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EDITORIALIs Concept of Hospitals out of Time ? 3OP YADAVA

REVIEW ARTICLE

5Acute Rheumatic Fever and Newer Jones CriteriaIB VIJAYALAKSHMI

REVIEW ARTICLEThe New Brave World of Drugs for Dyslipidemia: Ready to Target ASCVD Beyond Statins 11PC MANORIA

REVIEW ARTICLERecent Developments in ICCU Care for Acute Cardiac Disorders 21SURAJ KUMAR, VIVEK GUPTA, ROHIN VINAYAK, GURPREET S WANDER

Cardiology Today VOL.XXII NO. 1 JANUARY-FEBRUARY 2018 1

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IMAGEIsolated Right Ventricular Hypertrophic Cardiomyopathy 26SR MITTAL

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2 Cardiology Today VOL.XXII NO. 1 JANUARY-FEBRUARY 2018

Cardiology Today VOL. XXII NO. 1 JANUARY-FEBRUARY 2018 3

Is Concept of Hospitals out of Time ?

EDITORIAL

DR. OP YADAVACEO and Chief Cardiac Surgeon

National Heart Institute,New Delhi

4 Cardiology Today VOL. XXII NO. 1 JANUARY-FEBRUARY 2018

REFERENCE1. Wiler JL, Harish NJ. Zane RD. Do hospitals still make sense? The case for decentralization of health care. NEJM Catalyst. Feb

15,2018.


Acute Rheumatic Fever and Newer Jones Criteria

REVIEW ARTICLE

IB VIJAYALAKSHMIKeywords

Dr. I B Vijayalakshmi is Professor of Cardiology, PMSSY, Bengaluru Medical College and Research Institute, Bengaluru, India

AbstractIntroduction: Globally India contributes nearly 25%-50% of newly diagnosed cases of acute rheumatic fever (ARF), hospitalizations and deaths due to its sequel rheumatic heart disease (RHD). According to World Health Organization (WHO) bulletin of 1981, more than 50% of acute rheumatic fever (ARF)/RHD detected in surveys and health checkup camps are unaware of their disease, and more than 70% do not receive secondary prophylaxis regularly. The objective of the recently revised Jones criteria (2015) is to include technology–driven (ECHO) and also focus on epidemiological differences seen in high-risk and low-risk populations so that more ARF patients are detected in time and receive secondary prophylaxis. Discussions: Given the heterogeneity in global disease burden, a single set of diagnostic criteria may no longer be suf cient for all population groups and in all geographic regions. The addition of echocardiography and Doppler to the armamentarium of tests in the diagnosis of ARF will lead to diagnosis of more subclinical carditis cases. The introduction of especially subclinical carditis detected by Echocardiography and polyarthralgia as signi cant criteria in high-risk populations like in India will bring more patients into the net of secondary prophylaxis. Conclusion: The proper application of revised Jones criteria-2015, especially Echo in all suspected cases of ARF, will change the epidemiological face of ARF in India.

INTRODUCTION


BACKGROUND

Jones criteria

Epidemiological considerations:

Carditis

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Table 1. Shows the serial changes made in original Jones criteriaSymptomsSymptoms 19441944 19561956 19651965 19841984 19921992 20022002 20152015

CarditisCarditis MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor MajorMajorSub CliniSub Clini

PolyarthralgiaPolyarthralgia MajorMajor MinorMinor MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor

PolyarthralgiaPolyarthralgia MajorMajor MinorMinor MinorMinor MinorMinor MinorMinor MinorMinor MajorMajor

ChoreaChorea MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor

SubcutaneousSubcutaneousnodulesnodules MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor

ErythemaErythemamarginatummarginatum MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor MajorMajor

EchoEchocardiographycardiography MajorMajor


Application of Vijaya’s ECHO Criteria

Application of revised Jones criteria:

Arthritis

Polyarthralgia

Figure 1. Parasternal long axis view shows Myxomatous Mitral Valve with grade III mitral valve prolapse (MVP) in 8 years old boy of Mucopolysaccharidosis. Echo score according to Vijaya’s criteria is 4 (MVP-2,MR-2,ECHO SCORE). So this child does not have ARF

Figure 2. Parasternal long axis view with color Doppler shows thickened mitral valve-2, beaded appearance-2 hyper echogenic submitral structures- 2, Aortic regurgitation-2 in 12 years old girl with ARF. According to Vijaya’s criteria the total echo score is 8.So it is rheumatic.

Box 1 - Doppler Findings in Rheumatic valvulitisBox 1 - Doppler Findings in Rheumatic valvulitis

Pathological mitral regurgitation (all 4 criteria met) Pathological mitral regurgitation (all 4 criteria met)

Seen in at least 2 viewsSeen in at least 2 views

Jet length Jet length 2 cm in at least 1 view2 cm in at least 1 view

Peak velocity >3 m/sPeak velocity >3 m/s

Pansystolic jet in at least 1 envelopePansystolic jet in at least 1 envelope

Pathological aortic regurgitation (all 4 criteria met)Pathological aortic regurgitation (all 4 criteria met)

Seen in at least 2 viewsSeen in at least 2 views

Jet length Jet length 1 cm in at least 1 view1 cm in at least 1 view

Peak velocity >3 m/sPeak velocity >3 m/s

Pan diastolic jet in at least 1 envelopePan diastolic jet in at least 1 envelope


Minor criteria

Evidence of Preceding Streptococcal Infection

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Figure 3. Parasternal long axis view shows, partial subaortic membrane just below the aortic valve in 12 years old boy with no features of ARF on Echo. This patient was put on steroids for mistaken clinical diagnosis of ARF according to old Jones criteria, had flare up of primary complex and developed tubercular meningitis due to wrong diagnosis.

Figure 4. 2D echo in apical four chamber view with colour Doppler shows pathological mitral regurgitation-2 and mitral valve prolapse-2 (Vijaya’s Echo score is 4) and glistening endocardium indicating subendocardial ischemia which is not a feature of ARF, in a 11 years old girl with anomalous left coronary artery from pulmonary artery (ALCAPA), who was wrongly diagnosed as RHD and put on penicillin prophylaxis.

