Dilated cardiomyopathy

Dr. Avinash D. ArkeMD FNB

Introduction

• Definition:– Dilated left ventricle with systolic dysfunction

– not caused by Ischaemic or valvular heart disease

– Cardiac dilatation with systolic dysfunction

Learning objectives

• Epidemiology • Etiology • Pathology • Genetics • Clinical features• Natural history • Diagnosis • Management

IDIOPATHIC DILATED CARDIOMYPATHYEPIDEMIOLOGY

• ANNUAL INCIDENCE 5-8/100,000

• PREVELANCE 36/ 100,000

• INCREASED RISK ASSOCIATED WITH:– MALE GENDER– BLACK RACE– HYPERTENSION– CHRONIC BETA-AGONIST USE

Causes

Causes • Ischemic: = 50% atherosclerosis,

Kawasaki disease, anomalous origin of left coronary artery

• Idiopathic = 45%• Hereditary: = 25 – 35% autosomal dominant,

autosomal recessive, X-linked, mitochondrial

• Acute and chronic myocarditis: coxsackievirus, HIV adenovirus,

• Autoimmune diseases • Chronic tachycardia

• Drugs: alcohol, sympathomimetics, anthracyclines• End-stage hypertrophic cardiomyopathy

• Endocrine: growth hormone deficiency, hyperthyroidism, hypothyroidism, hypocalcemia,

diabetes mellitus, pheochromocytoma

• Inborn errors of metabolism• Muscular dystrophies• Nutritional deficiency: selenium, carnitine,

thiamine• Peripartum• Structural heart disease• Systemic hypertension• Toxins: cobalt, lead

Pathology • Cardiac dilatation

– ? Adaptive – due to increased loading conditions– Idiopathic DCM – maladaptive..

• Myocellular hypertrophy and cell death– Cardiac hypertrophy – adaptive response increase

in collagen content preserves myocardial performance

– Cumulative loss of myofibrils and cardiac myocytes

apoptosis, cellular necrosis decrease in the wall thickness

• Extracellular matrix remodeling – Cardiac fibroblast proliferate– Mechanically stable cross linked collagen is

degraded by metalloproteinases– Excess of poorly cross-linked collagen is deposited

into interstitium – Increase myocardial mass, intersitial fibrosis,

ventricular dilatation

IDIOPATHIC DILATED CARDIOMYOPATHYPATHOLOGIC FINDINGS

GENETICS

Sarcomere CytoskeletonSarcolemma Nucleus

MOLECULAR DEFECTS IN DILATED CARDIOMYOPATHY

Fatkin D, et al. NEJM 1999;341

GENESLamin A/Cδ-sarcoglycanDystrophinDesminVinculinTitinTroponin-Tα-tropomyosinß-myosin heavy chainActinMitochondrial DNA mutations

FAMILIAL DILATED CARDIOMYOPATHYCOMMON ASSOCIATED ABNORMALITIES

• Conduction system disease• Skeletal muscle myopathy or muscular

dystrophy• autosomal dominant inheritance pattern is

most common• Recessive , X-linked, mitochondrial • Extracardiac manifestations:

– Sensorineural hearing loss– Neutropenia

HISTOPATHOLOGY OF ACUTE LYMPHOCYTIC MYOCARDITIS

INCIDENCE OF BIOPSY-PROVEN MYOCARDITIS IN PATIENTS WITH DILATED CARDIOMYOPATHY

Series Year Patients Positive BiopsyKunkel et al 1978 66 6%Mason et al 1980 400 3%Noda 1980 52 0.5%Baandrup et al 1981 132 1%O’Connell et al 1981 68 7%Nippoldt et al 1982 170 5%Fenoglio et al 1983 135 25%Unverferth et al 1983 59 6% Parillo et al 1984 74 26%Zee-Cheng et al 1984 35 63% Daly et al 1984 69 17%Bolte et al 1984 91 20%Hosenpud et al 1985 38 16%Mason et al 1995 2233 10%McCarthy et al 1997 1757 14%TOTAL 5379 11.5%

