What is the approach to managing a patient with Hypertrophic Obstructive Cardiomyopathy (HOCM)?

Management of Hypertrophic Obstructive Cardiomyopathy (HOCM)

Beta-blockers are the first-line pharmacologic therapy for all symptomatic HOCM patients, titrated to a resting heart rate of 60-65 bpm, with non-dihydropyridine calcium channel blockers (verapamil or diltiazem) as second-line when beta-blockers fail or are contraindicated. 1, 2, 3

Initial Pharmacologic Management Algorithm

First-Line Therapy

• Nonvasodilating beta-blockers (metoprolol, atenolol, propranolol) should be initiated and titrated to maximum tolerated doses to achieve resting heart rate <60-65 bpm. 1, 2, 3
• Beta-blockers reduce left ventricular outflow tract (LVOT) gradients through negative inotropic effects and prolonged diastolic filling time, alleviating dyspnea, chest pain, and improving quality of life. 1, 3
• Either metoprolol tartrate (100-200 mg divided twice daily) or metoprolol succinate (50-200 mg once daily) are acceptable formulations, as guidelines do not mandate one over the other for HOCM. 2

Second-Line Therapy

• Verapamil (titrated up to 480 mg/day) or diltiazem are Class I recommended alternatives when beta-blockers are ineffective, not tolerated, or contraindicated. 1, 2
• These non-dihydropyridine calcium channel blockers improve diastolic dysfunction and reduce contractility, but must be used cautiously in patients with severe outflow tract obstruction (resting gradient >100 mmHg) due to vasodilatory effects. 1, 2
• Never combine beta-blockers with non-dihydropyridine calcium channel blockers due to increased risk of bradycardia and heart block. 2

Third-Line Therapy

• Disopyramide (combined with an AV nodal blocking agent to prevent rapid ventricular response if atrial fibrillation develops) is an alternative when beta-blockers and calcium channel blockers fail. 1, 2, 3
• Disopyramide provides strong negative inotropic effects that can abolish basal gradients and improve exercise tolerance, but requires careful QTc monitoring. 2, 4

Novel Cardiac Myosin Inhibitor

• Mavacamten is a Class I recommendation for adults with persistent NYHA class II-III symptoms despite optimal beta-blocker or calcium channel blocker therapy. 1, 2, 3
• Mavacamten improves LVOT gradients, functional capacity, and quality of life in 30-60% of patients, but requires mandatory REMS program monitoring due to risk of LVEF reduction <50%. 3, 4
• This represents a disease-modifying therapy that can produce favorable cardiac remodeling including reduction in left ventricular mass and maximum wall thickness. 5

Critical Medications to AVOID in HOCM

Absolute Contraindications

• Dihydropyridine calcium channel blockers (nifedipine, amlodipine, felodipine) are Class III: Harm recommendations as they worsen LVOT obstruction through vasodilation. 1, 2
• Alpha-blockers (terazosin, doxazosin) are contraindicated as they cause vasodilation that can precipitate hemodynamic collapse. 2
• Nitrates, hydralazine, ACE inhibitors, and ARBs should be avoided in patients with resting or provocable LVOT obstruction. 2, 4
• Digoxin increases contractility and worsens obstruction. 2

Diuretics: Use with Extreme Caution

• Diuretics should only be used at low doses for congestive symptoms, as aggressive diuresis decreases preload and worsens LVOT obstruction. 2
• In asymptomatic patients, diuretics can be used more liberally, but remain contraindicated in symptomatic patients with significant LVOT obstruction. 2

Septal Reduction Therapy (SRT)

Indications for SRT

• SRT is recommended for patients with obstructive HCM who remain severely symptomatic (NYHA class III-IV) despite guideline-directed medical therapy. 1, 2
• Eligibility criteria include: 2
  • Severe dyspnea or chest pain interfering with everyday activity despite optimal medical therapy
  • Dynamic LVOT gradient ≥50 mmHg at rest or with physiologic provocation
  • Septal thickness adequate for intervention

Surgical Myectomy vs. Alcohol Septal Ablation

• Surgical myectomy is the preferred SRT when performed by experienced operators at comprehensive HCM centers, achieving >90% relief of obstruction with perioperative mortality <1%. 1, 2

• Myectomy is mandatory for patients requiring concomitant cardiac surgery (e.g., mitral valve repair, coronary artery bypass). 2

• Earlier myectomy may be reasonable for: 2

  • Severe progressive pulmonary hypertension attributable to LVOTO
  • Left atrial enlargement with ≥1 episodes of symptomatic atrial fibrillation
  • Poor functional capacity on treadmill testing despite medical therapy
  • Children and young adults with very high resting LVOT gradients (>100 mmHg)

