Heart Failure With Preserved Ejection FractionEdit

Heart Failure With Preserved Ejection Fraction (Heart Failure With Preserved Ejection Fraction) is a form of heart failure in which patients experience typical symptoms and signs of heart failure despite a left ventricular ejection fraction in the normal or near-normal range. It is a sizable and growing portion of the heart failure population, often linked to aging, obesity, hypertension, diabetes, and atrial fibrillation. Rather than a single disease, HFpEF is increasingly understood as a syndrome with multiple interacting pathways that drive symptoms, hospitalizations, and adverse outcomes.

HFpEF traditionally centers on problems with the heart muscle relaxing between beats, leading to poor filling and elevated filling pressures. But the full picture also includes abnormalities in the arteries, the coronary microcirculation, the right ventricle, and systemic organs. Because of this complexity, patients with HFpEF present with a wide range of clinical phenotypes that reflect different dominant mechanisms, rather than a one-size-fits-all pathology. This has implications for diagnosis, treatment, and prognosis, and it underpins ongoing debates about the best ways to classify and manage the condition.

Pathophysiology and Phenotypes

HFpEF arises from an interplay between structural heart changes and systemic comorbidities. Key elements include stiffening of the left ventricle, altered myocardial relaxation, and increased ventricular-arterial coupling, which together raise filling pressures during activity. Myocardial fibrosis, microvascular dysfunction, and abnormal calcium handling contribute to diastolic dysfunction, while obesity, hypertension, and metabolic disease amplify these processes. Atrial remodeling and atrial fibrillation frequently accompany HFpEF and can worsen symptoms and hospitalization risk. The right heart and pulmonary circulation may become affected as filling pressures rise.

The syndrome is best understood as comprising several phenotypes, each with its own dominant drivers. Common themes include obesity-related HFpEF, hypertensive heart disease–related HFpEF, diabetes-associated HFpEF, and AF-associated HFpEF, among others. Recognizing these phenotypes helps explain why a single treatment approach may not work equally well for all patients. Related concepts include diastolic dysfunction and the broader notion of ventricular-arterial coupling, as well as systemic factors such as hypertension and obesity that shape the disease course. Researchers also emphasize the role of comorbidity-driven systemic inflammation and endothelial dysfunction in many HFpEF patients.

Clinical Features and Diagnosis

Patients with HFpEF most often report exertional dyspnea, fatigue, and reduced exercise tolerance. Peripheral edema and other signs of congestion may appear as the disease progresses, but the preserved ejection fraction means the heart’s pumping function on standard measurements can appear relatively intact. Because symptoms can overlap with other cardiovascular and noncardiovascular conditions, clinicians rely on a combination of history, physical examination, imaging, and laboratory data.

Diagnosis generally involves confirming heart failure symptoms and signs and demonstrating preserved left ventricular systolic function. The standard measure is the left ventricular ejection fraction (often reported as an EF near or above 50%). Diagnostic workups commonly include echocardiography to assess diastolic function and filling pressures, biomarkers such as natriuretic peptides, and evaluation for comorbidities. In some cases, noninvasive stress testing or invasive hemodynamic assessment may be used to unmask filling abnormalities during exercise. The goal is to differentiate HFpEF from other causes of dyspnea and from HF with reduced ejection fraction and mildly reduced ejection fraction.

Other important considerations include the presence of atrial fibrillation, systemic hypertension, obesity, diabetes, chronic kidney disease, and vascular stiffness, all of which can influence symptoms and prognosis. For readers and clinicians, it is useful to think of HFpEF as a spectrum of disease states rather than a single uniform condition, with diverse implications for management. See atrial fibrillation and cardiorenal syndrome as related concepts in this context.

Management

Management of HFpEF emphasizes symptom relief, control of comorbidities, and prevention of hospitalizations, as no therapy has proven universal mortality benefit across all patients with HFpEF. A combination of lifestyle measures, pharmacotherapy targeted at comorbid conditions, and, when appropriate, device or procedural interventions forms the cornerstone of care.