Box 2: Morphological Findings on Echocardiogram in Rheumatic ValvulitisBox 2: Morphological Findings on Echocardiogram in Rheumatic Valvulitis

Acute mitral valve changesAcute mitral valve changes

Acute mitral valve changesAcute mitral valve changes

Annular dilationAnnular dilation

Chordal elongationChordal elongation

Chordal rupture resulting in flail leaflet with severe mitral regurgitationChordal rupture resulting in flail leaflet with severe mitral regurgitation

Anterior (or less commonly posterior) leaflet tip prolapseAnterior (or less commonly posterior) leaflet tip prolapse

Beading/nodularity of leaflet tipsBeading/nodularity of leaflet tips

Leaflet thickeningLeaflet thickening

Chordal thickening and fusionChordal thickening and fusion

Restricted leaflet motionRestricted leaflet motion

CalcificationCalcification

Aortic valve changes in either acute or chronic carditisAortic valve changes in either acute or chronic carditis

Irregular or focal leaflet thickeningIrregular or focal leaflet thickening

Coaptation defectCoaptation defect

Restricted leaflet motionRestricted leaflet motion

Leaflet prolapseLeaflet prolapse


Rheumatic Fever Recurrences

“Possible” Rheumatic Fever

Impact of recent Modifi cations of Jones Criteria

CONCLUSION

Box 3. Minor criteria for blood testsBox 3. Minor criteria for blood tests

Low-risk population Moderate to high risk poulationsLow-risk population Moderate to high risk poulations

Erythrocyte ErythrocyteErythrocyte Erythrocyte

Sedimentation rate >60 mm Sedimentation rate >30mm/h and/orSedimentation rate >60 mm Sedimentation rate >30mm/h and/or

in the first hour and/orin the first hour and/or

C-reactive protein >3/0 mg/dL C-reactive protein >3.0 mg/dLC-reactive protein >3/0 mg/dL C-reactive protein >3.0 mg/dL

Low-risk populations are those with ARF incidence Low-risk populations are those with ARF incidence ≤≤ 2 per 100,000 school-aged children or 2 per 100,000 school-aged children or all-age RHD prevalence of all-age RHD prevalence of ≤≤ 1 per 1000 population per year. 1 per 1000 population per year.

Table 3. Revised Jones Criteria - 2015Low-risk populations Modrate-and high-risk populationLow-risk populations Modrate-and high-risk population

Major criteriaMajor criteria

Carditis CarditisCarditis Carditis

• Clinical and/or subclinical • Clinical and/or subclinical • Clinical and/or subclinical • Clinical and/or subclinical

Arthritis ArthritisArthritis Arthritis

• Polyarthritis only • • Polyarthritis only • Monoarthritis or polyarthritisMonoarthritis or polyarthritis

• Polyarthralgia • Polyarthralgia

Chorea ChoreaChorea Chorea

Erythema marginatum Erythema marginatumErythema marginatum Erythema marginatum

Subcutaneous nodules Subcutaneous nodulesSubcutaneous nodules Subcutaneous nodules

Minor criteriaMinor criteria

PolyarthralgiaPolyarthralgia MonoarthralgiaMonoarthralgia

Fever (Fever (≥≥38.5°C)38.5°C)ESR ESR ≥≥ 60 mm in the first hour and/or ESR 60 mm in the first hour and/or ESR ≥≥mm in the first hour and/ormm in the first hour and/orCRP CRP ≥ ≥ 3.0mg/dL CRP 3.0mg/dL CRP ≥≥3.0 mg/dL3.0 mg/dLProlonged PR interval, after accounting for Prolonged PR interval, after accounting forProlonged PR interval, after accounting for Prolonged PR interval, after accounting for

Age variability (unless carditis is a major age variability (unless carditis is a majorAge variability (unless carditis is a major age variability (unless carditis is a major

criterion) criterion)criterion) criterion)

ARF - acute rheumatic fever; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; and GAS, group A streptococcal infection.ARF - acute rheumatic fever; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; and GAS, group A streptococcal infection.*Low-risk populations are those with ARF incidence *Low-risk populations are those with ARF incidence 2 per 100 000 school-aged children or all-age rheumatic heart disease prevalence of 2 per 100 000 school-aged children or all-age rheumatic heart disease prevalence of

1 per 1000 population per year.1 per 1000 population per year.As in past versions of the criteria, erythema marginatum and subcutaneous nodules are rarely “stand-alone” major criteria. Additionally, As in past versions of the criteria, erythema marginatum and subcutaneous nodules are rarely “stand-alone” major criteria. Additionally, joint manifestations can only be considered in either the major or minor categories but not both in the same patient. CRP value must be joint manifestations can only be considered in either the major or minor categories but not both in the same patient. CRP value must be greater than upper limit of normal for laboratory. Also, because ESR may evolve during the course of ARF, peak ESR values should be used.greater than upper limit of normal for laboratory. Also, because ESR may evolve during the course of ARF, peak ESR values should be used.


REVIEW ARTICLE

REFERENCES1. Kumar RK, Tandon R. Rheumatic fever & rheumatic heart

disease: The last 50 years. Indian J Med Res 2013;137: 643-658.

2. Shrivastava S. Rheumatic heart disease: Is it declining in India? Indian Heart J 2007;59:9–10.

3. Gewitz MH, Baltimore RS, Tani LY, et al. Revision of the Jones criteria for the diagnosis of acute rheumatic Fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young. Circulation. 2015;131:1806-18.

4. Strasser T, Dondog N, Kholy A, et al. et al. The community control of rheumatic fever and rheumatic heart disease: Report of a WHO international cooperative project. Bulletin of the World Health Organization 1981;59:285-94.

5. Jones TD. Diagnosis of rheumatic fever. JAMA. 1944; 126:481–484.

6. Beg A, Sadiq M. Subclinical valvulitis in children with acute rheumatic fever. Pediatric Cardiology. 2008;29:619-623.

7. Caldas AM, Terreri MT, Moises VA, et al. What is the true frequency of carditis in acute rheumatic fever? A prospective clinical and Doppler blind study of 56 children with up to 60 months of follow-up evaluation. Pediatric Cardiology. 2008;29:1048-1053.

8. Vijayalakshmi IB, Mithravinda J, Deva AN. The role of echocardiography in diagnosing carditis in the setting of acute rheumatic fever. Cardiol Young 2005;15:583-8.

9. Vijayalakshmi IB, Vishnuprabhu RO, Chitra N, et al. The efficacy of echocardiographic criterions for the diagnosis of carditis in acute rheumatic fever. Cardiol Young 2008;18:586-92.

TABLE 4 :Vijaya’s criteria for diagnosis of carditis in ARF


The New Brave World of Drugs for Dyslipidemia: Ready to Target ASCVD Beyond Statins

REVIEW ARTICLE

PC MANORIAKeywords dyslipidemia cardiovascular events lipoproteins proprotein convertase subtilisin/kexin

type 9 atherogenic risk

Dr. PC Manoria is Director; Manoria Heart & Critical Care Hospital, Bhopal (M.P.) India

AbstractWith kicking off of second revolution in lipid management by proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition by fully humanized monoclonal antibodies (MoAbs) after the statin era, we are amidst a new brave world of drugs for dyslipidemia which is ready to target atherosclerotic cardiovascular disease (ASCVD) beyond statins and ezetimibe. Dyslipidemia related atherogenic cardiovascular (CV) events account for 50% of cases. The high-intensity statins decrease LDL-C by about 1 mmol, and this transforms into 20-25 % reduction in the cardiovascular events. PCSK9 MoAbs decrease LDL-C by another 1 mmol on top of statins and this decrease CVE by another 20%. Therefore, the era has come when we can minimize the dyslipidemia related atherogenic risk to a very high extent. The PCSK9 MoAbs however, require 12-26 injection per year. Inclisiran which is a small interfering RNA has shown to consistently decrease LDL-C by 50% over a period of 6 months after a single injection and is therefore poised to greatly improve compliance compared to PCSK9 MoAbs. It may emerge as a competitor to PCSK9 MoAbs in future. The future ongoing trials will tell us more about this molecule.

