Hypertrophic cardiomyopathy (HCM)

A 23-year-old male presents to the emergency department after a syncopal episode during a football match. He reports intermittent exertional chest pain, palpitations, and progressive shortness of breath over the past several months. He denies any history of hypertension or valvular disease. His father died suddenly at the age of 35. On physical examination, a harsh crescendo–decrescendo systolic murmur is heard best at the left lower sternal border. The murmur increases with Valsalva maneuver and standing and decreases with squatting and handgrip. A fourth heart sound (S4) is present. Electrocardiography shows left ventricular hypertrophy with deep, narrow (“dagger-like”) Q waves in the inferior and lateral leads. Transthoracic echocardiography demonstrates asymmetric septal hypertrophy with a maximal wall thickness of 18 mm, systolic anterior motion (SAM) of the mitral valve, and a resting left ventricular outflow tract (LVOT) gradient of 60 mmHg. Cardiac MRI shows patchy late gadolinium enhancement. Diagnosis?

Diagnosis is Hypertrophic cardiomyopathy (HCM) with obstructive LVOT physiology and high risk of sudden cardiac death.

1. Definition

Hypertrophic cardiomyopathy is an autosomal dominant disorder caused by mutations in sarcomeric proteins, characterized by unexplained left ventricular hypertrophy, dynamic LVOT obstruction, diastolic dysfunction, myocardial ischemia, and increased risk of arrhythmias and sudden cardiac death.

2. Etiology

1. Autosomal dominant inheritance with variable penetrance
2. Sarcomeric mutations (~60%):
• β-myosin heavy chain (MYH7)
• Myosin-binding protein C (MYBPC3)
3. Sporadic/nonfamilial cases (~40%)
4. Rare mutations involving thin filament proteins

3. Pathophysiology

1. Asymmetric septal hypertrophy leads to reduced LV cavity size
2. Diastolic dysfunction due to impaired relaxation and increased stiffness
3. Dynamic LVOT obstruction:
• Caused by septal hypertrophy + systolic anterior motion (SAM) of mitral valve
• May be present at rest or only with provocation (e.g., exercise, Valsalva)
• Gradient ≥30 mmHg is significant; ≥50 mmHg indicates intervention
4. Mitral regurgitation due to SAM
5. Myocardial ischemia due to microvascular dysfunction
6. Arrhythmias:
• Atrial fibrillation (most common)
• Ventricular tachycardia → ventricular fibrillation → sudden cardiac death
7. Autonomic dysfunction:
• Abnormal blood pressure response to exercise

4. Clinical Features

4.1 Classic Features

1. Dyspnea
2. Angina
3. Exertional syncope
4. Sudden cardiac death (especially in young athletes)

4.2 Additional Features

1. Palpitations
2. Fatigue
3. Family history of sudden cardiac death
4. Symptoms worsened by dehydration or exertion

5. Physical Examination

1. Harsh systolic murmur at left lower sternal border
2. Murmur characteristics:
• ↑ with ↓ preload (Valsalva, standing)
• ↓ with ↑ preload (squatting)
• ↓ with ↑ afterload (handgrip)
3. Pulsus bisferiens
4. S4 heart sound
5. Apical holosystolic murmur (mitral regurgitation)

6. Diagnosis

6.1 Electrocardiography

1. Left ventricular hypertrophy
2. Deep, narrow (“dagger-like”) Q waves in inferior and lateral leads
3. T-wave inversions
4. Arrhythmias (AF, VT)

6.2 Imaging

1. Echocardiography (gold standard):
• LV wall thickness ≥15 mm
• 13–14 mm may be diagnostic with family history or ECG abnormalities
• Asymmetric septal hypertrophy
• Systolic anterior motion (SAM) of mitral valve (highly specific)
• LVOT gradient ≥30 mmHg
2. Cardiac MRI:
• Detects fibrosis (late gadolinium enhancement)
• Helps risk stratification

6.3 Additional Evaluation

1. Holter monitoring (detects NSVT)
2. Exercise testing (assesses BP response and LVOT gradient)
3. Genetic testing and family screening

7. Management

7.1 General Measures

1. Screen first-degree relatives
2. Avoid dehydration and maintain adequate preload
3. Avoid competitive sports (shared decision-making recommended)
4. Avoid drugs that reduce preload or afterload

7.2 Medical Therapy

1. Beta-blockers (first-line)
2. Non-dihydropyridine calcium channel blockers (verapamil, diltiazem)
3. Disopyramide (for refractory obstructive HCM)
4. Mavacamten (for symptomatic obstructive HCM, NYHA class II–III)

7.3 Drugs to Avoid

1. Nitrates and vasodilators
2. ACE inhibitors/ARBs (in obstructive HCM, may worsen LVOT obstruction)
3. Positive inotropes (e.g., dobutamine)
4. Excess diuretics

7.4 ICD Indications

1. Prior cardiac arrest or sustained VT
2. Family history of sudden cardiac death
3. Unexplained syncope
4. LV wall thickness >30 mm
5. Non-sustained VT on Holter
6. Extensive fibrosis (late gadolinium enhancement on MRI)
7. Abnormal blood pressure response to exercise
8. Apical aneurysm (if present)

