How is beta blocker (beta-adrenergic blocking agent) therapy administered in patients with obstructive gradients, such as those with hypertrophic obstructive cardiomyopathy (HOCM)?

Beta-Blocker Treatment in Patients with Obstructive Gradients

Nonvasodilating beta-blockers, titrated to effectiveness or maximally tolerated doses, are the first-line treatment for patients with obstructive hypertrophic cardiomyopathy (HCM) and symptoms attributable to left ventricular outflow tract obstruction (LVOTO). 1

First-Line Therapy: Beta-Blockers

Beta-blockers are the mainstay of pharmacologic therapy for patients with obstructive gradients due to their:

• Negative inotropic effects that reduce contractility and outflow obstruction
• Ability to attenuate adrenergic-induced tachycardia
• Prolongation of diastolic filling period, improving ventricular filling
• Reduction in myocardial oxygen demand

Administration and Dosing

• Start with low doses and titrate upward
• Target a resting heart rate of 50-60 beats per minute 1, 2
• Continue titration until:
  • Symptoms improve
  • Maximum tolerated dose is reached
  • Evidence of physiologic beta-blockade is observed (suppressed resting heart rate) 1

Evidence of Effectiveness

Recent research shows that beta-blockers can effectively prevent exercise-induced LVOT obstruction. In one study, treatment with nadolol or bisoprolol reduced post-exercise LVOT gradients from 87 ± 29 mmHg to 36 ± 22 mmHg, with complete abolition of significant obstruction in 52% of patients 3.

Second-Line Therapy: Non-dihydropyridine Calcium Channel Blockers

For patients who do not respond to beta-blockers or cannot tolerate them:

• Verapamil (starting at low doses and titrating up to 480 mg/day) 1
• Diltiazem (alternative to verapamil) 1

Important Cautions with Calcium Channel Blockers

• Verapamil is potentially harmful in patients with:
  • Severe dyspnea at rest
  • Hypotension
  • Very high resting gradients (>100 mmHg)
  • Children <6 weeks of age 1, 4
• Use with caution in patients with elevated pulmonary arterial pressure and marked outflow obstruction 1
• Monitor for hypotension as vasodilatory effects may worsen obstruction 1

Third-Line Therapy for Persistent Symptoms

For patients with persistent symptoms despite beta-blockers or calcium channel blockers:

1. Add disopyramide in combination with beta-blockers or calcium channel blockers 1

   • Monitor for QTc prolongation
   • Use with caution with other QT-prolonging medications

2. Consider myosin inhibitors in adult patients (recent addition to guidelines) 1

3. Consider septal reduction therapy (SRT) at experienced centers for refractory symptoms 1

Management of Acute Situations

For patients with obstructive HCM and acute hypotension who don't respond to fluid administration:

• Intravenous phenylephrine or other vasoconstrictors without inotropic activity, alone or combined with beta-blockers 1

Medications to Avoid or Use with Caution

• Avoid dihydropyridine calcium channel blockers (e.g., nifedipine) as they may aggravate outflow obstruction 1
• Discontinue vasodilators (ACE inhibitors, ARBs) as they can worsen symptoms caused by dynamic outflow tract obstruction 1
• Use diuretics cautiously and only at low doses in patients with volume overload and high left-sided filling pressures 1
• Avoid combination of verapamil with beta-blockers unless carefully monitored due to risk of high-grade atrioventricular block 1, 4

Special Considerations

• In children and adolescents, beta-blockers should be monitored for side effects including depression, fatigue, or impaired scholastic performance 1
• The most recent evidence suggests that newer myosin inhibitors like aficamten may provide superior symptom relief compared to traditional beta-blockers like metoprolol 5, but more research is needed before changing first-line recommendations

Treatment Algorithm

1. Start with nonvasodilating beta-blockers (propranolol, metoprolol, nadolol, atenolol)

   • Titrate to heart rate 50-60 bpm or maximum tolerated dose
   • Assess symptom response

2. If ineffective or not tolerated → Switch to verapamil or diltiazem

   • Start low and titrate up (verapamil up to 480 mg/day)
   • Avoid in patients with severe obstruction, hypotension, or high resting gradients

3. If symptoms persist → Add disopyramide OR consider myosin inhibitors (adults)

   • Monitor for QT prolongation with disopyramide

4. If medical therapy fails → Refer for septal reduction therapy

   • Surgical myectomy or alcohol septal ablation at experienced centers

This approach has been shown to provide meaningful symptom relief with low mortality rates in patients with obstructive HCM 6.