WHAT ARE THE VALIDATED LIPID TARGETS?


REVIEW ARTICLE

GOALS FOR LIPID TARGETS

TRIGLYCERIDES

60%60%

50%50%

40%40%

30%30%

20%20%

10%10%

0%0%

%co

ntr

ibu

tio

n t

o C

HD

%co

ntr

ibu

tio

n t

o C

HD

Systolic BP >115 mmHgSystolic BP >115 mmHg DyslipidaemiaDyslipidaemia Dietary factorsDietary factors Physical inactivityPhysical inactivity

22%22%

31%31%

56%56%

49%49%

Major Major

Modifiable Modifiable

Most CommonMost Common

Figure 1: Relation of lipid to coronary heart disease

Figure 2: Evolution of lipid guidelines during last 29 years after ATP1

Table 1: Conventional goals for LDL-CRISK GROUP LDL GoalRISK GROUP LDL Goal

VERY HIGHVERY HIGH

CVD, DM + Proteinuria or with a major risk factor CVD, DM + Proteinuria or with a major risk factor

CKD with eGFR 10% < 70 mg/dL

HIGHHIGH

Very high cholesterol TC > 310 mg/Dl, DM, Very high cholesterol TC > 310 mg/Dl, DM,

CKD eGFR 30-60 mL/min/1.73 mCKD eGFR 30-60 mL/min/1.73 m22, ,

10 year risk of fatal CVD 5-10% < 100 mg/dL10 year risk of fatal CVD 5-10% < 100 mg/dL

MODERATEMODERATE

10 year risk of CVD 1-5% < 115 mg/dL10 year risk of CVD 1-5% < 115 mg/dL

LOWLOW

10 year risk of CVD < 1% < 115 mg/dL10 year risk of CVD < 1% < 115 mg/dL


What are the drugs for dyslipidemia

Table 2: Treatment goals for LDL-C and Non LDL-C as per Lipid association of India Risk Category Treatment goal Consider drug therapyRisk Category Treatment goal Consider drug therapy

LDL-C Non-HDL-C LDL-C Non-HDL-CLDL-C Non-HDL-C LDL-C Non-HDL-C(mg/dL) (mg/dL) (mg/dL) (mg/dL) (mg/dL) (mg/dL) (mg/dL) (mg/dL)

Very high risk


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Non Statin drugs

Table 4: Drugs for treatment of dyslipidemiaLDL-C Non-HDL-C TG HDLLDL-C Non-HDL-C TG HDL

Statins Intensify statin Fibrate No drug recommendedStatins Intensify statin Fibrate No drug recommended

Ezetimibe Fibrates Omega 3 fatty acid Ezetimibe Fibrates Omega 3 fatty acid

PCSK9 inhibitors Omega 3 fatty acid Saroglitazar#PCSK9 inhibitors Omega 3 fatty acid Saroglitazar#

a. Evolocumab a. Evolocumab

b. Aliorocumab b. Aliorocumab

Colesevelam Colesevelam

Lomipatide (For FH*) Lomipatide (For FH*)

Mipomersen (For FH*) Mipomersen (For FH*)

siRNA Inclisiran+ siRNA Inclisiran+

*Familial Hypercholesterolemia*Familial Hypercholesterolemia+Under evaluation. +Under evaluation. #Available only in India, no approved by FDA.#Available only in India, no approved by FDA.

Figure 7: CTT Collaboration meta-anlaysis of statin trials

Table 5: Effect of LDL-C reduction on atherogenic cardiovascular eventsAtherogenic Risk Reduction in Drug Utilized Decrease inAtherogenic Risk Reduction in Drug Utilized Decrease inNon Lipid Lipid LDL-C CV eventsNon Lipid Lipid LDL-C CV eventsrelated related related related

50% 50%50% 50% 1 mmol High intensity statins 25% 1 mmol High intensity statins 25%

2 mmol Statins + PCSK9 inhibitors 45% 2 mmol Statins + PCSK9 inhibitors 45%

Figure 8. KM Curves for the primary efficacy endpoint of IMPROVE IT trial


vs

vsvs

vs

vs

vs

vs

vsvs

vsvs

vs

Familial hypercholesterolemia

What is PCSK9 ?

Table 6: PCSK9 loss-of-function MutationsStudies PCSK9 LDL-C CHD Risk Hazard RatioStudies PCSK9 LDL-C CHD Risk Hazard Ratio

Mutation Reduction, % Reduction, % (95% CI)Mutation Reduction, % Reduction, % (95% CI)

Dallas Heart Study Y142X or 40 N/A Dallas Heart Study Y142X or 40 N/A

C679X C679X

ARIC Y142X or 28 88 0.11ARIC Y142X or 28 88 0.11

C679X (0.02 to 0.81) C679X (0.02 to 0.81)

R46L 15 47 0.50 R46L 15 47 0.50

(0.31 to 0.79) (0.31 to 0.79)

Benn et al R46L 13 130 0.70Benn et al R46L 13 130 0.70

(0.58 to 0.86) (0.58 to 0.86)

Table 7: Trials of PCSK9 inhibitor Evolocumab in the PROFICIO GLOBAL ProgrammePHASE II STUDIESPHASE II STUDIES

S.No. Trial Nu Drug SubsetS.No. Trial Nu Drug Subset

1. MENDEL1. MENDEL1717 405 Evolocumab Monotherapy 405 Evolocumab Monotherapy

2. GAUSS2. GAUSS1818 160 Evolocumab Statin-intolerant 160 Evolocumab Statin-intolerant

3. LAPLACE-TIMI 543. LAPLACE-TIMI 541919 600 Evolocumab Combination therapy 600 Evolocumab Combination therapy

4. RUTHERFORD4. RUTHERFORD2020 168 Evolocumab Heterozygous (HeFH) 168 Evolocumab Heterozygous (HeFH)

5. OSLER5. OSLER2121 1104 Evolocumab 1104 Evolocumab

PHASE III STUDIESPHASE III STUDIES

6 MENDEL -26 MENDEL -22222 614 Evolocumab Monotherapy 614 Evolocumab Monotherapy

7 GAUSS-27 GAUSS-22323 307 Evolocumab Statin-intolerant 307 Evolocumab Statin-intolerant

8 LAPLACE -28 LAPLACE -22424 1899 Evolocumab Combination therapy 1899 Evolocumab Combination therapy

9 RUTHERFORD -29 RUTHERFORD -22525 331 Evolocumab Heterozygous FH 331 Evolocumab Heterozygous FH

10 DESCARTES10 DESCARTES2626 901 Evolocumab Combination therapy 901 Evolocumab Combination therapy

11 TESLA11 TESLA2727 49 Evolocumab Homozygous familial 49 Evolocumab Homozygous familial

hypercholesterolemia hypercholesterolemia

(HoFH) (HoFH)

12 TAUSSIG (ongoing)12 TAUSSIG (ongoing)2828 61 Evolocumab Homozygous familial 61 Evolocumab Homozygous familial

hypercholesterolemia hypercholesterolemia

13 YUKAWA13 YUKAWA2929 404 Evolocumab High CV Risk 404 Evolocumab High CV Risk

14 GLAGOV 910 Evolocumab Looking at atherosclerosis14 GLAGOV 910 Evolocumab Looking at atherosclerosis

regression by IVUS. regression by IVUS.


