Update on Hypertrophic and Non Compaction Cardiomyopathy

Donna Mancini, MD

Professor of Medicine

Left Ventricular Non- Compaction

• Intrauterine arrest of myocardial compaction w persistence of deep trabecular recesses in the endomyocardium

• Genetic Cardiomyopathy by AHA

• Unclassified cardiomyopathy by European Society

• Genetic heterogeneity--Autosomal dominant, X linked; mitochondrial

• Symptoms: CHF, Arrhythmias, clots

LVNC

• Prevalence in patients undergoing ECHO: 0.01-1.3%

• Genetics: Autosomal dominant; X linked; familial or sporadic (rare)

• Overlap w hypertrophic, congenital, dilated cardiomyopathies (common)

• 10 genes described: MHC7; Lamin, Tafazzin, troponin

• yield for genetic testing is 40-50%

Clinical Presentation

• CHF 25%

• Abnormal Cardiac Exam 19%

• Abnl Echo 14%

• Abnormal EKG 16%

• Arrhythmia/Syncope 15%

• Sudden Cardiac arrest 2%

Diagnosis

• Prominent LV trabeculae

• Deep intertrabecular recesses

• Thin compacted layer

• ECHO or MRI

ECHO Diagnosis

• ECHO Jenni Criteria:

– Thickened LV w 2 layers; thin compacted epicardial layer and thickened endocardial layer; numerous promenint trabeculations w deep recesses

– Ratio of non compacted to compacrted myocardium 2:1 at end systole parasternal short axis view

– Color Doppler flow in deep intertrabecular recesses

– Prominent Trabecular meshwork in LV apex or mid ventricular segments

MRI Criteria

• Trabeculated LV mass >20% of global LV mass

• End diastolic non compacted to compacted myocardial thickness of >2.3

• End systolic non compacted to compacted ratio >2.0

• Late gadolinium enhancement

Differential Diagnosis

• Athletes: 8% will have similar echo findings

• Hypertensive heart Disease

• Pregnancy

• Sickle Cell Anemia

• Cardiomyopathies –apical HCM, infiltrative (Fabry’s), endomyocardial fibrosis; congenital heart disease

• Black race

Establish Diagnosis

• Similar finding in first degree relatives

• Absence of other conditions

• Symptoms

• Treatment of LVNC and CHF-same as CHF

• Treatment of LVNC and afib: low threshold for anticoagulation

• Treatment of LVNC and ICD standard indications for primary and secondary prevention

Cardiac Compaction

• Very Rare

• Extensive overlap with other cardiomyopathies.

• Phenotypic variation

• Physiologic hypertrophy

Hypertrophic Cardiomyopathy (HCM)

• Hypertrophic – an excessive thickening of the heart muscle

• Diastole

– impaired diastolic filling, filling pressure

• Systole

– dynamic outflow tract gradient

• Myocardial ischemia

– muscle mass, filling pressure, O2 demand

– abnormal intramural coronary arteries

– systolic compression of arteries

HCM vs. Normal

Who Does HCM affect?

• 1 in 500 people (most common genetic cardiovascular disease) – Incidence is about 0.2% to 0.5% of general population.

• An estimated 600,000 to 1.5 million Americans have HCM.

• HCM can present at anytime in any age of life

• Most people are not aware they have HCM because symptoms can go unnoticed and most people with the disease live healthy, normal lives

Genetics • Autosomal dominant trait

– Mutations in genes that encode one of the sarcomere proteins including • Beta-cardiac myosin heavy chain (the first gene

identified),

• Cardiac actin,

• Cardiac troponin T,

• Alpha-tropomyosin,

• Cardiac troponin I,

• Cardiac myosin-binding protein C, and

• Myosin light chains.

– >400 mutations in these genes.

– Frequency • 45% of mutations occur in β myosin heavy chain gene

• 35% involve cardiac myosin binding protein C gene.

Variants of HCM: Most common location: subaortic , septal, and ant. wall.

• Asymmetric hypertrophy (septum and ant. wall): 70 %.

• Basal septal hypertrophy: 15- 20 %.

• Concentric LVH: 8-10 %.

• Apical or lateral wall: < 2 % (25 % in Japan/Asia): characteristic giant T-wave inversion laterally & spade-like left ventricular cavity: more benign.

