Harvard Medical School Pulmonary Embolism: Current Concepts in Diagnosis and Management Gregory Piazza, MD July 26, 2005

Harvard Medical School

Pulmonary Embolism: Pulmonary Embolism: Current Concepts in Current Concepts in Diagnosis and Diagnosis and ManagementManagement

Gregory Piazza, MDGregory Piazza, MD

July 26, 2005July 26, 2005


ObjectivesObjectives• To examine the state-of-the-art in the To examine the state-of-the-art in the

evaluation of patients with suspected evaluation of patients with suspected pulmonary embolism (PE).pulmonary embolism (PE).

• To review the recent advances in risk To review the recent advances in risk stratification of patients with PE.stratification of patients with PE.

• To highlight current approaches to the To highlight current approaches to the treatment of PE.treatment of PE.


Spectrum of DiseaseSpectrum of Disease• A variety of clinical syndromes may A variety of clinical syndromes may

be seen:be seen:1.1. Normotensive with normal RV Normotensive with normal RV

functionfunction2.2. Normotensive with RV Normotensive with RV

dysfunction (submassive PE)dysfunction (submassive PE)3.3. Cardiogenic shock (massive PE)Cardiogenic shock (massive PE)4.4. Cardiac arrest (massive PE)Cardiac arrest (massive PE)


EpidemiologyEpidemiology• The incidence of PE in the U.S. is 1 per 1000 per The incidence of PE in the U.S. is 1 per 1000 per

year.year.• Only 1 out of every 3 cases of venous Only 1 out of every 3 cases of venous

thromboembolism (VTE) is diagnosed.thromboembolism (VTE) is diagnosed.• With approximately 450,000 cases detected per With approximately 450,000 cases detected per

year, a staggering 900,000 VTE cases may go year, a staggering 900,000 VTE cases may go unrecognized annually.unrecognized annually.

• In the Olmsted County registry, 30-day mortality In the Olmsted County registry, 30-day mortality after PE or DVT has been reported as high as 28%.after PE or DVT has been reported as high as 28%.

• The International Cooperative Pulmonary Embolism The International Cooperative Pulmonary Embolism Registry (ICOPER) estimates a 3-month mortality of Registry (ICOPER) estimates a 3-month mortality of 17.4%.17.4%.

• These data suggest PE is possibly as deadly as acute These data suggest PE is possibly as deadly as acute myocardial infarction.myocardial infarction.Lancet 2004; 363:1295-1305

Arch Intern Med 1999;159:445-453Lancet 1999;353:1386-1389Circulation 2003;108:2726-2729


Case: Patient No. 1Case: Patient No. 1• A 57 year old female with history of hypertension, A 57 year old female with history of hypertension,

diabetes, and asthma presents with acute onset diabetes, and asthma presents with acute onset right-sided chest pain and dyspnea.right-sided chest pain and dyspnea.

• She is currently taking lisinopril, metformin, She is currently taking lisinopril, metformin, albuterol, and estrogen with progesterone.albuterol, and estrogen with progesterone.

• She smokes half a pack per day.She smokes half a pack per day.• On exam, she is tachycardic, tachypneic, obese On exam, she is tachycardic, tachypneic, obese

and anxious-appearing, with an oxygen saturation and anxious-appearing, with an oxygen saturation of 93% on RA. She has mild left lower extremity of 93% on RA. She has mild left lower extremity pitting edema.pitting edema.


Case: Patient No. 1Case: Patient No. 1

How should this patient be worked up?How should this patient be worked up?


