Hypertrophic cardiomyopathy (HCM)

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by left ventricular hypertrophy without an identifiable cause (e.g. hypertension, aortic stenosis).

It is an autosomal dominant disorder with variable penetrance, most commonly caused by mutations in contractile sarcomeric proteins (e.g. beta myosin heavy chain and myosin binding protein C) of the cardiomyocytes.

Pathophysiology:-
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:-

1. Beta blockers (e.g. metoprolol) reduces heart rate, contractility and LVOT gradient.

2. Non-dihydropyridine CCBs (e.g. verapamil, diltiazem) improves diastolic filling, reduces heart rate and contractility. 

3. Disopyramide (Class Ia antiarrhythmic)is combined with beta blockers for refractory symptoms. It possesses negative inotropic and antiarrhythmic properties.

4. 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):-

1. Surgical myectomy.

2. Alcohol septal ablation.

Indications of Implantable Cardioverter Defibrillator (ICD) in HCM:-

1. Personal history of SCD or VT.

2. Family history of SCD in 1st degree relative.

3. Unexplained Syncope.

4. Massive (>30mm) LVH.

5. Repetitive NSVT or failure to augment SBP by 20 mmHg with exercise.

6. Late gadolinium enhancement on Cardiac MRI.

Unstable angina

Vignette says a 50 year old male presents to the emergency department with chief complaints of acute onset chest pain, that started 30 minutes ago; The pain is  sudden in onset, substernal, tight, and crushing in nature, severe in intensity with radiation to the left arm, jaw and neck; He also reports of shortness of breath, diaphoresis and vomiting;  He has a history of hypertension, diabetes mellitus and hyperlipidemia, but is not compliant with his medication; He is active smoker and drinks alcohol occasionally; The patient appears anxious; Vital signs show blood pressure of 130/90 mm of Hg, pulse rate of 98 bpm, respiratory rate of 18 breaths/min, oxygen saturation of 92% in RA and temperature of 97.9 F; ECG shows ST-segment depression in the anterior leads (V1-V4) and T-wave inversion; Cardiac troponins are negative; Echocardiography is normal; Diagnosis?

Diagnosis is Unstable angina.

Pathogenesis of unstable angina involves formation of nonocclusive thrombus over disrupted atherosclerotic plaques (MCC); Other mechanisms are coronary artery vasospasm, oxygen supply demand imbalance, and gradual narrowing of an epicardial coronary artery caused by progressive atherosclerosis or restenosis after stenting.

 

Presents with chest pain or heaviness or tightness with radiation to the left arm, jaw and neck, SOB, diaphoresis, nausea, vomiting.

 

Diagnosis:-

1. ECG shows ST depression and/or T-wave inversion.

2. Cardiac biomarkers (e.g. CK-MB, troponins) are negative.

3. Echocardiography is often normal in unstable angina.

4. Coronary angiography 

 

TIMI scores:-

1. Age > 65 years 

2. ≥ 3 risk factors for CAD 

3. Known stenosis > 50% % by prior angiography

4. ASA < 7 days 

5 ≥ 2 episodes of retrosternal chest pain within 24 hours

6. ST depression ≥ 0.5 mm 7) 

7. Elevated serum troponin or CK-MB

Early invasive strategy is deployed if the TIMI score ≥ 3; the patient is managed with urgent coronary revascularization. 

Conservative approach is deployed if the TIMI score is 0-1; the patient is managed with medical therapy.

 

Management:-

1. Oxygen supply to maintain saturation >90%. 

2. Anti ischemic therapy (e.g. nitrates, beta blockers, CCBs).

3. Anti platelet therapy (e.g. aspirin, P2Y12 inhibitors, GPIIb/IIIa inhibitors).

4. Anticoagulants therapy (e.g. UFH, LMWH).

5. Adjunctive therapy (e.g. statins, ACE inhibitors).

6. Percutaneous coronary intervention (PCI).

REMEMBER THROMBOLYTICS ARE CONTRAINDICATED IN UNSTABLE ANGINA.

Wellens syndrome

Vignette says a 50 year old male presents to the emergency department with an episode of chest pain induced by excretion 1 hour back, currently he doesn't complain of chest pain; He has a history of hypertension for which he takes amlodipine; Vital signs show blood pressure of 130/80 mm of Hg, pulse rate of 88 bpm, respiratory rate of 18 breaths/min, oxygen saturation of 98% in RA and temperature of 96.9 F; ECG shows biphasic T wave in lead V2; Cardiac biomarkers (i.e. troponins) are normal; Diagnosis?

Diagnosis is a type A wellens syndrome.

Wellens syndrome is characterized by biphasic T waves or deeply inverted T waves in leads V2-V3, that is highly specific for critical stenosis of the proximal left anterior descending coronary artery, usually pain free at presentation to the emergency department with normal or mild elevated cardiac biomarkers; Require immediate percutaneous coronary intervention (PCI) to relive the occlusion.

 Figure:- ECG showing biphasic T wave in lead V2 suggestive of type A wellens syndrome.