What medications can be given to a patient with exertional dyspnea of cardiac origin?

Treatment of Exertional Dyspnea of Cardiac Origin

For exertional dyspnea of cardiac origin, initiate beta-blockers as first-line therapy, titrating to a resting heart rate of 50-65 bpm, with verapamil as the alternative if beta-blockers are contraindicated or not tolerated. 1

Initial Diagnostic Considerations

Before initiating therapy, determine the specific cardiac etiology:

• Hypertrophic cardiomyopathy (HCM): Look for presence of left ventricular outflow tract (LVOT) obstruction, family history, and characteristic echocardiographic findings 1
• Heart failure with preserved ejection fraction (HFpEF): Assess for LVEF >40%, elevated natriuretic peptides, and evidence of diastolic dysfunction 2, 3
• Heart failure with reduced ejection fraction (HFrEF): Evaluate for LVEF ≤35% and signs of systolic dysfunction 4

First-Line Pharmacotherapy by Cardiac Etiology

For Hypertrophic Cardiomyopathy (Obstructive or Nonobstructive)

Beta-blockers are the recommended first-line treatment for symptomatic HCM patients with dyspnea 1:

• Start with propranolol, atenolol, metoprolol, or nadolol 1
• Titrate to achieve resting heart rate <60-65 bpm, up to maximum recommended doses (propranolol up to 480 mg/day) 1
• Beta-blockers work by decreasing heart rate, prolonging diastole and relaxation, increasing passive ventricular filling, and reducing myocardial oxygen demand 1
• Use caution in patients with sinus bradycardia or severe conduction disease 1

If beta-blockers are ineffective or contraindicated, use verapamil 1:

• Start at low doses and titrate up to 480 mg/day (usually sustained-release preparation) 1
• Critical warning: Use extreme caution in patients with high gradients, advanced heart failure, severe dyspnea at rest, or systemic hypotension, as verapamil can cause pulmonary edema, cardiogenic shock, and death in these settings 1
• Verapamil is contraindicated in infants due to sudden death risk 1

For refractory symptoms, add disopyramide to beta-blockers or verapamil 1:

• Disopyramide should be combined with beta-blockers or verapamil, not used alone (Class IIa recommendation) 1
• Never use disopyramide as monotherapy in patients with atrial fibrillation, as it enhances AV conduction and increases ventricular rate 1

Diuretics for persistent dyspnea 1:

• Add oral diuretics cautiously in nonobstructive HCM when dyspnea persists despite beta-blockers or verapamil (Class IIa) 1
• Use with extreme caution in obstructive HCM to avoid hypovolemia and worsening obstruction (Class IIb) 1

For Heart Failure with Preserved Ejection Fraction (HFpEF)

SGLT2 inhibitors are the first-line disease-modifying therapy for HFpEF 2, 5, 3:

• Initiate dapagliflozin or empagliflozin early in treatment (Class 2a recommendation) 2, 3
• Dapagliflozin reduced worsening HF and cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) in DELIVER trial 2
• Empagliflozin reduced HF hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED 3
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin 2

Loop diuretics for symptom management 2, 3:

• Use at the lowest effective dose to manage fluid retention and relieve congestion 2
• For acute symptoms: Start with 20-40 mg IV furosemide (or equivalent) 2
• Titrate diuretic dose based on symptoms and volume status before adding combination diuretics 2
• Avoid excessive diuresis which may cause hypotension and worsening renal function 2

Additional disease-modifying agents 2, 3:

• Consider spironolactone (Class 2b) particularly in patients with LVEF 40-50% 2, 3
• Consider sacubitril/valsartan (Class 2b) for selected patients, especially women and those with LVEF 45-57% 2, 3

For Heart Failure with Reduced Ejection Fraction (HFrEF)

If LVEF ≤35% with sinus rhythm and resting heart rate ≥70 bpm 4:

• Consider ivabradine to reduce hospitalization risk 4
• Start at 5 mg twice daily with food, titrating to achieve resting heart rate 50-60 bpm 4
• Maximum dose is 7.5 mg twice daily 4
• Monitor for atrial fibrillation and bradycardia, which are significant risks with ivabradine 4

Medications to Avoid

The following medications are potentially harmful in cardiac dyspnea 1:

• Nifedipine and other dihydropyridine calcium channel blockers: Potentially harmful in HCM with LVOT obstruction 1
• Digitalis: Potentially harmful for dyspnea in HCM without atrial fibrillation 1
• ACE inhibitors/ARBs: Not well established and potentially harmful in HCM with resting or provocable LVOT obstruction 1
• Diltiazem or verapamil in HFpEF: Increase risk of HF worsening and hospitalization 2
• Positive inotropes (dopamine, dobutamine, norepinephrine): Potentially harmful in obstructive HCM 1

Comorbidity Management

Optimize blood pressure control to target <130/80 mmHg using appropriate antihypertensives 2, 3

Manage diabetes with preference for SGLT2 inhibitors given their additional heart failure benefits 2, 5

For concurrent atrial fibrillation: Prescribe anticoagulation based on CHA₂DS₂-VASc score 5

For concurrent COPD: Use cardioselective beta-blockers cautiously for rate control, and optimize COPD management while monitoring for drug interactions 5

Monitoring Parameters

• Assess resting heart rate at 2 weeks and adjust beta-blocker or ivabradine dosing accordingly 1, 4
• Monitor for bradycardia, especially with beta-blockers, verapamil, or ivabradine 1, 4
• Regularly assess volume status, renal function, and electrolytes, particularly with diuretics or mineralocorticoid receptor antagonists 2, 3
• Monitor cardiac rhythm regularly for development of atrial fibrillation, especially with ivabradine 4
• Assess symptoms and functional capacity to guide treatment adjustments 2, 3

Common Pitfalls

Do not treat HFpEF patients the same as HFrEF patients, as response to therapies differs significantly between these populations 2

Avoid using verapamil in HCM patients with severe symptoms and high gradients, as vasodilation can worsen obstruction and cause death 1

Do not overlook comorbidity management, which significantly impacts outcomes in cardiac dyspnea 2, 5, 3

Monitor children and adolescents on beta-blockers closely for depression, fatigue, and impaired school performance 1