The History and The History and PhysicalPhysical

History:History:• Dyspnea (most Dyspnea (most

frequent symptom)frequent symptom)• Pleuritic chest painPleuritic chest pain• CoughCough• HemoptysisHemoptysis• SyncopeSyncope

Physical Exam:Physical Exam:• Tachypnea (most Tachypnea (most

frequent sign)frequent sign)• Anxious appearanceAnxious appearance• TachycardiaTachycardia• FeverFever• Elevated JVD (most Elevated JVD (most

specific sign)specific sign)• Loud P2Loud P2• Tricuspid regurgitationTricuspid regurgitation• Paradoxical Paradoxical

bradycardiabradycardia


The Diagnostic The Diagnostic ArmamentariumArmamentarium

• Arterial blood Arterial blood gasesgases

• ElectrocardiographElectrocardiographyy

• Chest X-rayChest X-ray• Plasma D-dimerPlasma D-dimer• Lower extremity Lower extremity

ultrasoundultrasound• EchocardiographyEchocardiography

• Ventilation-Ventilation-perfusion lung perfusion lung scanningscanning

• Spiral chest CTSpiral chest CT• Magnetic resonance Magnetic resonance

(MR) angiography(MR) angiography• Contrast pulmonary Contrast pulmonary

angiographyangiography

“Everything you can do is not everything you should do.”


ElectrocardiographyElectrocardiographyCommon electrocardiographic findings:Common electrocardiographic findings:• Sinus tachycardiaSinus tachycardia• iRBBB/RBBBiRBBB/RBBB• RADRAD• S in I,L > 1.5mmS in I,L > 1.5mm• Q waves in III,F but not in IIQ waves in III,F but not in II• TWI in III,F or V1-V4TWI in III,F or V1-V4• S1Q3T3S1Q3T3• Qr pattern in V1Qr pattern in V1

Circulation 2002;106:459


Chest X-rayChest X-ray• Chest X-ray serves an important role in Chest X-ray serves an important role in

formulation of clinical suspicion for PE and formulation of clinical suspicion for PE and may help suggest alternative pathology.may help suggest alternative pathology.

• A recent review noted the most common A recent review noted the most common chest X-ray interpretations:chest X-ray interpretations:- cardiomegaly (27%)- cardiomegaly (27%)- normal (24%)- normal (24%)- pleural effusion (23%)- pleural effusion (23%)- elevated hemidiaphragm (20%)- elevated hemidiaphragm (20%)- pulmonary artery enlargement (19%)- pulmonary artery enlargement (19%)- atelectasis (18%)- atelectasis (18%)- pulmonary infiltrate (17%)- pulmonary infiltrate (17%)

Chest 2000;118(1):33-8


Plasma D-dimerPlasma D-dimer• D-dimers are non-specific markers of ineffective D-dimers are non-specific markers of ineffective

endogenous fibrinolysis and may be elevated in endogenous fibrinolysis and may be elevated in many conditions, especially among inpatients.many conditions, especially among inpatients.

• A recent evaluation of D-dimer ELISA in a high-A recent evaluation of D-dimer ELISA in a high-volume ED revealed a sensitivity of 96.4% and volume ED revealed a sensitivity of 96.4% and NPV of 99.6%.NPV of 99.6%.

• The D-dimer ELISA alone can exclude PE in up to The D-dimer ELISA alone can exclude PE in up to 30% of patients without further costly tests.30% of patients without further costly tests.

• There is currently inadequate evidence to stop There is currently inadequate evidence to stop the evaluation for PE in patients with high the evaluation for PE in patients with high clinical suspicion and normal D-dimer levels.clinical suspicion and normal D-dimer levels.

• Qualitative latex agglutination assays Qualitative latex agglutination assays (SimpliRED) lack the NPV to safely exclude PE.(SimpliRED) lack the NPV to safely exclude PE.

Ann Intern Med 2004;140:589-602

J Am Coll Cardiol 2002;40:1475-78

Ann Emerg Med 2002;39:144-52


Ventilation Perfusion (V/Q) Ventilation Perfusion (V/Q) ScanScan

• V/Q scans are no longer the initial test of V/Q scans are no longer the initial test of choice in the PE work-up.choice in the PE work-up.

• Lung scanning is reserved for patients with Lung scanning is reserved for patients with renal failure, anaphylaxis to contrast, or renal failure, anaphylaxis to contrast, or pregnancy.pregnancy.

• V/Q scans provide definitive information less V/Q scans provide definitive information less than 50% of the time.than 50% of the time.

• Normal V/Q scans practically exclude the Normal V/Q scans practically exclude the possibility of PE while high-probability scans possibility of PE while high-probability scans in the right setting guarantee the diagnosis.in the right setting guarantee the diagnosis.