(b) Gain of function mutation

PCSK9 inhibition

EVOLOCUMAB

vs

Figure 9: LDL levels in the FOURIER trial

REVIEW ARTICLE


Alirocumab:

Figure 10 a,b: Primary and secondary efficacy endpoint in the FOURIER trial

Table 8: Odyssey Global ProgrammeOdyssey Global Programme phase 2/3 (11 Trials) Odyssey Global Programme phase 2/3 (11 Trials)

Alirocumab 150 mg. biweekly sc 22,000 patientsAlirocumab 150 mg. biweekly sc 22,000 patients

- FH I, FH II AND HIGH FH - ALTERNATIVE ODYSSEY- FH I, FH II AND HIGH FH - ALTERNATIVE ODYSSEY

- COMBO I & II - OPTIONS I & II OUTCOME TRIAL- COMBO I & II - OPTIONS I & II OUTCOME TRIAL

- MONO - LONG TERM- MONO - LONG TERM


Bococizumab

CLINICAL APPROVAL IN EUROPE AND USA (a) Europe

(b) U.S.A.

WHERE WILL THIS CLASS OF AGENTS FIT IN?

Future developments in PCSK9 inhibition

Table 9: Incidence of antidrug and neutralizing antibody with PCSK9 MoAbsDrug Anti-drug antibody Neutralizing antibody Injection site reactionDrug Anti-drug antibody Neutralizing antibody Injection site reactionBococizumab 48% 29% 10.4% vs. 1.3%Bococizumab 48% 29% 10.4% vs. 1.3% P


CONCLUSION

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9. Stein EA, Dufour R, Gagne C, et al. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation 2012 Nov. 6;126:2283-2292.

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11. Cohen J, et al. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9 Nat Genet. 2005;37:161-165.

12. Cohen J, et al. Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease N Engl J Med. 2006;354:1264-1272.

13. Been M, et al. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses J Am Coll Cardiol. 2010;55:2833-2842.

14. Abifadel M, Varret M, Rabes JP, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154-156. Abstract.

15. Ason B, Tep S, Davis HR Jr, et al. Improved efficacy for ezetimbie and rosuvastatin by attenuating the induction of PCSK9. J Lipid Res. 2011;52:679-87.

16. Marais DA, Blom DJ, Petrides F, Goueffic Y, Lambert G. Proprotein convertase subtilisin/ kexin type 9 inhibition. Curr Opin Lipidol, 2012;23:511-17.

17. Koren MJ, Scott R, Kim JB, et al. Efficacy, safety and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomized, double- blind, placebo-controlled, phase 2 study. Lancet. 2012;380:1995-2006.

18. Sullivan D, Olsson AG, Scott R. Effect of a Monocional Antibody to PCSK9 on Low- Density Lipoprotein Cholesterol Levels in Statin- Intolerant Patients The GAUSS Randomized Trial. JAMA. 2012;308:2497-2506

19. Giugliano RP, Desai NR, Kohli P, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57); a randomized, placebo- controlled, dose-ranging, phase 2 study. Lancet. 2012;380:2007-17.

20. Raal F, Scott R, Somaratne R, Bridges I, Li G, Wasserman SM, et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 inhibition Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation.2012;126:2408-17.

21. Sabatine MS, Giugliano RP, et al. Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events N Engl J Med 2015;372:1500-1509.

22. Koren MJ, Lundqvist P, et al. Anti-PCSK9 monotherapy for hypercholesterolemia. The MENDEL-2 Randomized, Controlled Phase III Clinical Trial of Evolocumab. J Am Coll Cardiol.2014;63(23):2531-2540.

23. Stroes E, Colquhoun D. Anti-PCSK9 Antibody Effectively Lowers Cholesterol in Patients With Statin Intolerance The GAUSS-2 Randomized, Placebo-Controlled Phase 3 Clinical Trial of Evolocumab. J Am Coll Cardiol. 2014;63(23):2541-2548.

24. Robinson JG, Nedergaard BS, et al. Effect of evolocumab or ezetimibe added to moderate-or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. JAMA 2014;311(18):1870-82.

25. Raal FJ, Stein EA, et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomized, double-blind, placebo-controlled trial. Lancet 2014; 385:331-340.

26. Blom DJ, Hala T, et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. NEJM 2014;371(19):1809-1819.

Figure 11: ORION-1 Trial showing effect of inclisiran on LDL-C

Robust, sustained LDL-C reductions – optimal start regimenRobust, sustained LDL-C reductions – optimal start regimen

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erce

nt

chan

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ean

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95%

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Days form first injectionDays form first injection


27. Raal FJ, Honarpour N, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet 2015;385:341-50.

28. Bruckert E, Blaha V, el al., Trial Assessing Long-Term Use of PCSK9 Inhibition in Patients with Genetic LDL Disorders (TAUSSIG): Efficacy and Safety in Patients with Homozygous Familial Hypercholesterolemia Receiving Lipid Apheresis. Circulation 2014;130:A17016.

29. Kiyosue A, Honarpour N. et al. Effect of evolocumab (AMG 145) in hypercholesterolemic, statin-treated, Japanese patients at high cardiovascular risk: results from the phase III YUKAWA 2 study. J Am Coll Cardiol 2015;65(10_S):A1369.

30. Marc S. Sabatine M C,Giugliano,Keech A C,et al .for

the FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017:376:1713-1722.

31. Kastelein JJ, Robinson JG, et al. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies. Cardiovasc Drugs Ther 2014;28:281-9.

32. Cannon Cp, Carious B, et al. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled trial. Eur Heart J 2015;36:1186-94.

33. Kohli P, Desai NR, et al. Design and rationale of the LAPLACE-TIMI 57 trial: a phase II, double-blind, placebo-

controlled study of the efficacy and tolerability of a monoclonal antibody inhibitor of PCSK9 in subjects with hypercholesterolemia on background statin therapy. Clin Cardiol 2012;35:385-91.

34. Moriarty PM, Jacobson, et al. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol 2014;8:554-61.

35. Robinson JG, Farnier M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Eng. J Med 2015;372:1489-99.

36. Ray K K, Landmesser Ulf, Leiter A L, et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol.N Engl J med 2017;376:1430-1440.

