What is the recommended management and treatment for a patient with hypertrophic cardiomyopathy?

Management of Hypertrophic Cardiomyopathy

Begin with beta-blockers as first-line therapy for all symptomatic patients, titrate to a resting heart rate of 60-65 bpm, and obtain transthoracic echocardiography with provocative maneuvers to assess for left ventricular outflow tract obstruction (LVOTO). 1

Initial Diagnostic Evaluation

Obtain a comprehensive 3-generation family history documenting unexplained sudden death, heart failure, cardiac transplantation, or early ICD/pacemaker implants in relatives. 1, 2

• Perform a 12-lead ECG immediately in all patients with suspected HCM, looking for left ventricular hypertrophy patterns, conduction abnormalities, or superior QRS axis. 1, 2
• Order transthoracic echocardiography (TTE) as the primary imaging modality to assess left ventricular wall thickness (≥15 mm diagnostic in adults, ≥13 mm in first-degree relatives of confirmed cases), presence of LVOTO, diastolic and systolic function, and valvular abnormalities. 1, 2
• For patients with resting left ventricular outflow tract gradient <50 mm Hg, perform TTE with provocative maneuvers (Valsalva, standing) to detect dynamic obstruction. 1
• If echocardiography is inconclusive or inadequate, obtain cardiac MRI for diagnostic clarification and assessment of hypertrophy distribution. 1, 2

Perform 24- to 48-hour ambulatory electrocardiographic monitoring at initial evaluation to identify patients at risk for sudden cardiac death and detect nonsustained ventricular tachycardia. 1

Pharmacologic Management Algorithm

First-Line Therapy: Beta-Blockers

Start nonvasodilating beta-blockers (metoprolol, atenolol, propranolol) in all symptomatic patients, titrating to achieve resting heart rate of 60-65 bpm. 1, 3

• Beta-blockers reduce LVOT gradients through negative inotropic effects and prolonged diastolic filling time, alleviating dyspnea and chest pain. 3, 4
• Do not declare beta-blocker failure until maximally tolerated doses are achieved with documented heart rate suppression below 60-65 bpm. 3
• Typical dosing: metoprolol tartrate 100-200 mg divided twice daily or metoprolol succinate 50-200 mg once daily. 3

Second-Line Therapy: Non-Dihydropyridine Calcium Channel Blockers

If beta-blockers are ineffective, not tolerated, or contraindicated, substitute with verapamil (up to 480 mg/day) or diltiazem as Class I alternatives. 1, 3

• Verapamil improves physical resilience and can be titrated to high doses for symptom control in both obstructive and nonobstructive HCM. 3, 4
• Never combine beta-blockers with non-dihydropyridine calcium channel blockers due to increased risk of bradycardia and heart block. 3
• Verapamil has negative inotropic effects and should be avoided in patients with severe left ventricular dysfunction (ejection fraction <30%) or moderate to severe heart failure symptoms. 5

Third-Line Therapy: Mavacamten

For adults with persistent NYHA class II-III symptoms despite beta-blockers or calcium channel blockers, add mavacamten (cardiac myosin inhibitor) as Class I recommended therapy. 3, 4

• Mavacamten lowers LVOT gradients and improves quality of life. 4
• Monitor for reversible reduction of left ventricular ejection fraction to <50%, which occurs in 7-10% of patients. 4

Fourth-Line Therapy: Disopyramide

Consider disopyramide as an alternative third-line agent when beta-blockers and calcium channel blockers fail, utilizing its strong negative inotropic effects. 3

Critical Medications to AVOID

Immediately discontinue the following medications in symptomatic patients with LVOTO: 3

• Dihydropyridine calcium channel blockers (amlodipine, nifedipine, felodipine) - Class III: Harm recommendation due to vasodilation worsening LVOT obstruction. 3
• ACE inhibitors and ARBs - potentially harmful in patients with resting or provocable LVOT obstruction. 3
• Alpha-blockers (terazosin, doxazosin) - contraindicated as they cause vasodilation precipitating hemodynamic collapse. 3
• Nitrates and hydralazine - avoid all vasodilators in obstructive HCM. 3

Use diuretics cautiously at low doses only for congestive symptoms, as aggressive diuresis worsens LVOT obstruction by decreasing preload. 3

Septal Reduction Therapy (SRT)

Refer for SRT when patients remain severely symptomatic (NYHA class III-IV) despite guideline-directed medical therapy with documented LVOT gradient ≥50 mm Hg at rest or with physiologic provocation. 1, 3

Surgical Myectomy (Preferred)

Surgical myectomy is the preferred SRT when performed by experienced operators at comprehensive HCM centers, achieving >90% relief of obstruction with perioperative mortality <1%. 3

• Mandatory for patients requiring concomitant cardiac surgery. 3
• Consider earlier myectomy in presence of severe progressive pulmonary hypertension attributable to LVOTO, left atrial enlargement with ≥1 episodes of symptomatic atrial fibrillation, poor functional capacity on treadmill testing, or children/young adults with very high resting LVOT gradients (>100 mm Hg). 3
• Perform intraoperative transesophageal echocardiogram to assess mitral valve anatomy and adequacy of septal myectomy. 1