• However, the majority of scans fall into the However, the majority of scans fall into the intermediate or indeterminate range intermediate or indeterminate range requiring further testing.requiring further testing.


Chest CT ScanChest CT Scan• Spiral chest CT is now the first choice for imaging Spiral chest CT is now the first choice for imaging

PE.PE.• The sensitivity of chest CT is highest in the proximal The sensitivity of chest CT is highest in the proximal

pulmonary arteries.pulmonary arteries.• Early generation (“single-detector”) scanners are Early generation (“single-detector”) scanners are

prone to miss small segmental or large prone to miss small segmental or large subsegmental PE and have a sensitivity of subsegmental PE and have a sensitivity of approximately 70%.approximately 70%.

• Third generation “multi-detector” scanners have Third generation “multi-detector” scanners have yielded a 40% increased detection rate for yielded a 40% increased detection rate for subsegmental PE and a 70% decrease in subsegmental PE and a 70% decrease in indeterminate studies. Sensitivity has improved to indeterminate studies. Sensitivity has improved to over 90%.over 90%.

• Chest CT provides information regarding the Chest CT provides information regarding the condition of the RV as well as conditions that mimic condition of the RV as well as conditions that mimic PE such as pneumonia.PE such as pneumonia.

• PIOPED II should provide the most thorough analysis PIOPED II should provide the most thorough analysis of the efficacy of chest CT to date.of the efficacy of chest CT to date.

Ann Intern Med 2001;217:447-455

Radiology 2002;222:483-490


EchocardiographyEchocardiography• Transthoracic echocardiography is insensitive in Transthoracic echocardiography is insensitive in

screening for PE but plays an important role in risk screening for PE but plays an important role in risk stratification based on the findings of RV dysfunction.stratification based on the findings of RV dysfunction.

• Transesophageal echocardiography (TEE) has the Transesophageal echocardiography (TEE) has the potential to diagnose pulmonary embolism by direct potential to diagnose pulmonary embolism by direct visualization.visualization.

• TEE provides information about the extent and surgical TEE provides information about the extent and surgical accessibility of the PE if open embolectomy is accessibility of the PE if open embolectomy is considered.considered.

• TEE provides excellent visualization of main PA and right TEE provides excellent visualization of main PA and right PA until it divides into lobar arteries.PA until it divides into lobar arteries.

• In sudden cardiac compromise or PEA arrest, TEE may be In sudden cardiac compromise or PEA arrest, TEE may be a quick and effective method for diagnosing massive PE.a quick and effective method for diagnosing massive PE.

Arch Intern Med 2000;160(10):1529-35


Contrast Pulmonary Contrast Pulmonary AngiographyAngiography

• Contrast angiography is indicated in the PE Contrast angiography is indicated in the PE work-up when initial studies such as spiral work-up when initial studies such as spiral CT or V/Q scan are nondiagnostic and CT or V/Q scan are nondiagnostic and clinical suspicion remains high.clinical suspicion remains high.

• Pulmonary angiography is being utilized Pulmonary angiography is being utilized with declining frequency and the number with declining frequency and the number of experienced radiologists is decreasing.of experienced radiologists is decreasing.

• Contrast angiography is an invasive study Contrast angiography is an invasive study with the potential for significant morbidity with the potential for significant morbidity and mortality.and mortality.

Circulation 1992;85(2):462-68


An Integrated An Integrated ApproachApproach

History and Physical

Eval. clinical likelihood

ElectrocardiogramChest radiograph

Inpatient or high prob.

Patient in ED

D-dimer

HighNormal

Chest CTV/Q if dye allergy or renal insufficiency

Normal Positive Equivocal Normal

Ultrasonography

Positive Negative

No PE Treat for PE Consider PA-gram

No PE

No PE

Lancet 2004;363:1295-1305


Case: Patient No. 2Case: Patient No. 2• A 67 year old male with history of CAD, HTN, A 67 year old male with history of CAD, HTN,

and prostate cancer presents with acute and prostate cancer presents with acute onset dyspnea, lightheadedness, and dull onset dyspnea, lightheadedness, and dull chest pressure.chest pressure.