REVIEW ARTICLE


Recent Developments in ICCU Care for Acute Cardiac Disorders

REVIEW ARTICLE

SURAJ KUMAR, VIVEK GUPTA, ROHIN VINAYAK, GURPREET S WANDERKeywords cardiac intensive care cardiogenic shock heart failure intraaortic balloon impella extracorporeal membrane oxygena-

tion cardiac care unit tandemHeart

Dr Suraj Kumar is DM Resident (Cardiology); Dr Vivek Gupta is Consultant Cardiac Anaesthesia and intensive Care; Dr Rohin Vinayak, Student; Dr Gurpreet S Wander is Professor & Head of Cardiology, Hero DMC Heart Institute, Dayanand Medical College & Hospital, Ludhiana

AbstractThe eld of cardiac intensive care continues to advance in tandem with disorders and complexity of procedures. Acute cardiac disorders include wide range of cardiac emergencies that can develop into rapidly evolving life-threatening situations requiring ef cient and rapid interventions to help return cardiac perfusion.In its original concept, the cardiac care unit (CCU) was designed for monitoring of arrhythmias and treatment of patients with acute coronary syndromes. In present scenario, the CCU has evolved into a critical care environment that delivers care both to patients with acute single-system cardiovascular illness and to patients with multiple co-morbidities and multisystem organ dysfunction.There have been major developments in critical care in terms of speci c new treatments and substantial evidence exist regarding the use of certain strategies, though not always guidelines based. Certain older concepts have also changed in light of new data. Here we summarize what we believe to be the most important features of progress in cardiac intensive care in recent years.

IONOTROPES


Figure 1: An illustration of options for MCS: (A) IABP, (B) Impella, (C) TandemHeart

REVIEW ARTICLE


INTRA-AORTIC BALLOON PUMP

PERCUTANEOUS VENTRICULAR SUPPORT DEVICES


EXTRACORPOREAL MEMBRANE OXYGENATION

HIGH-DOSE DIURETICS VS ULTRAFILTRATION

Figure 2. Circuit configuration for VA and VV-ECMO

REVIEW ARTICLE

VA-ECMO VV-ECMOVA-ECMO VV-ECMO

Femoral ArteryFemoral Artery Internal Jugular VeinInternal Jugular Vein

Returning OxygenatedReturning OxygenatedBloodBlood

De-oxygenatedDe-oxygenatedBloodBlood


NON-INVASIVE VENTILATION

CONCLUSION

REFERENCES1. De Backer D, Biston P, Devriendt J, et al. Comparison of

dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010; 362:779.

2. Francis GS, Bartos JA, Adatya S. Inotropes. J AmCollCardiol2014;63:2069–78.

3. Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, Richardt G, Hennersdorf M, Empen K, Fuernau G, Desch S, Eitel I, Hambrecht R, Fuhrmann J, Bohm M, Ebelt H, Schneider S, Schuler G, Werdan K; IABP-SHOCK II Trial Investigators. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012;367:1287-1296.

4. Patel MR, Smalling RW, Thiele H, Barnhart HX, Zhou Y, Chandra P, Chew D, Cohen M, French J, Perera D, Ohman EM. Intra-aortic balloon counterpulsation and infarct size in patients with acute anterior myocardial infarction without shock: the CRISP AMI randomized trial. JAMA. 2011;306:1329–1337.

5. Perera D, Stables R, Thomas M, Booth J, Pitt M, Blackman D, de Belder A, Redwood S; BCIS-1 Investigators. Elective intra-aortic balloon counter pulsation during high-risk percutaneous coronary intervention: a randomised controlled trial. JAMA. 2010;304:867–874.

6. Thiele H, Sick P, Boudriot E, et al. Randomized comparison of intra-aortic balloon support with a percutaneous left ventricular assist device in patients with revascularized acute myocardial infarction complicated by cardiogenic shock. Eur Heart J. 2005;26(13):1276–83.

7. Burkhoff D, Cohen H, Brunckhorst C, O’Neill WW; TandemHeart Investigators Group. A randomized multicenter clinical study to evaluate the safety and efficacy of the TandemHeart percutaneous ventricular assist device versus conventional therapy with intraaortic balloon pumping for treatment of cardiogenic shock. Am Heart J. 2006;152(3):469.e1–8.

8. O’Neill WW,KleimanNS,MosesJ,HenriquesJP,DixonS,Mass

aro J, Palacios I, Maini B, Mulukutla S, Dzavik V, Popma J, Douglas PS, Ohman M. A prospective, randomized clinical trial of hemodynamic support with Impella 2.5 versus intra-aortic balloon pump in patients undergoing high-risk percutaneous coronary intervention: the PROTECT II study. Circulation 2012; 126:1717.

9. Lauten A, Engstrom AE, Jung C, et al. Percutaneous left-ventricular support with the Impella-2.5-assist device in acute cardiogenic shock: results of the Impella-EUROSHOCK-registry. Circ Heart Fail. 2013;6(1):23–30.

10. O’Neill WW, Schreiber T, Wohns DH, et al. The current use of Impella 2.5 in acute myocardial infarction complicated by cardiogenic shock: results from the USpella Registry. J IntervCardiol. 2014;27(1):1–11.

11. Sjauw KD, Remmelink M, Baan J Jr, et al. Left ventricular unloading in acute ST-segment elevation myocardial infarction patients is safe and feasible and provides acute and sustained left ventricular recovery. J Am CollCardiol. 2008;51(10):1044–6.

12. Chen YS, Lin JW, Yu HY, et al. Cardiopulmonary resuscitation with assisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: an observational study and propensity analysis. Lancet 2008; 372:554

13. Shin TG, Choi JH, Jo IJ, et al. Extracorporeal cardiopulmonary resuscitation in patients with inhospital cardiac arrest: A comparison with conventional cardiopulmonary resuscitation. Crit Care Med 2011; 39:1.

14. Combes A, Leprince P, Luyt CE, et al. Outcomes and long-term quality-of-life of patients supported by extracorporeal membrane oxygenation for refractory cardiogenic shock. Crit Care Med 2008; 36:1404.

15. Kagawa E, Dote K, Kato M, et al. Should we emergently revascularize occluded coronaries for cardiac arrest?: rapid-response extracorporeal membrane oxygenation and intra-arrest percutaneous coronary intervention. Circulation 2012; 126:1605.

16. Ronco C, Cicoira M, McCullough PA. Cardiorenal syndrome type 1: pathophysiological crosstalk leading to combined heart and kidney dysfunction in the setting of acutely decompensated heart failure. J Am CollCardiol2012;60:1031-42.

17. Bart BA, Goldsmith SR, Lee KL, et al. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med 2012;367:2296-304.

18. Weng CL, Zhao YT, Liu QH, et al. Meta-analysis: Noninvasive ventilation in acute cardiogenic pulmonary edema. Ann Intern Med 2010; 152:590.

19. Vital FM, Ladeira MT, Atallah AN. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database Syst Rev 2013; :CD005351.

20. Gray A, Goodacre S, Newby DE, Masson M, Sampson F, Nicholl J; 3CPO Trialists. Noninvasive ventilation in acute cardiogenic pulmonary edema. N Engl J Med. 2008;359:142-51.


Isolated Right Ventricular Hypertrophic Cardiomyopathy

IMAGE

SR MITTAL

AbstractIsolated right ventricular hypertrophic obstructive cardiomyopathy without involvement of interventricular septum and left ventricle is rare. Two cases are reported and available literature is reviewed. Dyspnoea, chest pain and palpitation are common symptoms. Ejection systolic murmur is best audible in left 3rd intercostal space and increases on inspiration. Absence of pulmonary valvular click and normal intensity and splitting of second sound differentiate it from pulmonary valve stenosis. Electrocardiogram shows right ventricular overload. 2-D echocardiography with Doppler evaluation con rms diagnosis and excludes left ventricular involvement and any other coexisting lesion.

