac interventional centre in the public health sector that provides cardiac health to afghan refugees as well. Out-patient department patients with CCF were not included in the study.

The modalities utilized for the diagnosis of ischemic heart disease were electrocardiograms (ECG), echocardiography, and coronary angiography. Hypertension was defined as systolic blood pressure more than 140 mmHg and diastolic blood pressure more than 90 mmHg in our study. Cardiomyopathies were diagnosed via echocardiography.

A detailed history of the patients was taken with the help of a predesigned questionnaire, prepared in accordance with the objectives of this study. The questionnaire also contained information regarding the age, sex, address, and occupation of the patients.

All the patients with CCF, irrespective of age and sex, were included. The chief complaints and a detailed history of all the patients were recorded. The past and family history of major risk factors such as hypertension, ischemic heart diseases, valvular heart diseases, congenital heart diseases, and thyroid diseases were also registered. The clinical symptoms recorded were shortness of breath, history of ischemic heart diseases, peripartum history, palpitation, and swelling of the body. Tachycardia, positive leg edema, valvular abnormalities on auscultation, and cardiomyopathies were considered the signs of CCF. The blood pressure of all the patients was recorded. Fasting blood sugar, random blood sugar; serum cholesterol level, and triglyceride levels were also recorded from the ward record of the patients. ECG, echocardiography, and chest X-ray findings suggestive of CCF were also noted. In a few cases, thyroid function tests and Troponin T cardiac enzymes tests were carried out to further assess the patients with CCF secondary to ischemic heart disease and thyroid dysfunction. Exclusion criteria were all patients with similar clinical features to CCF due to other causes such as asthma and chronic obstructive pulmonary disease that had yet not progressed to CCF.

Finally, the results were analyzed and the association between the risk factors and CCF was studied.

Results

This study included 1019 patients with an established diagnosis of CCF on the basis of clinical findings and pertinent investigations. The study population was comprised of 583 (57.12%) men and 436 (42.78%) women. The patients’ age ranged from 6 years to 82 years with a mean age of 48.5 years and a mode of age of 45 years (Table 1). The respective mean age of the males and females was 49.3 and 45.6 years.

The distribution of the causative factors of CCF was:

TEHRAN HEART CENTER


A Hospital-Based Study on Causes Peculiar to Heart Failure

ischemic heart disease in 38.56%; hypertension in 26.30%; dilated cardiomyopathy in 10.10%; obstructive and restrictive cardiomyopathies in 5.39%; valvular heart diseases in 9.32%; congenital heart diseases such as ventricular septal defects and atrial septal defects in 4.41% and 0.58%, respectively; constrictive pericarditis in 1.07%; pericardial effusion in 0.68%; chronic obstructive pulmonary disease and pulmonary hypertension in 1.47%; thyrotoxicosis in 0.68%; complete heart block in 0.29%; and Paget’s disease in 0.09% of the cases (Table 2).

Age range Number of patients Percentage of total (%)

Table 1. Age-wise distribution of congestive cardiac failure patients (n=1019)

Table 2. Distribution of causes of congestive cardiac failure (n=1019)

COPD, Chronic obstructive pulmonary disease

0-20 (y)

21-40 (y)

41-60 (y)

>60 (y)

Ischemic heart disease

Hypertension

Dilated cardiomyopathy

Obstructive and restrictive

cardiomyopathies

Mitral valve diseases

Mitral and aortic involvement

Combined mitral, aortic and

tricuspid diseases

Tricuspid incompetence alone

Ventricular septal defects

Atrial septal defects

Constrictive pericarditis

Pericardial effusion

COPD and pulmonary hypertension

Thyrotoxicosis

Complete heart block

Paget disease

152

225

468

174

370

268

103

55

33

47

13

2

45

6

11

7

15

7

3

1

14.91

22.08

45.92

17.07

38.56

26.30

10.10

5.39

3.23

4.61

1.27

0.19

4.41

0.58

1.07

0.68

1.47

0.68

0.29

0.09

Number of patientsCause

Percentageof total (%)

Discussion

CCF is a condition in which the function of the heart as a pump to deliver oxygen-rich blood to the body is inadequate to meet the requirements of the body. CCF can be caused by diseases that weaken the heart muscle, diseases that lead to the stiffening of the heart muscles, or diseases that increase oxygen demand by the body tissues beyond the capability of the heart to deliver.10 In the present study, we assessed patients within an age range of 6 years to 82 years (mean age,

48.5 years; mode of age, 45 years). The prevalence of CCF is known to rise with increasing age and affects about 10% of the population older than 75 years of age.11 We observed that ischemic heart disease was the most common cause of CCF as it was recorded in 36.31% of our cases. The findings of many studies reported from various countries of the world chime in with our findings.12-14 Hypertension, recorded in 26.30% of the cases, was the second most common risk factor for CCF in our patients. Hypertension is a major risk factor for developing cardiac hypertrophy and heart failure. It has been reported that hypertrophied and failing hearts display alterations in excitation-contraction (E-C) coupling. However, it is unclear whether the remodeling of the E-C coupling system occurs before or after the development of heart disease. Chen-Izu Y et al.15 reported that hypertension caused changes in the E-C coupling system, which in turn induced hypertrophy.

Cardiomyopathies were the third most important cause of CCF in our patients (15.49%). Cardiomyopathy is regarded as primary when the heart is considered to be the only organ involved. In secondary cardiomyopathy, heart lesion is part of a systemic disease.

Dilated cardiomyopathy was recorded alone in 10.10% of our cases and obstructive and restrictive cardiomyopathies in 5.39% of the cases. Our finding is concordant with that of Khan MA et al.16 from Pakistan. In the present study, 9.32% cases of CCF were attributed to valvular heart diseases. Mitral valve disease was encountered in 3.23% of the cases, which is line with the Aizawa K et al. study.17 Aortic, tricuspid, and pulmonary involvement was also significant in our study, and this finding matches results observed in various international studies correlating valvular diseases with CCF. 18,19 Congenital heart disease is believed to be the leading factor for the development of CCF. Ventricular septal defect was observed in 45 patients in our series. The prevalence of congenital heart disease is likely to be underestimated because of the trend towards home deliveries and the brief stay of neonates in the hospital in case of hospital deliveries. Most cases are detected upon referral for cyanosis, clubbing, or cardiac murmur. The number of patients with congenital heart disease is on the increase because of a steady addition and increased longevity.20 The prevalence of ventricular septal defect and atrial septal defect in a study reported from Pakistan was 21% and 16% of the patients, respectively.21

There were 7 cases of pericardial effusion in our series. These patients had developed pericarditis of myocarditis due to underlying pericardial effusion and had then developed left ventricular dysfunction. CCF is a serious condition, for which no definite cure has thus far been discovered. Be that as it may, CCF patients can live a full and enjoyable life with the right treatment and constant attention to their lifestyle. Fortunately, the major risk factors for CCF are modifiable and can easily be prevented.

28


Conclusion

In our patients, ischemic heart disease, hypertension, cardiomyopathy, valvular heart disease, and congenital heart disease were the major contributors to CCF, whereas constrictive pericarditis, pericardial effusion, chronic obstructive pulmonary disease and pulmonary hypertension, thyroid disease, complete heart failure, and Paget’s disease were the minor contributors to CCF.

Acknowledgments

This study was approved and supported by lady Reading Hospital, Peshawar, Pakistan.

References

Hamzullah Khan et al

1. Neubauer S. The failing heart: an engine out of fuel. N Engl J Med

2007;356:1140-1151.

2. Krumholz HM, Chen YT, Wang Y, Vaccarino V, Radford MJ,

Horwitz RI. Predictors of readmission among elderly survivors of

admission with heart failure. Am Heart J 2000;139:72-77.

3. Raphael C, Briscoe C, Davies J. Limitations of the New York heart

association functional classification system and self-reported walking

distances in chronic heart failure. Heart 2007;93:476-482.

4. Auble TE, Hsieh M, McCausland JB, Yealy DM. Comparison of

four clinical prediction rules for estimating risk in heart failure. Ann

Emerg Med 2007;50:127-135.

5. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural

history of congestive heart failure: the Framingham study. N Engl J

Med 1971;285:1441-1446.

6. Carlson KJ, Lee DC, Goroll AH, Leahy M, Johnson RA. An

analysis of physicians’ reasons for prescribing long-term digitalis

therapy in outpatients. J Chronic Dis 1985;38:733-739.

7. Harlan WR, Oberman A, Grimm R, Rosati RA. Chronic

congestive heart failure in coronary artery disease: clinical criteria. Ann

Intern Med 1977;86:133-138.

8. Raphael C, Briscoe C, Davies J. Limitations of the New York heart

association functional classification system and self-reported walking

distances in chronic heart failure. Heart 2007;93:476-482.

9. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS,

Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates

JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW, Antman EM,

Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Halperin

JL, Hiratzka LF, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel

B; American College of Cardiology; American Heart Association

Task Force on Practice Guidelines; American College of Chest

Physicians; International Society for Heart and Lung Transplantation;

Heart Rhythm Society. ACC/AHA 2005 Guideline Update for the

Diagnosis and Management of Chronic Heart Failure in the Adult:

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Association Task Force on Practice Guidelines (Writing Committee

to Update the 2001 Guidelines for the Evaluation and Management of

Heart Failure): developed in collaboration with the American College

of Chest Physicians and the International Society for Heart and Lung

Transplantation: endorsed by the Heart Rhythm Society. Circulation

2005;112:e154-235.

10. Balaguru D, Artman M, Auslender M. Management of heart

failure in children. Curr Probl Pediatr 2000;30:1-35.

11. Collins SP, Hinckley WR, Storrow AB. Critical review and

recommendations for nesiritide use in the emergency department. J

Emerg Med 2005;29:317-329.

12. Bradshaw D, Norman R, Pieterse D, Levitt NS; South African

Comparative Risk Assessment Collaborating Group. Estimating the

burden of disease attributable to diabetes in South Africa in 2000. S Afr

Med J 2007;97:700-706.

13. Biccard BM, Bandu R. Clinical risk predictors associated with

cardiac mortality following vascular surgery in South African patients.

Cardiovasc J Afr 2007;18:216-220.

14. Finsterer J, Stollberger C. Noncompaction and neuromuscular

disease with positive troponin-T in a nonagenerian. Clin Cardiol

2007;30:527-528.

15. Chen-Izu Y, Chen L, Banyasz T, McCulle SL, Norton B.

Hypertension-induced remodeling of cardiac excitation-contraction

coupling in ventricular myocytes occurs prior to hypertrophy

development. Am J Physiol Heart Circ Physiol 2007;293:3301-3310.

16. Khan MA, Mohammad J, Hussain M. Frequency and

echocardiographic study of dilated cardiomyopathy in children

presenting with cardiac failure. Pak J Med Sci 2004;20:113-116.

17. Aizawa K, Tateishi A, Sakano Y, Kaminishi Y, Ohki S, Saito T,

Konishi H, Kawada M, Misawa Y. Repair of paravalvular leak after a

third mitral valve replacement. Kyobu Geka 2007;60:903-905.

18. Aqel RA, Hage FG, Zoghbi GJ. Percutaneous aortic

valvuloplasty as a bridge to a high-risk percutaneous coronary

intervention. J Invasive Cardiol 2007;19:238-241.

19. Yang X, Wu Q, Xu J, Shen X, Gao S, Liu F. Repair of flail leaflet

of the tricuspid valve by a simple cusp remodeling technique. J Card

Surg 2007;22:333-335.

20. Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neill CA, Perry

LW, Hepner SI, Downing JW. Congenital heart disease: prevalence at

live birth. The Baltimore Washington infant study. Am J Epidemiol

1985;121:31-36.

21. Ahmad R, Awan ZA, Bukshi F. A prevalence study of congenital

heart disease in NWFP, Pakistan. Pak J Med Sci 2002;18:95-98.


TEHRAN HEART CENTER

Efficacy of Two Streptokinase Formulations in

Acute Myocardial Infarction: A Double-Blind

Randomized Clinical Trial

Mojtaba Salarifar, MD*, Saeed Sadeghian, MD, Ali Abbasi, MD, Gholamreza Davoodi,MD, Alireza Amirzadegan, MD, Seyed Kianoosh Hosseini, MD, Navid Paydari, MD, AidaBiria, MD, Parisa Moemeni, MD


Original Article

*Corresponding Author: Mojtaba Salarifar, Assistant Professor of Interventional Cardiology, Cardiology Department, Tehran Heart Center, North

Kargar Street, Tehran, Iran. 1411713138. Tel: +98 21 88029257. Fax: +98 21 88029256. E-mail: [email protected].

Background:

country, namely Heberkinasa (Heberbiotec, Havana, Cuba) and Streptase (Aventis Behring GmbH, Marburg, Germany).

Methods: We conducted a double-blind randomized clinical trial to compare the two streptokinase formulations, i.e.

Heberkinasa (HBK) or Streptase (STP), in patients with acute myocardial infarction who needed thrombolysis. Thrombolysis

Results:

and complications of both streptokinase formulations.

Conclusion: The present study demonstrated that Heberkinasa is as effective and as safe as a standard streptokinase,

namely Streptase, in a clinical setting.


Received 13 August 2008; Accepted 24 December 2008

Abstract

Keywords:

Introduction

Increasing affluence in the developing countries has ushered in soaring rates of coronary heart disease and death from acute myocardial infarction necessitating increases in treatment, mainly with thrombolysis and primary

percutaneous coronary intervention. In fact, tackling coronary artery disease has become a strategic priority for the World Health Organization.1 Currently, thrombolytics such as streptokinase are the leading agents for the treatment of acute myocardial infarction. Streptokinase is now produced in many countries worldwide. Furthermore, approximately

30


400,000-500,000 patients receive this thrombolytic therapy per year the world over.2 There are various streptokinase preparations in different countries.

Streptokinase is a 47-kDa protein that interacts with the protein plasminogen to form a streptokinase-plasminogen complex capable of converting other plasminogen molecules to plasmin, the well-known proteolytic enzyme, culminating in significant reduction of thrombosis formation and further clotting, because plasmin cannot only degrade fibrin but also fibrinogen. Therefore, this streptokinase-plasminogen complex with its potentials produces a systemic lytic state.2

In our country, Iran, different streptokinase products, including Heberkinasa and Streptase, are available. The former, manufactured by a company in Cuba, is a recombinant streptokinase which is obtained by the isolation and cloning of a streptokinase gene of a strain of Streptococcus equisimilis group C. It contains five mutated amino acids in relation to streptokinase of S. equisimilis of group C. However, these amino acid changes in the molecule do not affect the safety, purity, and potency of this product. Moreover, no difference has thus far been observed regarding tissue distribution and clearance mechanism when comparing Heberkinasa with the natural production in pharmacokinetic studies.3

The latter, Streptase, is a highly purified streptokinase derived from the culture filtrate of beta-hemolytic streptococci of Lancefield group C. Being produced by Aventis Behring GmbH, a marketing authorization holder in Germany, it has been frequently used as the reference formulation for measuring the potency of a number of streptokinase preparations due to its strongest fibrinolytic activity.

Interestingly, there has been a debate among our cardiologists over some significant differences between these two formulations of streptokinase in terms of potency, efficacy, and complications. In other words, Heberkinasa, streptokinase produced in Cuba, was used cautiously and under suspicion of not being as effective and as safe as a reference streptokinase such as Streptase, although there were no supporting and documented data for this claim.

Not only have previous studies been successful in confirming that Heberkinasa meets the standard criteria for being an effective anti-thrombolytic agent such as using clot lysis assay described in the British Pharmacopoeia of 1998 for the determination of potency of streptokinase in quality control laboratories,3 but also clinical implications have frequently confirmed this claim through different investigations.

More importantly, there are several means by which the efficacy and success rate of a thrombolytic agent in bringing back the patency of vessels can be evaluated. As an example, angiography done within 90 minutes post-myocardial infarction is a very efficient way in assessing the efficacy of thrombolysis. As it is a time-consuming and

Mojtaba Salarifar et al

money-demanding procedure that sometimes can be threatening to the patient’s unstable hemodynamic status, it would not be feasible for all patients. Nevertheless, there are some other invaluable criteria such as noticeable ST resolution in leads which have ST-segment elevation, or abrupt cessation or moderate significant diminish in the chest pain, and the different pattern of enzyme rise that are specific for myocardial infarction and myocardial tissue reperfusion like creatine kinase MB (CKMB), which can be addressed as a sign of improvement in the tissue reperfusion and success of thrombolysis.4-9

In this randomized double-blind clinical trial, we evaluated the efficacy and safety of these two formulations.

Methods

This survey is an ongoing randomized double-blind clinical trial that commenced collecting participants in 2004 in Tehran Heart Center. The data in this article, however, have a limited time interval, namely between December 2004 and January 2006. The project was confirmed by the Ethics Committee of Tehran Heart Center Research Bureau, according to the Declaration of Helsinki. All the streptokinases were safe to use. In this study, we did not require informed consent of the patients inasmuch as we sought to decrease the probable potential stress and the acuity of the clinical situation.

The study group was comprised of patients who were between 18 and 75 years of age and met the characteristics of acute myocardial infarction for which thrombolysis was indicated. These characteristics were: chest discomfort within the last 12 hours in addition to one of the following: ST segment elevation more than 2 mm in two or more contiguous precordial leads, ST segment elevation more than 1 mm in two or more contiguous limb leads, posterior infarction (dominant R waves and ST depression in V1-V3), and finally new onset left bundle branch block.

Patients in whom thrombolysis was contraindicated were excluded from our study. These contraindications were active bleeding and a history of stroke, which was defined with creatinine blood level more than 2 mg/d, systolic blood pressure more than 200 mmHg, diastolic blood pressure more than 110 mmHg, being on warfarin, and pregnancy.