65% 35%

10%

Types of HCM

ASH

Symmetric

Apical

HOCM

Mitral valve presses against septum

MR

LVOT Obstruction

-Septal bulge

-Mitral valve is large and

slack

~2/3 of HCM pts have

abnormal MV

-Mitral valve papillary

muscles and leaflets are

anteriorly positioned

Sherrid MV Progress in Card. Diseases 2012

Klues HG et al Circulation 1992

Prevalence of LVOT Obstruction

Rest obstruction

≥30mmHg

37%

With exercise

33%

Non obstructive

30%

70%

Maron, M et al Circulation 2006

Sensitivity

of Valsalva 40%

Echocardiography in Hypertrophic Cardiomyopathy

• Define pattern of hypertrophy asymmetric; concentric • Assess systolic function • Assess diastolic function • Quantitate obstruction • Assess concomitant mitral regurgitation • Risk stratify • Differentiate from athlete’s heart • Differentiate from restrictive CM • Help guide myomectomy and alcohol ablation

Mitral Valve assessment

• Because the anterior leaflet motion is greater than that of the posterior leaflet during SAM an interleaflet gap occurs

• The jet of mitral regurgitation is directed laterally and posteriorly and predominates during mid and late systole

• Not all MR in HCM is due to SAM

• Intrinsic disease

Presentation of HCM

Causes of Sudden Death in Young Athletes

Prognosis – Sudden Cardiac Death

• Adults - 2-3% SCD per year

• Adolescents - 4-6% SCD per year

• Infants (less than 1 yr old), mortality = 50%

Risk Factors for SCD

• Massive LVH (e.g > 30 mm)

• Family history of sudden death

• Unexplained/recurrent syncope

• Nonsustained VT (Holter Monitoring)

• Drop in blood pressure during exercise

Br Heart J 1994; 72:S13

•? Genetic mutations prone to SCD •? Gadolinium enhancement on MRI >20% •Risk models to estimate rate of SD and guide ICD placement

High Risk Genes

• Beta-myosin heavy chain (MYH7) – R403Q

– R453C

– G716R

– R719W

• Cardiac troponin T gene (TNNT2) – R92W

• Only 3 of 293 (<1%) were positive for these mutations

J Am Coll Cardiol 2002;39:2042– 8)

Differential Diagnosis:

HCM • Can be asymmetric

• Wall thickness: > 15 mm

• LA: > 40 mm

• LVEDD : < 45 mm

• Diastolic function: always abnormal

Athletic heart • Concentric & regresses

• < 15 mm

• < 40 mm

• > 45 mm

• Normal

Natural History/Prognosis

• Annual mortality 3% in referral centers, probably closer to 1% for all patients

• Risk of SCD higher in children may be as high as 6% per year

– Majority have progressive hypertrophy

• Clinical deterioration usually is slow

• Progression to DCM occurs in 10-15%

Natural History Aging is Good in HCM

Maron B et al Circulation 2000

Maron B et al Circulation 2013

Cohort >60 years

Obstruction and Prognosis Obstruction is not good

Maron MS et al NEJM 2003

Atrial Fibrillation Poor Prognostic Factor

20% of patients

• 4x the risk of general population

• Amiodarone

• Coumadin

• CHADS score not validated

in this cohort

• RFA/ AVN ablation

Maron BJ, et al. J Am Coll Cardiol 2002

Olivotto I, et al Circulation 2001

Sudden death Heart failure “ Burned out HCM”

AF&

Stroke

Treatment

ICD

Rx Surgery Septal

ablation

Transplant

Rx RFA

Maze

Management

• Lifestyle Modifications

• Medications

– Beta-adrenergic blockers

– Calcium antagonist

– Disopyramide

– Amiodarone, Sotolol

• DDD pacing

• Surgery

– Myectomy/Septal Ablation

– Mitral Valve Repair/Replacement

– Heart Transplantation

Obstructive HCM with SXS

Verapamil

+

Disopyramide

PM with short AV delay

Septal myectomy or ablation

Symptoms Anterior MV leaflet

>33mm Rest

Gradient>90mmHg

Symptoms

Sherrid MV Progress in Cardiovascular dz. 2012

BB

Beta Blockers

• First line therapy, due to negative inotropy

• Reduces exercise induced gradient, not expected to reduce resting gradients

• Improves exertional dyspnea and chest pain

• Titrate to HR 60-65 • Favor: Metoprolol, Bisoprolol, Atenolol • Avoid: Carvedilol and Labetalol

Flamm Circulation 1968

Stenson Am J Cardiol 1973

Cabrera Bueno Int J Cardiol 2007

Calcium Channel Blockers: Verapamil / Diltiazem

• Lower inotropic effect than beta blockers

• Usually reserved for patients with mild to moderate obstruction and/or contraindications to BB therapy

Disopyramide

Pollick C NEJM 1982

• Negative Inotropy

• Blocks Na and Ca channels

• Most effective in

decreasing resting gradient

Transplant

-NYHA Class III/IV symptoms refractory to all medical

and surgical options.

-Low LVEF is not absolutely required

Maron B Circ HF 2010

Kato TS AJC 2012

Conclusion

• HCM is a common genetic cardiomyopathy

• Prevention of SD questions remain as to timing of ICD

• Screening of first degree relatives

• Expanding medical and surgical options for treatment—Septal ablation for young patients as long term efficacy of alcohol ablation is unknown