Keywords echocardiography ejection systolic murmur electrocardiography hypertrophic cardiomyopathy right ventricle right ventricular hypertrophy

INTRODUCTIONRight ventricle can be involved in some cases of left ventricular hypertrophic car-diomyopathy. Isolated right ventricular hypertrophic obstructive cardiomyopa-thy is, however, rare.

CASE REPORTSCase 1: A 40 years male presented with uneasiness and palpitation on eff ort. He was known to have cardiac murmur for more than ten years. Patient was not aware of any cardiac disease in the fam-ily. On examination blood pressure was 170/96 mmHg. Precordial examination revealed left parasternal heave, right sid-ed fourth heart sound and a grade 3 sys-tolic murmur in left 3rd to 5th intercostal space. Murmur increased on inspiration. On echocardiography right atrium and right ventricle were dilated (Figure 1A). Maximum left ventricular wall thickness

Dr. SR Mittal is Head, Department of Cardiology at Mittal Hospital and Research Centre, Ajmer, Rajasthan

was 9 mm at interventricular septum. In parasternal long axis view, free wall of right ventricular outfl ow tract (RVOT) was hypertrophied with narrowing of right ventricular outfl ow tract (Figure 1B). Doppler evaluation of tricuspid fl ow was normal. M-mode echocardiography from parasternal long axis view (Figure 1 C) confi rmed normal thickness of inter-ventricular septum (9 mm) and increased thickness (11 mm) of free wall of right ventricular Doppler evaluation (Figure 1D) revealed turbulent fl ow across RVOT with a gradient of 27.04 mmHg. Th ere was no other lesion.

CASE 2A 50 years old female presented with chest pain, palpitation and eff ort breath-lessness. Patient was not aware of any cardiac disease in the family. On exami-nation pulse was 86/minute. It was regu-


Table 1: Summary of reported cases of isolated right ventricular hypertrophic obstructive cardiomyopathyRef Age/sex Symptoms Signs ECG Echo OthersRef Age/sex Symptoms Signs ECG Echo Others

4 17 years /F Tiredness, exertional dyspnoea, LPSH+4/6 ESM RVH LV- Normal NA4 17 years /F Tiredness, exertional dyspnoea, LPSH+4/6 ESM RVH LV- Normal NA

murmur detected at age 3 years Left 3 murmur detected at age 3 years Left 3rdrd ICS, RV- hypertrophy ICS, RV- hypertrophy

P2- N of anterior wall P2- N of anterior wall

occupying outflow tract occupying outflow tract

3 13 years /M Exertional dyspnoea, HOCM in 4/6 ESM left RAD NA Cardiac Cath 3 13 years /M Exertional dyspnoea, HOCM in 4/6 ESM left RAD NA Cardiac Cath

two brothers sternal border RVH systolic gradient two brothers sternal border RVH systolic gradient

and apex S2- N of 18 mm across and apex S2- N of 18 mm across

RVOT RVOT

6(a) 10 years /M Occasional palpitation SM- left 3rd ICS Junctional LV-normal NA6(a) 10 years /M Occasional palpitation SM- left 3rd ICS Junctional LV-normal NA

rhythm RAD IVS- Normal rhythm RAD IVS- Normal

CWR RV- hypertrophy CWR RV- hypertrophy

of free wall with of free wall with

mid cavity mid cavity

obstruction obstruction

(b) 21 years /F Breathlessness, mild chest LPSH+ QRS axis +90o, LV- Normal NA(b) 21 years /F Breathlessness, mild chest LPSH+ QRS axis +90o, LV- Normal NA

pain and presyncope on effort 4/6 SM left 3rd 0.5 mm ST depression IVS- Normal pain and presyncope on effort 4/6 SM left 3rd 0.5 mm ST depression IVS- Normal

ICS, No click II, III, aVF, prominent RV- Hypertrophy ICS, No click II, III, aVF, prominent RV- Hypertrophy

S2- Normal R with T inversion V S2- Normal R with T inversion V11-V-V44 of free wall of free wall

- RVOT obstruction - RVOT obstruction

7 24 years /F Breathlessness on effort, 3/6 SM left 2nd RAD LV-Normal NA7 24 years /F Breathlessness on effort, 3/6 SM left 2nd RAD LV-Normal NA

murmur detected in early and 3rd ICS, RVH IVS-Mild hypertrophy murmur detected in early and 3rd ICS, RVH IVS-Mild hypertrophy

childhood No click, S2- Normal RV- hypertrophy childhood No click, S2- Normal RV- hypertrophy

of free wall, RVOT of free wall, RVOT

obstruction obstruction

8 19 years /M Breathlessness, palpitation, LPSH+ 3/6 RAD Hypertrophy of NA8 19 years /M Breathlessness, palpitation, LPSH+ 3/6 RAD Hypertrophy of NA

chest pain, murmur detected holosystolic RAE RV free wall and IVS chest pain, murmur detected holosystolic RAE RV free wall and IVS

at age 1 and 1/2 years, one murmur along Biventricular LV-N at age 1 and 1/2 years, one murmur along Biventricular LV-N

brother-Non compaction of LV left sternal border hypertrophy brother-Non compaction of LV left sternal border hypertrophy

increased on with strain increased on with strain

inspiration No inspiration No

click S click S22-Normal -Normal

Present 40 years /M Ghabrahat and LPSH+, RAD RA & RV dilated, NA Present 40 years /M Ghabrahat and LPSH+, RAD RA & RV dilated, NA

Report Palpitation on effort, Right sided S4, RVOT hypertrophy,Report Palpitation on effort, Right sided S4, RVOT hypertrophy,

(a) cardiac murmur 3/6 SM left 3rd Turbulent flow across(a) cardiac murmur 3/6 SM left 3rd Turbulent flow across

detected 10 years back to 5th ICS, increased RVOT, detected 10 years back to 5th ICS, increased RVOT,

on inspiration LV-Normal, on inspiration LV-Normal,

IVS- Normal IVS- Normal

(b) 50 years /F Chest pain, SM left parasternal RAD RVH, TMT- Negative(b) 50 years /F Chest pain, SM left parasternal RAD RVH, TMT- Negative

Palpitation, region, increased Increased RVOT Palpitation, region, increased Increased RVOT

Effort breathlessness on inspiration thickness, IVS- Normal Effort breathlessness on inspiration thickness, IVS- Normal LV- Normal LV- Normal

AbbreviationsSex- M-male, F-Female.Signs- LPSH- Left parasternal heave, SM- Systolic murmur, ESM- Ejection systolic murmur, ICS- Intercostal space. S2- Second heart sound, P2- Pulmonary component of S2, S4- Fourth heart sound.ECG- RAD- Right axis deviation, CWR- Clockwise rotation, RVH- Right ventricular hypertrophy, RAE- Right atrial enlargement.Echo- LV- Left ventricle, IVS- Interventricular septum, RV- Right ventricle, RA- Right atrium, RVOT- Right ventricular outflow tract, TR- Tricuspid regurgitation. Others- TMT- Treadmill stress test. NA- Not available.


obstructive cardiomyopathy without any involvement of left ventricle is, however, rare. Th ere are only, isolated case reports (Table 1). Dyspnoea, chest pain increas-ing on eff ort and palpitation are com-mon symptoms. Patients with severe ob-struction can have presyncope on eff ort. Murmur could be detected in child hood. Th ere could be family history of classical left ventricular hypertrophic cardiomyo-pathy. Presence of left parasternal heave supports possibility of right ventricular outfl ow tract obstruction. Ejection sys-tolic murmur is best audible along left sternal border. Murmur increases on in-spiration. Right axis deviation and right ventricular hypertrophy are common electrocardiographic fi ndings. With onset of failure, right atrium and right ventricle may dilate with appearance of tricuspid regurgitation.