• He is currently taking metoprolol, lisinopril, He is currently taking metoprolol, lisinopril, and aspirin.and aspirin.

• On exam, he is tachycardic, tachypneic, On exam, he is tachycardic, tachypneic, hypoxic, but normotensive. He has elevated hypoxic, but normotensive. He has elevated neck veins and new lower extremity edema.neck veins and new lower extremity edema.

• His EKG reveals sinus tachycardia.His EKG reveals sinus tachycardia.• His chest X-ray is read as “no pneumonia, no His chest X-ray is read as “no pneumonia, no

CHF.”CHF.”• Because of high clinical suspicion for PE, he Because of high clinical suspicion for PE, he

undergoes chest CT.undergoes chest CT.


Case: Patient No. 2Case: Patient No. 2• The patient is started on a weight-based The patient is started on a weight-based

protocol of intravenous unfractionated protocol of intravenous unfractionated heparin and admitted to a telemetry floor.heparin and admitted to a telemetry floor.

• That evening, the patient’s roommate calls That evening, the patient’s roommate calls the nurses station to report that the patient the nurses station to report that the patient has “slumped over in his chair.”has “slumped over in his chair.”

• The patient is found unresponsive and a The patient is found unresponsive and a code is called.code is called.

• The patient is found to be in pulseless The patient is found to be in pulseless electrical activity (PEA) and expires after electrical activity (PEA) and expires after resuscitative efforts are unsuccessful.resuscitative efforts are unsuccessful.



Did we see this coming?Did we see this coming?


Risk StratificationRisk StratificationRisk Stratification Tools:Risk Stratification Tools:• History and physicalHistory and physical• Clinical prognostic scoresClinical prognostic scores• Cardiac biomarkers including cardiac Cardiac biomarkers including cardiac

troponin and brain-type natriuretic peptide troponin and brain-type natriuretic peptide (BNP)(BNP)

• Chest CTChest CT• EchocardiographyEchocardiography


History and PhysicalHistory and Physical

• ICOPER reported ICOPER reported several independent several independent clinical predictors of clinical predictors of increased mortality at increased mortality at 3 months.3 months.

Variable Hazard Ratio (95% CI)

Age > 70 years 1.6 (1.1-2.3)

Cancer 2.3 (1.5-3.5)

CHF 2.4 (1.5-3.7)

COPD 1.8 (1.2-2.7)

SBP <90 mmHg 2.9 (1.7-5.0)

Lancet 1999;353:1386-9


Cardiac BiomarkersCardiac Biomarkers• Cardiac troponins and BNP have been Cardiac troponins and BNP have been

extensively studied in the evaluation of patients extensively studied in the evaluation of patients with acute PE. with acute PE.

• Cardiac troponins and BNP accurately identify Cardiac troponins and BNP accurately identify low-risk PE patients with negative predictive low-risk PE patients with negative predictive values for in-hospital death ranging from 97 to values for in-hospital death ranging from 97 to 100%. 100%.

• Patients presenting with acute PE and elevated Patients presenting with acute PE and elevated cardiac biomarkers should undergo transthoracic cardiac biomarkers should undergo transthoracic echocardiography to assess RV function.echocardiography to assess RV function.

• In patients with acute PE and normal levels of In patients with acute PE and normal levels of cardiac biomarkers, echocardiography is not cardiac biomarkers, echocardiography is not routinely required as RV function will most often routinely required as RV function will most often be normal.be normal.Circulation 2003;108:2191-2194


Cardiac BiomarkersCardiac Biomarkers

Circulation 2003;108:2191-2194

↑ RV pressure

↑ PVR

RV micro-infarction

↑ RV shear stress

Myofibril degradation

↑ Natriuretic peptide mRNA

↑ Troponins ↑ BNP


Cardiac BiomarkersCardiac Biomarkers

Circulation 2003;108:2191-2194

No shock Shock

BNP ↓Troponin ↓

BNP ↑Troponin ↑

RV dysfunctionNo RV dysfunction

Anticoagulation alone Consider thrombolysis or embolectomy

Echocardiography


Chest CT ScanChest CT Scan• Although chest CT is used primarily for the Although chest CT is used primarily for the

diagnosis of PE, right ventricular dilatation diagnosis of PE, right ventricular dilatation may also be observed.may also be observed.

