Orlando, Florida – October 7-9, 2011

Hypertrophic Cardiomyopathy Update 2011

Rami Kahwash, MDAssistant Professor in Internal medicine

Division of Cardiovascular MedicineSection of Heart Failure/Transplant

The Ohio State University

What is Hypertrophic Cardiomyopathy?

Presence of left ventricular hypertrophy unexplained by the loading condition

Epidemiology of HCM

Common monogenetic cardiac disease Inherited as autosomal dominant with variable penetrance and expressionPrevalence is 0.2 % 1Incidence of sudden cardiac death (SCD) 1-2 % in children and adolescence and 0.5 to 1 % in adult 2, 3

1. Maron BJ et al, J Am Coll Cardiol. 20032. Elliot PM et al, J Am Coll Cardiol . 20003. Elliot PM et al, Lancet. 2004

Clinical Presentation of HCM

Asymptomatic

Diastolic heart failure ( Mild refractory symptoms brunt out stage)

Arrhythmia syncope

SDC

Genetics of HCM - 2011 Update

60 % of cases, HCM is caused by mutations in genes coding for cardiac sarcomere proteins

> 600 different sarcomeric gene mutations are reported , majority are missense

< 5 % of cases, mutations in genes encoding Z-disc proteins and proteins involved in Ca regulation

Autosomal dominant, but with incomplete penetrance and variable clinical expression

7Desai MY et al, Circ Cardiovac Imaging. 2011

Genes Mutations & Risk Stratification

Role of genes and risk stratifications is controversialEarly data suggested association:

a) MHC mutations and ↑ mortality

b) MYBPC mutations and later manifestation in life with milder form of the disease

c) Troponin T mutations and less hypertrophy but more disarray, fibrosis and SCD

d) ↑ CV events when positive genetic screening compared to negative test

e) Multiple mutations and more severe phenotype and ↑ SDC

a) Watkins H et al, N EngJ Med. 1992. b) Niimura H et al, N Eng J Med. 1998. C) Watkins H et al, N Eng J Med. 1995. d) Olivotto I et al, Mayo Clin proc. 2008. e) Ingles J et al, J Med Genet. 2005

Role of Genetic Testing in 2011Family studies showed heterogeneous expressions of the same mutation among individuals within the same family.

No Role in DiagnosisNo Role in ICD decision

A= B/C

Role of Genetic Testing in 2011Family Screening

Desai MY et al, Circ Cardiovac Imaging. 2011

IMAGING and HCM- 2011

1-Assessment of MorphologyLV GeometryEvaluation of mitral valve and subvalvular apparatusEvaluation of myocardial perfusionEvaluation of myocardial fibrosis

2-Functional AssessmentEvaluation of LV cavity obstructionEvaluation of systolic and diastolic LV function

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ADVANTAGEAssessment of LV thicknessMitral valveLVOT gradientGlobal and regional function

LIMITATIONOperator dependantLimited acoustic windowsSuboptimal assessment of subvalvualr apparatusLimited septal and temporal resolution

ECHO

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ADVANTAGEGold standard to assess cardiac structure/LV massPapillary muscle morphologyMyocardial fibrosisRegional myocardial mechanics

LIMITATIONlimited availabilityDevice related contraindicationsPrognostic value of fibrous assessment is not well established

MRI

27 year old man with HCM

Desai MY et al, Circ Cardiovac Imaging. 2011

35 year old man with HCM

Desai MY et al, Circ Cardiovac Imaging. 2011

Fibrosis and HCM Facts

Gadolinium-enhanced CMR provides an accurate method for detection of myocardial fibrosis 1

In HCM, fibrosis is patchy, midmyocardial and most commonly found in the regions of hypertrophy 2

The pattern and amount of fibrosis correlates closely with histolopathology 2

1)Simonetti OP et al, Radiology. 20012)Kwon DH et al, J Am Coll Cardiol. 2009

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O'Hanlon, R. et al. J Am Coll Cardiol 2010;56:867-874

Autopsy Correlation of Fibrosis With In Vivo LGE-CMR

Fibrosis and SCD in HCM - 2011

Extent of fibrosis in patients aged < 40 years is associated with clinical markers of SCD, whereas in older patients, it is associated with progressive ventricular dysfunction 1Studies demonstrated association between degree of fibrosis and ventricular arrhythmia 2, 3

Emerging data demonstrates incremental prognostic values of myocardial fibrosis in predicting hard outcomes 4, 5

1) Moon JC et al, JACC. 2003 2) Kwon DH et al, JACC. 2009 3) Rubinshtein R, Circ Heart Fail. 2009 4) O’Hanlon R et al, JACC. 20105) Bruder O et al, JACC. 2010

Fibrosis in HCM Conclusion - 2011

The long term clinical significance of fibrosis is uncertain

Long term prospective studies are still needed

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Sudden Cardiac Death in Hypertrophic Cardiomyopathy

Ommen S R , Gersh B J Eur Heart J 2009;eurheartj.ehp307

Who Needs an ICD?

Risk factors Recommendations

0 Reassurance1 Individualize (MRI?)

2 + ICDPrior SCD ICD

Sustained VT ICD

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HCM

decrease obstructive Sx(dyspnea, CP, fatigue) Prevention of SCD

SymptomaticObstructive HCM

Beta-blockade Verapamil or Diltiazem Disopyramide

Drug-refractorysymptoms

Surgical Septal Myectomy

Special Circumstances (i.e., comorbidity)

Septal Ablation

ACC/ESC Consensus Recommendation

Thank You