After the inclusion of patients, a study coordinator used a computer-driven random number algorithm to assign each patient to receive either Heberkinasa (n=119) or Streptase (n=102). All streptokinases were delivered to the observer in syringes coded by a randomizer. The staff of the emergency department was unaware of coding. The sample size was estimated to be 102 patients in group 1 (Streptase) and 119 patients in group 2 (Heberkinasa).

The observer took the patients’ data using a special questionnaire. Demographic, clinical, procedure conduct, hemodynamic, and angiographic data as well as clinical

TEHRAN HEART CENTER


adverse events or side effects were all recorded by the observer and angiographers and were refined by the study coordinator using a standard data collection form. The patients were infused with streptokinase in accordance with a well-defined protocol ordered by a cardiologist.

According to our protocol, our ideal plan was to perform angiography within 72 hours for all the patients, and the patency rate according to thrombolysis in myocardial infarction (TIMI) was computed. TIMI 3 flow was regarded as patent arteries.

Systemic blood pressure was monitored, and any change in hemodynamic stability was recorded during streptokinase infusion.

Electrocardiogram (ECG) at baseline and three hours after starting thrombolysis was obtained. In ECG, the significant ST resolution that could be addressed as a sign of successful treatment was defined as at least a 50% decrease in the sum of ST segment elevation on concordant leads and was assessed in both groups. Blood samples were collected at baseline, 12, and 24 hours within starting infusion to monitor the serum levels of the CKMB isoenzyme level, total CK, and troponin.

The patients were followed closely for adverse events during and 24 hours after the thrombolysis. The side effects were categorized according to their severity and were defined as follows:1) Severe side effects: life-threatening conditions, including intracranial hemorrhages, anaphylaxis, or compromised hemodynamic. In this case, streptokinase was discontinued and could not been reordered. 2) Moderate side effects: streptokinase was discontinued, but it could be restarted on the physician’s order. 3) Mild side effects: minor complaints. The medication was continued with no intervention or only treated conservatively. Within 48 hours, coronary angiography was performed with standard technique and the TIMI flow was documented. The patency rate according to TIMI was computed. TIMI 3 flow was regarded as patent arteries. The catheterization laboratory staff was blinded to the categorization of the patients.

All the patients were followed for 30 days by revisiting or calling to assess 30 days’ mortality or reinfarction. The normally distributed continuous data were presented as mean±SD and analyzed using the Student’s t-test, and the paired t-test was applied to compare before and after intervention levels of the favorable parameters in each group. The non-parametric data (analyzed by Kolmogorov-Smirnov and Shapiro-Wilk tests) were reported as the median (25%, 75%) for the quantitative variables and were analyzed using the Mann-Whitney U-test and Wilcoxon signed ranks tests as appropriate. For the categorical data, the chi-square test was utilized if applicable. All the statistical analyses were performed using Statistical Package for Social Sciences version 16 (SPSS Inc., Chicago, IL, USA). Probability values of P< 0.05 were considered statistically significant.

Results

The mean age of the patients was 56.93±10 years, and men accounted for 88.2% of the study population. The average of body mass index was 26.61±3.65. The patients’ characteristics are summarized in Table 1. The mean pain-to-needle time and door-to-needle time was 262.7±220 minutes (ranged from 0 to 1500 min) and 102.3±62.2 minutes (ranged from 0 to 370 min), respectively.

Chest pain did not subside in 48 (21.7%) patients, while in 6 patients streptokinase infusion was discontinued due to life-threatening side effects. From 139 patients whose pain was subsided, 66 (72 %) patients had ST segment resolution. The clinical success rate and frequency of ST resolution were not significantly different between the two groups. Approximately, half of the streptokinase-treated patients either with Streptase or Heberkinasa were reported having ST segment resolution (Table 2).

Angiography was done for 158 (71.5%) patients: within the first 24 hours for 20 (9%) patients and within 72 hours for 88 (39.8%) patients. The rest of them had angiography after 72 hours. The angiographic patency rate was 69.3% for Heberkinasa and 74.2% for Striptease (P=0.448). The success rate of streptokinase treatment was also similar between the groups (67.7% for Streptase and 67.5% for Heberkinasa; P=0.23). The clinical success rate, which was defined as improvement in the clinical presentation of myocardial infarction in the patients, was 64.5% for Heberkinasa and 68% for Streptase (P=0.583).

Overall, 95 (43%) patients developed complications within the first 24 hours, which were hemorrhage in 4 (1.8%), allergic reactions in 34 (15.4%), hyperthermia in 4 (1.8%), hypotension in 46 (20.8%), and arrhythmia in 27 (12.2%). Some uncommon complications only with Streptase were found, namely hypertension in 3 patients and respiratory distress and cerebrovascular accident, both occurring only once. During hospitalization, 12 (5.4%) patients died; only one patient died due to streptokinase side effects and 11 patients died from other cardiac causes. During follow-up, we documented 4 cases of reinfarction (2 cases in each group) and 3 cases of cardiac death (2 cases in the Streptase group and one in the Heberkinasa group) among the study population up. In-hospital and short clinical outcomes were not significantly different between the two streptokinase-formulation groups (Table 2).

Discussion

Mortality reduction in acute myocardial infarction is dependent upon the efficacy of thrombolytic regimens in terms of re-establishing a normal infarct-related arteryflow. Successful reperfusion of initially occluded infarct-related coronary arteries is the result of complex interplay

32


among clinical, hemodynamic, mechanical, and biochemical factors. Clinical variables that determine the efficacy of thrombolytic therapy, however, have been poorly described. The Global Utilization of Streptokinase and t-PA for occludedcoronary arteries (GUSTO-I) angiography study of fered the unique opportunity to determine the clinicaldeterminants of infarct-related artery patency.

*

*Data are presented as the number of patients (related percentage in parenthesis) or mean±SDMI, Myocardial infarction; RV, Right ventricle; LVEF, Left ventricular ejection fraction; CKMB, Creatine kinase MB; LAD, Left anterior descending; LCx, Left circumflex; RCA, Right coronary artery

Age (y)

Male

Positive family history

Hypertension

Systolic blood pressure

(mmHg)

Diastolic blood pressure

(mmHg)

Diabetes mellitus

Cigarette Smoking

Dyslipidemia

MI location

Posterior

Inferior

Anterior

Anteroseptal

Lateral

RV

Unknown

LVEF (%)

CKMB (IU/l)

Baseline

At 12h

At 24h

Pain-to-needle time (min)

Door-to-needle time (min)

Coronary angiography not

performed

Stenosis >50%

LAD

Proximal

Middle

Distal

LCx

Proximal

Middle

Distal

RCA

Proximal

Middle

Distal

56.9±11.1

92 (90.2)

15 (16.9)

38 (40)

142.2±17.1

91.5±16.3

28 (30.1)

51 (55.4)

43 (44.8)

0

45 (47.4)

28 (29.5)

15 (15.8)

2 (2.1)

5 (5.3)

7 (6.9)

46.5±12

30 (22, 50)

117 (57.5, 186.5)

74 (46, 137.3)

252.2±201.4

105.7±68.9

33 (32.3)

54 (78.3)

46 (66.7)

22 (31.9)

34 (49.3)

0

31 (44.9)

41 (59.4)

30 (43.5)

18 (26.1)

57±10.6

103 (86.6)

15 (13.2)

33 (28.2)

126.5±20.6

78.4±23.2

27 (23.3)

50 (42.4)

54 (47)

2 (1.8)

51 (45.5)

28 (25)

23 (20.5)

5 (4.5)

3 (2.7)

7 (5.9)

46.4±12.4

33 (24.7, 67.5)

101.5 (52.7, 171.6)

74 (37.5, 102.6)

270.9±235.8

99.5±56.3

30 (25.2)

67 (75.3)

51 (57.3)

19 (21.3)

34 (38.2)

3 (3.4)

25 (28.1)

53 (59.6)

44 (49.4)

25 (28.1)

0.944

0.402

0.462

0.070

0.007

0.034

0.265

0.060

0.753

0.483

0.958

0.370

0.489

0.303

0.592

0.475

0.243

0.661

0.231

0.134

0.257

0.163

0.028

0.987

0.457

0.779

Streptase(n=102) P value

Heberkinasa(n=119)

MI, myocardial infarction; RV, right ventricle; LVEF, left ventricular ejec-tion fraction; LAD, left anterior descending; LCx, left circumflex; RCA, right coronary artery

Streptase Heberkinasa P value

Table 2. In-hospital and short-term clinical outcomes and complication of the patients with acute MI

Systolic blood pressure (mmHg)

Diastolic blood pressure (mmHg)

Clinical response (n=193)

Sustained pain

Pain improvement

Incomplete Thrombolysis therapy

ST resolution

Patency rate of Thrombolysis (n=158)

TIMI 3 flow

Clinical

Complications

Hypotension

Allergic reactions

Arrhythmia

Bleeding

Fever and chill

Re-infarction

In-hospital mortality

Total mortality

0.370

0.194

0.093

0.486

0.448

0.230

0.583

0.753

0.687

0.524

0.838

0.238

0.404

0.854

0.744

0.953

86.1±14.8

59.7±13

28 (32.2)

56 (64.4)

3 (3.4)

48 (54.5)

48 (69.3)

(67.7)

66 (64.5)

45 (44.1)

20 (19.6)

14 (13.7)

13 (12.7)

3 (2.9)

1 (1)

2 (2.9)

6 (6)

7 (6.9)

81.4±18.9

54.1±15.1

20 (18.9)

83 (78.3)

3 (2.8)

53 (49.5)

66 (74.2)

(67.5)

81 (68)

50 (42)

26 (21.8)

20 (16.8)

14 (11.8)

1 (0.8)

3 (2.5)

2 (2.5)

6 (5)

8 (6.7)

Streptokinase has been produced extensively by several medication-producing companies, and several research projects have been conducted to evaluate the efficacy of these streptokinases in order to standardize them as safe and effective thrombolytics. In a double-blind multi-centric and parallel study done in India, researchers compared the efficacy and safety of indigenous recombinant streptokinase (Shankinase, r-SK) and natural streptokinase in 150 patients. They reported that in establishing reperfusion, which was assessed by non-invasive parameters such as myocardial creatinine kinase and ST-segment resolution, recombinant streptokinase was as efficacious as natural streptokinase.10

Furthermore, in a clinical trial in China, scientists found out that the China-made recombinant streptokinase was a safe and effective thrombolytic agent.11 In another multi-center, randomized, comparative study of recombinant vs. natural streptokinase in acute myocardial infarction carried out in Cuba in 1999, the researchers randomized 224 patients and investigated fibrinogen levels, Fibrine degradation products (FDP), and thrombin time in all the patients. Coronary angiography was also performed after 5-10 days in patients who had given consent, and the rate of side effects was evaluated in both groups of patients. They found out the recombinant streptokinase behaved similarly to natural streptokinase in terms of coronary patency assessed by angiography and the changes induced on fibrinogen, FDP, and thrombin time. They concluded that recombinant streptokinase met the criteria of being a potent and effective

Mojtaba Salarifar et al

TEHRAN HEART CENTER


thrombolytics.12

In May 2005, the researchers reported that there was enough clinical experience throughout Cuba to support Heberkinasa as a safe streptokinase. First, coronary patency (TIMI 3) was achieved in 14/20 (70%) acute myocardial infarction patients after intracoronary administration of this product. Then clinical studies were performed in acute myocardial infarction patients treated with intravenous 1.5x106 IU of recombinant streptokinase. A randomized trial in 224 patients compared it to the same reference product used by Hermentin et al. (natural streptokinase: Streptase).12 Similar results were obtained with respect to coronary patency, changes in hemostasis, and safety profile. Additionally, anti-streptokinase antibody titres and their anti-streptokinase neutralizing activities in serum were not only comparable between both groups, but also cross-reacting, which shows that the small differences in structure do not seem to have clinical or immunological repercussions. A recent study with this recombinant streptokinase in an albumin-free formulation suggested that its intravenous administration was a safe and appropriate therapy to obtain early (90 min) coronary patency in patients with acute myocardial infarction.13 Moreover, this product had already been successfully used in other applications of thrombolysis such as heart valve prosthesis thrombosis.14 Therefore, they concluded that Heberkinase was clinically useful and safe.15

Furthermore, a national extension study in 2923 acute myocardial infarction patients from 52 hospitals throughout Cuba evaluated Heberkinasa in clinical practice. A 28.3% relative and 4% absolute mortality reduction was found when compared with a survey made before recombinant streptokinase treatment was introduced. Intracranial hemorrhage was only reported in 9 (0.3%) patients.16

More importantly, it is worth mentioning here a study conducted to compare the in vitro characteristics of 16 different streptokinase preparations (among which 3 were recombinant).The amino acid sequences of these three recombinant products tested (recombinant streptokinase from China, Heberkinasa, and STPase) were deviated from the published S. pyogenes streptokinase sequence. Furthermore, the behavior of the recombinant streptokinase proteins in polyacrylamide gel electrophoresis (PAGE) differed considerably from that of the purified native protein. Two of the recombinant products [i.e. Heberkinasa and STPase (two batches)] exhibited very low biological activity [37.2% (Heberkinasa) respectively 20.8% and 23.3% (STPase, two batches) the label claim], and the activity of the third recombinant product (recombinant streptokinase from China) resisted determination. Therefore, the observed differences in recombinant protein sequence and behavior in PAGE were correlated with alterations in the activity of the drug.17

In the present study, the rising ambiguity about the potency of a type of streptokinase preparation namely Heberkinasa prompted us to compare this formulation with a reference

streptokinase such as Streptase in several ways. We mainly focused our analysis of their discrepancy on the results of angiographic findings performed most frequently within 72 hours. However, we did not overlook other criteria, albeit less strong, of successful thrombolysis such as ST-segment elevation, the degree of resolution, and subsiding of chest pain. Our data were consistent with those in previous articles in terms of the efficacy and rate of complications of meeting the criteria of a potent streptokinase. With regard to the angiographic patency rate of TIMI 3 flow, Heberkinasa was obviously as efficient as Streptase. In addition, the frequency of the resolution of elevated ST-segment in the patients who had received Heberkinasa was very close to this number in the patients who had been given Streptase. In fact, several studies have demonstrated the standard efficacy of recombinant streptokinase using laboratory assays such as euglobulin lysis test, plasminogen activation assay, and clot lysis assay plus clinical assessment by means of angiography and ST-segment resolution. Not only were our clinical findings successful in confirming these surveys, but also we showed that the rate of complications of this formulation does not exceed its European counterpart.

Conclusion

Streptokinase is the most widely used thrombolytic agent in Iran, and different trademark formulations of this product that may vary in terms of cost-effectiveness and rate of side effects are available on the market. We evaluated a frequently used streptokinase in our hospitals throughout Iran, namely Heberkinasa, to confirm its effectiveness as a standard thrombolytic formulation. The results of this study were consistent with those of other research programs in demonstrating the standard efficacy of this formulation.

Acknowledgments

This study has been approved by Tehran Heart Center's Review Board and Ethics Committee; and has been supported by Tehran Heart Center, Tehran University of Medical Sciences.

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2. Couto LT, Donato JL, de Nucci G. Analysis of five streptokinase

formulations using the euglobulinlysis test and the plasminogen

activation assay. Braz J Med Biol Res 2004;37:1889-1894.

3. Hernández L, Martinez Y, Quintana M, Besada V, Martinez E.

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Heberkinasa: recombinant streptokinase. Eur Heart J 2005;26:1691.

4. Lundergan CF, Reiner JS, McCarthy WF, Coyne KS, Califf RM,

Ross AM. Clinical predictors of early infarct-related artery patency

following thrombolytic therapy: importance of body weight, smoking

history, infarct-related artery and choice of thrombolytic regimen: the

GUSTO-I experience. Global utilization of streptokinase and t-PA for

occluded coronary arteries. Am Coll Cardiol 1998;32:641-647.

5. Kucia AM, Stewart S, Zeits CJ. Continuous ST-segment

monitoring: a non-invasive method of assessing myocardial perfusion

in acute myocardial infarction. Eur J Cardiovasc Nurs 2002;1:41-43.

6. Davies CH, Ormerod OJ. Failed coronary thrombolysis. Lancet

1998;351:1191-1196.

7. Cundiff DK. Thrombolysis for acute myocardial infarction: drug

review. Med Gen Med 2002;4:6.

8. Qasim A, Chauhan A, More RS. Failed thrombolysis in myocardial

infarction. Int J Cardiol 2000;75:5-14.

9. Gaylani N, Davies S, Tovey J, Kinnarid T, Duly E, Buchalter MB.

Systemic lytic state is not a predictor of coronary reperfusion in acute

myocardial infarction. Int J Cardiol 1996;57:45-50.

10. Diwedi SK, Hiremath JS, Kerkar PG, Reddy KN, Manjunath

CN, Ramesh SS, Prabhavati S, Dhobe M, Singh K, Bhusari P, Rao R.

Indigenous recombinant streptokinase vs natural streptokinase in acute

myocardial infarction patients: phase III multicentric randomized

double blind trial. Indian J Med Sci 2005;59:200-207.

11. Clinical trial of China-made recombinant streptokinase in acute

myocardial infarction. Collaborative Study Group on Thrombolysis with

China-made recombinant streptokinase. Chin Med J (Engl) 1997;

110:50-52.

12. Multicenter, randomized, comparative study of recombinant

vs. natural streptokinases in acute myocardial infarct (TERIMA).

The TERIMA group investigators. Thrombolysis with recombinant

streptokinase in acute myocardial infarct. Thromb Haemost

1999;82:1605-1609.