Alcohol Septal Ablation

Alcohol septal ablation is recommended for adult patients who remain severely symptomatic despite guideline-directed medical therapy when surgery is contraindicated or risk is unacceptable due to serious comorbidities or advanced age. 3

• Use TTE or intraoperative TEE with intracoronary ultrasound-enhancing contrast injection of candidate septal perforator(s) for intraprocedural guidance. 1
• Perform TTE within 3 to 6 months after the procedure to evaluate results. 1

Do not perform SRT in asymptomatic patients with normal exercise capacity. 3

Management of Acute Hypotension in HOCM

Acute hypotension in obstructive HCM is a medical urgency requiring immediate intervention with phenylephrine (pure vasoconstrictor) as the preferred agent. 3

• Maximize preload and afterload while avoiding increases in contractility or heart rate. 3
• Add beta-blockade in combination with vasoconstrictors to dampen contractility and improve preload by prolonging diastolic filling. 3
• Never use vasodilators or inotropes like dopamine or dobutamine in acute hypotension with obstructive HCM. 3

Atrial Fibrillation Management

Prescribe oral anticoagulation with direct-acting oral anticoagulants (DOACs) as the default treatment for all patients with HCM and persistent or paroxysmal atrial fibrillation, irrespective of CHA₂DS₂-VASc score. 3

• Patients with HCM and atrial fibrillation have sufficiently increased stroke risk that anticoagulation is recommended independent of traditional risk stratification tools. 3
• Consider extended ambulatory monitoring in patients with additional risk factors for atrial fibrillation (left atrial dilatation, advanced age, NYHA class III-IV heart failure) to screen for asymptomatic paroxysmal AF. 1

Sudden Cardiac Death Risk Stratification

Assess sudden cardiac death risk as an important component of management, integrating established risk markers (family history of sudden cardiac death, unexplained syncope, nonsustained ventricular tachycardia on Holter monitoring, massive left ventricular hypertrophy ≥30 mm, abnormal blood pressure response to exercise) with individual risk tolerance. 3

• Repeat 24- to 48-hour ambulatory electrocardiographic monitoring every 1 to 2 years as part of periodic follow-up to detect ventricular tachycardia. 1
• Facilitate shared decision-making regarding implantable cardioverter-defibrillator placement based on patient's personal level of risk tolerance and specific treatment goals. 3

Surveillance and Follow-Up

Perform repeat TTE every 1 to 2 years in clinically stable patients to assess degree of myocardial hypertrophy, dynamic LVOTO, mitral regurgitation, and myocardial function. 1

• Obtain repeat TTE immediately for patients who experience a change in clinical status or new clinical event. 1
• Perform 12-lead ECG every 1 to 2 years as part of periodic follow-up. 1
• Consider exercise stress testing every 2 to 3 years when functional capacity or symptom status is uncertain. 1

Family Screening Protocol

Screen all first-degree relatives with physical examination, 12-lead ECG, and transthoracic echocardiography. 1, 2

• Screening intervals: every 12-18 months for children and adolescents, approximately every 5 years for asymptomatic adults. 1, 2
• Offer genetic testing in the index patient to facilitate identification of first-degree family members at risk for developing HCM. 1
• In genotype-positive/phenotype-negative individuals, perform serial echocardiography at periodic intervals (1-2 years in children/adolescents, 3-5 years in adults). 1
• Do not continue clinical screening in genotype-negative relatives in families with HCM. 1

Management of Comorbidities

Use beta-blockers and non-dihydropyridine calcium channel blockers as preferred antihypertensive agents in obstructive HCM. 3

• Implement lifestyle modifications and medical therapy for hypertension management. 3
• Provide counseling and comprehensive lifestyle interventions for achieving and maintaining weight loss, as obesity is present in >70% of adult HCM patients and independently associated with increased burden of left ventricular hypertrophy, more symptoms, and worse outcomes. 3
• Assess for symptoms of sleep-disordered breathing (affects 55-70% of HCM patients) and refer to sleep medicine specialist if present, as it is associated with greater symptom burden, reduced exercise capacity, and higher prevalence of atrial fibrillation and nonsustained ventricular tachycardia. 3

Exercise and Activity Recommendations

Advise avoidance of particularly strenuous activity or competitive athletics for patients with HCM. 3

• Perform exercise stress testing to determine overall exercise tolerance and detect latent exercise-provoked LVOT obstruction. 3
• For symptomatic patients without resting or provocable outflow tract gradient ≥50 mm Hg on TTE, perform exercise TTE for detection and quantification of dynamic LVOTO. 1

Common Pitfalls to Avoid

• Do not dismiss lesser degrees of wall thickening (13-14 mm) in the context of positive family history, as this may represent early disease. 2
• Do not rely solely on resting echocardiography if symptoms suggest dynamic obstruction; perform exercise echocardiography to detect exercise-induced LVOTO. 2
• Do not abruptly discontinue beta-blockers, as this can precipitate rebound tachycardia and worsening symptoms. 3
• Do not confuse heart failure evidence favoring metoprolol succinate with a specific requirement for HOCM—either metoprolol formulation is acceptable. 3
• Do not use flecainide or other Class IC antiarrhythmics for LVOT obstruction management, as they are not part of the established pharmacologic strategy. 3