Absence of pulmonary valvular click and normal intensity and splitting of second sound diff erentiate it from pulmonary valve stenosis. Absence of left ventricular enlargement on clinical examination, inspiratory increase

lar. Blood pressure was 150/80 mmHg. Th ere was a systolic murmur in left parasternal region which increased on inspiration. Echocardiographic exami-nation revealed normal left ventricular thickness (Left ventricular mass index 91.16 gm/m2). Left atrial dimension was normal (LA volume index (12.6 ml/m2). Flow across mitral and aortic valve was normal. Subcostal four chamber view (Figure 2A) revealed increased thickness of right ventricular free wall. Right ven-tricular outfl ow tract thickness was also increased (15.6 mm) (Figure 2b). Short axis view (Figure 2 c) revealed oblitera-tion of RVOT during systole. Doppler evaluation of tricuspid fl ow (Figure 2d) revealed impaired relaxation of right ventricle. Th ere was no other lesion. Treadmill stress test did not reveal any inducible ischemia.

DISCUSSIONRight ventricular outfl ow tract obstruc-tion can occur in classical left ventricu-lar hypertrophic cardiomyopathy.1,2,3 Isolated right ventricular hypertrophic

Figure 1 a. Apical four chamber view showing dilated right atrium and right ventricle.b. Parasternal long axis view showing hypertrophy of right ventricular outflow tract (RVOT) with partial obliteration(O) of lumen, IVS- Interventricular septum, LV- Left ventricle, LA- Left atrium, Ao- Aorta. c. M- mode echocardiogram from parasternal long axis view showing hypertrophy of right ventricular outflow tract (RVOT) with normal thickness of interventricular septum (IVS) and left ventricular posterior wall (PW). RV- Right ventricle, LV- Left ventricle.d. Doppler evaluation of flow across right ventricular outflow tract showing turbulent flow.

Figure 2 a. Subcostal four chamber view showing thickening of right ventricular free wall. b. M- mode echocardiogram from parasternal long axis view showing increased thickness of anterior wall of right ventricular outflow tract and normal left ventricle(LV). RV- Right ventricle. c. End diastolic (ED) and end systolic (ES) short axis views showing obliteration of right ventricular outflow tract (RVOT) during systole. Ao- Aorta, LA- left atrium. d. Doppler evaluation of tricuspid flow showing impaired relaxation of right ventricle.

IMAGE


in systolic murmur and absence of left ventricular enlargement on electrocardiogram diff erentiate it from ventricular septal defect. Best audibility of murmur in left third intercostal space and absence of prominent ‘V’ wave in jugular venous pulse diff erentiate it from tricuspid regurgitation.

Echocardiography is a diagnostic tool. It confi rms isolated hypertrophy of right ventricular outfl ow tract with systolic turbulence across RVOT. Normal pulmonary valve and left

ventricle are important negative fi ndings. Echocardiography also helps in identifying any ventricular septal defect or tricuspid regurgitation. Congenital infundibular stenosis can produce similar echocardiographic fi ndings. Detection of murmur during infancy and presentation in childhood help clinical diff erentiation.

Like classical hypertrophic obstructive cardiomyopathy, patients may have partial relief of symptoms with beta-blockers. Non responders may need surgical intervention.4,5

REFERENCES1. Recupero A, Di bella G, Patane S, et al. Right ventricular

outflow tract obstruction in hypertrophic cardiomyopa-thy. International Journal of Cardiology 2010;144:e56-e57.

2. Cardiel E A, Alonso M, Delean JL, Menarguez L. Echo-cardiographic sign of right sided hypertrophic obstructive cardiomyopathy. British Heart J 1978;40:1321-24.

3. Reyes LC, Vazquez C, Bobadilla A, Garrido M, Osnaya H. Hypertrophic cardiomyopathy of the right ventricle. Pres-entation of three cases. Acta Pediatr Mex 2005;26: 231-8.

4. Taylor RR, Bernstein L, Jose DA. Obstructive phenomena in ventricular hypertrophy. Br Heart J 1964;26:193-8.

5. Morrow AG, Fisher RD, Fogarty TJ, Bethesda MD. Isolated hypertrophic obstruction to right ventricular outflow. Clin-ical, hemodynamic and angiographic findings before and after operative treatment. Am Heart J 1969;77:814-7.


T wave

ECG OF THE MONTH

SR MITTAL

Abstract‘T’ wave is produced by repolarization of the ventricles. Normally the ‘T’ wave is in the same direction as accompanying QRS. Proximal limb is sloping, apex is blunt and distal limb is relatively sharp. Normally ‘T’ wave is inverted in lead aVR and may be biphasic or inverted in lead V1. Sometimes T wave may show shallow inversion in lead III and aVF. Normally the amplitude of T wave is less than the accompanying R wave and more than the amplitude of U wave if the latter is present.

Keywords electrocardiography ‘T’ wave repolarization U wave

‘T’ WAVET wave is produced by repolarization of the ventricles.

Normally T wave is in the same direction as accompanying QRS. In leads V1 and V2, ‘T’ wave may be upright inspite of a dominantly negative QRS. Repolarization of the ventricular cells causes fl ow of ions in a direction opposite to that of depolarization. It is, therefore, expected that direction of T wave should be opposite to that of QRS. However, epicardial cells repolarize earlier than the endocardial cells.1 Th is causes the wave

Dr. SR Mittal is Head, Department of Cardiology at Mittal Hospital and Research Centre, Ajmer, Rajasthan

Figure 1. Diagrammatic representation of depolarization (a) and repolarization(b) of free wall of ventricle producing T wave in the same direction as QRS.

Figure 2. Electrocardiogram showing normal ‘T’ waves.

of repolarization to spread in the same direction as depolarization. T wave is, therefore, in the same direction as that of QRS complex (Figure 1).

Normally the proximal limb of the T wave is sloping and distal limb is relatively sharp. (Figure 2). Sloping of distal limb results in widening of T wave and prolongation of QT interval (Figure 3). Inversion of proximal limb in right precardial leads suggest diagnosis of atrial septal defect (ASD).2,3 Inversion of distal limb with ST segment elevation suggests myocardial infarction.


Figure 3. Electrocardiogram showing slop-ing of distal limb of ‘T’ wave (arrow) with prolongation of QT interval.