13. Llerena LD, Quirós JJ, Sainz B, Valdés JA, Zorio B, Villanueva

LH, Filgueiras CE, Cabrera F, Echarte JC, Pérez del Todo JM, Guerrero

I, López L, García EJ, Nadal B, Betancourt BY, Díaz-Rojo G, García

AI, López-Saura P. Angiographic patency study of an albumin-free

recombinant streptokinase formulation in acute myocardial infarction. J

Pharm Pharm Sci 2004;7:372-377.

14. López HP, Cáceres Lóriga FM, Hernàndez KM, Sánchez

HF, González Jimenez N, Marrero Mirayaga MA, López Saura P,

Sigarroa F, Mendoza Y, Rodríguez Alvarez J. Thrombolytic therapy

with recombinant streptokinase for prosthetic valve thrombosis. J Card

Surg 2002;17:387-393.

15. Llerena LD, Cáceres-Lóriga FM, Betancourt BY. Recombinant

streptokinase: evidences from clinical use. Eur Heart J 2005;26:

1448-1449.

16. The TERIMA Group of Investigators. TERIMA-2: national extension

of thrombolytic treatment with recombinant streptokinase in acute

myocardial infarct in Cuba. Thromb Haemost 2000;84:949-954.

17. Hermentin P, Cuesta-Linker T, Weisse J, Schmidt KH, Knorst M,

Scheld M, Thimme M. Comparative analysis of the activity and content

of different streptokinase preparations. Eur Heart J 2005;26:933-940.


TEHRAN HEART CENTER

Relationship between Blood Transfusion and

Increased Risk of Atrial Fibrillation after Coronary

Artery Bypass Graft Surgery

Hassan Radmehr, MD1*, Ali Reza Bakhshandeh, MD1, Mehrdad Salehi, MD1, PouranHajian MD2, Ahmad Reza Nasr, MD1

1Imam Khomeini Medical Center, Tehran University of Medical Sciences, Tehran, Iran.2Besat Hospital, Hamedan University of Medical Sciences, Hamedan, Iran.

Original Article

*Corresponding Author: Hassan Radmehr, Associate Professor of Cardiac Surgery, Tehran University of Medical Sciences, Imam Khomeini Hospital

Complex, Keshavarz Beulevard, Tehran, Iran. Tel: +98 21 61192791. Fax: +98 21 66581595. Email: [email protected].

Background:

of stay, and resource utilization. Although many aspects of AF after cardiac surgery have already been elucidated, the

mechanism by which cardiac surgery predisposes patients to AF has hitherto remained unknown. Recent evidence supports

AF.

Methods: This retrospective study was conducted on 2095 patients who underwent coronary artery bypass grafting (CABG)

alone or accompanied by valve surgery between January 2005 and July 2007. Variables associated with the development of

Results:

Conclusion: Homologous blood transfusion can increase the incidence of new-onset AF after CABG. This factor should

complication and the adverse consequences thereof.


Received 24 June 2008; Accepted 06 December 2008

Abstract

Keywords:

Introduction

New-onset atrial fibrillation (AF) occurs in 10% to 43% of patients in hospital in the wake of cardiac surgical procedures1-6 and is believed to contribute to increased morbidity,1-4 hospital length of stay,1-3 and resource utilization.2,3 Although the demographic, clinical, and

electrophysiological substrates as well as the peri-operative risk factors of new-onset AF have been identified, the mechanism whereby cardiac surgery predisposes patients to AF has eluded the scientific community.1-5 Usually, the incidence of AF is greater in patients with previous AF, chronic obstructive pulmonary disease, right coronary artery stenosis, valve surgery, and increased P-wave duration as

36


well as in patients not receiving beta–blockers after surgery and in those with a low left ventricular ejection fraction.3,4

Furthermore, the technical considerations that may predispose patients to AF include venting through superior pulmonary vein, more systemic hypothermia, division of the anterior aortic fat pad, and post-operative right atrium pacing.

Appropriate management of AF requires the identification and treatment of potential risk factors.1-3 AF can result from ischemia, atrial distention, increased sympathetic tone, electrolyte imbalance particularly hypokalemia and hypomagnesemia precipitated by diuresis, acid-base disturbance, sympathomimetic medications, pneumonia atelectasis, and pulmonary edema.2-8

Recent evidence supports an inflammatory mechanism in the development of AF.7-9 Given that red blood cell (RBC) transfusion modulates the inflammatory response to cardiac surgery by changing the plasma concentrations of inflammatory mediators and augmenting the inflammatory response,10 we sought to test the hypothesis that RBC transfusion could increase the risk of post-operative AF in patients undergoing cardiac surgery with cardiopulmonary bypass. The clinical classifications of AF are summarized in Table 1.

Table 1. Clinical classifications of atrial fibrillation (AF)

Paroxysmal

Persistent

Permanent

AF lasting 7 or fewer days and terminating

spontaneously

AF lasting more than 7 days that does not

terminate spontaneously but requires

cardioversion. If the first episode of AF

does not terminate spontaneously, it is also

designated persistent

AF in which sinus rhythm cannot be

sustained after cardioversion and the

patient and physician have decided against

further efforts to restore sinus rhythm

Methods

This study was performed on 1623 patients who underwent CABG alone in Imam Khomeini Medical Center, Tehran University of Medical Sciences, between January 2005 and July 2007. The pre-operative data of the patients are shown in Table 2. Patients and procedural variables associated with the development of new-onset AF were identified by logistic regression. All the patients had continuous, round-the-clock heart rhythm monitoring during their intensive care unit (ICU) stay. After the patients were transferred to the post-operative ward, any irregular rhythm was detected

Hassan Radmehr et al

through a routine vital sign checking conducted every 6 hours; long lead II was recorded immediately if any irregularity was felt in the pulse. The patients were divided into two groups: those with new post-operative AF (whether or not receiving blood products) and the ones without new-onset AF (whether or not receiving blood products) during observation. The total amount of the homologous transfused blood and the number of its products in the operating room and ICU were accurately detected in the files.

*Data are presented as mean±SDNYHA, New York heart association classification

Table 2. Pre-operative data of patients (n=1623)

Age (y)*

Gender

Male

Female

NYHA 1/2/3/4 (%)

Diseased coronary artery*

62±15

802(49.4%)

821(50.6%)

15/48/37/0

3±0.5

For the analysis of the descriptive statistics and the categorical variables, the chi-square or Fisher’s exact test was used as appropriate. The level of statistical significance was set at a P-value<0.05. All the statistical analyses were performed with SPSS software.

Results

The present study recruited 1623 patients, comprising 802 (49.4%) men and 821 (50.6%) women with a mean age of 62±15 years. Table 2 depicts the pre-operative characteristics of the patients.

AF was detected in 223 (45.9%) of 487 patients who received blood products and in 571 (37.9%) of 1508 patients who did not. The mean cross-clamp time was 58.9±5 and 65.6±5 minutes in those who developed and the ones who did not develop new-onset AF, respectively. Further results are summarized in Table 3.

*Data are presented as mean±SDAF, Atrial fibrillation; NO AF, No Atrial fibrillation; OR, Operating room; ICU, Intensive care unit

Variable AF NO AF P value

Table 3. Homologous transfused blood products and risk of AF*

Total transfused blood units

Transfused blood units in OR

Transfused blood units in ICU

Transfused platelet in OR (%)

Transfused platelet in ICU (%)

Transfused fresh frozen plasma

in ICU (%)

1.1±2

0.7±1.4

0.5±1.3

5.9

5.2

6.8

<0.01

<0.01

<0.01

<0.01

<0.01

<0.01

2±2.8

1±1.8

1.2± 2.2

10.2

10.4

11.4

TEHRAN HEART CENTER


Relationship between Blood Transfusion and Increased ...

Discussion

In the present study, aside from older age, prior history of AF, beta-blocker withdrawal, longer aortic clamp time, and ICU inotropic usage, ICU blood transfusion increased the risk of AF (odds ratio unit transfused, 1.16; 95% confidence limits, 1.14, 1.24; P<0.001). Our findings offer important prognostic information for the development of post-operative AF beyond the traditionally described risk factors. Whether the increased occurrence of AF in patients receiving transfusion is related to inflammatory changes or whether it is through another mechanism is unknown; nevertheless, it appears that transfusion is strongly and consistently associated with an increased risk of AF.9

According to a study performed in Cleveland clinic by Koch and collaborators between February 2002 and January 2005, 5841 patients underwent isolated CABG with or without valve replacement. Patients and procedural variables associated with the development of new-onset AF were identified by logistic regression. ICU blood transfusion increased the risk of AF (odds ratio per unit transfused, 1.18; 95% confidence limits, 1.14, 1.23; P<0.0001). For the 1360 propensity-matched pairs, ICU and RBC transfusion was associated with a significant increase in AF (620 (46%) vs. 522 (38%); P<0.001). They concluded that blood transfusion following cardiac surgery could increase the incidence of new-onset AF.11

Also, a prospective study in the field was performed on 140 consecutive patients in the Netherlands by Fransen E. and collaborators to investigate whether intra-operative blood transfusion could affect the release of pro-inflammatory mediators in patients undergoing cardiac surgery. They measured the plasma levels of bactericidal/permeability-increasing (BPI) protein as a marker of neutrophil activation, interleukin-6 (IL-6), lipopolysaccharide-binding protein (LBP), and C-reactive protein (CRP). In addition, these mediators, except for CRP, were also measured in packed red cell (PC) units administered to these patients. Thirty-six patients received PC units intra-operatively. BPI levels in the patients who received transfusion were significantly higher at 0.5 and 4 hours after aortic unclamping than those in the patients without transfusion (P<0.05). In addition, the levels increased in tandem with the number of PC units administered. IL-6 levels at 0.5, 4, and 18 hours after aortic unclamping were also significantly higher in the patients who received transfusion (P<0.01). BPI was found in all the units of PC tested at concentrations up to 15 times the pre-operative plasma levels in the patients. However, PC IL-6 could be detected in none of the samples. The plasma levels of LBP and CRP were similar in both patient groups. LBP was found in very low concentrations in all PC units. The patients who received intra-operative transfusions had a worse post-operative performance. The authors

concluded that intra-operative PC transfusions contributed to the inflammatory response after cardiac surgery both by enhancing the response and by directly changing the plasma concentrations of inflammatory mediators.12

Furthermore, chiming in with our findings, they reported that intra-operative PC transfusion was associated with a worse post-operative performance.

A peri-operative identification of factors related to the development of AF is valuable because AF is a frequent complication associated with post-operative morbidity and cost.13,14 To successfully risk-stratify patients for interventional pharmacological trials aimed at reducing AF, there needs to be a clearer understanding of the factors that predispose patients to the development of AF in the post-operative period. Transfusion of RBC is a modifiable process of care that increases the risk of this common post-operative complication.11,15 Strategies to reduce the complication following cardiac surgery will impact morbid outcomes and hospital resource utilization. ICU blood transfusion is allied with an increased occurrence of post-operative AF after cardiac surgery. This factor should be taken into account in identifying patients who might benefit from prophylaxis to prevent this common post-operative complication.

Conclusion

The results of this study showed that homologous blood transfusion could increase the incidence of new-onset AF after CABG. This factor should be considered in identifying patients who might benefit from prophylaxis in order to prevent this common post-operative complication and the adverse consequences thereof, although further more extensive studies are necessary to confirm it.

Acknowledgments

We would like to thank Mrs. Zargaran for her perseverance in completing data collection in our cardiac surgery database. This study was supported by Tehran University of Medical Sciences.

References

1. Almassi GH, Schowalter T, Nicolosi AC, Aggarwal A, Moritz

TE, Henderson WG, Tarazi R, Shroyer AL, Sethi GK, Grover FL,

Hammermeister KE. Atrial fibrillation after cardiac surgery: a major

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2. Amar D, Shi W, Hogue CW Jr, Zhang H, Passman RS, Thomas

B, Bach PB, Damiano R, Thaler HT. Clinical prediction rule for atrial

fibrillation after coronary artery bypass grafting. J Am Coll Cardiol

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The Journal of Tehran University Heart Center Hassan Radmehr et al

2004;44:1248-1253.

3. Aranki SF, Shaw DP, Adams DH, Rizzo RJ, Couper GS, Vander

Vliet M, Collins JJ Jr, Cohn LH, Burstin HR. Predictors of atrial fibril-

lation after coronary artery surgery current trends and impact on hospi-

tal resources. Circulation 1996;94:390-397.

4. Borzak S, Tisdale JE, Amin NB, Goldberg AD, Frank D, Padhi ID,

Higgins RS. Atrial fibrillation after bypass surgery: does the arrhyth-

mia or the characteristics of the patients prolong hospital stay? Chest

1998;113:1489-1491.

5. Funk M, Richards SB, Desjardins J, Bebon C, Wilcox H. Incidence,

timing, symptoms, and risk factors for atrial fibrillation after cardiac

surgery. Am J Crit Care 2003;12:424-435.

6. Hravnak M, Hoffman LA, Saul MI, Zullo TG, Whitman GR,

Griffith BP. Predictors and impact of atrial fibrillation after isolated

coronary artery bypass grafting. Crit Care Med 2002;30:330-337.

7. Anderson JL, Allen Maycock CA, Lappé DL, Crandall BG, Horne

BD, Bair TL, Morris SR, Li Q, Muhlestein JB; Intermountain heart

collaborative study group. Frequency of elevation of C-reactive protein

in atrial fibrillation. Am J Cardiol 2004;94:1255-1259.

8. Lo B, Fijnheer R, Nierich AP, Bruins P, Kalkman CJ. C-reactive

protein is a risk indicator for atrial fibrillation after myocardial

revascularization. Ann Thorac Surg 2005;79:1530-1535.

9. Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL,

Rautaharju P, Kronmal RA, Tracy RP, Van Wagoner DR, Psaty

BM, Lauer MS, Chung MK. Inflammation as a risk factor for atrial

fibrillation. Circulation 2003;108:3006-3010.

10. Fransen E, Maessen J, Dentener M, Senden N, Buurman W.

Impact of blood transfusions on inflammatory mediator release in

patients undergoing cardiac surgery. Chest 1999;116:1233-1239.

11. Koch CG, Li L, Van Wagoner DR, Duncan AI, Gillinov AM,

Blackstone EH. Red cell transfusion is associated with an increased

risk for postoperative atrial fibrillation. Ann Thorac Surg 2006;82:

1747-1756.

12. Fransen E, Maessen J, Dentener M, Senden N, Buurman W.

Impact of blood transfusions on inflammatory mediator release in

patients undergoing cardiac surgery. Chest 1999;116:1233-1239.

13. Hosokawa K, Nakajima Y, Umenai T, Ueno H, Taniguchi S,

Matsukawa T, Mizobe T. Predictors of atrial fibrillation after off-pump

coronary artery bypass graft surgery. Br J Anaesth 2007;98:575-580.

14. Nisanoglu V, Erdil N, Aldemir M, Ozgur B, Berat Cihan H,

Yologlu S, Battaloglu B. Atrial fibrillation after coronary artery bypass

grafting in elderly patients: incidence and risk factor analysis. Thorac

Cardiovasc Surg 2007;55:32-38.

15. Whitson BA, Huddleston SJ, Savik K, Shumway SJ. Bloodless

cardiac surgery is associated with decreased morbidity and mortality. J

Card Surg 2007;22:373-378.


TEHRAN HEART CENTER

Impact of Diabetes Mellitus on Peripheral Vascular

Disease Concomitant with Coronary Artery Disease

Mehrab Marzban, MD1*, Mohammadreza Zafarghandi, MD2, Mohsen Fadaei Araghi, MD2,Abbasali Karimi, MD1, Seyed Hossein Ahmadi, MD1, Namvar Movahedi, MD1, KyomarsAbbasi, MD1, Naghmeh Moshtaghi, MD1

1Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. 2Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Original Article

*Corresponding Author: Mehrab Marzban, Assistant Professor of Cardiac Surgery, Tehran University of Medical Sciences, Tehran Heart Center, North

Karegar Street, Tehran, Iran. 1411713138. Tel: +98 21 88029256. Fax: +98 21 88029256. E-mail: [email protected].

Background: The aim of this study was to evaluate the impact of diabetes mellitus (DM) on peripheral vascular disease

(PVD) in patients with coronary artery disease (CAD).

Methods: A total of 13702 consecutive patients who underwent coronary artery bypass grafting (CABG) at Tehran Heart

Center between January 2002 and March 2007 were included in this study. The demographic data, PVD, and outcome of

Results:

difference between the two groups with regard to family history and left main disease. Also, the mean ejection fraction (EF)

had a higher incidence of stenosis than those in the non-diabetics.

Conclusion: We conclude that in diabetic patients with concomitant CAD, special attention must be directed towards

angiography. Also, in risk assessment, the presence of PVD should be strongly considered for CAD patients.