Clinical features

• Heart failure – congestion : edema, orthopnea, paroxysmal

nocturnal dyspnea– reduced cardiac output : fatigue, dyspnea on

exertion• Arrhythmias and/or conduction system disease• Thromboembolic disease (from left ventricular

mural thrombus)- stroke

• Heart failure symptoms 75%-85%• Anginal chest pain 8%-20%• Emboli (systemic or pulmonary) 1%-4%• Syncope <1%• Sudden cardiac death <1%

Diagnosis

• ECG• CXR• 2 D - Echo

DILATED CARDIOMYOPATHYELECTROCARDIOGRAPHIC FINDINGS

Disease Etiology Pathologic Q-waves

Ischemic cardiomyopathy 10/12 (83%)* (n=15)Idiopathic cardiomyopathy 2/21 (10%)+ #

(n=21)*LBBB (n=2); paced rhythm (n=1)+ LVH (n=10); IVCD (n=3)# P < 0.003

Feld H, et al. Am J Med 1993;94:547-8

SEGMENTAL WALL MOTION ABNORMALITIES IN DILATED CARDIOMYOPATHY

• Regional wall motion abnormalities observed in at least 50% of patients with non-ischemic causes of dilated cardiomyopathy

• Most frequent wall motion abnormalities:– anterior wall & apex

• Posterior and lateral walls most likely to be preserved• Type of abnormality:

– hypokinesis (83%)– akinesis (11%)– dyskinesis (6%)

• Heterogeneity in regional oxidative metabolism using C-11 acetate clearance has been demonstrated in DCM

AJC 1990;65:364-70; Arch Int Med 1992;152:769-72; JACC 1995;25:1258-62

MRI

• black blood images: enlarged cardiac chambers and thin myocardial walls

• Cine images: show LV hypokinesia, increased volumes, (end-diastolic volumes that constitute a dilated CMP: > 140 mL for the LV and > 150 mL for the RV

• Phase-contrast sequences: impaired diastolic function. transvalvular flow may be characterized by a restrictive pattern

• Late gadolinium-enhancement

Non ischaemic DCM

Ischemic DCM

Differentiation of ischaemic from non-ischaemic DCM

ACC/AHA HEART FAILURE EVALUATION GUIDELINESCLASS I & II RECOMMENDATIONS

• Laboratory Studies– Blood count, urinalysis, electrolytes, renal function,

glucose, LFTs (class I; level C)– Thyroid stimulating hormone (class I; level C)– Fe/TIBC, ferritin (class IIa, level C)– Urinary screening for hemochromatosis (class IIa; level C)– Measurement of ANA, rheumatoid factor, urinary VMA and

metanepherines in selected patients (class IIa; level C)– HIV testing (class IIb; level C)

• Electrocardiogram (class I; level C)• Chest x-ray (class I; level C)• Echocardiogram/Doppler or radioventriculogram (class I;level

C)

-Adapted from Hunt SA et al. Circulation 2001;104:2996-3007

Genetic test • Genetic Cardiomyopathy dilated panel Next Generation Sequencing Panel: • ABCC9, ACTC1, ACTN2, BAG3, CSRP3, DES, DMD, DSG2, EYA4, FKTN, GATAD1, LAMP2, LDB3,

LMNA, MYBPC3, MYH6, MYH7, NEXN, PLN, PSEN1, MT-ND1, MT-ND5, MT-ND6, MT-TD, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TQ, MT-TS1, MT-TS2, PSEN2, RBM20, SCN5A, SDHA, SGCD, TAZ, TCAP, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TTR, VCL DNA Test

IDIOPATHIC DILATED CARDIOMYOPATHYNATURAL HISTORY

Dec GW, Fuster V. NEJM 1994;331:1564-75

Transplant free survival in acute DCM

SPONTANEOUS IMPROVEMENT IN ACUTE DILATED CARDIOMYOPATHY

UNIVARIATE PREDICTORS OF IMPROVEMENTshort duration of symptomshigher cardiac outputlower NYHA functional classificationsmaller LV end-diastolic dimensionlower filling pressureshigher serum sodium concentration

