What are the management options for Obstructive Hypertrophic Cardiomyopathy (OHCM) symptoms?

Management of Obstructive Hypertrophic Cardiomyopathy (OHCM) Symptoms

Start with nonvasodilating beta-blockers (e.g., metoprolol, propranolol) titrated to a resting heart rate of 60-65 bpm as first-line therapy for all symptomatic OHCM patients. 1, 2

Pharmacological Management Algorithm

First-Line Therapy: Beta-Blockers

• Nonvasodilating beta-blockers are the Class I recommended initial treatment for symptomatic OHCM, regardless of gradient severity 1, 2
• Titrate to resting heart rate of 60-65 bpm or maximally tolerated doses 1, 2
• Beta-blockers reduce LVOT gradients during exercise (not at rest), alleviate dyspnea, and improve quality of life 2, 3
• Common side effects include bradycardia and hypotension 4

Second-Line Therapy: Calcium Channel Blockers

• If beta-blockers are ineffective or not tolerated, substitute with non-dihydropyridine calcium channel blockers (verapamil or diltiazem) 1, 2
• Verapamil can be titrated up to 480 mg/day for symptom control 5
• Critical warning: Verapamil is potentially harmful in patients with severe dyspnea at rest, hypotension, very high resting gradients (>100 mmHg), and all children <6 weeks of age 1
• The FDA label warns that verapamil has negative inotropic effects and should be avoided in severe left ventricular dysfunction 6

Third-Line Therapy: Advanced Options

For patients with persistent symptoms despite beta-blockers or calcium channel blockers, three options exist: 1

1. Mavacamten (cardiac myosin inhibitor) - Class I recommendation for adults with NYHA class II-III symptoms 1, 2

   • Improves LVOT gradients, functional capacity, and quality of life in 30-60% of patients 2
   • Requires mandatory REMS program monitoring due to risk of LVEF reduction <50% 2

2. Disopyramide (in combination with AV nodal blocking agent) 1, 5

   • Most effective at lowering resting gradients in head-to-head comparisons 3
   • Vagolytic side effects can be mitigated with pyridostigmine 3

3. Septal Reduction Therapy (SRT) - proceed to invasive management algorithm below 1

Critical Medications to AVOID

Discontinue all vasodilators immediately in symptomatic OHCM patients: 1, 5, 2

• Dihydropyridine calcium channel blockers (amlodipine, nifedipine, felodipine) - Class III: Harm recommendation 5
• ACE inhibitors and ARBs - worsen LVOT obstruction 1, 5
• Alpha-blockers (terazosin, doxazosin) - can precipitate hemodynamic collapse 5
• Digoxin - worsens dynamic obstruction 1
• Nitrates and hydralazine 5

Diuretics: Use With Extreme Caution

• Low-dose oral diuretics may be considered cautiously for persistent dyspnea with volume overload despite other GDMT 1, 5
• Aggressive diuresis worsens LVOT obstruction by decreasing preload 5

Invasive Management: Septal Reduction Therapy (SRT)

Eligibility Criteria for SRT

SRT is recommended for patients meeting ALL of the following: 1, 5

• Clinical: Severe dyspnea or chest pain (NYHA class III-IV) attributable to LVOTO that interferes with everyday activity despite optimal medical therapy 1, 5
• Hemodynamic: Dynamic LVOT gradient ≥50 mmHg at rest or with physiologic provocation 1, 5
• Anatomic: Sufficient anterior septal thickness to perform procedure safely 1

SRT Options: Surgical Myectomy vs. Alcohol Septal Ablation

Surgical myectomy is the preferred SRT approach - Class I recommendation 1, 5

• Achieves >90-95% clinical success with <1% mortality at experienced HCM centers 1, 5
• Mandatory for patients requiring concomitant cardiac surgery (multivessel CAD, valvular aortic stenosis, intrinsic mitral valve disease, anomalous papillary muscle, markedly elongated anterior mitral leaflet) 1, 5
• Long-term survival similar to age-matched general population 1
• Recurrent outflow tract obstruction is rare 1

Alcohol septal ablation - Class I recommendation for specific populations 1, 5

• Reserved for adult patients when surgery is contraindicated or risk is unacceptable due to serious comorbidities or advanced age 1, 5
• Also achieves <1% procedural mortality at experienced centers 1

Earlier (NYHA Class II) Myectomy May Be Reasonable

Consider earlier surgical myectomy at comprehensive HCM centers in presence of: 1, 5

• Severe and progressive pulmonary hypertension attributable to LVOTO or associated mitral regurgitation 1, 5
• Left atrial enlargement with ≥1 episodes of symptomatic atrial fibrillation 1, 5
• Poor functional capacity attributable to LVOTO on treadmill exercise testing 1, 5
• Children and young adults with very high resting LVOT gradients (>100 mmHg) 1, 5

SRT as Alternative to Medical Escalation

• SRT may be considered as an alternative to escalation of medical therapy after shared decision-making including risks and benefits of all treatment options 1, 5
• SRT is NOT recommended for asymptomatic patients with normal exercise capacity 1, 5

Mitral Valve Replacement

• Mitral valve replacement should NOT be performed for the sole purpose of relieving LVOTO in symptomatic obstructive HCM patients 1

Management of Acute Hypotension in OHCM

Acute hypotension in obstructive HCM is a medical urgency requiring immediate intervention: 5

1. Maximize preload with intravenous fluids first 1, 5
2. If fluids fail, use intravenous phenylephrine (pure vasoconstrictor without inotropic activity) - Class I recommendation 1, 5
3. Beta-blockade can be added in combination with vasoconstrictors to dampen contractility and prolong diastolic filling 5
4. NEVER use vasodilators or inotropes (dopamine, dobutamine) - these worsen obstruction 5

Common Pitfalls to Avoid

• Do not confuse dihydropyridine with non-dihydropyridine calcium channel blockers - only verapamil and diltiazem are safe; amlodipine and nifedipine are harmful 5
• Do not combine beta-blockers with non-dihydropyridine calcium channel blockers due to increased risk of bradycardia and heart block 5
• Do not abruptly discontinue beta-blockers - can precipitate rebound tachycardia and worsening symptoms 5
• Do not use verapamil in patients with severe symptoms at rest, hypotension, or very high resting gradients (>100 mmHg) - the FDA label specifically warns about pulmonary edema risk in OHCM patients with severe left ventricular outflow obstruction 6
• Do not perform SRT in asymptomatic patients - it provides no benefit 1, 5
• All SRT procedures must be performed at experienced HCM centers with demonstrated excellence in clinical outcomes 1