Received 21 July 2008; Accepted 28 December 2008

Abstract

Keywords:

40

The Journal of Tehran University Heart Center Mehrab Marzban et al

Introduction

Atherosclerosis is a generalized disease, several manifestations of which may coexist in the same patient. Peripheral vascular disease (PVD) is characterized by a gradual reduction in the blood flow to one or more limbs secondary to atherosclerosis.1 Patients with PVD often have coexisting cerebrovascular disease and/or coronary artery disease (CAD) and, therefore, have poor prognosis and reduced life expectancy.2,3

It can be hypothesized that PVD patients have a more severe impairment of endothelial function, which leads to a more frequent occurrence of acute coronary syndromes.4

PVD may be diagnosed using non-invasive methods in 20-28% of patients with CAD as documented by coronary arteriography.5 Amongst patients with CAD, PVD is more frequent in those with diabetes mellitus (DM).6

Epidemiological evidence confirms the association between DM and the increased prevalence of PVD. Individuals with DM have a two to fourfold increase in the rate of PVD. DM changes the nature of PVD in that diabetic patients have infrapopliteal arterial occlusive disease and vascular calcification more commonly than do non-diabetic cohorts.7

Strandness et al.8 reported that DM patients had more infrapopliteal disease, whereas King et al.9 found a greater involvement of the profunda femoris in diabetics. A recent study in the U.K. showed that the cost of revascularization procedures was more in diabetic patients than that in non-diabetic patients with PVD.10 Although much is known regarding PVD in the general population, the assessment and management of PVD in those with DM is less clear and poses some special issues. At present, there are no established guidelines regarding the care of patients with both DM and PVD.11 The aim of this study was to evaluate the impact of DM on PVD in CAD patients.

Methods

A total of 13702 consecutive patients who underwent isolated coronary artery bypass grafting (CABG) at Tehran Heart Center between January 2002 and March 2007 were included in this study. The demographic data, PVD, and outcome of these patients were reviewed. CABG patients

abdominal aorta; renal, carotid, and iliac arteries; or more than 15 mm Hg systolic blood pressure difference between the two arms or any other peripheral vascular system) using medical history and physical examination (pulse-less femoral arteries, intermittent claudication, and absence of both pedal and posterior tibial artery pulses). Suspected cases of PVD were confirmed via Doppler sonography.

Some cases of PVD, especially those of renal artery stenosis, were found on angiography. In our center, patients with the following criteria were candidates for carotid

3) history of transient ischemic attack or cerebrovascular accident (CVA), and 4) carotid bruit. The patients were divided into 2 groups: a group of 4344 (31.7%) diabetic patients and a group of 9358 (68.3%) non-diabetic patients. Patient data comprised age, sex, smoking, hyperlipidemia, hypertension, PVD, left ventricular ejection fraction (LVEF), left main disease (stenosis>50%), pre- and post-operative renal failure, post-operative CVA, and in-hospital mortality (death occurring within 30 days after CABG). The study protocol was approved by the ethics committee of Tehran Heart Center.

The numerical variables were presented as mean±SD, while the categorized variables were summarized by absolute frequencies and percentages. The continuous variables were compared using Student’s t-test, and the categorical variables were compared using the chi-square or Fisher’s exact test.

A logistic regression model was performed as the multivariate analysis of choice to evaluate the effect of DM on PVD in the presence of confounding factors. A multivariate forward stepwise logistic regression model for the risk factors predicting mortality was constructed. The variables were included into the multivariate model if the P-value was found to be less than or equal to 0.15 in the univariate analysis. The associations between the independent predictors and mortality in the final results were expressed as odds ratios (OR) with 95% Confidence Intervals. Model discrimination was measured using the c statistics, which is equal to the area under the Receiver Operating Characteristic (ROC) curve. Model calibration was estimated using the Hosmer-Lemeshow goodness-of-fit statistics, with higher P-values implying that the model fit the observed data better. For the statistical analysis, the statistical software SPSS version 13.0 for Windows (SPSS Inc., Chicago, I.L.) and the statistical package SAS version 9.1 for Windows (SAS Institute Inc., Cary, N.C., U.S.A.) were used. All the P-values were 2-tailed, with statistical significance defined

Results

This study recruited 4344 diabetic patients with a mean age of 59.30±8.7 years and 9358 non-diabetic patients with a mean age of 58.42±9.9 years. Whereas 37.6% of the DM patients were female, only 19.6% of the non-diabetics were female (P<0.001). The diabetics were significantly older (P<0.001) and had a higher incidence of PVD (2.7% vs. 1.8%; P=0.001), hypertension (64.4% vs. 47.5%; P<0.001),

TEHRAN HEART CENTER


Impact of Diabetes Mellitus on Peripheral Vascular ...

renal failure (2.8% vs. 1.2%; P<0.001), smoking (28.8% vs. 44.1%; P<0.001), and dyslipidemia (73.6% vs. 63.1%; P<0.001) than those without DM (Table 1). There was no significant difference between the two groups with respect to family history and left main disease. The mean EF was 48.85±10.4 and 49.35±10.0 in the patients with and without DM, respectively; and this difference was significant (P=0.008). The incidence of post-operative renal failure (1.7% vs. 0.6%) and CVA (0.7% vs. 0.3%) in the DM patients was significantly higher than that in the non-diabetic patients. The in-hospital mortality rate (mortality occurring within 30 days after CABG) was 1.8% amongst the DM patients and 0.7% in the non-diabetics (P<0.001). After adjustment for confounding factors, in the multivariate logistic regression analysis, PVD was slightly significantly higher in the DM patients than that in those without DM (OR=1.264, 95% CI:0.989-1.617; P=0.0616). The univariate and multivariate analyses for in-hospital mortality in isolated CAGB patients are shown in Tables 2 and 3. The final model had good discrimination (area under the ROC curve, c=0.79908) and calibration (Hosmer-Lemeshow goodness-of-fit test, P=0.9388). Table 4 depicts the univariate analysis for the in-hospital mortality rate in the diabetic patients. In the multivariate analysis, PVD, left main disease, age, female gender, and EF were significant in the development of mortality in the diabetic patients with a respective odds ratio

final model had good discrimination (area under the ROC curve, c=0.80007) and calibration (Hosmer-Lemeshow goodness-of-fit test, P=0.9390). In the patients with DM, carotid (1.13% vs. 0.83%), subclavian (0.05% vs. 0.02%), femoral (0.18% vs. 0.09%), renal (0.62% vs. 0.25%), and tibialis (0.16% vs. 0.06%) arteries had a higher incidence of stenosis than those amongst the patients without DM. The distribution of vessel stenosis in the diabetic and non-diabetic patients with PVD is illustrated in Table 6.

* Number are presented as mean±SD or percentage

Variables P valueDiabetic

(n=4344)(31.7%)

Non-diabetic(n=9358)(68.3%)

Table 1. Baseline characteristics*

Age (y)

Female

Hypertension

Peripheral vascular disease

Smoking

Left ventricular ejection

fraction (mean±SD)

Renal failure

Left main disease

Family history

Hyperlipidemia

58.42±9.99

19.6

47.5

1.8

44.1

49.35±10

1.2

9.9

35.8

63.1

<0.001

<0.001

<0.001

0.001

<0.001

0.008

<0.001

0.238

0.886

<0.001

59.30±8.77

37.6

64.4

2.7

28.8

48.85±10.46

2.8

9.3

35.6

73.6


Variables P valueNon-surviving

(n=148)Surviving(n=13554)

Table 2. Univariate analysis of pre-operative variables for mortality in isolated CABG patients

Age (y)

Female

Hypertension

Peripheral vascular

disease

Smoking

Left ventricular

ejection fraction

Renal failure

Left main disease

Family history

Hyperlipidemia

Diabetes

64.18±9.10

43.9

74.3

14.2

31.1

45.24±11.51

6.8

33.1

35.6

77

52.7

58.64±9.61

25.1

52.6

2

39.3

49.23±10.13

1.7

9.4

35.7

66.3

31.5

<0.001

<0.001

<0.001

<0.001

0.041

<0.001

<0.001

<0.001

0.976

0.006

<0.001

Variables P valueOdds ratio 95% CI

Table 3. Results of multivariate analysis for mortality in isolated CABG patients

Peripheral vascular

disease

Hypertension

Female

Left main disease

Age

Diabetes

Renal failure

Ejection fraction

4.157

1.842

2.031

4.251

1.052

1.855

2.378

0.961

2.465-7.008

1.253-2.707

1.428-2.887

2.966-6.094

1.031-1.073

1.317-2.613

1.161-4.871

0.946-0.976

<0.0001

0.0012

<0.0001

<0.0001

<0.0001

<0.0001

0.0149

<0.0001


Variables P valueNon-surviving

(n=78)Surviving(n=4266)

Table 4. Univariate analysis of pre-operative variables for mortality in diabetic patients

Age (y)

Female

Hypertension

Peripheral vascular

disease

Smoking

Left ventricular

ejection fraction

Renal failure

Left main disease

Family history

Dyslipidemia

62.72±8.46

59

71.8

12.8

21.8

44.36±12.49

6.4

35.9

38.2

79.5

59.24±8.77

37.2

64.3

2.5

29

48.93±10.40

2.7

8.8

35.6

73.5

0.001

<0.001

0.169

<0.001

0.166

0.002

0.063

<0.001

0.645

0.235

42

The Journal of Tehran University Heart Center Mehrab Marzban et al

Variables Odds ratio 95% CI P value

Table 5. Results of multivariate analysis for mortality in diabetic patients

Peripheral vascular

disease

Ejection fraction

Female

Left main disease

Age

4.174

0.956

2.863

5.549

1.037

2.026-8.600

0.937-0.976

1.788-4.585

3.409-9.034

1.009-1.067

<0.0001

<0.0001

<0.0001

<0.0001

0.0103

*Data are presented as percentage

Vessel stenosis Diabetic Non-diabetic

Table 6. Distribution of vessel stenosis in diabetic and non-diabetic patients*

Carotid

Iliac

Subclavian

Femoral

Renal

Pedis dorsalis

Tibialis

Abdominalaorta aorta

Proneal

Popliteal

Axillary

Renal + Iliac

Carotid + Iliac

Femoral + Popliteal

Tibialis + Renal

Pedis dorsalis + Tibialis

Carotid + Renal

Femoral + Iliac

Tibialis + Carotid

Subclavian + Renal

Tibialis + Proneal

Tibialis + Femoral

Subclavian + Abdominalaorta

Tibialis + Proneal + Femoral

Carotid + Iliacl + Femoral

Sum

1.13

0.12

0.05

0.18

0.62

0.12

0.16

0

0

0

0

0.05

0.02

0.02

0.02

0.07

0.07

0.02

0.05

0

0

0

0

0.02

0

2.72

0.83

0.21

0.02

0.09

0.25

0.16

0.06

0.04

0

0.01

0.01

0

0

0.01

0

0.02

0.04

0.02

0

0.01

0.01

0.01

0.01

0

0.01

1.82

Discussion

PVD is a clinical manifestation of the atherosclerotic process, which is associated with cardiovascular disease and the increased risk thereof. A major chronic disease, DM is able to accelerate atherosclerosis and numerous studies have identified it as a key risk factor for PVD.12 Coronary arteriography shows that amongst patients with documented CAD, PVD is more frequent in patients with DM.6

Classic major risk factors for CAD (smoking, hypertension, DM, and hypercholesterolemia) are associated with the presence of PVD and the prevalence of cerebrovascular

disease. PVD in patients with CAD is particularly enhanced by the concomitant occurrence of two or more of these risk factors.4 Gianluca Rigatelli showed that age>65 years, multiple risk factors, and three- to four-vessel CAD appeared to be the independent predictors of PVD.13

In our study, DM was more prevalent amongst the women (P<0.001). Our DM patients were significantly older and had a higher incidence of PVD (P=0.001), hypertension, renal failure, smoking, and dyslipidemia (P<0.001). Premature CAD was more prevalent in our series than that in reports from Western countries, which may explain the older age of ordinary CAD patients with known risk factors such as non insulin dependent DM. Minakata et al.14 showed that patients with PVD were significantly older and had a higher incidence of DM, hypertension, pre-operative cerebral infarction, and chronic renal dysfunction. These data suggest that patients with PVD have more severe systemic atherosclerosis.

On the other hand, the in-hospital mortality rate was significantly higher (P<0.001) in our diabetic patients than that amongst our non-diabetic subjects. Several large studies have demonstrated that the presence of PVD is an important, independent predictor of in-hospital mortality rates.14

Our findings indicated that the carotid and renal arteries had the highest prevalence of stenosis amongst vessels, and this explains the higher incidence of CVA and post-operative renal dysfunction in our series.

It is important to diagnose PVD in patients with DM to elicit symptoms, prevent disability and limb loss, and identify a patient at high risk of death. The method of the pre-operative diagnosis of PVD in candidates for CABG is still a matter of debate. Each non-invasive technique such as duplex ultrasonography has drawbacks in precisely depicting the extracranial region, renal arteries, subclavian vessels, and aortoiliac artery due to poor sonographic window, severe calcification of the vessel wall, obesity, and being highly operator dependent. As a result, the interventional or surgical treatment of PVD is often planned using invasive angiographic studies.

Conclusion

We conclude that in DM patients with concomitant CAD, special attention must be directed towards the diagnosis of PVD by means of physical examination, Doppler sonography, and where needed, CT- angiography or invasive angiography. On the other hand, due to the high impact of PVD on the outcome in these patients, it should be strongly considered in the risk assessment and the choice of proper surgical techniques to minimize mortality and major complications such as CVA or post-operative renal impairment.

TEHRAN HEART CENTER


Impact of Diabetes Mellitus on Peripheral Vascular ...

Acknowledgments

The authors thank Dr. Seyed Hesameddin Abbasi and Dr. Sheikhfathollahi for their expert assistance in data management and statistical analysis. This study was approved and supported by Tehran Heart Center, Tehran University of Medical Sciences.

References

1. Jude EB, Oyibo SO, Chalmers N, Boulton AJ. Peripheral arterial

disease in diabetic and nondiabetic patients: a comparison of severity

and outcome. Diabetes Care 2001;24:1433-1437.

2. Dormandy J, Heeck L, Vig S. The natural history of claudication:

risk to life and limb. Semin Vasc Surg 1999;12:123-137.

3. Cheng SW, Ting AC, Lau H, Wong J. Survival in patients with

chronic lower extremity ischemia: a risk factor analysis. Ann Vasc Surg

2000;14:158-165.

4. Perrone-Filardi P, Chiariello M. Coronary artery disease and

intermittent claudication: how to manage the patient. Eur Heart J

Supplements 2002;4:B58-62.

5. Papanas N, Tziakas D, Maltezos E, Kekes A, Hatzinikolaou E,

Parcharidis G, Louridas G, Hatseras D. Peripheral arterial occlusive

disease as a predictor of the extent of coronary atherosclerosis in

patients with coronary artery disease with and without diabetes

mellitus. J Int Med Res 2004;32:422-428.

6. Barzilay JI, Kronmal RA, Bittner V, Eaker E, Foster ED. Coronary

artery disease in diabetic and nondiabetic patients with lower extremity

arterial disease: a report from the coronary artery surgery study registry.

Am Heart J 1998;135:1055-1062.

7. Yosefy C. Hyperglycaemia and its relation to cardiovascular

morbidity and mortality: has it been resolved? Acta Diabetol 2003;Suppl

2:S380-388.

8. Strandness DE Jr, Priest RE, Gibbons GE. Combined clinical and

pathologic study of diabetic and non-diabetic peripheral arterial disease.

Diabetes 1964;13:366-372.

9. King TA, Depalma RG, Rhodes RS. Diabetes mellitus and

atherosclerotic involvement of the profunda femoris artery. Surg

Gynecol Obstet 1984;159:553-556.

10. Panayiotopoulos YP, Tyrrell MR, Arnold FJ, Korzon-Burakowska

A, Amiel SA, Taylor PR. Results and cost analysis of distal (crural/

pedal) arterial revascularization for limb salvage in diabetic and

non-diabetic patients. Diabet Med 1997;14:214-220.

11. American diabetes association. Peripheral arterial disease in

people with diabetes. Diabetes Care 2003;26:3333-3341.

12. Li J, Luo Y, Xu Y, Yang J, Zheng L, Hasimu B, Yu J, Hu D. Risk

factors of peripheral arterial disease and relationship between low

ankle-brachial index and mortality from all- cause and cardiovascular

disease in Chinese patients with type 2 diabetes. Circ J 2007;71:

377-381.

13. Rigatelli G, Rigatelli G. Screening of peripheral vascular disease

in patients facing coronary surgery: is invasive angiography really out?

Ann Thorac Surg 2005;80:788-789.

14. Minakata K, Konishi Y, Matsumoto M, Aota M, Sugimoto A,

Nonaka M, Yamada N. Influence of peripheral vascular occlusive

disease on the mortaliy and morbidity of coronary artery bypass

grafting. Jpn Circ J 2000;64:905-908.


TEHRAN HEART CENTER

Primary Percutaneous Coronary Intervention in

Patients with Acute Myocardial Infarction

Morteza Safi, MD*, Hassan Rajabi Moghadam, MD, Roxana Sadeghi, MD, HabibollahSaadat, MD, Mohammad Hassan Namazi, MD, Hossein Vakili, MD, Seyed AhmadHassantash, MD, Mohammad Reza Motamedi, MD

Modarres Hospital, Cardiovascular Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.

Original Article

*Corresponding Author: Associate Professor of Cardiology, Department of Cardiovascular Medicine, Modarres Hospital, Shaheed

@yahoo.com.

Background: Primary percutaneous coronary intervention (primary PCI) is the method of choice in establishing reperfu-

sion in acute myocardial infarction (AMI) patients. The aim of this study was to determine the success rate of primary PCI

centers with established catheterization labs across the country.

Methods: All cases of AMI admitted between September 2001 and September 2005 underwent primary PCI. The achieved

admission for major adverse cardiac events (MACE).

Results:

-

nary artery disease risk factors. More patients in the mortality group had a longer door-to-balloon (DTB) time compared to

the surviving group (P<0.05).

Conclusion: In light of the results of this study, primary PCI may also be practiced as the therapy of choice for AMI patients

in centers with established equipment in our region with acceptable rates of MACE and complications. Better procedural

success rates are achieved in younger patients and in those with a shorter DTB time.