• In a recent study, a ratio of RV dimension In a recent study, a ratio of RV dimension to LV dimension > 0.9 on a reconstructed 4 to LV dimension > 0.9 on a reconstructed 4 chamber view was an independent chamber view was an independent predictor of adverse events (OR 4.02, predictor of adverse events (OR 4.02, 95%CI 1.06-15.19; p = 0.041) when 95%CI 1.06-15.19; p = 0.041) when adjusted for age, obesity, cancer, and adjusted for age, obesity, cancer, and recent surgery. recent surgery.

Circulation 2004;110:3276-3280


EchocardiographyEchocardiography• Echocardiography is Echocardiography is

very sensitive in very sensitive in identifying RV identifying RV dysfunction in PE.dysfunction in PE.

• RV dysfunction has RV dysfunction has proven to be one of proven to be one of the strongest the strongest predictors of adverse predictors of adverse outcomes and outcomes and recurrent PE.recurrent PE.

Typical findings in PE Typical findings in PE include:include:

• RV dilatationRV dilatation• Moderate to severe RV free Moderate to severe RV free

wall hypokinesis with apical wall hypokinesis with apical sparing (McConnell Sign)sparing (McConnell Sign)

• Paradoxical interventricular Paradoxical interventricular septal motionseptal motion

• TR/Pulmonary HTNTR/Pulmonary HTN• Loss of respiratory-phasic Loss of respiratory-phasic

changes in IVCchanges in IVC• Decrease in the difference Decrease in the difference

between LV area during between LV area during diastole and systole diastole and systole (marker of cardiogenic (marker of cardiogenic shock)shock)

Ann Intern Med 2002;136:691-700

Crit Pathways in Cardiol 2003;2:247-265


Case: Patient No. 3Case: Patient No. 3• A 44 year old female with no significant past A 44 year old female with no significant past

medical history presents with sudden onset medical history presents with sudden onset dyspnea and chest discomfort.dyspnea and chest discomfort.

• She also notes left lower extremity swelling She also notes left lower extremity swelling and pain for the past three days.and pain for the past three days.

• On physical exam, she is normotensive but On physical exam, she is normotensive but mildly tachypneic, tachycardic, and hypoxic. mildly tachypneic, tachycardic, and hypoxic. She has moderate pitting edema of the left She has moderate pitting edema of the left leg.leg.

• Because of her symptoms and exam, a chest Because of her symptoms and exam, a chest CT is performed and reveals bilateral PE.CT is performed and reveals bilateral PE.



How should we manage this patient?How should we manage this patient?


Primary v. Secondary Primary v. Secondary TherapyTherapy

Primary therapy:Primary therapy:• ThrombolysisThrombolysis• Open surgical Open surgical

embolectomyembolectomy• Catheter-assisted Catheter-assisted

embolectomyembolectomy

Secondary therapy:Secondary therapy:• IV unfractionated IV unfractionated

heparinheparin• Low-molecular weight Low-molecular weight

heparin (LMWH)heparin (LMWH)• FondaparinuxFondaparinux• WarfarinWarfarin• IVC filterIVC filter


ManagementManagement• In patients with massive PE, primary therapy with In patients with massive PE, primary therapy with

thrombolytics is considered a lifesaving thrombolytics is considered a lifesaving intervention.intervention.

• Surgical or catheter-assisted embolectomy may be Surgical or catheter-assisted embolectomy may be considered for massive PE if thrombolysis is considered for massive PE if thrombolysis is contraindicated.contraindicated.

• For submassive PE, thrombolysis remains For submassive PE, thrombolysis remains controversial as no mortality benefit has been controversial as no mortality benefit has been shown in this patient population.shown in this patient population.

• However, MAPPET-3 demonstrated a reduction in However, MAPPET-3 demonstrated a reduction in need for escalation of therapy in patients receiving need for escalation of therapy in patients receiving up-front t-PA (alteplase) for submassive PE.up-front t-PA (alteplase) for submassive PE.