Figure. 4. Electrocardiogram showing all pointed (peaked) ‘T’ waves in a case with hyperkalemia.

Figure 5. Electrocardiogram showing notch on the apex of ‘T’ wave (arrow).

Figure 6. Electrocardiogram showing notch on the apex of ‘T’ wave (arrow).

Figure 7. Electrocardiogram showing fusion of prominent ‘U’ wave with ‘T’ wave.

Figure 8. Electrocardiogram showing nor-mal ‘T’ inversion in lead aVR and V1 (arrow).

Figure 9. Electrocardiogram showing nor-mal T inversion in lead III and aVR (arrow).

Figure 10. Electrocardiogram showing ‘Q’ wave and ‘T’ wave inversion in leads III and aVF due to inferior infarction(arrow).

Figure 11. Electrocardiogram showing ‘T’ wave amplitude equal to or more than amplitude of accompanying ‘R’ wave (arrows).

Figure 12. Electrocardiogram showing ‘T’ wave amplitude less than the amplitude of accompanying ‘U’ wave.

Figure 13. Electrocardiogram showing effect of movement of V5 electrode on ‘T’ wave configuration (arrows). N-normal T wave.


Figure 14. Amplitude of T wave less than the accompanying U wave is abnormal

Figure 16. Electrocardiogram showing effect of movement of cable on configuration and direction of ‘T’ wave (b), (a) and (c) have been recorded after stabilizing the cable.

Figure 15. Movement of electrods

Normally the apex of the T wave is blunt. Pointed and tall T waves are seen in hyperkalemia (Figure 4). Asynchronous repolarization of the two ventricles may result in a notch in the apex of T wave “ Dart T wave”. (Figure 5, 6). Prominent ‘U’ wave can fuse with T wave and give impression of notched T wave (Figure 7). Analysis of complete ECG can help in diff erentiation.

Uncommonly lead aVL may record cavity potential. In such a situation all waves (P, QRS and T) may be negative in lead aVL (Figure 9). Th is fi nding is usually seen in vertical heart. High lateral infarct can also produce QRS complex with inverted T wave in lead aVL (Figure 10). However, in this situation ST segment is coved and lead I also shows Q wave and inverted T wave. Isolated T inversion in lead aVL with positive P wave and QRS is usually abnormal.

In horizontal heart, as in obese

persons, T wave may be inverted in lead III (Figure 11) and inverted or biphasic in lead aVF. In such a situation T wave may become less deep or even fl at on deep inspiration. On deep inspiration, diaphragm moves down, and heart becomes relatively vertical. Symmetrical T inversion with broad and deep Q wave is abnormal in lead III (Figure 12). In dextrocardia or technical dextrocardial (interchange of leads of right and left upper limbs). ‘P’, ‘QRS’ and ‘T’ waves are inverted in leads I and aVL.

Amplitude of T wave is usually less than the accompanying R wave and more than the amplitude of U wave if the latter is present. T wave equal to or

more than the amplitude of R wave is abnormal (Figure 13). Amplitude of T wave less than the accompanying U wave is abnormal (Figure 14).

Movement of the electrode (Figure 15) or cable (Figure 16) can produce beat to beat variation in confi guration of T wave. REFERENCES1. Wagner GS, Lim TH. Cardiac electrical activity. In Wagner

GS(ed). Marriott’s Practical Electrocardiography. Wolters Kluwere, New Delhi 2001;1-20.

2. Bayar N, Arstan S, Koklu E, et al. The importance of elec-trocardiographic findings in the diagnosis of atrial septal defect. Kardiologia Polska 2015;73:331-6.

3. Wong MX, Wu GF, Gu JL, et al. Defective T wave com-bined with incomplete right bundle branch block: a new electrocardiographic index for diagnosing atrial septal defect. Chinese Medical Journal 2012;125:1057-62.

ECG OF THE MONTH


Q.1. T wave is produced by (A) Atrial repolarization (B) Atrial depolarization (C) Ventricular depolarization (D) Ventricular repolarization

Q.2. Normally, in lead V1, T wave may be

(A) Inverted (B) Biphasic (C) Upright (D) Any shape

Q.3. In a normal person T wave can be inverted in

(A) Lead V1(B) Lead III(C) Lead aVF(D) All

Q.4. In normal persons, T wave of lead aVR is

(A) Upright (B) Biphasic

Q.8. What suggests an abnormal T wave ?

(A) Amplitude greater than accompa-nying ‘R’ wave

(B) Amplitude lesser than accompa-nying ‘U’ wave

(C) Inversion of initial portion of ‘T’ wave

(D) All

Q.9. Inversion of terminal portion of T wave with ST segment eleva-tion suggests.

(A) Myocardial infarction (B) Left ventricular hypertrophy (C) Myocarditis (D) All

Q.10. Inverted proximal limb of T wave in right precordial leads suggests diagnosis of

(A) ASD(B) VSD(C) PDA(D) TOF

(C) Inverted (D) Any shape

Q.5. T wave can be inverted in lead I and aVL in

(A) High lateral myocardial infarction (B) Dextrocardia (C) Technical dextrocardia(D) All

Q.6. What is correct for normal T wave ?

(A) Proximal limb is sloping(B) Apex is blunt(C) Distal limb is sloping(D) All

Q.7. What suggests an abnormal T wave ?

(A) Pointed apex(B) Notched apex(C) Terminal inversion of a positive T

wave(D) All

MCQsST Segment Depression

Answers: (1) D, (2) D, (3) D, (4) C, (5) D, (6) A,B (7) D, (8)D, (9)A, (10) A.


PICTORIAL CME

MONIKA MAHESHWARI

Dr. Monika Maheshwari is Professor at Jawahar Lal Nehru Medical College, Ajmer, Rajasthan

Congenital Rubella Syndrome

For prevention, women who are planning to get pregnant should be vaccinated. Live attenuated viral rubella vaccine - one dose is given by the intramuscular or subcutaneous route as monovalent, MR or MMR.

Figure 1. Angiocardiogram (LAO view) showing Patent ductous arteriosus (PDA) connecting descending aorta (DA) with pulmonary artery (PA)

Figure 2. Angiocardiogram (Frontal view) showing left pulmonary artery (LPA) stenosis.

Figure 3. Angiocardiogram showing pulmonary valve stenosis with post stenotic dilatation of pulmonary artery.

As many as 85-90% of babies born to mothers who had rubella shortly before or during the fi rst three months of pregnancy may develop congenital rubella syndrome. Classic triad includes sensori-neural deafness (58%), eye abnormalities (43%)-cataracts, retinopathy and micro-ophthalmia (43%), and congenital heart anomalies (50%) – patent ductus arteriosus (PDA) (Figure 1), pulmonary artery (PA) stenosis (Figure 2) and pulmonary valve (PV) stenosis (Figure 3). Diagnosis and therapy of the cardiac complications of the rubella syndrome is possible in the fi rst few months of life. Early recognition with echocardiography and cardiac catheterisation, permits aggressive medical management and in selected cases developing heart failure, surgical intervention involving interruption of PDA and balloon dilatation of PA and PV.


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