Received 21 July 2008; Accepted 18 November 2008

Abstract

Keywords:

Introduction

The restoration of the blood flow to the ischemic myocardium is established as the preeminent objective for

the treatment of patients with acute myocardial infarction (AMI). Primary angioplasty or percutaneous coronary intervention (PCI) has advanced through the continued evolution of the method and dissemination to an expanding

46


proportion of patients. Catheter-based reperfusion technique attains thrombolysis in myocardial infarction (TIMI-3) flow in 93 to 98% of patients. By contrast, only 54% of patients are reported to have achieved this reperfusion benchmark with accelerated tissue plasminogen activator (t-PA).1

Although reperfusion therapy is based upon thrombotic coronary occlusion, thrombus may not play the predominant role in a significant proportion of AMI cases. Dynamic occlusive events apart from thrombus, including plaque rupture, intramural hemorrhage, dissection, and spasm, may explain at least some of the advantages of primary angioplasty over thrombolysis. Many patients have contraindications to thrombolytic therapy. Also, even after successful thrombolysis, the majority of patients are left with a high-grade stenosis that may limit the flow, impair subsequent myocardial recovery, and increase the risk of reinfarction.2

Multiple centers have described their experience with primary angioplasty over the past 20 years.3,4 However, concern persists as to whether the results of highly specialized centers could be generalized to clinical practice.

The object of this study was to determine the success rate of primary PCI in a university center in order to recommend this mode of treatment as the first-line therapy of AMI patients by expert interventional cardiologists, practicing in centers with sufficiently equipped catheterization labs in our country.

Methods

All patients suffering from AMI with a pre-hospital delay of up to 12 hours were included in this study. AMI was diagnosed in the presence of the two following criteria: 1) persistent angina pectoris for 20 minutes and, 2) ST segment elevation of 1mm in at least 2 contiguous leads or the presence of a left bundle branch block. It was later confirmed by the elevation of cardiac enzymes of more than twice the normal upper range. Pre-hospital delay was defined as the time from the onset of symptoms until admission to our hospital. Informed consent was obtained from all the participants, and the study was approved by the ethics committee of the center. The patients were taken to the cardiac catheterization laboratory as soon as possible to undergo emergency coronary angiography. All the parameters were assessed according to the American College of Cardiology (ACC) guidelines. The patients received 325mg of chewable aspirin and 300mg clopidogrel. 100u/kg heparin was used and titrated around 300 seconds, based on near-patient activated clotting time (ACT) monitoring. In patients without contraindications, beta- blockers, angiotensin-converting enzyme inhibitors, and stains were administered.5

The door-to-balloon (DTB) time was defined as the

interval between arrival at the hospital and intracoronary balloon inflation. Anatomical or angiographic success was defined as the attainment of residual diameter stenosis less than 50% and normal TIMI-3 flow. Procedural success was defined as angiographic success without the occurrence of major complications (death, MI, or coronary artery bypass grafting [CABG]) during the admission. Clinical success was defined as procedural success without the need for urgent repeated PCI or surgical revascularization within the first 30 days of the procedure.6

The chi-square test was used for the comparison of sex, age, and the other parameters with the success rate. A pair-wise multiple comparison test was performed using the independent T-test method and Pearson. Correlations were taken into consideration. A P-value 0.05 was considered significant.

Results

The present study recruited 180 patients, comprised of 36 (20%) women and 144 (80%) men, with a mean age of 56±2.1 years (30-85 years). Amongst the patients, 91 (50.6%) were smokers, 79 (43.9%) had hyperlipidemia, 53 (29.4%) were hypertensive, 37 (20.6%) had a positive family history of coronary artery disease, and 35 (19.4%) had diabetes mellitus.

The target vessel was the left anterior descending artery in 119 (66.1%), right coronary artery in 49 (27.2%), and left circumflex artery in 12 (6.7%). The DTB time was below 60 minutes in 14 (7.8%), 60 to 89 minutes in 56 (31.1%), 90 to 120 minutes in 104 (57.8%), and beyond 120 minutes in 6 (3.3%) patients (Table 1). Amongst the mortality group, 11 patients had a DTB time longer than 90 minutes and only one patient had a DTB time less than 90 minutes. Mortality showed a meaningful correlation with the DTB time (P<0.05).

DTB time (minutes)

Table 1. Mortality according to door-to-balloon time (DTB)

Patients

Mortality (%)

14

1(7)

56

0(0)

104

7(4)

6

4(67)

180

12(6.7)

Anatomical success was achieved in 170 of the 180 (94.4%) patients and procedural success in 162 (90%) patients. Three patients had TIMI-1 after angioplasty and 7 patients developed no reflow phenomenon. Mortality was 6.7% (12 patients). Emergency CABG was performed in 2 (1.1%) patients. Re-MI occurred in 4 (2.2%) patients during hospitalization. Of the latter, 2 patients underwent successful repeat PCI, and the other 2 patients received thrombolytics, with no complications.

TEHRAN HEART CENTER


Primary Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction

Although no correlation was present between the anatomical success rate and age, a meaningful correlation (P<0.05) was seen between procedural success and age group (Table 2). No significant relation was observed between the success rate and sex, target vessel, or major CAD risk factors (Table 3).

Age(y)

Success <65 (n=140) 65 (n=40)

Table 2. Anatomical and procedural success rates according to Age

Anatomical

Procedural

133(95%)

131(93.6%)

37(92.5%)

31(77.5%)

Success Rate (%) Anatomical Procedural

Table 3. Anatomical and procedural success rates according to sex and risk factors

Sex

Diabetes Mellitus

Hypertension

Hyperlipidemia

Smoking

Family history

malefemale

yesno

yesno

yesno

yesno

yesno

95.191.7

88.685.7

92.595.3

94.994.1

94.594.4

10093

91.783.3

95.991

92.589

88.691.1

91.288.8

94.688.8

Discussion

The purpose of this study was to assess the clinical outcomes after the use of primary PCI for acute ST elevation MI in an Iranian university-affiliated tertiary medical center compared with the results published in the medical literature from other countries.

Our data demonstrated that both anatomical and procedural results were clearly within the range of the reported results published. Yet, our success rates appeared to be improving overtime, which could be attributed to improved technology as well as greater understanding of the importance of pretreatment with anti-platelet agents and adequate anticoagulation. During the study period, we had no access to glycoprotein IIb-IIIa inhibitors and were, therefore, unable to administer them to our patients.4

We observed a meaningful correlation between the DTB time and mortality.7-9 Recently, McNamara et al. reported that a longer DTB time was associated with increased in-hospital mortality (mortality rates of 3.0%, 4.2%, 5.7%, and 7.4% for DTB times of <90 minutes, 91 to 120 minutes, 121 to 150 minutes, and >150 minutes, respectively; P<0.01

for trend). Adjusted for patient characteristics, patients with a DTB time >90 minutes had increased mortality (odds ratio: 1.42; 95% confidence interval [CI] of 1.24 to 1.62) compared with those who had a DTB time <90 minutes.10

Luca et al. found that after adjustment for age, gender, diabetes, and previous revascularization, each 30 minutes of delay was associated with a relative risk for 1-year mortality of 1.075 (95% CI:1.008 to 1.150; P<0.041).11

We also achieved favorable results in terms of death and recurrent ischemia rates, the rate of the latter observed after primary PCI being lower than that reported in other trials. On account of the fact that blinding was not feasible in this trial, we were concerned about possible bias in the reporting of ischemia by the investigators. The electrocardiograms were, consequently, independently reviewed by a physician for the presence of ischemic changes. Chest pain in the absence of electrocardiographic changes was considered non-ischemic.1 There were no complications due to primary angioplasty, which can be related to the small sample size in this study.

Our elderly patients had an anatomical success rate similar to that of our younger patients, but the procedural success rate was lower, probably due to a higher risk score in the elderly patients. The population of elderly patients (older than 65 years) accounts for 85% of deaths from MI (Biostatistical Fact Sheet. Older Americans and Cardiovascular Diseases. Chicago. American Heart Association, 1998.). A 15% reduction in mortality for eligible patients older than 75 years compared with conservative therapy has already been demonstrated.12

Despite this evidence, reperfusion therapy is applied to less than half of eligible elderly patients.13

Apprehension regarding the risk of intracranial hemorrhage significantly contributes to this diminished treatment. Pooled analyses from randomized trials have revealed a significant mortality reduction for the elderly subgroup treated with angioplasty but not for younger patients.14 Boer et al. randomly assigned a total of 87 patients with AMI who were older than 75 years to treatment with angioplasty or intravenous streptokinase. The primary end point, a composite of death, reinfarction, or stroke, at 30 days had occurred in 4 (9%) patients in the angioplasty group as compared with 12 (29%) in the thrombolysis group (P=0.01, relative risk [RR]: 4.3, 95% CI: 1.2 to 20.0).15

Primary PCI may, therefore, be very beneficial for elderly patients.

Conclusion

In this study, primary PCI was performed safely in patients with acute ST elevation MI. It resulted in a high success rate and, also, low morbidity and mortality. Thus, when the

48


necessary facilities and personnel are available, primary angioplasty is preferred to intravenous thrombolysis and must be carried out.

Acknowledgements

The authors wish to thank the catheterization laboratory of the Department of Cardiovascular Medicine, Modarres Hospital. This study has been approved and supported by Shaheed Beheshti University of Medical Sciences.

References

1. Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O’Keefe

J, Overlie P, Donohue B, Chelliah N, Timmis GC. A comparison of

immediate angioplasty with thrombolytic therapy for acute

myocardial infarction. The primary angioplasty in myocardial

infarction study group. N Engl J Med 1993;328:673-679.

2. Lane GE, Holmes DR. Primary percutaneous coronary intervention

in the management of acute myocardial infarction. In: Braunwald E,

Zipes DP, Libby P, Bonow RO, eds. Heart Disease. 7th ed. Philadelphia:

W.B. Saunders; 2005. p. 1227-1237.

3. O’keefe JH Jr, Bailey WL, Rutherford BD, Hartzler GO. Primary

angioplasty for acute myocardial infarction in 1000 consecutive

patients. Result in an unselected population and high- risk subgroups.

AM J Cardiol 1993;72:107-115.

4. Giri S, Mitchel JF, Hirst JA, McKay RG, Azar RR, Mennett R,

Waters DD, Kiernan FJ. Synergy between intracoronary stenting and

abciximab in improving angiographic and clinical outcomes of primary

angioplasty in acute myocardial infarction. Am J Cardiol 2000;86:

269-274.

5. Harjai KJ, Stone GW, Boura J, Grines L, Garcia E, Brodie B, Cox

D, O’Neill WW, Grines C. Effects of prior beta-blocker therapy on

clinical outcomes after primary coronary angioplasty for acute

myocardiol infarction. Am J Cardiol 2003;91:655-660

6. Popma JR, Kuntz RE, Baim DS. Percutaneous Coronary and

Valvular Intervention. In: Braunwald E, Zipes DP, Libby P, Bonow

Ro, eds. Heart Disease. 7th ed. Philadelphia: W.B. Saunders; 2005.

p. 1377-1378.

7. Curtis JP, Portnay EL, Wang Y, McNamara RL, Herrin J, Bradley

EH, Magid DJ, Blaney ME, Canto JG, Krumholz HM; National

Registry of Myocardial Infarction-4. The pre-hospital electrocardiogram

and time to reperfusion in patients with acute myocardial

infarction. J Am Coll Cardiol 2006;47:1544-1552.

8. Brodie BR, Stuckey TD, Muncy DB, Hansen CJ, Wall TC,

Pulsipher M, Gupta N. Importance of time to reperfusion in patients

with acute myocardial infarction with and without cardiogenic shock

treated with primary percutaneous coronary intervention. Am Heart J

2003;145:708-715.

9. Resnic FS, Wainstein M, Lee MK, Behrendt D, Wainstein RV,

Ohno-Machado L, Kirshenbaum JM, Rogers CD, Popma JJ, Piana R.

No-reflow is an independent predictor of death and myocardial

infarction after percutaneous coronary intervention. Am Heart J

2003;145:42-46.

10. McNamara RL, Wang Y, Herrin J, Curtis JP, Bradley EH, Magid

DJ, Peterson ED, Blaney M, Frederick PD, Krumholz HM; NRMI

Investigators. Effect of door-to-balloon time on mortality in patients

with ST-segment elevation myocardial infarction. J Am Coll Cardiol

2006;47:2180-2186.

11. De Luca G, Suryapranata H, Ottervanger JP, Antman EM. Time delay

to treatment and mortality in primary angioplasty for acute myocardial

infarction: every minute of delay counts. Circulation 2004;109:

1223-1225.

12. White HD. Thrombolytic therapy in the elderly. Lancet

2000;356:2028-2030.

13. Berger AK, Schulman KA, Gersh BJ, Pirzada S, Breall JA,

Johnson AE, Every NR. Primary coronary angioplasty vs thrombolysis

for the management of acute myocardial infarction in elderly patients.

JAMA 1999;282:341-348.

14. OÕNeill WW, de Boer MJ, Gibbons RJ, Holmes DR, Timmis GC,

Sachs D, Grines CL, Zijlstra F. Lessons from the pooled outcome of the

PAMI, Zwolle and Mayo clinic randomized trials of primary angioplasty

versus thrombolytic therapy of acute myocardial infarction. J Invasive

Cardiol 1998;10:A4-10.

15. de Boer MJ, Ottervanger JP, van ‘t Hof AW, Hoorntje JC,

Suryapranata H, Zijlstra F; Zwolle Myocardial Infarction Study

Group. Reperfusion therapy in elderly patients with acute myocardial

infarction. A randomized comparison of primary angioplasty and

thrombolytic therapy. J Am Coll Cardiol 2002;39:1729-1732.


TEHRAN HEART CENTER

Introduction

Primary tumors of the heart are extremely rare, with a prevalence rate of around 0.01% in collective autopsy studies.1 Angiosarcomas with the inclusion of Kaposi sarcomas account for 30% of primary cardiac sarcomas.2

In this article, we describe a case of a malignant angiosarcoma.

Case Report

A 22-year-old man presented with dyspnea functional class II-III. Aside from a history of progressive exertional dyspnea commencing one month previously, the patient had no other symptoms. Because of massive pleural effusion, a chest tube had been inserted and pleural and pericardial biopsy obtained. The pericardial biopsy showed fibrinoid pericarditis, and the cytology of his pleural effusion revealed no malignant cells. He was subsequently referred to our center for further evaluations. On presentation, the patient’s vital signs were stable, but there was a decreased lung sound especially in the left lung and the laboratory

Left-Sided Angiosarcoma of Heart: A Rare Case

Maryam Moshkani Farahani, MD*, Davood Kazemi Saleh, MD, Yahya Dadjoo, MD, Bahram Pishgoo, MD

Baqiatollah Medical and Research Center, Baqiatallah University of Medical Sciences, Tehran, Iran.

Received 24 June 2008; Accepted 14 August 2008

Case Report

Abstract

*Corresponding Author: Maryam Moshkani Farahani, Assistant Professor of Cardiology, Baqiatallah Medical and Research Center, Baqiatollah

Hospial, Sheikh Bahai Street, Molasadra Street, Tehran, Iran. 1435913343. Tel: +98 21 88211864. Fax: +98 21 88211864. Email: moshkani_farahani@

yahoo.com.

Keywords:

A 22-year-old man presented with exertional dyspnea commencing one month prior to his admission. Echocardiography

revealed a non-homogenous mass, and the pathology examination of the pericardial biopsy was compatible with

angiosarcoma.


studies were all normal. Transthoracic and transesophageal echocardiographic examinations were conducted, which demonstrated a large left atrium mass (5×6 cm) with the involvement of the interatrial septum, roof, and the lateral side of the right atrium with extra cardiac extension and pleuropericardial effusion (Figures 1, 2, and 3). A thoracic surgeon was consulted, and biopsy was taken via thoracoscopy so as to define the nature of the mass, which was determined to be malignant secondary to the pleuropericardial effusion and the extension of the mass. Thoracoscopy revealed multiple small nodules on the pericardium, and biopsy was taken. The result of the pathological examination was compatible with angiosarcoma, which was confirmed by immunohistochemistry staining. Chemotherapy was commenced at the discretion of our hematologist, but an acute sudden dyspnea in the first session of chemotherapy led to the patient’s death.

Discussion

Primary tumors of the heart are extremely rare, with a prevalence rate of around 0.01% in collective autopsy

50

The Journal of Tehran University Heart Center Maryam Moshkani Farahani et al

Figure 1. Left atrial mass (arrow) with pericardial effusion (4-chamber view)LV, Left ventricle; LA, Left atrium

Figure 2. Transesophageal echocardiographic view of the mass (arrow) with involvement of interatrial septumRA, Right atrium; LV, Left ventricle; RV, Right ventricle; LA, Left atrium

Figure 3. Transesophageal echocardiographic view of the mass (arrows)AO, Aorta; RA, Right atrium; LA, Left atrium

studies. The majority of primary cardiac tumors are benign. Myxomas are the most common primary cardiac tumors, while angiosarcomas are the commonest primary malignant tumors.1 Angiosarcomas with the inclusion of Kaposi sarcomas account for 30% of primary cardiac sarcomas.2

There is a 3:1 male-to-female ratio amongst patients with angiosarcomas.3 Patients usually present with right-sided heart failure or tamponade as well as systemic signs such as fever and weight loss 3 This case of angiosarcoma of the heart is presented herein because of the extreme rarity of its location. Not only did our patient have extensive cardiac involvement but his other organs were involved as well and the tumor was not primarily from the right side of the heart. Unfortunately, the progression of the disease after diagnosis was extremely rapid and the patient died following the first course of chemotherapy.

References

1. Amonkar GP, Deshpande JR. Cardiac angiosarcoma. Cardiovasc

Pathol 2006;15:57-58.