• Normotensive patients with normal RV function are Normotensive patients with normal RV function are considered low-risk and receive standard considered low-risk and receive standard anticoagulation.anticoagulation.

J Thromb Thrombolysis 1995;2:227-229

N Engl J Med 2002;347:1143-1150


Low Molecular Weight Low Molecular Weight HeparinHeparin

• LMWHs have a longer half-life, better LMWHs have a longer half-life, better bioavailability, and more predictable dose-bioavailability, and more predictable dose-response.response.

• In clinical trials, enoxaparin, reviparin, and In clinical trials, enoxaparin, reviparin, and tinzaparin have all been proven as safe and tinzaparin have all been proven as safe and effective as unfractionated heparin in “bridging” effective as unfractionated heparin in “bridging” patients with PE to oral anticoagulation.patients with PE to oral anticoagulation.

• LMWH is renally-cleared while unfractionated LMWH is renally-cleared while unfractionated heparin is largely cleared by the liver.heparin is largely cleared by the liver.

• The PTT should not be used to monitor/adjust The PTT should not be used to monitor/adjust LMWH. Instead, an anti-Xa level should be checked LMWH. Instead, an anti-Xa level should be checked 4-6 hours after the 2nd/3rd dose. 4-6 hours after the 2nd/3rd dose.

• Anti-Xa levels may be required in patients Anti-Xa levels may be required in patients with renal insufficiency, obesity (>110kg), with renal insufficiency, obesity (>110kg), pregnancy, or unexpected bleeding or pregnancy, or unexpected bleeding or thromboembolism despite standard LMWH thromboembolism despite standard LMWH dosing.dosing.

N Engl J Med 1997;337:657-662

N Engl J Med 1997;337:663-669

Ann Intern Med 2001;134(3):191-202


WarfarinWarfarin• Warfarin is very effective in preventing Warfarin is very effective in preventing

recurrent VTE but carries a significant risk recurrent VTE but carries a significant risk of bleeding.of bleeding.

• Loading doses of greater than 5 mg daily Loading doses of greater than 5 mg daily remain controversial although a recent remain controversial although a recent study showed 10 mg initiation safely study showed 10 mg initiation safely allowed for more rapid achievement of a allowed for more rapid achievement of a therapeutic INR.therapeutic INR.

• Patients taking warfarin potentiators such Patients taking warfarin potentiators such as quinolones, anti-platelet agents, and as quinolones, anti-platelet agents, and amiodarone are at higher risk for bleeding.amiodarone are at higher risk for bleeding.

Ann Intern Med 2003;138:714-719


Duration of Anticoagulation: Duration of Anticoagulation: PREVENTPREVENT

• The multicenter NIH-The multicenter NIH-sponsored PREVENT trial of sponsored PREVENT trial of 508 patients with idiopathic 508 patients with idiopathic VTE evaluated indefinite low VTE evaluated indefinite low intensity warfarin (INR 1.5-intensity warfarin (INR 1.5-2.0) versus placebo. 2.0) versus placebo.

• The trial was terminated The trial was terminated early after a mean follow-up early after a mean follow-up of 2.1 years.of 2.1 years.

• A 2/3 reduction in recurrent A 2/3 reduction in recurrent VTE was observed without VTE was observed without an increase in major an increase in major bleeding.bleeding.

• Risk reductions were similar Risk reductions were similar for all subgroups including for all subgroups including those with and without those with and without thrombophilias.thrombophilias.

N Engl J Med 2003;348:1425-34 Cumulative risk of recurrent venous thromboembolism


Duration of Anticoagulation: Duration of Anticoagulation: ELATEELATE

• ELATE evaluated 738 ELATE evaluated 738 patients assigned to patients assigned to indefinite low-intensity indefinite low-intensity therapy versus indefinite therapy versus indefinite conventional intensity conventional intensity therapy. therapy.

