What is the medical therapy for heart failure with preserved ejection fraction (HFpEF) or diastolic dysfunction?

From the Guidelines

Medical therapy for diastolic heart failure should prioritize symptom management, treating underlying causes, and preventing complications, with a focus on diuretics, blood pressure control, and rate control in patients with atrial fibrillation, as evidenced by the most recent guidelines 1. The cornerstone treatments include diuretics like furosemide (20-80mg daily) or hydrochlorothiazide (12.5-25mg daily) to reduce fluid overload and relieve symptoms of congestion.

• Blood pressure control is essential, with ACE inhibitors such as lisinopril (10-40mg daily) or ARBs like valsartan (80-320mg daily) recommended for patients with hypertension.
• Beta-blockers including metoprolol succinate (25-200mg daily) or carvedilol (3.125-25mg twice daily) help control heart rate and improve ventricular filling.
• For patients with atrial fibrillation, rate control with beta-blockers or calcium channel blockers like diltiazem (120-360mg daily) is important, along with anticoagulation therapy using warfarin or direct oral anticoagulants to prevent stroke, as suggested by recent studies 1. However, a recent study found that digoxin may be a viable alternative to beta blockers for rate control in patients with atrial fibrillation and heart failure with preserved ejection fraction, with similar heart rate reduction and improved quality of life outcomes 1. Mineralocorticoid receptor antagonists such as spironolactone (25-50mg daily) may reduce hospitalization risk.
• Treatment should also address comorbidities like diabetes, obesity, and sleep apnea.
• Unlike systolic heart failure, SGLT2 inhibitors have shown promise in reducing composite of cardiovascular death or HF hospitalizations in patients with HFpEF, as demonstrated by recent randomized controlled trials 1. Regular monitoring of renal function, electrolytes, and symptoms is necessary to adjust medications appropriately. These treatments work by reducing cardiac workload, improving ventricular relaxation, and preventing the progressive remodeling that worsens diastolic dysfunction. The management of HFpEF has evolved in recent years, with updated clinical practice guidelines emphasizing the importance of symptom improvement, reducing congestion, and treating cardiovascular and non-cardiovascular comorbidities 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

Indications and usage 1.1 Heart Failure Spironolactone tablets are indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure.

The FDA drug label does not answer the question about medical therapy for diastolic heart failure. The label only mentions heart failure with reduced ejection fraction, but does not specifically address diastolic heart failure. 2

From the Research

Medical Therapy for Diastolic Heart Failure

• The diagnosis of diastolic heart failure (DHF) can be made when a patient has both symptoms and signs on physical exam of congestive heart failure (CHF), and normal left ventricular volume and ejection fraction 3.
• Treatment should be targeted at symptoms, causal clinical disease, and underlying basic mechanisms, including symptom-targeted therapy, disease-targeted therapy, and mechanism-targeted therapy 3.
• Symptom-targeted therapy includes decreasing pulmonary venous pressure using diuretics and long-acting nitrates, maintaining atrial contraction and atrial ventricular synchrony, reducing heart rate using beta-adrenergic blockers and calcium channel blockers, and increasing exercise tolerance by reducing exercise-induced increases in blood pressure and heart rate using angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, and calcium channel blockers 3.

Treatment Options

• The European Society of Cardiology specifies the type of therapy in diastolic HF based on: angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, non-dihydropyridine calcium channel blockers, diuretics 4.
• Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts, but there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and ARB as well as nitric oxide donors can be beneficial 5.
• Treatment of the underlying disease is currently the most important therapeutic approach, and treatments are aimed more towards associated conditions, such as hypertension, rather than the underlying pathophysiology 6.

Specific Therapies

• The ACE inhibitor lisinopril has been shown to be effective in reducing the risk of major clinical events in patients with heart failure, and is at least as effective and as well tolerated as other members of the ACE inhibitor class for the treatment of congestive heart failure 7.
• High doses of lisinopril were more effective than low doses in reducing the risk of all-cause mortality, death or hospitalisation for any reason, and hospitalisations for heart failure 7.