2. Burke AP, Cowan D, Virmani R. Primary sarcomas of the heart.

Cancer 1992;69:387-395.

3. Sabatin MS, Colucci WS, Schoen FJ. Primary tumors of the heart.

In: Zipes DP, Libby P, Bonow RO, Braunwald E, eds. Braunwald’s heart

disease. 7th ed. Philadelphia: W. B. Sunders; 2005. p. 1741-1755.


TEHRAN HEART CENTER

A Combined Approach to Severe

Multi-Organ Atherosclerosis

Mohammad Hasan Namazi, MD , Roxana Sadeghi, MD, Hosein Vakili, MD, Habibollah Saadat, MD, Morteza Safi, MD, Mohammad Reza Motamedi, MD

Cardiovascular Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.

*Corresponding Author: Mohammad Hasan Namazi, Associate Professor of Cardiology, Shaheed Modarres Hospital, Cardiovascular Research Center

of Shaheed Beheshti University of Medical Sciences, Tehran, Iran. Tel: + 98 21 22083106. Fax: +98 21 22083106. Email: [email protected].

Severe coronary artery disease often coexists with peripheral vascular atherosclerosis. The assessment of the supra-aortic

circulation is, therefore, of clinical relevance. We herein describe a case of coronary artery disease treated with surgical

revascularization using the internal mammary artery and thereafter the progressive atherosclerotic disease of the native

coronary arteries as well as the left subclavian and left renal arteries.

We also describe and discuss the clinical presentation, the diagnostic procedures, and the therapeutic approach with respect

to the percutaneous transluminal angioplasty of the subclavian, renal, and right coronary arteries.

Received 15 January 2008; Accepted 08 June 2008

Abstract

Keywords:

Introduction

Patients with atherosclerosis often have a diffuse manifestation of the vascular disease. Particularly, coronary artery disease is associated with a flow-limiting stenosis of the supra-aortic vessels.1-3 Thus, in patients with previous coronary revascularization, either surgical or percutaneous and recurrent angina, the evaluation must include the native coronary circulation and implanted grafts together with the peripheral non-coronary circulation.1

This report describes a case of supra-aortic vessel disease with coronary-subclavian steal syndrome and the concomitant ostial lesion of the right coronary artery and left renal artery.

Case Study

A 65-year-old woman presented with a six-month history

of progressive exertional angina and left upper extremity claudication, despite maximum medical treatment. She also reported left upper extremity pain, associated with dizziness and exacerbation of angina. She had no syncope. Her medical history was indicative of dyslipidemia and atherosclerotic heart disease with coronary artery bypass graft surgery 13 years previously. Her father died of myocardial infarction in his 70s.

On admission, the patient was on ASA, Plavix, Atenolol, Isosorbide dinitrate, Diltiazem, Atorvastatin, Gemfibrosil, and Captopril.

On physical examination, the blood pressure in the right and left arms was 170/90 and 80/55 mmHg, respectively. Additionally, the patient’s PR was 80/min and her RR was

carotid bruit and no other positive findings were detected in the head and neck. The patient’s chest and lungs were clear to auscultation. A cardiac examination revealed prominent S4 and a systolic murmur with II/VI intensity at the left

Case Report

J Teh Univ Heart Ctr 1 (2009) 51 - 57

52


lower sternal border; the findings were otherwise normal. The examination of the abdomen proved non-contributory.

Weak and delayed pulse in the left radial, brachial, and axillary arteries was detected in the examination of the extremities. The findings of the neurological examination were within the normal limits.

The patient’s laboratory findings on admission were as follows: glucose=100 mg/dl, K=3.8, creatinine=1 mg/dl, blood urea nitrogen=19 mg/dl, hemoglobin=13 g/dl and platelet count=260000×109 /L.

ECG demonstrated ST-T abnormalities in the precordial

limit of normal on chest X-ray. Transthoracic echocardiog-raphy revealed preserved left ventricular systolic function (ejection fraction=50%) with diastolic dysfunction (impaired relaxation pattern) and septal wall hypokinesia; moderate tricuspid regurgitation; mild mitral regurgitation; moderate aortic insufficiency; and mild pulmonary insufficiency. The estimated pulmonary artery pressure was 40 mmHg.

A Computed Tomography angiography was performed, which showed that the left anterior descending had some narrowing at the proximal part with cut-off at the mid portion. In addition, the left circumflex coronary artery had 90% stenosis proximally, and the right coronary artery had significant stenosis at the origin and another 50% stenosis before the patent ductus arteriosus branch. The saphenous vein graft on the obtus marginatum was patent.

The patient also underwent cardiac catheterization, which revealed a normal left main trunk, narrowing at the proximal part with cut-off at the mid portion of the left anterior descending, 90% stenosis at the proximal part of the left circumflex coronary artery, 95% calcified ostial stenosis of the right coronary artery, 50% stenosis before the patent ductus arteriosus branch, and patent saphenous vein graft on the obtus marginatum.

An angiogram of the aortic arch and great vessels (Figure 1) demonstrated Type 1 arch, normal right internal carotid artery, normal left internal carotid artery, and occluded left subclavian artery. The patient’s left renal artery angiogram was indicative of severe left renal artery stenosis.

The most important step in the management of a patient is the identification of the cause of symptoms. Therapeutic options at this point in the presence of failing medical therapy include repeat surgery or percutaneous transluminal angioplasty of the left subclavian artery. The decision was made to proceed with angioplasty and stenting of the left subclavian.

Procedures

Procedure 1: Left subclavian revascularization

An approach was undertaken from the right transfemoral

Mohammad Hasan Namazi et al

Figure 1. Angiogram of the aortic arch and great vessels in the anteroposterior (A) and lateral (B) views showing total occlusion of the left proximal subclavian artery (arrows)

artery. Unfractionated heparin was administered to achievean activated clotting time>250 seconds. A 6-Fr MP guide(Cordis, Miami, U.S.A.) was used to engage the ostium of the subclavian artery. A 0.014 BMW wire (Guidant, Santa Clara, U.S.A.) was employed to cross the lesion.

Angioplasty was performed with a 3.75×12 mm Maverick Balloon (Boston Scientific, M.A., U.S.A.) at 12 atm (Figure 2). The post-balloon angioplasty angiogram is shown in Figure 3. A 5×18 mm Genesis Stent (Cordis, Miami, U.S.A.) was subsequently deployed at 10 atm successfully with no residual stenosis, no dissection, and normal flow (Figures 4 and 5). Immediate equalization of blood pressure in both arms was acquired. Left radial approach was used for an evaluation of the left internal mammary artery, which showed a normal antegrade flow of the artery (Figure 6).

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Figure 2. Angiogram showing a 3.75×12 mm Maverick Balloon (Boston Scientific, MA, U.S.A.) in the proximal part of the subclavian artery

(arrow)

Figure 3. Angiogram showing the resolution of the proximal subclavian

artery stenosis after the balloon angioplasty (arrow)

Figure 4. Angiogram showing a 5×18 mm Genesis Stent (Cordis, Miami, U.S.A.) in the proximal part of the subclavian artery (arrow)

Figure 5. Angiogram of the stent being deployed within the left proximal subclavian artery (arrow)

Figure 6. Left radial approach was used for evaluation of the left internal mammary artery, which showed a normal antegrade flow of the artery (arrow)

Procedure 2: Left renal artery revascularization (5 days later)

A 6-Fr renal double-curve guide (Cordis, Miami,U.S.A.) was used to employ a BMW guidewire (Guidant, Santa Clara, U.S.A.) in order to cross the left renal artery stenosis (Figures 7 and 8). The lesion was predilated with a 3.75×15mm Maverick Balloon (Boston Scientific, M.A., U.S.A.) at 6 atm (Figure 9). A 6×15 mm Genesis Stent (Cordis, Miami, U.S.A.) was deployed at 10 atm (Figure 10). A final angiogram revealed no left renal artery residual stenosis as well as a normal flow (Figure 11). Despite the debatable benefits of unilateral renal intervention, we opted to treat it given the patient’s documented uncontrolled hypertension despite being on multiple antihypertensive medications.

54


Figure 7. Angiogram of the abdominal aorta showing severe left ostial renal artery stenosis (arrow)

Figure 8. Angiogram showing the selective engagement of left renal artery using a 6-Fr renal double-curve guiding catheter (Cordis, Miami, U.S.A.) (arrow)

Figure 9. Angiogram showing a 3.75×15 mm Maverick balloon (Boston Scientific, MA, USA) in the ostial part of the left renal artery (arrow)

Figure 10. Angiogram showing a 6×15 mm Genesis Stent (Cordis, Miami, U.S.A.) in the ostial part of the left renal artery (arrow)

Figure 11. Angiogram of the stent being deployed within the left renal artery (arrow)

Procedure 3: Right coronary artery revascularization

The right coronary artery was engaged using a 6-Fr JR4 guide (Cordis, Miami, U.S.A.). Pressure damping was noted as soon as it was sitting on the right coronary artery ostium (Figure 12). A BMW guidewire was advanced into the distal right coronary artery. The guiding catheter was withdrawn slightly and kept in close proximity to the right coronary artery ostium along with the guidewire. Predilation was performed with a 2.75×9 Maverick Balloon and a 3.5×10 cutting balloon (Figure 13). Finally, a 3.5×13 mm Cypher Stent (Cordis, Miami, U.S.A.) was successfully deployed (Figure 14). A 3.5×10 Quantum Balloon (Boston Scientific, M.A., U.S.A.) was utilized to postdilate the lesion (Figure 15). The patient has done well since the procedure with better control of her blood pressure and no neurological or cardiac complications.


TEHRAN HEART CENTER


Figure12. Angiogram showing severe ostial stenosis of the right coronary artery (arrow)

Figure 13. Angiogram showing a 3.5×10 mm cutting balloon (Boston Scientific, M.A., U.S.A) in the ostial part of the right coronary artery (A) and resolution of the stenosis after the balloon angioplasty (B) (arrows)

Figure 14. Angiogram showing a 3.5×13 mm Cypher Stent (Cordis, Miami, U.S.A.) in the ostial part of the right coronary artery and better resolution of the stenosis after the stent angioplasty (arrows)

Figure 15. Angiogram showing a 3.5×10 mm Quantum Balloon (Boston Scientific, M.A., U.S.A.) used for postdilatation (A) and final result of the

right coronary artery angioplasty

56


Follow- up

A duplex scan confirmed that there was no subclavian restenosis after 3 months’ follow-up. The patient was asymptomatic, and she experienced no more angina as well as no more dizziness while working with her left arm. Systolic blood pressure at both arms was120 mmHg at rest.

Discussion

In daily clinical practice, the measurement of systolic blood pressure in both arms is recommended for hypertension screening.4,5 This is to avoid a misdiagnosis in the case of lower systolic blood pressure in one arm, which may typically occur in case of subclavian stenosis, mostly because of atherosclerotic lesions occurring proximally, including the lesions of the innominate artery on the right side.6

Recently, two epidemiological studies7,8 reported a significant correlation between subclavian stenosis and major cardiovascular disease risk factors such as age, smoking, and dyslipidemia. The presence of subclavian stenosis predicts total and cardiovascular disease mortality independent of both cardiovascular disease risk factors and existent cardiovascular disease at baseline.9

Coronary subclavian steal syndrome was first described by Hargola1 and Tyras2 in the 1970s. This syndrome is caused by atherosclerosis in most cases; nonetheless, it can occur in patients with a malformation of the left internal mammary artery, in the presence of large fistulas, in case of collateral vessels not adequately closed, arteritis, exterior compression, or iatrogenic arterial injury.2,10

The stenosis of the subclavian artery, proximal to the take-off of the left internal mammary artery, produces the inversion of the flow in left internal mammary artery itself and a steal of blood from the coronary circulation when this conduit is used as a bypass graft. The prevalence of significant subclavian arteries stenosis is low; it has been reported to be 0.4%.2 In a recently published series, out of 780 patients treated with surgical myocardial revasculariza-tion, a concomitant occlusive disease of the subclavian artery was observed in 13 patients (1.6%).11 This relatively uncom-mon cause of myocardial ischemia is, however, increasingly reported secondary to the more frequent use of the internal mammary arteries in cardiac revascularization.12-14

The typical manifestation of the syndrome consists of the recurrence of ischemia or angina despite a complete surgical myocardial revascularization, but it may also include other arterial territories, namely the carotid and vertebral-basilar. The stenosis of the subclavian artery also causes hypo-perfusion to the ipsilateral arm, with dullness, pain, functional impairment, reduction in radial pulse amplitude,


and decrease in blood pressure.10-12 The reversal of the flow in the mammary artery can be enhanced by the vasodilatation in the ipsilateral arm during physical activity, but can occur at rest in case of tight stenosis.

The onset of symptoms in the first two years after surgery suggests the presence of severe stenosis at the time of surgery;12 this underlines the importance of a complete pre-operative assessment of peripheral arterial circulation in patients with ischemic heart disease that must include the proximal portion of the supra-aortic trunks. A simple measurement of arterial blood pressure in both arms and finding of a difference may arouse the suspicion and guide the indication to further non-invasive or invasive testing.15

A recurrence of symptoms indicative of subclavian artery stenosis more than two years after surgery is consistent with an obstruction originated or worsened after the pre-operative evaluation.

Conventionally, the treatment of coronary subclavian steal syndrome has been surgical via the creation of a carotid to subclavian or axillary-axillary bypass grafting or by the use of the internal mammary artery as a free graft on the ascending aorta.16 Complications of the surgical treatment of subclavian stenosis have been reported in 5-20% of cases, including mortality in 5% of patients. The 5-year graft patency rate is 58-78%, and the most frequent non-fatal complications described are pleural effusion, cervical lymphatic fistula, wound infection, Horner syndrome, graft thrombosis, and stroke.16

Balloon angioplasty for subclavian artery stenosis was described in the early 1980s, with acute success and patency rates comparable to surgery. Successful revascularization was achieved in more than 90%.17-19 Peri-procedural complications and strokes were uncommon. Primary patency ranged from 94% at 20 months to 75% at 8 years.17

As to the percutaneous treatment of subclavian stenosis, the immediate success rate approaches 100% of cases after stent implantation.20 Complications associated with endovascular treatment occur in 5-14% of cases and are generally minor compared with those of surgical treatment; these include: hematoma of the puncture site, thrombosis, arteritis, and pseudoaneurysm. Both intimal dissection of the vessel at the dilation site and embolization through the vertebral artery with neurologic deficit are generally transient.20,21

The long–term clinical outcome of subclavian artery angioplasty seems to be independent of traditional risk factors for atherosclerosis. In a series of 91 consecutive patients evaluated retrospectively over a 9-year period, overall survival in the first 5 years was 93%, 88%, 84%, 81%, and 76%, respectively, and the overall clinical patency was 96%, 91%, 86%, 77%, and 72%.20 Similarly, in a smaller series, clinical recurrence was observed in 15-30% of the patients over 2-year follow-up.13,15

TEHRAN HEART CENTER


In our case, we treated the patient by percutaneous balloon angioplasty and stent implantation of the subclavian artery seeing that the myocardial ischemia was due to the subclavian stenosis as a possible cause of blood flow steal. This approach is currently a valid alternative to surgical treatment achieving an optimal and immediate result while reducing the invasiveness, cost, and length of hospital stay.

Conclusion

The flow-limiting stenosis of the subclavian artery can be the cause of myocardial ischemia in patients with patent left internal mammary artery to coronary circulation. The percutaneous diagnostic and interventional approach is a safe and effective modality to identify and treat this infrequent pathology that is becoming an entity with increasing significance as the survival of patients with coronary artery disease improves.

The percutaneous coronary intervention of the aorto-ostial right coronary artery is difficult, not least when attempts are made to obtain a good guiding catheter support. It requires well-planned, quick technique of ballooning, and the procedure must be managed very swiftly. We hereinpresented a combined approach to severe multi-organ atherosclerosis.

References

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angiography before coronary reconstruction. Chest 1974;66:436-438.

2. Gutierrez GR, Mahrer P, Aharonian V, Mansukhani P, Bruss J.

Prevalence of subclavian artery stenosis in patients with peripheral

vascular disease. Angiology 2001;52:189-194.

3. Ribichini F, Maffe S, Ferrero V, Ferrero V, Cotroneo A, Vassanelli

C. Percutaneous angioplasty of the subclavian artery in patients with

mammary-coronary bypass grafts. J Interven Cardiol 2005;18:39-44.

4. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA,

Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ.

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M, Imai Y. Patient characteristics and factors associated with inter-arm

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Gamst AC, McDermott MM. Subclavian stenosis: the prevalence, risk

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1977;112:1125-1129.

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Pett S, Crawford MH. Failure of internal mammary artery grafts in

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KD, Leung DA, Tribble CG. Percutaneous angioplasty and stenting of

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14. Mulvihill NT, Loutfi M, Salengro E, Boccalatte M, Laborde JC,

Fajadet J, Marco J. Percutaneous treatment of coronary subclavian

steal syndrome. J Invasive Cardiol 2003;15:390-392.

15. Westerband A, Rodriguez JA, Ramaiah VG, Diethrich EB.

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clavian steal. J Vasc Surg 2003;38:699-704.

16. Mingoli A, Feldhaus RJ, Farina C, Schultz RD, Cavallaro A.

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bypass in patients with symptomatic subclavian disease. Eur J Vasc

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II HD, Iyer SS, Roubin GS. Immediate and late outcomes of subclavian

artery stenting. Catheter Cardiovasc Interv 1999;46:169-172.

