Hypertrophic cardiomyopathy Dipin.s Junior resident Internal medicine

Autosomal dominant disease of the heart muscle, characterized by a small left ventricular cavity and marked hypertrophy of the myocardium with myofibril disarray. Overall prevalence is 1:500 to 1:1000 Disease of the myofilaments, with alteration in structure and function Most common cause of sudden cardiac death in young people.

Asymmetric septal hypertrophy (ASH) Idiopathic hypertrophic subaortic stenosis (IHSS) Muscle subaortic stenosis Hypertrophic obstructive cardiomyopathy (HOCM).

Etiology Most common genetic cardiovascular disease Mutation in genes encoding proteins of the cardiac sarcomere myofilaments Beta-myosin heavy chain, myosin-binding protein C, cardiac troponin T and I,alpha -tropomyosin, actin, titin, and myosin light chains Other genes outside of the sarcomere myofilaments have also been recently implicated Deletions, insertions, missense, and splice site mutations.

Hypothesis is that sarcomeric dysfunction leads to compensatory hypertrophy.

pathology Asymmetrical hypertrophy with a small LV cavity Mural endocardium thickened by fibrous tissue Elongation of chordae and ant. displacement of the hypertrophied papillary muscles LA is usually dilated

Histology Short runs of severely hypertrophied fibers interrupted by connective tissue Large and bizarre nuclei and fibrosis, with degenerating muscle fibers. Whorling of muscle fibers is characteristic of HCM

Pathophysiology Diastolic dysfunction Impaired ventricular relaxation and chamber stiffness Compensatory increase in late diastolic filling by atrial systole. During exercise or any other type of catecholamine stimulation, diastolic filling period decreases as well as myocardial ischemia occurs Leads to severe diastolic dysfunction- dyspnoea

LVOT obstruction Multifactorial During systolic contraction the hypertrophied basal septum encroaches to the outflow tract Mitral leaflets are pulled in by the venturi force In midcavitary region hypertrophied pappillary muscles pressing against septum may cause obstruction

LVOT obstruction is dynamic Increased myocardial contractility, decreased ventricular volume, or decreased afterload ----increases Myocardial ischaemia Supply-demand mismatch compromised coronary blood flow to the LV myocardium -- abnormally small and partially obliterated intramural coronary arteries

Autonomic dysfunction Either a failure of systolic blood pressure to rise >20 mmHg or a fall in systolic blood pressure during excercise. Speculated that there is high degree of abnormal autonomic tone in HCM Assoc. with poor prognosis

Mitral regurgitation Secondary phenomenon due to systolic anterior motion of leaflets due to LVOT obstruction During mid and late systole- jet directed post. and laterally

Clinical presentation Most are asymptomatic Dyspnoea-diastolic dysfunction and elevated LV filling pressures Angina – epicardial coronary disease may be absent Syncope or presyncope- LV baroreceptors causes reflex vasodilatation Atrial fibrillation occurs more in elderly

Physical examination Carotid pulse- spike and dome pattern rapid rise (percussion wave) midsystolic drop secondary wave (tidal wave) Jugular venous pressue- usually normal; sometimes prominent a wave (hypertrophy and lack of compliant RV and powerful Rt atrial contraction)

Apical impulse- forceful, sustained, diffuse double or triple apical impulse (outward thrust of ventricular contraction, a presystolic accentuated atrial contraction, and expansion of early diastolic filling) Cardiac sounds- usually split sometimes paradoxically split S4 if severe hypertrophy

Murmurs =crescendo–decrescendo murmur located primarily at the left sternal border. (usually ends before S2) May radiate to the base or apex, but seldom radiation to the carotid arteries.

Any condition which increases the LVOT outflow gradient – more obstruction – murmur is louder longer and peak late in systole

LVOT obstruction and systolic murmur increased by………. A reduction in LV cavity volume and pressure ( less preload) A decrease in systemic vascular resistance / arterial pressure ( less after load ) An increase in LV contractility Converse is also true

Anterior Mitral Leaflet

Myocardial Contractility Exercise Cathecolamines Digitalis Ventricular Volume Valsalva Standing Nitroglycerine Tachycardia Gradient / Murmur Per Arterial Pressure Methoxamine Sustained Handgrip Passive Leg Raise BV Expansion Gradient / Murmur

ECG Abnormal in % patients LVH LAE Deep and narrow q waves in inferolateral leads Diminished R waves in lateral precordial leads

Large negative precordial T waves Left axis deviation No ECG finding is predictive of future events Tall R and deep S waves weakly corelated with magnitude of LV hypertrophy

SVT 46% PVCs 43% Non sustained VT 26% AF can occur in 25-30% of elderly

Chest X-Ray Mild to moderate enlargement of the cardiac silhouette. The left ventricular contour is rounded consistent with concentric LVH. Enlargement of the left atrium Right-sided chambers are usually normal.

Echocardiography Gold standard for the diagnosis of HCM Increased wall thickness in the absence of other etiology Septum>=1.3 times LV post.free wall Subaortic Gradient > 30mm Hg ( rest) >50(provocation) Vigorous motion of post. Free wall with reduced septal excursion Avg. LV wall thickness in HCM is mm ECG and echo has to be correlated. Low voltages in ECG in the presence of increased wall thickness is seen in infiltrative disorder

Small LV cavity/ Septal immobility Primary tool for defining the presence and severity of LVO tract obstruction Systolic anterior motion of mitral valve Presence and severity of MR (laterally and posteriorly directed jet in mid to late systole) Cardiac MRI

Subaortic gradient >30 is a determinant of heart failure but risk of sudden death Elderly patients are not targeted for risk stratification(SCD is uncommon and survival to old age itself suggests low risk) Beta myosin heavy chain and trop T mutations are assoc. with higher risk for premature death.

Management Prevention of SCD ICD implantation – as primary prevention following cardiac arrest -as secondary prevention if one or more high risk factors Empirical pharmacological therapy with amiodarone is now obsolete

Medical treatment Heart failure Beta blockers (slows heart rate, reduce force of LV contraction, augments ventricular filling and relaxation, decreases myocardial O2 demand, blunts outflow gradient triggered by sympathetic activity) Verapamil (improves LV relaxation and filling) Disopyramide End stage failure –ACE,ARBs, ICD to prevent SCD

Atrial fibrillation- most common sustained arrhythmia in HCM Paroxysmal AF occurs in 20% Increases with age and is related to LA dilatation Acute decompensation- cardioversion Amiodarone prevents reccurences Rate control with beta blockers or verapamil Started on anticoagulation

Diuretics…………….. Can be use alone judiciously or with betablockers / verapamil to lessen pulmonary congestion

Non medical treatment Surgery Severe drug refractory heart failure symptoms Severe functional disability (NYHA class III, IV) Associated with LV outflow obstruction at rest or with physiological exercise (>50mm gradient) Transaortic ventricular septal myectomy (morrow procedure)-small portion from basal septum

Alcohol ablation % ethanol (1-3 ml)introduced into major septal perforator vessel Necrosis and permanent MI in proximal septum is created Thinning and reduced excursion of septum, Outflow tract enlarges- reduction of subaortic obstruction and MR alternative treatment strategy for selected patients— (advanced age, significant comorbidity and increased operative risk, without access to expert surgical centers, or pt.against surgical intervention)

Alcohol ablation

Dual chamber pacing – no definite evidence

Infective endocarditis Vegetations most commonly seen on anterior mitral leaflet or septal endocardium at the site of mitral valve–septum contact standard antimicrobial prophylaxis is indicated prior to dental or surgical procedures

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