What is the optimal medical treatment for heart failure with preserved ejection fraction (HFpEF) and pulmonary hypertension (PH)?

From the Guidelines

The optimal medical treatment for heart failure with preserved ejection fraction (HFpEF) complicated by pulmonary hypertension involves a multifaceted approach targeting both conditions, with diuretics, SGLT2 inhibitors, and careful management of comorbidities being key components. The treatment should focus on managing volume overload and reducing pulmonary congestion, with diuretics such as furosemide (20-80mg daily) or torsemide (10-20mg daily) being the cornerstone of therapy 1. SGLT2 inhibitors like empagliflozin (10mg daily) or dapagliflozin (10mg daily) have shown benefit in HFpEF by reducing hospitalizations and cardiovascular death, as highlighted in recent guidelines and reviews 1. For patients with elevated blood pressure, ACE inhibitors (like lisinopril 5-40mg daily), ARBs (such as valsartan 40-320mg daily), or the ARNi sacubitril/valsartan (24/26mg to 97/103mg twice daily) should be considered, taking into account the patient's specific clinical profile and comorbidities 1. Beta-blockers may be used cautiously, particularly if the patient has atrial fibrillation or coronary artery disease, but their role in HFpEF is more nuanced and should be guided by individual patient needs and responses 1. For the pulmonary hypertension component, phosphodiesterase-5 inhibitors like sildenafil (20mg three times daily) may be considered in selected patients, though evidence is limited and such treatment should be approached with caution and careful monitoring 1. Aggressive management of comorbidities is essential, including treatment of hypertension, diabetes, obesity, and sleep apnea, as these conditions can significantly impact the prognosis and quality of life of patients with HFpEF 1. Regular physical activity should be encouraged as tolerated, as it can improve functional capacity and reduce symptoms in patients with HFpEF. This approach addresses the complex pathophysiology of HFpEF with pulmonary hypertension, which involves left ventricular diastolic dysfunction, increased left atrial pressure, and subsequent pulmonary vascular remodeling leading to pulmonary hypertension. Given the evolving nature of evidence and guidelines, it's crucial to stay updated with the latest recommendations, such as those from the European Heart Journal and other reputable sources 1, to provide the best possible care for patients with HFpEF and pulmonary hypertension.

From the FDA Drug Label

Sildenafil is an inhibitor of cGMP specific phosphodiesterase type-5 (PDE-5) in the smooth muscle of the pulmonary vasculature, where PDE-5 is responsible for degradation of cGMP. In patients with PAH, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation.

The optimal medical treatment for preserved ejection fraction heart failure with pulmonary hypertension may include sildenafil, as it can lead to vasodilation of the pulmonary vascular bed. However, the provided drug label does not explicitly address the treatment of preserved ejection fraction heart failure with pulmonary hypertension, only pulmonary arterial hypertension (PAH) 2.

From the Research

Optimal Medical Treatment for Preserved Ejection Fraction Heart Failure with Pulmonary Hypertension

• The development of pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a significant contributor to clinical worsening and increased mortality 3.
• PH becomes a relevant clinical phenotype in approximately 50% of patients with HFpEF, representing a challenge in clinical follow-up and management 3.
• Current treatment strategies for PH in HFpEF focus on managing symptoms and comorbidities, with no approved treatments specifically indicated for HFpEF 4.
• Therapies targeting the pulmonary vasculature, such as phosphodiesterase inhibitors, prostacyclin analogs, endothelin receptor antagonists, and soluble guanylate cyclase stimulators, have shown inconsistent results in improving hemodynamics or functional outcomes in PH-HFpEF 5.
• Emerging evidence suggests that newer HF therapies, such as sodium-glucose transporter 2 inhibitors and angiotensin-receptor-neprilysin inhibitors, may improve hemodynamics and quality of life in patients with PH-HFpEF 5.
• Robust phenotyping of PH and right ventricular function may hold promise for therapeutic strategies in patients with PH-HFpEF 5.

Pathophysiology and Diagnosis

• HFpEF is characterized by abnormal systolic and diastolic functions, left atrial enlargement, and pulmonary hypertension, which can lead to right ventricular hypertrophy, enlargement, and systolic dysfunction 6.
• Diagnosis of HFpEF relies on signs and symptoms of heart failure, preserved ejection fraction, and detection of diastolic function abnormalities based on echocardiographic findings and abnormally elevated natriuretic peptide levels or invasive measurements of wedge pressure at rest or with exercise 6.

Treatment Challenges

• The lack of effective medical therapy for PH in HFpEF remains a significant challenge, with limited evidence to support the use of pulmonary vasculature-targeting therapies in PH-HFpEF 5.
• The mainstay of therapy remains the treatment of the underlying HFpEF condition, with a focus on managing symptoms and comorbidities 5.