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Z. Percutaneous transluminal angioplasty of the subclavian arteries. J

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58


1. Kyomars Abbasi

2. Seyed Hesamedine Abbasi

3. Seyed Hossein Ahmadi

4. Zohair Al-Halees

5. Mohammad Alidoosti

6. Majid Amiri

7. Alireza Amirzadegan

8. Edmo Atique Gabriel

9. Kamran Babazadeh

10. Jamshid Bagheri

11. Bahadour Baharestani

12. Khosro Barkhordari

13. Mehrdad Behmanesh

14. Mohammad Ali Boroumand

15. Chi Wen Cheng

16. Alexandru Cozma

17. Morteza Daliri Joupari

18. Sirous Darabyan

19. Gholamreza Davoodi

20. Saeed Davoodi

21. Ali Dodge-Khatami

22. Masoud Eslami

Note of Thanks

“The Journal of Tehran University Heart Center” wishes to extend its heartfelt thanks to the following reviewers, who for all their hectic scientific schedules, voluntarily offered their invaluably incisive and impartial evaluation of the receivedrejected manuscripts in 2008.

23. Maryam Esmaeilzadeh

24. Homa Falsoleiman

25. Mohammad Farahbakhsh

26. Saeedeh Forghani

27. Armen Gasparyan

28. Abbas Ghiasi

29. Hamidreza Goodarzynejad

30. Ali mohammad Haji Zeinali

31. Mehdi Hasanzadeh Delui

32. Seyed Ahmad Hassantash

33. Seyed Kianoosh Hoseini

34. Abbasali Karimi

35. Seyed Ebrahim Kassaian

36. Ali Kazemisaeed

37. Maryam Keshtkar

38. Mohammadreza Khatami

39. Amit Kumar

40. Mehrab Marzban

41. Carlos - A. Mestres

42. Seyed Rasoul Mirsharifi

43. Majid Moeeni

44. Mohammadreza Mohajeri

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45. Ali Montazeri

46. Sina Moradmand

47. Randa Mostafa

48. Namvar Movahedi

49. Atabak Najafi

50. Mehdi Najafi

51. Afshin Niakan

52. Saeed Oraii

53. Fausto Pinto

54. Hamidreza Pour Hosseini

55. Shahram Rabbani

56 Hassan Radmehr

57. Rezayat Parvizi

58. Soheil Saadat

59. Hakimeh Sadeghian

60. Saeed Sadeghian

61. Mohammad Sahebjam

62. Mojtaba Salarifar

63. Mohammad Salasel

64. Abbas Salehi Omran

65. Mahmood Sheikh Fathollahi

66. Shapour Shirani

67. Mahmood Shirzad

68. Hatef Shojaee

69. Abbas Soleimani

70. Maryam Sotoudeh

71. Murat Ugurlucan

72. Samuel Wann

73. Ahmad Yamini Sharif

74. Fardin Yousefshahi

75. Mohammad Reza Zafarghandi

76. Aliakbar Zeinaloo

77. Arezou Zoroufian

60


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Congress Time-Location Address

Introduction to Cardiothoracic Surgery

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Surgery Symposium (CREF)

Florida Valve 2009-”Valvular Heart Disease

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that Unify Practice”

Surgeon-Cardiologist Collaboration: A Patient

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Appropriate Use Criteria

Joint Meeting-27th Cardiovascular Surgical Symposium

and 4th Cardiac Surgery Update and Progress

17th Annual Meeting of Asian Society for

Cardiovascular and Thoracic Surgery (ASCVTS)

Re-Evolution Summit: Minimal Access

Cardiac Surgery

EACTS Academy: European School for

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2009 Society For Cardiothoracic Surgery In Great

Britain and Ireland Annual Meeting BIC

6 FEBRUARY 2009 EDIBURGH

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12-15 FEBRUARY 2009SAN DIEGO, CAUNITED STATES

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EACTS Academy: Open and Endovascular

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58th International Congress of the European

Society for CardioVascular Surgery

Advanced Cardiac Techniques in Surgery (ACTS) 2009: Latest Surgical and Interventional Techniques & Tech-nologies for Repair of Heart Valves, Aortic Aneurysms,

Coronary Revascularization and Atrial Ablation

55th Annual Conference of the Indian Association of

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Emgergency in Cardiovascular Surgery:

An Integrated Approach

Postgraduate Course In General Thoracic Surgery

XIV Congress of the Catalan Society for Cardiac Surgery

3rd Ukrainian-Polish Congress of

Cardiovascular Surgery

The 17th European Conference on

General Thoracic Surgery organized by ESTS


25-27 MARCH 2009BERGAMO

ITALY

13-14 APRIL 2009MOSCOW

RUSSIAN FEDERATION

16-18 APRIL 2009KAUNAS

LITHUANIA

17-18 APRIL 2009BARIITALY

17 APRIL 2009DUBLIN

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22-24 APRIL 2009VIENNA

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22-25 APRIL 2009PARIS

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62


2009 International Society for Minimally

Invasive Cardiothoracic Surgery (ISMICS)

12th Annual Scientific Meeting

4th Global Forum On Humanitarian

Medicine In Cardiology And Cardiac Surgery

62th Congress of the French Society for

Thoracic and Cardiovascular Surgery

The New Orleans Conference: Practices in

Cardiac Surgery and Extracorporeal Technologies

Liverpool Aortic Surgery Sumposium III

35th Annual Toronto Thoracic

Surgery Refresher Course

5th World Congress of Paediatric

Cardiology and Cardiac Surgery

Perfusion Safety & Best

Practices in Perfusion 2009

First Joint Scandinavian Conference in Cardiothoracic

Surgery (SATS/SCANSECT/SATNU)

“Bail Outs” in the Treatment of Thoracic

Aortic Pathologies-When Surgeons &

Interventional Radiologist Depend on Each Other

EACTS Academy: European School for

Cardio-Thoracic Surgery, Cardiac Course C

ESTS School of Thoracic Surgery

23rd EACTS Annual Meeting

19th Biennial Congress Association of Thoracic and

Cardiovascular Surgeon of Asia-ATCSA 2009

Vanderbilt Valve Symposium: 21st Century

Techniques for Complex Valve Surgery

Fifty-Sixth Southern Thoracic Surgical

Association Annual Meeting


3-6 JUNE 2009SAN FRANCISCO, CA

UNITED STATES

4-6 JUNE 2009GENEVA

SWITZERLAND

10-13 JUNE 2009LILLE

FRANCE

10-13 JUNE 2009NEW ORLEANS, LA

UNITED STATES

11-12 JUNE 2009LIVERPOOL

UNITED KINGDOM

12-13 JUNE 2009TORONTO, ON

CANADA

22-26 JUNE 2009CAIRNS, QLDAUSTRALIA

25-27 JUNE 2009NEW ORLEANS, LA

UNITED STATES

20-22 AUGUST 2009STOCKHOLM

SWEDEN

10-11 SEPTEMBER 2009GRAZ

AUSTRIA

21-26 SEPTEMBER 2009BERGAMO

ITALY

8-9 OCTOBER 2009ELANCOURT

FRANCE

17-21 OCTOBER 2009VIENNA

AUSTRIA

25-28 OCTOBER 2009SEOUL KOREA

29-30 OCTOBER 2009NASHVILLE, TNUNITED STATES

4-7 NOVEMBER 2009MARCO ISLAND, FL

UNITED STATES

http://www.ismics.org

[email protected]

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[email protected]

http://events.cmetoronto.ca/website/index/SUR0907

http://www.pccs2009.com/

http://www.amsect.org

http://www.sats2009.org/?type=static&id=1&mo=1

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http://www.estsschool.org/

http://www.eacts.org/

http://atcsa2009.org/

[email protected]

http://www.stsa.org/

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Surgery of The Thoracic Aorta-Live Surgery Session

from the Operating Room of the S. Orsola Hospital

5th International Meeting of the Onassis

Cardiac Surgery Center: Current Trends in

Cardiac Surgery and Cardiology

14TH Congress on Cardio-Thoracic Surgery

International Joint Meeting on Thoracic Surgery

90th Annual Meeting-American

Association for Thoracic Surgery

2009 International Society for Minimally

Invasive Cardiothoracic Surgery (ISMICS)

12th Annual Scientific Meeting

91st Annual Meeting-American


92nd Annual Meeting-American


9-10 NOVEMBER 2009BOLOGNA

ITALY

12-14 NOVEMBER 2009ATHENS GREECE

14 NOVEMBER 2009WOLUWE, BRUSSELS

BELGIUM

25-27 NOVEMBER 2009BARCELONA

SPAIN

1-5 MAY 2010TORONTO, ON

CANADA

16-19 MAY 2010BERLIN

GERMANY

7-11 MAY 2011PHILADELPHIA, PA

UNITED STATES

28 APRIL - 2 MAY 2012SAN FRANCISCO, CA

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http://www.aats.org/annualmeeting

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64


INTERNATIONAL CARDIOVASCULAR MEETING

AND CONGRESSES CALENDER (2009-2010)

Cardiology 2009-12th Annual Update on

Pediatric and Congenital Cardiovascular Disease

Myocardial Velocity and Deformation Imaging

Cardiac Pacing, ICD and Cardiac Resynchronisation Therapy

Cardiovascular Disease Prevention 2009: Seventh Annual

Comprehensive Symposium (CME)

XIVth Annual Conference of the Indian

Academy of Echocardiography

12th Annual Comprehensive Review & Update of Perioperative Echo Basic: Clinical Decision Making in the Cardiac Surgery Patient (CME)

The Ninth Annual International Symposium on Congenital

Heart Disease Special Focus: Cardiac Septal Defects

9th Annual International Symposium on

Congenital Heart Disease

Cardiology Update

Difficult Valve Disease: Focus 2009

Primary Care: Update in Lipidology and Cardiac

Health-7-Night Eastern Caribbean Cruise (CME)

Cardiovascular Congress 2009 (CME)

Title City Start Date End Date

Strasbourg

France

Leuven

Belgium

Tolochenaz

Switzerland

Florida

United States

Maradu, Kochi,

Kerala, India

California

United States

ST. Petersburg, FL

United States

ST. Petersburg, FL

United Stated

Davos

Switzerland

Sophia Antipolis

France

Florida

United States

Florida

United States

4 February 2009

5 February 2009

5 February 2009

5 February 2009

6 February 2009

9 February 2009

13 February 2009

13 February 2009

15 February 2009

19 February 2009

14 February 2009

19 February 2009

7 February 2009

6 February 2009

7 February 2009

7 February 2009

8 Feb 2009

11 February 2009

17 February 2009

17 February 2009

20 February 2009

21 February 2009

21 February 2009

21 February 2009

TEHRAN HEART CENTER



CardioRhythm 2009 (CME)

16th Annual Mayo Clinic Arrhythmias and the Heart

14th Annual 2009 Cardiology

Cardiac Pacing ICD and Cardiac Resynchronisation Therapy

13th European Vascular Course (EVC)

Cardio Egypt 2009: 36th Annual Conference

of the Egyptian Society of Cardiology

Adult Echocardiography-March 2009 (CME)

Spring Break Cardiac Summit

Percutaneous Catheter Ablation of Atrial Fibrillation: How to

Incorporate this Therapeutic Option into Your Practice (CME)

Interventional Cardiology 2009:

24th Annual International Symposium

Emergency Support of Heart and Lungs

The 5th Libyan Cardiac Society Annual Meeting

Cardiac Disease: Development, Regeneration and Repair (CME)

Cardiovascular MR Course

8th Joint Cyprus-Greek Cardiololy Conference

Coronary Reperfusion & Secondary Prevention

Houston Aortic Symposium: Frontiers in

Cardiovascular Diseases-The Second in the Series

58th Annual Scientific Session: American

College of Cardiology Annual Meeting

75th Anniversary of the Netherlands Society of Cardiology

Cardiac Pacing ICD and Cardiac Resynchronisation Therapy

Common Mechanisms in Arrhythmias and Heart Failure (CME)

5th Belgrade Summit of Interventional Cardiologists

Wanchai

Hong Kong

OAHU, HI

United States

Cancun Mexico

Sophia antipolis

France

Maastricht

Netherlands

Sharm El Sheikh

Egypt

North Carolina

United States

Freeport

Bahamas

California

United States

Snowmass Village,

CO, United States

London

United Kingdom

Tripoli

Libya

North Carolina

United States

London

UK

Nicosia

Cyprus

Oberlech

Austria

Houston, TX

United States

Orlando, FL

United States

Amsterdam

Netherlands

Sophia antipolis

France

Colorado

United States

Belgrade

Serbia

20 February 2009

23 February 2009

23 February 2009

26 February 2009

26 February 2009

24 February 2009

2 March 2009

4 March 2009

7 March 2009

8 March 2009

13 March 2009

13 March 2009

15 March 2009

18 March 2009

21 March 2009

21 March 2009

26 March 2009

28 March 2009

2 April 2009

2 April 2009

2 April 2009

5 April 2009

22 February 2009

26 February 2009

27 February 2009

28 February 2009

28 February 2009

28 February 2009

6 March 2009

8 March 2009

7 March 2009

13 March 2009

13 March 2009

15 March 2009

20 March 2009

20 March 2009

22 March 2009

26 March 2009

28 March 2009

31 March 2009

3 April 2009

4 April 2009

7 April 2009

8 April 2009

66



BASICS FUNCTIONAL ISCHAEMIC

MITRAL REGURGITATION (FIMR)

75th Annual Meeting of the German Cardiac Society

XXX Annual Congress of the Portuguese Society of Cardiology

Euroaction-Spring Meeting Precourse in Preventive Cardiology

Swedish Cardiovascular Spring Meeting

Mediterranean cardiovascular course

Coronary Physiology in the Catheterization Laboratory

6th International Symposium on Stem Cell Therapy

and Applied Cardiovascular Biotechnology

4th Clinical Update on Cardiac MRI & CT

2nd Annual Sudden Cardiac Arrest (CME)

The haemostatic system-on and off the fibrin surface

11th Annual Echocardiography Conference:

State-of-the-Art 2009 (CME)

Annual Meeting of the Working Group on Myocardial Function and the Working

Group on Cellular Biology of the Heart-2009

Annual Meeting of the Danish Society of Cardiology

Biomarkers in Heart Failure-2009

Annual Congress of the Hungarian Society of Cardiology

Coronary Artery Disease

EuroPRevent 2009

Annual Meeting of the Czech Society of Cardiology

Nuclear Cardiology & Cardiac CT ICNC 9

Cardiology & Vascular Medicine, Update and Perspective

Rome Cardiology Forum 2009

London

United Kingdom

Mannheim

Germany

Vilamoura

Portugal

Dublin

Ireland

Uppsala

Sweden

Marrakech

Morocco

Sophia Antipolis

France

Madrid

Spain

Cannes

France

California

United States

Ebeltoft

Denmark

New York

United States

Varenna

Italy

Nyborg

Denmark

Sophia Antipolis

France

Balatonfüred

Hungary

Kaunas

Lithuania

Stockholm

Sweden

Brno

Czech Republic

Barcelona

Spain

Rotterdam

Netherlands

Rome

Italy

3 April 2009

16 April 2009

19 April 2009

22 April 2009

22 April 2009

22 April 2009

23 April 2009

23 April 2009

24 April 2009

25 April 2009

27 April 2009

29 April 2009

30 April 2009

1 May 2009

3 May 2009

6 May 2009

7 May 2009

6 May 2009

10 May 2009

10 May 2009

11 May 2009

13 May 2009

3 April 2009

18 April 2009

22 April 2009

23 April 2009

24 April 2009

25 April 2009

25 April 2009

24 April 2009

26 April 2009

26 April 2009

30 April 2009

1 MAY 2009

3 May 2009

2 May 2009

5 May 2009

9 May 2009

7 May 2009

9 May 2009

13 May 2009

13 May 2009

13 May 2009

16 May 2009

TEHRAN HEART CENTER



6th Metabolic Syndrome, type II Diabetes and Atherosclerosis

Annual Meeting of Slovenian Society of Cardiology

International Congress on Geriatric Cardiology and

Noninvasive Cardiac Imaging in conjunction with XVI

Annual International Conference “Cardiology Update”

EACTA 2009

Cardiac Nuclear and CT Imaging in Clinical Practice 2009

Heart Failure

Heart Rhythm

Annual Meeting of the British Cardiovascular Society

XXII Nordic-Baltic Congress of Cardiology

The Treatment of Cardiovascular Disease:

Legacy and Innovation (CME)

Annual Meeting of the Austrian Society of Cardiology

40th Annual Meeting of the Italian Association

of Hospital Cardiologists (ANMCO)

20th Annual ASE Scientific Sessions: 2009

Back to Basics- Emphasis on a Cardiovascular

Ultrasound Core Curriculum

Daily Arrhythmia and Device Practice

Annual Congress of the Swiss Society of Cardiology

European Meeting on Hypertension 2009

8th International Congress on Complications During Coronary

Intervention: Management and Prevention

Sudden Cardiac Death, Cardiovascular Therapy

6th Tunisian and Europeans days of Cardiology Practice

EUROPACE 2009

Magna Graecia Aortic Interventional (MAORI) Symposium-

UPDATE ON THE TREATMENT OF THORACIC AND

THORACO-ABDOMINAL AORTIC DISEASES

Anti-Thrombotic Therapy- Update 2009

Berlin

Germany

Radenci

Slovenia

Tyumen

Russia

Athens

Greece

Sophia Antipolis

France

Nice

France

Berlin

Germany

London

United Kingdom

Reykjavik

Iceland

Ohio

United States

Salzburg

Austria

Florence

Italy

Washington DC

United States

Sophia antipolis

France

Lausanne

Switzerland

Milan

Italy

Lausanne

Switzerland

Copenhagen

Denmark

Hammam Sousse

Tunisia

Berlin

Germany

Catanzaro

Italy

Sophia Antipolis

France

20 May 2009

22 May 2009

27 May 2009

27 May 2009

28 May 2009

30 May 2009

21 June 2009

1 June 2009

3 June 2009

3 June 2009

3 June 2009

4 June 2009

6 June 2009

8 June 2009

10 June 2009

12 June 2009

17 June 2009

18 June 2009

18 June 2009

21 June 2009

24 June 2009

25 June 2009

24 May 2009

23 May 2009

29 May 2009

30 May 2009

30 May 2009

2 June 2009

24 June 2009

3 June 2009

5 June 2009

5 June 2009

6 June 2009

7 June 2009

10 June 2009

10 June 2009

12 June 2009

16 June 2009

19 June 2009

19 June 2009

20 June 2009

24 June 2009

24 June 2009

27 June 2009

68



Fifth Biennial Meeting of The Society for Heart Valve Disease

International Academy of Cardiology 15th World Congress on

Heart Disease, Annual Scientific Sessions 2009 (CME)

