What is the management approach for a patient with Hypertrophic Obstructive Cardiomyopathy (HOCM)?

Management of Hypertrophic Obstructive Cardiomyopathy (HOCM)

Start all symptomatic HOCM patients on nonvasodilating beta-blockers as first-line therapy, titrated to a resting heart rate of 60-65 bpm, and immediately discontinue any vasodilators (ACE inhibitors, ARBs, dihydropyridine calcium channel blockers) that worsen outflow obstruction. 1, 2

Initial Pharmacologic Management Algorithm

First-Line Therapy: Beta-Blockers

• Nonvasodilating beta-blockers are the Class I recommended initial treatment for all symptomatic HOCM patients, regardless of gradient severity 1, 2, 3
• Titrate to achieve resting heart rate of 60-65 bpm, which provides physiologic evidence of adequate beta-blockade 1, 2
• Beta-blockers reduce LVOT gradients through negative inotropic effects and prolonged diastolic filling time, alleviating dyspnea, chest pain, and improving quality of life 2, 3
• Do not declare beta-blocker failure until maximally tolerated doses are achieved with documented heart rate suppression 1

Second-Line Therapy: Non-Dihydropyridine Calcium Channel Blockers

• Switch to verapamil or diltiazem (NOT dihydropyridines like amlodipine or nifedipine) if beta-blockers are ineffective, not tolerated, or contraindicated 1, 2, 3
• Verapamil can be titrated up to 480 mg/day for symptom control 2
• Critical warning: Verapamil is potentially harmful in patients with severe dyspnea at rest, hypotension, very high resting gradients (>100 mm Hg), and all children <6 weeks of age 1, 4
• The FDA label warns that in 120 HOCM patients treated with verapamil, 3 died in pulmonary edema (all had severe LVOT obstruction and prior left ventricular dysfunction), and 8 others developed pulmonary edema and/or severe hypotension 4
• Never combine beta-blockers with non-dihydropyridine calcium channel blockers due to excessive bradycardia and AV block risk 2, 4

Third-Line Therapy: Mavacamten or Disopyramide

• For persistent NYHA class II-III symptoms despite optimal beta-blocker or calcium channel blocker therapy, add mavacamten (cardiac myosin inhibitor) as a Class I recommendation 2, 3, 5
• Mavacamten improves LVOT gradients, functional capacity, and quality of life in 30-60% of patients 3, 5
• Mandatory REMS program monitoring is required because LVEF reduction <50% occurs in 5.7-10% of patients 5
• Mavacamten is contraindicated in pregnancy due to teratogenic effects 5
• Disopyramide (with mandatory AV nodal blocking agent) is an alternative third-line option when beta-blockers and calcium channel blockers fail 1, 2, 3

Critical Medications to AVOID in HOCM

Vasodilators That Worsen Obstruction (Class III: Harm)

• Immediately discontinue dihydropyridine calcium channel blockers (amlodipine, nifedipine, felodipine) 1, 2
• Stop ACE inhibitors and ARBs in symptomatic patients with LVOT obstruction 1, 2, 3
• Avoid alpha-blockers (terazosin, doxazosin), nitrates, hydralazine, and digoxin 1, 2
• These agents promote outflow tract obstruction by reducing preload and afterload or increasing contractility 1

Diuretics: Use With Extreme Caution

• High-dose diuretics are relatively contraindicated because aggressive diuresis worsens LVOT obstruction by decreasing preload 1, 2
• Low-dose diuretics may be cautiously considered (Class 2b) for persistent dyspnea with clinical evidence of volume overload despite other guideline-directed medical therapy 1, 2

Septal Reduction Therapy (SRT)

Indications for SRT

• SRT is recommended for patients with severe dyspnea or chest pain attributable to LVOTO that interferes with everyday activity despite optimal medical therapy 2
• Eligibility requires dynamic LVOT gradient ≥50 mmHg at rest or with physiologic provocation 2
• Do not perform SRT in asymptomatic patients with normal exercise capacity 2