• 16 patients had recurrent 16 patients had recurrent VTE in the low-intensity VTE in the low-intensity group compared to 6 in the group compared to 6 in the conventional group (1.9 v. conventional group (1.9 v. 0.7 events per 100 person-0.7 events per 100 person-years). years).

• There was no significant There was no significant difference in frequency of difference in frequency of major bleeding.major bleeding.

N Engl J Med 2003;349:632-9

Cumulative probability of recurrent venous thromboembolism


An Approach To An Approach To Treatment Treatment

Circulation 2003;108:2834-2838

Heparin

Risk Stratify

Not High Risk High Risk

Anticoagulation Consider 1˚ Therapy

Warfarin for 6 months

Stop if PE was caused by surgery or trauma

If idiopathic PE, continue anticoagulation indefinitely


Novel AnticoagulantsNovel Anticoagulants• FondaparinuxFondaparinux is a subcutaneously- is a subcutaneously-

administered synthetic pentasaccharide with administered synthetic pentasaccharide with anti-Xa activity.anti-Xa activity.

• It has been approved for thromboprophylaxis It has been approved for thromboprophylaxis in major orthopedic surgery.in major orthopedic surgery.

• It is now FDA-approved for use in PE and DVT.It is now FDA-approved for use in PE and DVT.• In REMBRANDT, fondaparinux reduced the In REMBRANDT, fondaparinux reduced the

rate of recurrent VTE by 64% compared to rate of recurrent VTE by 64% compared to the LMWH dalteparin.the LMWH dalteparin.

• In MATISSE PE, fondaparinux was equivalent In MATISSE PE, fondaparinux was equivalent to IV unfractionated heparin.to IV unfractionated heparin.

Circulation 2000;102:2726-2731

Bauer K. Pentasaccharides. October 16, 2003.


Inferior Vena Cava (IVC) Inferior Vena Cava (IVC) FiltersFilters

Indicated to reduce Indicated to reduce the incidence of PE the incidence of PE in:in:

• PE or recurrent PE PE or recurrent PE despite adequate despite adequate anticoagulationanticoagulation

• Patients with Patients with contraindications to contraindications to anticoagulationanticoagulation

• Open surgical Open surgical pulmonary pulmonary embolectomyembolectomy

Limitations:Limitations:• Do not address the Do not address the

thrombotic processthrombotic process• Peripheral leg edema can Peripheral leg edema can

ensueensue• Large venous collaterals Large venous collaterals

can develop and permit PEcan develop and permit PE• Filters may be deployed Filters may be deployed

improperly or have improperly or have technical problemstechnical problems

• Increased incidence of DVT Increased incidence of DVT (at 2 years, 21% v. 12%, (at 2 years, 21% v. 12%, p=0.02)p=0.02)

• No survival benefitNo survival benefit

Arch Intern Med 2000;160(13):2003-41


Retrievable IVC FiltersRetrievable IVC Filters

• Recently introduced retrievable IVC filters Recently introduced retrievable IVC filters provide a safe option for patients with provide a safe option for patients with transient contraindications to transient contraindications to anticoagulation such as trauma, surgery, anticoagulation such as trauma, surgery, or temporary bleeding.or temporary bleeding.

• Filters must be retrieved within 2 weeks to Filters must be retrieved within 2 weeks to prevent endothelialization.prevent endothelialization.

J Vasc Interv Radiol 2001;12:1053-1058

Radiology 2002;225:835-844


ConclusionsConclusions• Pulmonary embolism is a common and Pulmonary embolism is a common and

potentially life-threatening disorder.potentially life-threatening disorder.• The work-up of suspected PE requires an The work-up of suspected PE requires an

integrated application of clinical suspicion, integrated application of clinical suspicion, blood tests, and imaging.blood tests, and imaging.

• Risk stratification is an important component Risk stratification is an important component in the evaluation of patients with acute PE.in the evaluation of patients with acute PE.

• For a significant subset of patients, VTE For a significant subset of patients, VTE represents a chronic illness warranting represents a chronic illness warranting chronic therapy.chronic therapy.


The End…The End…

Documents

Harvard Medical School Pulmonary Embolism: Current Concepts in Diagnosis and Management Gregory Piazza, MD July 26, 2005