Basic Cardiovascular Sciences Annual Conference

2009-Molecular Mechanisms of Cardiovascular Disease (CME)

35th Ten-Day Seminar on the Epidemiology and

Prevention of Cardiovascular Disease (CME)

Cardiology Update-Eastern Mediterranean Cruise (CME)

ESC Congress 2009

EACTA ECHO 2009

Conference of Cardiologists of the

Moldavian Society of Cardiology

2009 Heart Valve Summit

Computers in Cardiology 2009

Annual Congress of the Romanian Society of Cardiology

13th International Congress of the Polish Cardiac Society

Venice 2009 Arrhythmias-11th International

Workshop on Cardiac Arrhythmias

Pacs 2009-International Symposium on

Progress in Acute Coronary Syndromes

EuroThrombosis Summit 2009

Annual Congress of the Slovak Society of Cardiology

60th Annual General Meeting of the Irish Cardiac Society

ICCAD 2009-8th International

Congress on Coronary Artery Disease

Annual Autumn Meeting of the Finnish Cardiac Society

9th Biennial Congress of the Syrian

Cardiovascular Association

XVII Congress of the Cardiology Society of Serbia

International Congress of the Lebanese

Society of Cardiology and Cardiac Surgery

Berlin

Germany

Vancouver

Canada

Nevada

United States

California

United States

Civitavecchia

Italy

Barcelona

Spain

Leicester

United Kingdom

Chisinau

Moldova

Chicago, IL

United States

Park City, Utah

United States

Sinaia

Romania

Poznan

Poland

Venice

Italy

Rome

Italy

Oslo

Norway

Bratislava

Slovakia

Killarney, Co. Kerry

Ireland

Prague

Czech Republic

Helsinki

Finland

Damascus

Syria

Belgrade

Serbia

Beirut

Lebanon

27 June 2009

18 July 2009

20 July 2009

26 July 2009

27 July 2009

29 August 2009

5 September 2009

9 September 2009

10 September 2009

13 September 2009

19 September 2009

24 September 2009

4 October 2009

8 October 2009

8 October 2009

8 October 2009

9 October 2009

11 October 2009

14 October 2009

15 October 2009

18 October 2009

21 October 2009

30 June 2009

21 July 2009

23 July 2009

7 August 2009

7 August 2009

2 September 2009

8 September 2009

9 September 2009

12 September 2009

16 September 2009

22 September 2009

26 September 2009

7 October 2009

10 October 2009

10 October 2009

10 October 2009

10 October 2009

14 October 2009

16 October 2009

17 October 2009

21 October 2009

24 October 2009

TEHRAN HEART CENTER



Annual Meeting of the Spanish Society of Cardiology

XXV National Cardiology Congress

of the Turkish Society of Cardiology

Invasive Cardiac Electrophysiology

20th Annual Coronary Interventions (CME)

Autumn Meeting of the Netherlands Society of Cardiology

Adult Congenital Heart Disease:

What You Always wanted to Know

ICCA 2009-International Course on Carotid Angioplasty

and other Cerebrovascular Interventions

Echocardiography

Annual Meeting of the Lithuanian Society of Cardiology

The 2nd World Congress on Controversies in

Cardiovascular Disease (C-Care) (CME)

Aortic Symposium 2010

Heart Failure 2010

21st International Congress on Thrombosis 2010

15th World Congress on Heart Disease,

Annual Scientific Congress 2010

Acute Cardiac Care 2010

Barcelona

Spain

Istanbul

Turkey

Sophia Antipolis

France

California

United States

Amsterdam

Netherlands

Antalya

Turkey

Frankfurt

Germany

Madrid

Spain

Kaunas

Lithuania

Istanbul

Turkey

New York, NY

United States

Berlin

Germany

Milan

Italy

British Columbia

Canada

Copenhagen

Denmark

22 October 2009

23 October 2009

26 October 2009

28 October 2009

5 November 2009

28 November 2009

3 December 2009

9 December 2009

18 December 2009

18 February 2010

29 April 2010

29 May 2010

6 July 2010

24 July 2010

16 October 2010

24 October 2009

26 October 2009

28 October 2009

30 October 2009

7 November 2009

29 November 2009

5 December 2009

12 December 2009

18 December 2009

21 February 2010

30 April 2010

1 June 2010

9 July 2010

27 July 2010

19 October 2010

70


Information for Authors

The first three consecutive issues of "The Journal of Tehran University Heart Center" were published under the title of "The Journal of Tehran Heart

Center" with ISSN: 1735-5370. From the fourth issue onward, however, the journal has been entitled ‘’The Journal of Tehran University Heart Center" with

ISSN:1735-8620.

"The Journal of Tehran University Heart Center" aims to publish the highest quality material, both clinical and scientific, on all aspects of Cardiovascular

Medicine. It includes articles related to research findings, technical evaluations, and reviews. In addition, it provides a forum for the exchange of

information on all aspects of Cardiovascular Medicine, including educational issues. "The journal of Tehran University Heart Center" is an international,

English language, peer reviewed journal concerned with Cardiovascular Medicine. It is an official journal of the Cardiovascular Research Center of the

Tehran University of Medical Sciences (in collaboration with the Iranian Society of Cardiac Surgeons) and is published quarterly. Papers submitted to this

journal which do not adhere to the Instructions for Authors will be returned for appropriate revision to be in line with the Instructions for Authors. They may

then be resubmitted. Submission of an article implies that the work described has not been published previously (except in the form of an abstract or as part

of a published lecture or academic thesis), that it is not under consideration for publication elsewhere, that its publication is approved by all Authors and

tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form,

in English or in any other language, without the written consent of the publisher.

Four double spaced copies on 8 1/2 × 11 in. paper should be sent to:

Dr. A. Karimi,

Editor in Chief,

"The Journal of Tehran University Heart Center" ,

Tehran Heart Center,

North Kargar Street,

Tehran, Iran

1411713138

Photocopies or good reproductions of illustrations are acceptable only on the spare copies. Included also should be a set of the electronic files of the

manuscript on floppy – disk or CD-ROM. For preparation of electronic files, see the instructions herein below.

Also, manuscripts can be submitted electronically via the journal’s website: http://jthc.tums.ac.ir. On-line submission allows the manuscript to be handled

in electronic forms throughout the review process.

The Journal of Tehran University Heart Center” accepts the following categories of articles:”

Guest Editorial

Original Article

Clinical and pre-clinical papers based on either normal subjects or patients and the result of cardiovascular pre-clinical research will be Considered for

publication provided they have an obvious clinical relevance.

Brief communication

Case report

Review Article

"The Journal of Tehran University Heart Center" publishes a limited number of scholarly, comprehensive reviews whose aims are to summarize and criti-

cally evaluate research in the field addressed and identify future implications. Reviews should not exceed 5000 words.

Letter to editor

Letters to the editor must not exceed 500 words and should focus on a specific article published in

"The Journal of Tehran University Heart Center" within the preceding 12 weeks. No original data may be included. Authors will receive pre-publication

proofs, and the authors of the article cited invited to reply.

Scope of the journal

Article Categories

Submission of manuscripts

TEHRAN HEART CENTER


Authors whose first language is not English are requested to have their manuscripts checked carefully before submission. This will help expedite the

review process and avoid confusion. Abbreviations of standard SI units of measurement only should be used.

The Authors should state that their study complies with the Declaration of Helsinki that the locally appointed ethics committee has approved the research

protocol and that informed consent has been obtained from the subjects (or their guardians).

Authors should comply with the clinical trial registration statement from the ICMJE. More information can be found at www.icmje.org. Clinical trial

reports should also comply with the Consolidated Standards of Reporting Trials (CONSORT) and include a flow diagram presenting the enrollment,

intervention allocation, follow-up, and data analysis with number of subjects for each (www.consort-statement.org). Please also refer specifically to the

CONSORT Checklist of items to include when reporting a randomized clinical trial.

Original articles should be divided into the following sections: (1) Title page, (2) Abstract and Keywords, (3) Introduction, (4) Methods, (5) Results,

(6) Discussion, (7) Conclusion, (8) Acknowledgements, (9) References, (10) Figure legends, (11) Tables, (12) Figures.

Original articles should be divided into the following sections: (1) Title page, (2) Abstract and Keywords, (3) Introduction, (4) Methods, (5) Results,

(6) Discussion, (7) Conclusion, (8) Acknowledgements, (9) References, (10) Figure legends, (11) Tables, (12) Figures.

Prepare your manuscript text using a word processing package. Submissions of text in the form of PDF files are not permitted. Manuscripts should

be double-spaced, including text, tables, legends and references. Number each page. Please avoid footnotes; use instead, and as sparingly as possible,

parenthesis within brackets. Enter text in the style and order of the Journal. Type references in the correct order and style of the journal. Type unjustified,

without hyphenation, except for compound words. Type headings in the style of the journal. Use the TAB key once for paragraph indents. Where possible

use Times New Roman for the text font and Symbol for the Greek and special characters. Use the word processing formatting features to indicate Bold,

Italic, Greek, Maths, Superscript and subscript characters. Clearly identify unusual symbols and Greek letters. Differentiate between the letter o and zero,

and the letters I and i and the number 1. Mark the approximate position of each figure and table. Check the final copy of your paper carefully, as any spelling

mistakes and errors may be translated into the typeset version.

The title page should include the following: (1) the title, (2) the name (s) of authors and their highest degree ( no more than 12 authors are acceptable), (3)

Style and spelling

Declaration of Helsinki

Clinical trials

Section of the manuscripts

General format

General format

All manuscripts correctly submitted to will first be reviewed by the Editors. Some manuscripts will be returned to authors at this stage if the paper is

deemed inappropriate for publication in “The Journal of Tehran University Heart Center”, if the paper does not meet submission requirements, or if the

paper is not deemed to have a sufficiently high priority. All papers considered suitable by the Editors to progress further in the review process will undergo

appropriate peer review and all papers provisionally accepted for publication will undergo a detailed statistical review.

All submitted manuscripts must not exceed 5000 words, including References, Figure Legends and Tables. The number of Tables, Figures and

References should be appropriate to the manuscript content and should not be excessive. Authors should comply with the manuscript formatting and the

ethical conventions of the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” issued by the International Committee of Medical

Journal Editors ( http://www.icmje.org ).

Review of manuscripts Review of manuscripts

Preparation of manuscripts

Title page

72


the institution (s) where work was performed, (4) institution, and location of all authors, (5) the address, telephone number, fax number and e-mail address

of the corresponding author.

All abstracts may not contain more than 250 words and should also be submitted as a separate file. The abstract should be formatted with the following

heading: (1) Background, (2) Methods, (3) Results, (4) Conclusion.

A maximum of six Keywords may be submitted.

The review process will not begin until all figures are received. Figures should be limited to the number necessary for clarity and must not duplicate data

given in tables or in the text. They must be suitable for high quality reproduction and should be submitted in the desired final printed size so that reduction

can be avoided. Figures should be no larger than 125 (height)×180 (width) mm (5×7 inches) and should be submitted in a separate file from that of the

manuscript.

Figures should be saved in TIFF format at a resolution of at least 300 pixels per inch at the final printed size for colour figures and photographs, and

1200 pixels per inch for black and white line drawings. Although some other formats can be translated into TIFF format by the publisher, the conversion

may alter the tones, resolution and contrast of the image. Digital colour art should be submitted in CMYK rather than RGB format, as the printing process

requires colours to be separated into CMYK and this conversion can alter the intensity and brightness of colours. Therefore authors should be satisfied with

the colours in CMYK (both on screen and when printed) before submission. Please also keep in mind that colours can appear differently on different screens

and printers. Failure to follow these guides could result in complications and delays.

Photographs: Photographs should be of sufficiently high quality with respect to detail, contrast and fineness of grain to withstand the inevitable loss of

contrast and detail inherent in the printing process. Please indicate the magnification by a rule on the photograph. Colour figures: There is a special charge

for the inclusion of colour figures. Figure legends: These should be on a separate, numbered manuscript sheet grouped under the heading “Legends” on a

separate sheet of the manuscript after the References. Define all symbols and abbreviations used in the figure. All abbreviations and should be redefined in

the legend.

Tables should be typed with double spacing, but minimizing redundant space and each should be placed on a separate sheet. Tables should be submitted,

wherever possible, in portraits, as opposed to landscape, layout. Each Table should be numbered in sequence using Arabic numerals. Tables should also have

a title above and an explanatory footnote below. All abbreviations and should be redefined in the Footnote.

All sources of funding and support, and substantive contributions of individuals, should be noted in the Acknowledgements, positioned before the list of

references.

Number references sequentially and use Arabic number in superscript to cite the reference in the text. All references should be compiled at the end of the

article in the Vancouver style. Complete information should be given for each reference including the title of the article, abbreviated journal title and page

numbers. All authors should be listed. Personal communications; manuscripts in preparation and other unpublished data should not be cited in the reference

list but may be mentioned in parentheses in the text. Authors should get permission from the source to cite unpublished data.

Titles of journals should be abbreviated in accordance with Index Medicus (see list printed annually in the January issue of Index Medicus). If a journal is

not listed in Index Medicus then its name should be written out in full.

Article citation example:

Journal citation example: 1. Schroeder S, Baumbach A, Mahrholdt H. The impact of untreated coronary dissections on the acute and long-term outcome after

intravascular ultrasound guided PTCA. Eur Heart J 2000;21:137-145.

Chapter citation example: 2. Nichols WW, O’Rourke MF. Aging, high blood pressure and disease in humans. In: Arnold E, ed. McDonald’s Blood Flow in

Arteries: Theoretical, Experimental and Clinical Principles. 3rd ed. London/Melbourne/Auckland: Lea and Febiger; 1990. p. 398-420.

Abstract

Figures

Tables

Acknowledgements

Reference format

TEHRAN HEART CENTER


All manuscripts selected for publication will be reviewed for the appropriateness and accuracy of the statistical methods used and the interpretation of

statistical results. All papers submitted should provide in their Methods section a subsection detailing the statistical methods, including the specific method

used to summarize the data, the methods used to test their hypothesis testing and (if any) the level of significance used for hypothesis testing.

At submission, the editors require authors to disclose any financial association that might pose a conflict of interest in connection with the submitted

article. All sources of funding for the work should be acknowledged in a footnote on the title page and in the Acknowledgements within the manuscript, as

should all the institutional affiliations of the authors (including corporate appointments). Other kinds of associations, such as consultancies, stock ownership

or other equity interest or patent-licensing arrangements should be disclosed to the editors in the cover letter at the time of the of submission. If no conflict

of interest exists, please state this in the cover letter.

Page proofs will be sent to the corresponding author. Please provide an e-mail address to enable page proofs to be sent as PDF files via e-mail. These

should be checked thoroughly for any possible changes or typographic errors. Significant alterations instigated at this stage by the author will be charged

to the author. It is the intention of the Editor to review, correct and publish your article as quickly as possible. To achieve this it is important that all of your

corrections are returned to us in one all- inclusive mail or fax. Subsequent additional corrections will not be possible, so please ensure that your first com-

munication is complete.

Statistics

Proofs

Webpage citation example: 3. Panteghini M. Recommendations on use of biochemical markers in acute coronary syndrome: IFCC proposals. eJIFCC 14.

http://www.ifcc.org/ejifcc/vol14no2/1402062003014n.htm (28 May 2004). Where the date in parenthesis refers to the access date.

Subscription Form

The Journal of Tehran University Heart CenterNew Subscription: Continuation of Subscription:

Surname:

First Name:

Date of subscription:

Full mail address:

E-mail:

Please liquidate the total amount of Subscription and postal charges into:

Bank: Refah Branch Code: 1232 Account: Tehran Heart Center Account Number: 200001.28

and send the original Bank slip along with Duly completed form of Subscription to the following address:


North Karegar Street,

Tehran, Iran : 1411713138

88029702 21 +98

E-mail: [email protected]

TEHRAN HEART CENTER

Subscription Form

The Journal of Tehran University Heart CenterNew Subscription: Continuation of Subscription:

Surname:

First Name:

Date of subscription:

Full mail address:

E-mail:

Please liquidate the total amount of Subscription and postal charges into:

Bank: Refah Branch Code: 1232 Account: Tehran Heart Center Account Number: 200001.28

and send the original Bank slip along with Duly completed form of Subscription to the following address:


North Karegar Street,

Tehran, Iran : 1411713138

88029702 21 +98

E-mail: [email protected]

TEHRAN HEART CENTER

TEHRAN HEART CENTER

Documents

TEHRAN HEART CENTERthc.tums.ac.ir/UserFiles/File/all page.4.pdf · Primary Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction Morteza Safi, Hassan Rajabi