7.5 Surgical Management

Indications: Symptomatic patients with LVOT gradient ≥50 mmHg despite optimal medical therapy

1. Septal myectomy (gold standard)
2. Alcohol septal ablation

8. Key Clinical Insight

Young patient with exertional syncope + family history of sudden death = hypertrophic cardiomyopathy until proven otherwise

9. Exam Level Pearls

1. Young athlete with exertional syncope and family history → classic HCM
2. Murmur increases with Valsalva (key differentiator from aortic stenosis)
3. LVOT obstruction is dynamic and preload-dependent
4. Most common cause of sudden cardiac death in young athletes
5. Most common cause of death = ventricular arrhythmia (VT → VF)
6. Echocardiography is the diagnostic modality of choice

Unstable Angina

A 50-year-old male presents to the emergency department with acute chest pain that began 30 minutes ago. The pain is sudden, substernal, tight, and crushing, severe in intensity, and radiates to the left arm, jaw, and neck. It is not relieved by rest and is associated with shortness of breath, diaphoresis, nausea, and vomiting. He has a history of hypertension, diabetes mellitus, and hyperlipidemia, with poor medication compliance, and is an active smoker who drinks alcohol occasionally. On examination, he appears anxious and diaphoretic. His vital signs show a blood pressure of 130/90 mmHg, pulse rate of 98 beats/min, respiratory rate of 18 breaths/min, oxygen saturation of 92% on room air, and temperature of 97.9°F. Cardiovascular examination may reveal an S4 gallop. Electrocardiography demonstrates ST-segment depression in the anterior leads (V1–V4) with T-wave inversion, consistent with subendocardial ischemia. Initial high-sensitivity cardiac troponin is negative, and repeat measurements at 1–3 hours remain negative, making myocardial necrosis unlikely. Echocardiography shows no significant regional wall motion abnormalities. Diagnosis?

Diagnosis is Unstable Angina (Non–ST-Elevation Acute Coronary Syndrome without myocardial necrosis).

1. Definition

1. Unstable angina is a form of acute coronary syndrome (ACS) characterized by myocardial ischemia without biochemical evidence of myocardial necrosis.
2. It results from transient reduction in coronary blood flow.
3. It typically presents as:
• Angina at rest
• New-onset severe angina
• Crescendo (worsening) angina
4. It represents a high-risk pre-infarction state with potential progression to NSTEMI or STEMI.

2. Etiology

1. Rupture or erosion of atherosclerotic plaque with non-occlusive thrombus (most common)
2. Coronary artery vasospasm (Prinzmetal angina)
3. Coronary microvascular dysfunction
4. Oxygen supply–demand mismatch due to:
• Tachycardia
• Anemia
• Fever
• Thyrotoxicosis
5. Cocaine or stimulant-induced vasoconstriction

3. Pathophysiology

1. Atherosclerotic plaque becomes unstable and ruptures
2. Exposure of subendothelial collagen → platelet adhesion and activation
3. Formation of a platelet-rich thrombus (white thrombus typical of ACS)
4. Partial occlusion of coronary artery → reduced coronary perfusion
5. Results in subendocardial ischemia (most vulnerable region)
6. No sustained occlusion → no myocardial necrosis (troponin negative)
7. Associated with inflammatory activation (↑ CRP, cytokines)

4. Clinical Features

4.1 Classic Features

1. Chest pain at rest or minimal exertion
2. Crescendo angina (increasing frequency, severity, duration)
3. Prolonged chest pain (>20 minutes)
4. Incomplete relief with nitrates

4.2 Additional Features

1. Radiation to left arm, jaw, neck, or back
2. Shortness of breath
3. Diaphoresis
4. Nausea and vomiting
5. Dizziness or presyncope

4.3 High-Risk Features

1. Ongoing or recurrent chest pain
2. Hemodynamic instability
3. Signs of heart failure (S3, rales)
4. Dynamic ECG changes
5. Refractory angina despite medical therapy

5. Diagnosis

5.1 Electrocardiography

1. ST-segment depression (≥0.5 mm)
2. T-wave inversion
3. Transient ischemic changes
4. May be normal or nonspecific

5.2 Cardiac Biomarkers

1. High-sensitivity troponins negative on serial testing (0 and 1–3 hours)
2. Absence of myocardial necrosis distinguishes UA from NSTEMI

5.3 Echocardiography

1. May be normal
2. May show transient regional wall motion abnormalities
3. Helps exclude alternative diagnoses

5.4 Risk Stratification

TIMI Score (UA/NSTEMI)

1. Age ≥ 65 years
2. ≥ 3 CAD risk factors
3. Known coronary stenosis ≥ 50%
4. Aspirin use in last 7 days
5. ≥ 2 anginal episodes in 24 hours
6. ST deviation ≥ 0.5 mm
7. Elevated cardiac biomarkers (indicates NSTEMI within ACS spectrum)