Surgical Myectomy vs. Alcohol Septal Ablation

• Surgical myectomy is the gold standard and preferred SRT when performed by experienced operators at comprehensive HCM centers, achieving >90% relief of obstruction with perioperative mortality <1% 2, 6
• Myectomy is mandatory for patients requiring concomitant cardiac surgery 2
• Alcohol septal ablation is recommended for adult patients when surgery is contraindicated or risk is unacceptable due to serious comorbidities or advanced age 2
• Younger patients with extreme hypertrophy are typically offered myectomy, while older patients with comorbidities are directed to alcohol septal ablation 7

Earlier SRT May Be Reasonable For:

• Severe progressive pulmonary hypertension attributable to LVOTO 2
• Left atrial enlargement with ≥1 episodes of symptomatic atrial fibrillation 2
• Poor functional capacity attributable to LVOTO on treadmill testing 2
• Children and young adults with very high resting LVOT gradients (>100 mmHg) 2

Management of Acute Hypotension in HOCM

Emergency Treatment Protocol

• Acute hypotension in obstructive HCM is a medical urgency requiring immediate intervention 2
• Phenylephrine is the preferred agent to reverse acute hypotension (pure alpha-agonist vasoconstrictor) 2, 4
• Treatment priorities: maximize preload and afterload while avoiding increases in contractility or heart rate 2
• Never use vasodilators or positive inotropes like dopamine or dobutamine in acute hypotension 2, 4
• Beta-blockade can be useful in combination with vasoconstrictors to dampen contractility and improve preload by prolonging diastolic filling 2
• The FDA label specifically states that in HOCM patients with hypotension, alpha-adrenergic agents (phenylephrine, metaraminol, methoxamine) should be used, and isoproterenol and norepinephrine should be avoided 4

Management of Comorbidities

Hypertension in HOCM Patients

• Beta-blockers and non-dihydropyridine calcium channel blockers are the preferred antihypertensive agents 2, 3
• ACE inhibitors and ARBs have uncertain benefit and are potentially harmful in patients with resting or provocable LVOT obstruction 2

Atrial Fibrillation

• Oral anticoagulation with direct-acting oral anticoagulants is recommended for all HOCM patients with persistent or paroxysmal atrial fibrillation, irrespective of CHA₂DS₂-VASc score 2, 3
• HOCM patients with atrial fibrillation have sufficiently increased stroke risk that anticoagulation is mandatory independent of traditional risk stratification 2

Obesity and Sleep-Disordered Breathing

• Obesity is present in >70% of adult HCM patients and independently associated with increased left ventricular hypertrophy, more symptoms, and worse outcomes 2, 3
• Counseling and comprehensive lifestyle interventions are recommended for weight loss, potentially lowering risk of developing LVOTO, heart failure, and atrial fibrillation 2
• Screen for sleep-disordered breathing symptoms and refer to sleep medicine specialist if present, as it affects 55-70% of HCM patients and is associated with greater symptom burden and reduced exercise capacity 2

Sudden Cardiac Death Risk Stratification

• All HOCM patients require sudden cardiac death risk stratification using major noninvasive risk markers to identify candidates for implantable cardioverter-defibrillator placement 2, 3
• Risk stratification should incorporate the patient's personal level of risk tolerance and specific treatment goals to facilitate shared decision-making 2

Common Pitfalls to Avoid

• Never prescribe dihydropyridine calcium channel blockers (amlodipine, nifedipine) for HOCM patients—this is a Class III: Harm recommendation 1, 2
• Do not combine beta-blockers with verapamil or diltiazem due to excessive bradycardia and complete heart block risk 2, 4
• Avoid declaring beta-blocker failure until maximally tolerated doses with documented heart rate suppression (<60-65 bpm) are achieved 1
• Do not use aggressive diuresis, as this worsens LVOT obstruction by decreasing preload 1, 2
• Never abruptly discontinue beta-blockers, as this can precipitate rebound tachycardia and worsening symptoms 2
• In acute hypotension, never use vasodilators or inotropes—use phenylephrine instead 2, 4