• 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. 1, 2

• Younger patients with extreme hypertrophy are usually offered myectomy, while older patients with comorbidities are directed to alcohol septal ablation. 6

When NOT to Perform SRT

• SRT is not recommended for asymptomatic patients with normal exercise capacity. 2
• SRT may be considered as an alternative to escalation of medical therapy only after shared decision-making including risks and benefits of all treatment options. 2

Management of Acute Hypotension in HOCM

Acute hypotension in obstructive HCM is a medical urgency requiring immediate intervention with vasoconstrictors, NOT vasodilators or inotropes. 2

Treatment Algorithm

• Phenylephrine is the preferred agent to reverse acute hypotension through pure vasoconstriction that increases afterload and preload. 2
• Beta-blockade can be useful in combination with vasoconstrictors to dampen contractility and improve preload by prolonging diastolic filling. 2
• Never use dopamine, dobutamine, or other inotropes as they increase contractility and worsen LVOT obstruction. 2
• Maximize preload with IV fluids while avoiding increases in contractility or heart rate. 2

Management of Comorbidities

Hypertension

• Beta-blockers and non-dihydropyridine calcium channel blockers are preferred antihypertensive agents in obstructive HCM. 2
• Lifestyle modifications and medical therapy for hypertension are recommended, but avoid ACE inhibitors, ARBs, and dihydropyridine calcium channel blockers in patients with LVOT obstruction. 2, 4

Obesity and Metabolic Factors

• Counseling and comprehensive lifestyle interventions are recommended for achieving and maintaining weight loss, potentially lowering risk of developing LVOTO, heart failure, and atrial fibrillation. 2
• Obesity is present in >70% of adult HCM patients and is independently associated with increased burden of left ventricular hypertrophy, more symptoms, and worse outcomes. 2, 3

Sleep-Disordered Breathing

• Assessment for symptoms of sleep-disordered breathing is recommended, with referral to sleep medicine specialist if present. 2
• Sleep-disordered breathing affects 55-70% of HCM patients and is associated with greater symptom burden, reduced exercise capacity, and higher prevalence of atrial fibrillation and nonsustained ventricular tachycardia. 2

Atrial Fibrillation Management

• Oral anticoagulation with direct-acting oral anticoagulants (or alternatively warfarin) should be considered the default treatment option for patients with HCM and persistent or paroxysmal atrial fibrillation, irrespective of CHA₂DS₂-VASc score. 1, 3
• Patients with HCM and atrial fibrillation have a sufficiently increased risk of stroke that anticoagulation is recommended independent of traditional risk stratification tools. 1

Sudden Cardiac Death Risk Stratification

• Assessing a patient's risk for sudden cardiac death is an important component of management, integrating established risk markers with tools to estimate individual risk score. 1
• Risk stratification should incorporate the patient's personal level of risk tolerance and specific treatment goals to facilitate shared decision-making regarding implantable cardioverter-defibrillator placement. 1
• Risk factors for sudden cardiac death in children carry different weights than those in adults, and pediatric risk stratification varies with age and body size. 1

Family Screening and Genetic Counseling

• Careful ascertainment of family history, counseling patients about genetic transmission, and options for genetic testing are cornerstones of care. 1
• Screening first-degree family members using genetic testing, serial imaging, or electrocardiographic surveillance should begin at any age based on patient and family history. 1
• Reported pathogenicity of detected variants should be reconfirmed every 2-3 years, and input from specialized HCM centers with genetics expertise may be valuable. 1

When to Refer to Specialized HCM Centers

Referral to multidisciplinary HCM centers is important for challenging treatment decisions, particularly when reasonable alternatives exist or when strength of recommendation is weak. 1

• Specific scenarios warranting referral include: 1, 2
  • Interpretation of genetic testing results
  • Primary prevention implantable cardioverter-defibrillator decision-making
  • HCM-specific invasive procedures (myectomy, alcohol septal ablation)
  • Consideration of mavacamten or other advanced therapies
  • Management of refractory symptoms despite optimal medical therapy

Exercise and Activity Recommendations

• Exercise stress testing is particularly helpful in determining overall exercise tolerance and for detecting latent exercise-provoked LVOT obstruction. 1
• Avoidance of particularly strenuous activity or competitive athletics is recommended for patients with HCM. 1
• Hydration and avoidance of environmental situations where vasodilation may occur are important in patients with resting or provocable LVOT obstruction. 1