Myocardial Disease

1. Hypertrophic Cardiomyopathy (HCM)

1.1 Overview and Clinical Presentation

• Definition: HCM is an "autosomal dominant heritable disorder related to mutations in the genes that primarily encode sarcomeric proteins." It is characterized by increased left ventricular (LV) wall thickness without other underlying causes (e.g., hypertension).
• Prevalence: Affects approximately "1 in 500 persons" and can be identified in all age groups, though "index cases typically present within the third to fourth decades of life" in the U.S.
• Asymptomatic Nature: "Most patients with HCM are asymptomatic and have normal life expectancy," often diagnosed during evaluation for a heart murmur or abnormal ECG.
• Symptomatic Presentation: Symptomatic individuals typically present with "signs and symptoms of heart failure (dyspnea, fatigue) or arrhythmias (palpitations, syncope)."
• Sudden Cardiac Death (SCD): SCD "may be the initial manifestation in some patients."
• Pathophysiology of Symptoms: Heart failure symptoms are due to "abnormal LV filling (diastolic dysfunction)" and "dynamic left ventricular outflow tract (LVOT) obstruction."
• Diastolic Dysfunction: Involves "increased chamber stiffness, progressive fibrosis, and myocardial ischemia."
• Dynamic LVOT Obstruction: The "classic form of HCM," characterized by "asymmetric LV hypertrophy with prominent interventricular septal thickening." Found in 30% of patients at rest and an additional 40% with provocation.
• "Eject-obstruct-leak" triad: During systole, "anterior motion of the mitral valve results in early to midsystolic obstruction of the LVOT and subsequent mitral regurgitation related to leaflet malcoaptation."

1.2 Evaluation

• Physical Examination: May be normal without LVOT obstruction. A cardiac murmur is common with LVOT obstruction. Dynamic maneuvers (Valsalva, standing from squat, peripheral pulse after PVC) help differentiate HCM from fixed valvular aortic stenosis (see Table 27 in original source).
• Murmur Characteristics: Ejection-quality, usually best heard at the left lower sternal border, "generally does not radiate to the carotid arteries."
• Valsalva Maneuver: "Increase in intensity of murmur during strain phase."
• ECG: Abnormal findings in 75% to 95% of patients, including "increased QRS voltage, evidence of left atrial enlargement, LV conduction abnormalities, pathologic Q waves, and significant repolarization abnormalities."
• Echocardiography (TTE): Most common diagnostic tool. Demonstrates hypertrophy (≥15 mm LV region or 13-14 mm with first-degree relative with HCM), LVOT obstruction, and mitral regurgitation. Provocative maneuvers (Valsalva, squatting) and exercise echocardiography may be used.
• Cardiac Magnetic Resonance (CMR) imaging: Indicated for inconclusive echocardiographic findings to clarify diagnosis. Useful for differentiating HCM from other conditions causing increased LV wall thickness.
• Ambulatory ECG Monitoring: "24- to 48-hour ambulatory ECG monitoring should be performed to evaluate for arrhythmias." Nonsustained ventricular tachycardia indicates higher SCD risk.
• Exercise Stress Testing: Reasonable for functional status and prognostic information.
• Differential Diagnosis (Table 28): Must differentiate from other conditions with increased LV wall thickness like "Hypertension," "Athlete heart," "Amyloidosis," "Fabry disease," and "Friedreich ataxia."

1.3 Risk Stratification and Management

• Annual Mortality Risk: "Patients with HCM have an annual risk for death of 1%, primarily related to fatal arrhythmia and heart failure."
• SCD Risk Factors (Table 29):Previous SCD or sustained ventricular tachycardia
• LV wall thickness ≥30 mm
• ≥1 Episode of syncope thought to be arrhythmic in nature
• LV apical aneurysm
• LVEF <50%
• Implantable Cardioverter-Defibrillator (ICD):Secondary Prevention: Recommended for patients with previous SCD or sustained ventricular tachycardia.
• Primary Prevention: "Reasonable" for patients with one or more established risk factors.
• CMR in Risk Assessment: Beneficial for assessing maximum LV wall thickness, ejection fraction, LV apical aneurysm, and extent of myocardial fibrosis with late gadolinium enhancement (LGE). LGE ≥15% can serve as a risk modifier for ICD placement in indeterminate cases.
• Lifestyle Interventions: For overweight/obese patients, weight loss to decrease LVOT obstruction, heart failure, and atrial fibrillation risk. Avoid dehydration, excessive alcohol, and exposures causing vasodilation/decreased preload (e.g., saunas, hot tubs).
• Exercise: "Mild- to moderate-intensity exercise is generally safe and beneficial." Athletes require comprehensive evaluation and shared decision-making.
• Pharmacologic Therapy for Symptomatic Patients:First-line: Nonvasodilating β-blockers (avoid carvedilol, labetalol, nebivolol).
• Alternatives: Verapamil or diltiazem if β-blockers are contraindicated/intolerated.
• Persistent Symptoms with LVOT Obstruction: Adding a cardiac myosin inhibitor or disopyramide.
• Caution with Diuretics: Use cautiously for dyspnea, as small changes in volume can impact cardiac output.
• Avoid: Nitrates and phosphodiesterase-5 inhibitors due to LVOT obstruction exacerbation.
• Invasive Treatment for Obstruction: Recommended for severe obstructive symptoms refractory to maximal medical therapy and LVOT gradient ≥50 mm Hg.
• Surgical Septal Myectomy: "Associated with a higher likelihood of complete symptom resolution, greater obstruction relief, and a lower rate of repeat procedures." Favored in young patients.
• Catheter-based Alcohol Septal Ablation: Carries a higher risk for atrioventricular block requiring pacemaker. More appropriate for older patients with comorbidities.
• Atrial Fibrillation (AFib) Management:Rate control and anticoagulation (regardless of CHA2DS2-VASc score). Direct oral anticoagulants are first-line.
• Anticoagulation for subclinical AFib >24 hours detected by ambulatory monitoring.
• Consider rhythm control early for symptomatic patients.
• Avoid digoxin due to positive inotropic effects worsening LVOT gradient.
• End-Stage HCM: Fewer than 5% progress to dilated cardiomyopathy with systolic dysfunction. Guideline-directed therapy and ICD for primary prevention are recommended if LVEF <50%.

1.4 Surveillance

• Asymptomatic Patients: ECG every 1-2 years; 24-48-hour ambulatory ECG monitoring at diagnosis and every 1-2 years.
• Repeat TTE: Recommended with any change in clinical status or new cardiac event; every 1-2 years in asymptomatic patients to assess for mitral regurgitation, LV hypertrophy, function, and obstruction.

1.5 Role of Genetic Testing and Counseling

• Recommendation: Genetic testing is recommended for patients meeting the clinical definition of HCM to identify the causative mutation.
• Family Screening: First-degree relatives should undergo screening with ECG and echocardiography (every 1-2 years in children/adolescent...