New England Journal of Medicine: Volume 394, Issue 17 (April 30, 2026)

Heart failure with preserved ejection fraction (HFpEF) represents a significant clinical challenge for primary care providers, often remaining underdiagnosed due to the absence of the classic pumping failure seen in other forms of heart failure. A clinical guide published by the New England Journal of Medicine on April 30, 2026, outlines the essential strategies for identifying and managing this condition within the primary care setting.

Unlike heart failure with reduced ejection fraction, where the heart muscle is too weak to pump blood effectively, HFpEF occurs when the heart muscle becomes stiff or noncompliant. This prevents the ventricles from filling properly during the resting phase, leading to increased pressure in the heart and lungs, even though the ejection fraction—the percentage of blood leaving the heart with each contraction—remains at or above 50 percent.

Identifying HFpEF in Clinical Practice

The diagnosis of HFpEF often begins with a high index of suspicion in patients presenting with classic symptoms of heart failure, such as dyspnea on exertion, orthopnea, and peripheral edema. Because the ejection fraction is preserved, these symptoms are sometimes incorrectly attributed to pulmonary issues, obesity, or general aging.

Clinical guidelines emphasize a multi-step approach to confirmation in primary care:

• Evaluation of natriuretic peptides, such as B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP), to screen for myocardial stretch.
• Utilization of echocardiography to confirm a preserved ejection fraction and identify markers of diastolic dysfunction, such as left atrial enlargement or increased left ventricular wall thickness.
• Assessment of comorbidities that frequently coexist with HFpEF, including hypertension, type 2 diabetes, obesity, and chronic kidney disease.

The guidance notes that while biomarkers are helpful, they can be misleading; for example, BNP levels may be lower in patients with obesity, potentially leading to false negatives.

The Pillars of Management

For years, HFpEF was considered a condition with few effective treatment options beyond symptom management. However, the therapeutic landscape has shifted toward a combination of targeted pharmacotherapy and aggressive comorbidity control.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone of therapy. These medications have demonstrated a consistent ability to reduce the risk of heart failure hospitalizations and cardiovascular death across a broad range of ejection fractions, including those with preserved function.

Diuretics remain the primary tool for managing fluid overload. The goal in primary care is to maintain a state of euvolemia—balancing fluid levels to minimize edema and congestion without causing dehydration or acute kidney injury.

The management of associated conditions is equally critical to the patient’s outcome. This includes:

• Strict blood pressure control to reduce the workload on the left ventricle.
• Weight management and lifestyle interventions, particularly for patients with obesity-related HFpEF.
• Optimization of glycemic control in patients with diabetes to prevent further myocardial stiffness.

Other medications, such as mineralocorticoid receptor antagonists (MRAs) and angiotensin receptor-neprilysin inhibitors (ARNIs), may be considered on a patient-by-patient basis, particularly for those whose ejection fraction is on the lower end of the preserved spectrum.

The Role of Primary Care Coordination

Because HFpEF is a systemic syndrome rather than a localized heart problem, the primary care provider serves as the central coordinator of care. Managing the condition requires a longitudinal approach to medication titration and symptom monitoring.

Patients are encouraged to monitor their daily weights and report sudden increases, which often signal fluid accumulation before shortness of breath becomes severe. This proactive monitoring allows primary care providers to adjust diuretic dosages early, potentially preventing emergency department visits.

The ultimate goal of managing HFpEF in the primary care setting is not only the reduction of hospitalizations but the improvement of the patient’s functional status and overall quality of life.