a. Diastolic dysfunction (due to increased left ventricular thickness that decreases cavity of the left ventricle and hence compliance of the left ventricle; Also impairs relaxation of the left ventricle).
b. Left ventricular outflow tract obstruction in 2/3rd of the cases (i.e. narrowed tract 2° to hypertrophied septum and systolic anterior motion (SAM) of anterior MV leaflet towards the hypertrophied septum (i.e. venturi effect); The obstruction is dynamic (i.e. Also known as dynamic left ventricular dysfunction).
c. Mitral regurgitation (due to SAM of anterior leaflet of mitral valve towards the hypertrophied septum).
d. Myocardial ischemia.
e. Syncope.
Histologic shows extreme cardiomyocyte hypertrophy with exaggerated myocyte branching, myocyte disarray, and interstitial fibrosis.
Figure:- Pathophysiology of Hypertrophic Cardiomyopathy (Pathophysiology of Heart Disease, Sixth Edition)
Clinical features:-
1. Dyspnea
2. Angina
3. Syncope
4. Sudden cardiac death (SCD) in high risk patients
Physical examination:-
a. Harsh, crescendo-decrescendo systolic murmur heard best at LLSB. Murmur intensity decreases with increased preload or venous return (e.g. squatting, lying supine) and increased afterload or SVR (e.g. handgrip) whereas murmur intensity increases with decreased preload or venous return (e.g. Valsalva, standing) and decreased afterload or SVR (e.g. vasodilators).
b. Pulsus Bisferiens.
c. S4 (+).
d. Holosystolic murmur of MR at apex (due to SAM of anterior leaflet of mitral valve towards the hypertrophied septum causing MR).
Diagnosis:-
1. Chest X-ray shows LVH.
2. ECG shows VT/VFib, AFib, LVH, Deep Q waves in inferior leads (II, III, aVF) and lateral leads (I, aVL, V5-V6), diffuse T-wave inversions.
3. Echocardiography shows LV wall thickness >15mm, asymmetric wall thickness (due to hypertrophy of interventricular septum), decreased diameter of ventricular lumen, systolic anterior motion of anterior leaflet of mitral valve towards the hypertrophied septum; Doppler echocardiography shows left ventricular outflow tract obstruction, dynamic outflow tract obstruction, and mitral regurgitation.
4. Cardiac MRI detects fibrosis (i.e. late gadolinium enhancement).
5. Genetic testing is recommended for 1st degree relatives.
6. Cardiac catheterization.
7. Holter monitoring.
Treatment:-
1. Screen all 1st degree relatives with genetic testing or cardiac imaging.
2. Counsel the patients to avoid dehydration, medications (e.g. inotropes, vasodilators), competitive sports and strenuous activity.
3. Medical therapy includes:-
Beta blockers (e.g. metoprolol) reduces heart rate, contractility and LVOT gradient.
Non-dihydropyridine CCBs (e.g. verapamil, diltiazem) improves diastolic filling, reduces heart rate and contractility.
Disopyramide (Class Ia antiarrhythmic)is combined with beta blockers for refractory symptoms. It possesses negative inotropic and antiarrhythmic properties.
Cardiac myosin inhibitor (e.g. mavacametan) is indicated in symptomatic obstructive HCM (NYHA Class II-III) as it reduces contractility and LVOT obstruction. Monitor LVEF as it increases risk of systolic dysfunction (VALOR-HCM trial). Mavacamten significantly reduces septal reduction therapy eligibility and improves symptoms in obstructive HCM but needs regular LVEF monitoring as it increases risk of systolic dysfunction.
4. Surgical management (If symptoms are refractory to adequate medical therapy or significant LVOT obstruction i.e. ≥ 50 mmHg despite adequate medical therapy):-
Surgical myectomy.
Alcohol septal ablation.
Indications of Implantable Cardioverter Defibrillator (ICD) in HCM:-
Personal history of SCD or VT.
Family history of SCD in 1st degree relative.
Unexplained Syncope.
Massive (>30mm) LVH.
Repetitive NSVT or failure to augment SBP by 20 mmHg with exercise.
Late gadolinium enhancement on Cardiac MRI.