STEPWISE REGRESSION MODELshort duration of symptomshigher serum sodium concentrationlower right atrial pressurelower pulmonary capillary wedge pressure

-Steimle AE, et al. JACC 1994;23:553-9

CHANGE IN LVEF BY LVEDD: IMAC Trial

0.32

0.56

0.220.26

0.39

0.120.20

0.29

0.09

0

0.2

0.4

0.6

BaselineLVEF

6 monthsLVEF

12 monthsLVEF

< or = 6.0

>6 to 7.0

> 7.0

LVEDD (cm) LVEF

McNamara D, et al. AHA, 2001

N=82

IDCM:PROGNOSTIC FEATURES

• VENTRICULOGRAPHIC FINDINGS– Degree of impairment in LVEF– Extent of left ventricular enlargement– Coexistent right ventricular dysfunction– Ventricular mass/volume ratio– Global wall motion abnormalities– Left ventricular sphericity

• CLINICAL FINDINGS– Favorable prognosis: NYHA < IV, younger age, female

sex

– Poor prognosis: Syncope, persistent S3 gallop, right-sided heart failure, AV or bundle branch block, hyponatremia, troponin elevation, increased BNP, maximum oxygen uptake < 12 ml/kg/min

OUTCOME IN IDIOPATHIC DILATED CARDIOMYOPATHYPREDICTIVE VALUE OF TROPONIN T

Months

Even

t-Fre

e Ra

te (%

)

Sato Y et al. Circulation 2001;103:372

Grp 1: TnT < 0.02 ng/mL during follow-up period

Grp 2: TnT > 0.02 ng/mL initially but fell to < 0.02 ng/mL during follow-up

Grp 3: TnT > 0.02 ng/mL throughout follow-up period

N=33

N=10

N=17

MYOCARDIAL CONTRACTILE RESERVE PREDICTS IMPROVEMENT IN DILATED CARDIOMYOPATHY

Naqvi TS et al. J Am Coll Cardiol 1999;34:1537-44

668N =

Fas gene expression

HighModerateLow

Cha

nge

in E

F a

t 12

mon

ths

(%)

50.0

40.0

30.0

20.0

10.0

0.0

-10.0

-20.0668N =

Fas gene expression

HighModerateLow

Cha

nge

in E

F at

6 m

onth

(%)

40.0

30.0

20.0

10.0

0.0

-10.0

Fas Expression and LV Recovery

p=0.002 p=0.006

Six months Twelve months

Sheppard, AHA 2003

IMAC TRIAL RESULT:APOPTOSIS AND RECOVERY OF VENTRICULAR FUNCTION

Expression of TNF-alpha and FasL did not predict the recovery

Sheppard, AHA 2003

TNFR1 Expression and LV Recovery

Six months Twelve months

NONINVASIVE ASSESSMENT OF CORONARY ARTERY DISEASE IN NEW ONSET DILATED CARDIOMYOPATHY

• Retrospective studies have shown up to 94% of patients with idiopathic dilated cardiomyopathy will have myocardial perfusion defects– Reversible defect(s): 60%– Fixed defect(s): 15%– Reversible+ fixed defect(s): 25%

• Global myocardial blood flow reserve (dipyridamole-induced) is diminished in DCM patients compared to controls using PET imaging

• Low myocardial blood flow reserve correlates with high left ventricular wall stress and anaerobic metabolism

Ann Inter Med 1992;152:679-72; JACC 2000;35:19-28.