GRACE Score

1. Used for mortality risk prediction
2. Guides invasive vs conservative strategy

5.5 Definitive Investigation

1. Coronary angiography (gold standard)

6. Management

6.1 Initial Step

1. Rapid assessment of hemodynamic stability and risk
2. Continuous cardiac monitoring

6.2 Immediate Medical Therapy (ACS Protocol)

1. Aspirin (loading dose 162–325 mg)
2. P2Y12 inhibitor (clopidogrel/ticagrelor)
3. Anticoagulation (UFH, LMWH, or fondaparinux)
4. Nitrates (sublingual/IV)
5. Beta-blockers (if no contraindications: hypotension, acute HF, bradycardia)
6. High-intensity statins (e.g., atorvastatin 80 mg)

6.3 Oxygen Therapy

1. Administer only if SpO₂ < 90% or respiratory distress

6.4 Adjunctive Therapy

1. ACE inhibitors/ARBs (especially in diabetes, LV dysfunction)
2. Proton pump inhibitors if high bleeding risk
3. Consider ranolazine for refractory angina

6.5 Risk-Based Strategy

1. Very high risk → Immediate angiography (<2 hours)
2. High risk (TIMI ≥ 3 or high GRACE score) → Early invasive strategy (<24 hours)
3. Low risk → Conservative management + stress testing

6.6 Definitive Management

1. Percutaneous coronary intervention (PCI)
2. Coronary artery bypass grafting (CABG) if indicated

6.7 Secondary Prevention

1. Smoking cessation
2. Lipid control (LDL <70 mg/dL)
3. Blood pressure and diabetes control
4. Lifestyle modification and cardiac rehabilitation

7. Important Clinical Rule

1. Thrombolytics are contraindicated in unstable angina and NSTEMI
2. Thrombolytics are indicated only in STEMI when PCI is not immediately available

8. Key Clinical Insight

1. Chest pain + ST depression = subendocardial ischemia
2. Negative serial troponins distinguish unstable angina from NSTEMI
3. Always treat initially as acute coronary syndrome (ACS)
4. UA and NSTEMI differ only by presence of myocardial necrosis (troponin elevation)
5. Early recognition prevents progression to myocardial infarction

9. Exam Level Pearls

1. Negative troponin distinguishes unstable angina from NSTEMI
2. Subendocardial ischemia causes ST depression
3. Normal ECG does not exclude unstable angina
4. Always treat as acute coronary syndrome initially
5. Early intervention prevents myocardial infarction

Wellens Syndrome

A 50 year old male presents to the emergency department with an episode of exertional chest pain that occurred 1 hour earlier and has now resolved. He has a history of hypertension and is on amlodipine. Vital signs show blood pressure of 130/80 mm Hg, pulse rate of 88 beats per minute, respiratory rate of 18 breaths per minute, oxygen saturation of 98 percent on room air, and temperature of 96.9 F. ECG shows biphasic T waves in lead V2. Troponin is normal. Diagnosis?

Diagnosis is Type A Wellens syndrome.

1. Definition

Wellens syndrome is an ECG pattern seen in a pain free patient with recent angina, characterized by T wave abnormalities in V2–V3, and is highly suggestive of critical proximal left anterior descending artery stenosis, representing a pre-infarction state.

2. Types

1. Type A Wellens pattern
• Biphasic T waves with initial positivity followed by terminal negativity
• Seen in V2–V3
• Approximately 25 percent of cases
2. Type B Wellens pattern
• Deep, symmetric T wave inversions
• Seen in V2–V3, may extend anteriorly
• Approximately 75 percent of cases

3. Key Diagnostic Features

1. Recent history of anginal chest pain
2. Pain free at time of ECG
3. Characteristic T wave changes in V2–V3
4. Normal or mildly elevated troponin
5. Little or no ST segment elevation
6. No pathologic Q waves

4. Pathophysiology

1. Critical proximal LAD stenosis
2. Transient occlusion followed by spontaneous reperfusion
3. Leads to T wave changes without completed infarction
4. High risk of progression to large anterior myocardial infarction

5. Clinical Significance

1. Represents a pre-infarction state
2. Patient may appear stable and asymptomatic
3. High risk of extensive anterior MI within days if untreated

6. Diagnosis

1. ECG is highly suggestive in the appropriate clinical context
2. Troponin may be normal or mildly elevated
3. Coronary angiography confirms LAD stenosis

7. Management

1. Urgent coronary angiography with revascularization (PCI)
2. Avoid stress testing
3. Initiate acute coronary syndrome therapy
• Antiplatelets
• Anticoagulation
• Statins

8. Key Clinical Insight

Pain free patient with recent angina and biphasic or deeply inverted T waves in V2–V3 with normal troponin strongly suggests Wellens syndrome and requires urgent intervention

9. Exam Level Pearls

1. Wellens syndrome is a pre-infarction LAD lesion
2. Type A shows biphasic T waves, Type B shows deep symmetric inversions
3. Occurs when patient is pain free
4. Troponin may be normal despite critical stenosis
5. Stress testing is contraindicated

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