Lifestyle and risk factor modification

Regular aerobic and resistance exercise improves functional capacity and quality of life for many HFpEF patients, with benefits that extend beyond the heart. See exercise and related guidelines for structured programs.
Weight management is particularly relevant in obesity-related HFpEF, and weight loss strategies may improve exercise tolerance and symptoms.
Aggressive management of hypertension reduces afterload and can slow progression of diastolic dysfunction.
Smoking cessation and adequate treatment of sleep-disordered breathing are important components of comprehensive care.
Management of diabetes and lipid disorders aligns with general cardiovascular risk reduction, though these therapies have nuanced effects within HFpEF.

Pharmacologic therapy

Diuretics are used to relieve congestive symptoms and edema but do not reliably improve long-term survival; they address a key symptom cluster rather than the disease’s root driver.
SGLT2 inhibitors have emerged as a meaningful advance in HFpEF. Trials such as EMPEROR-Preserved and DELIVER demonstrated reductions in heart-failure–related hospitalizations and improvements in quality of life in many patients with HFpEF, supporting their use as part of standard management in appropriate patients. See sodium-glucose cotransporter 2 inhibitors, empagliflozin, and dapagliflozin.
ARNI therapy (sacubitril/valsartan) has a more nuanced history in HFpEF. The primary composite outcome often did not reach statistical significance in the overall HFpEF population, though some subgroups suggested potential benefit. See PARAGON-HF for details.
Mineralocorticoid receptor antagonists (MRAs) have shown mixed results; one pivotal trial raised questions about regional differences, and subsequent analyses emphasize cautious patient selection. See TOPCAT for background on this therapy in HFpEF.
Other standard heart-failure drugs such as certain beta-blockers or ACE inhibitors are used for comorbid conditions (e.g., ischaemia, hypertension) but have not demonstrated uniform mortality benefits specifically for the HFpEF population as a whole. Therapy is often individualized based on coexisting diseases and patient symptoms.

Device and interventional therapy

Device therapy is less established in HFpEF than in HFrEF, but management of coexisting rhythm disorders and conduction abnormalities can influence outcomes. Atrial fibrillation management, rhythm control strategies, and, where appropriate, rhythm-preserving interventions may improve functional status. See atrial fibrillation and cardiac rhythm management for related topics. In select cases, careful consideration of advanced therapies and participation in clinical trials may be appropriate.

Prognosis and Epidemiology

HFpEF is common among older adults and is closely linked to the same cardiovascular risk factors that drive other forms of heart disease—age, hypertension, obesity, and diabetes. The prognosis is serious, with frequent hospitalizations and substantial morbidity, and mortality risk is nontrivial, though actual outcomes vary markedly across phenotypes and comorbidity clusters. Hospitalization rates tend to be high, reflecting the burden of symptoms, volume overload, and comorbidity management challenges. The heterogeneity of HFpEF means that prognosis is often more closely tied to the burden and control of comorbid conditions than to a single cardiac measurement.

Controversies and Debates

Classification and scope: HFpEF is increasingly viewed as a syndrome with multiple phenotypes rather than a single disease entity. This has led to debates about whether LVEF thresholds alone adequately define HFpEF or if phenotype-driven criteria are needed to guide therapy. See discussions around diastolic dysfunction and left ventricular ejection fraction.
Treatment targets: A central controversy is whether therapies should focus on diastolic abnormalities, vascular stiffness, myocardial fibrosis, metabolic dysregulation, or a combination of these factors. The varying success of different pharmacologic classes across trials highlights this issue.
Role of SGLT2 inhibitors: The consistency of benefits across diverse HFpEF populations has been welcomed, but questions remain about which subgroups derive the most advantage and how best to integrate these agents with lifestyle and comorbidity management. See SGLT2 inhibitors and the trials EMPEROR-Preserved and DELIVER.
Use of ARNI and MRAs: While some patients may benefit from ARNI therapy or MRAs, not all trials have shown clear, uniform mortality benefits for HFpEF. Subgroup analyses and regional results have fueled ongoing discussion about patient selection and trial design. See PARAGON-HF and TOPCAT.
Focus on prevention vs treatment: Critics argue that upstream management of obesity, diabetes, and hypertension should take precedence, given the syndrome’s strong ties to systemic comorbidity. Proponents of a broader prevention approach emphasize the importance of integrated risk-factor control to reduce HFpEF incidence.