INDICATIONS FOR CORONARY ANGIOGRAPHY IN NEW ONSET CARDIOMYOPATHY

ACC/AHA CONSENSUS GUIDELINES (2001)

• Patients with Known Coronary Artery Disease/Angina Pectoris– Revascularization recommended in vast majority of such individuals

with multivessel disease. Little role for non-invasive testing.– Coronary angiography considered Class I Recommendation (Level of

evidence: B)• Patients with Known Coronary Artery Disease Who Lack Angina

– No controlled trials have examined whether coronary revascularization can improve outcomes in this population

– Many centers first evaluate patient for myocardial hibernation– Coronary angiography considered Class IIa Recommendation (Level of

Evidence:C) • Patients with or without Chest Pain in Whom Coronary Artery

Disease has Not Been Evaluated– Approximately 35% of patients with IDCM will report angina-like pain– Coronary angiography should be considered Class IIa

recommendation (Level of Evidence: C) Hunt SA,et al. Circulation 2001;104:2996

RIGHT VENTRICULAR BIOPSY TECHNIQUE

ENDOMYOCARDIAL BIOPSY IN DILATED CARDIOMYOPATHY

INDICATIONS FOR ENDOMYOCARDIAL BIOPSY

• Acute dilated cardiomyopathy with refractory heart failure symptoms

• Rapidly progressive ventricular dysfunction in an unexplained cardiomyopathy of recent onset

• New onset cardiomyopathy with recurrent ventricular tachycardia or high grade heart block

• Heart failure in the setting of fever, rash, and peripheral eosinophilia

• Dilated cardiomyopathy in setting of systemic diseases known to affect the myocardium (systemic lupus erythematosus, polymyositis, sarcoidosis)

Wu LA, et al. Mayo Clin Proc 2001;76:1030-8

DILATED CARDIOMYOPATHYPROVEN THERAPEUTIC OPTIONS

TREATMENT INDICATIONSACE Inhibitors Symptomatic heart failure and

asymptomatic LV dysfunctionARBs ACE intoleranceHydralazine- nitrates ACE intoleranceDiuretics Volume overloadPotassium/MagnesiumDiuretic-induced depletionBeta-blockers Symptomatic heart failure in addition to

ACE inhibitorDigoxin Persistent heart failure despite

diuretics, ACE inhibitorWarfarin Chronic or paroxysmal atrial fibrillation

LV thrombus or prior embolic eventICD Cardiac arrest; uncontrolled VT

Recommendations for ICD in DCM

Recommendations for CRT in DCM

Role of CRT

• Survival estimates at 4 years were 55% for ICM and 77% for DCM groups (P<.001), respectively, whereas no significant difference in the incidence of appropriate/inappropriate ICD shocks was observed

• Conclusion: In response to CRT and in contrast to ICM, DCM patients experienced greater improvement in left ventricular systolic function and reverse remodeling while also sustaining a greater survival benefit.

• Differential outcome of cardiac resynchronization therapy in ischemic cardiomyopathy and idiopathic dilated cardiomyopathyChristopher J et al, Heart rhythm, March 2011 Volume 8, Issue 3, Pages 377–382. et al

DCM with atrial fibrillation Rate control Rhythm control

Alcoholic cardiomypathy

• Diagnosis of exclusion • 3.8 – 43 % cases with IDCM• Ethanol consumption > 80 gm/day for male

and > 40 gm/ day for female for a period of > 5 years

• Absteinance from alcohol after the diagnosis may improve the LVEF.

Peripartum cardiomyopathy • definition --- four criteria: three clinical and one echocardiographic –

1. Development of heart failure during last trimester of pregnancy or first six months post partum.

2. Absence of any identifiable cause for cardiac failure.

3. Absence of any recognizable heart disease prior to last trimester of pregnancy.

4. Echocardiographic criteria- Demonstrable echocardiographic proof of left ventricular systolic dysfunction. Ejection fraction less than 45%, left ventricular fractional shortening less than 30% or left ventricular end-diastolic dimension >2.7cm/m square of body surface area.

Novel surgical options

• Mitral valve repair • Surgical ventricular reconstruction• Surgical attempts to regenerate lost or

damaged myocardium with transplanted stem cells.

• In refrctory cases –

• LVAD

• Heart transplatation

Summary

• DCM – important cause of morbidity and mortality

• Ischaemic CMP and Familial DCM – major causes of DCM: role of CAG and genetic counselling

• Advancement in immunoabsorption and immunosuppression therapy for myocarditis has improved the survival in recent years.

• further studies are needed to fill the lacuna in our knowledge about DCM

Thank you !