Heart failure with preserved ejection fraction (HFpEF, ) is a form of heart failure in which the ejection fraction – the percentage of the volume of blood ejected from the left ventricle with each heartbeat divided by the volume of blood when the left ventricle is maximally filled – is normal, defined as greater than 50%; this may be measured by multiple methods such as echocardiography – commonly used – cardiac magnetic resonance (CMR), which is the clinical "gold standard", nuclear scanning (MUGA), or, rarely in contemporary practice, by cardiac catheterization. Approximately half of people with heart failure have preserved ejection fraction, while the other half have heart failure with reduced ejection fraction (HFrEF).
Historically, early descriptions of HFpEF were based primarily on the presence of heart failure symptoms with preserved ejection fraction, often without systematic exclusion of alternative cardiac conditions. Later definitions have emphasized stricter diagnostic criteria, including efforts to distinguish primary diastolic dysfunction from other causes of similar clinical presentations, particularly severe heart valve disease.
Risk factors for HFpEF include hypertension, hyperlipidemia, diabetes, smoking, and obstructive sleep apnea. Those with HFpEF have a higher prevalence of obesity, type 2 diabetes, hypertension, atrial fibrillation and chronic kidney disease than those with heart failure with reduced ejection fraction. The prevalence of HFpEF is expected to increase as more people develop obesity and other medical co-morbidities and risk factors such as hypertension in the future.
Adjusted for age, sex, and cause of heart failure, the mortality due to HFpEF is less than that of heart failure with reduced ejection fraction. The mortality is 15% at 1 year and 75% 5–10 years after a hospitalization for heart failure.
HFpEF is characterized by diastolic dysfunction: there is an increase in the stiffness of the left ventricle, which causes a decrease in left ventricular relaxation during diastole, with resultant increased pressure and/or impaired filling. There is an increased risk for atrial fibrillation and pulmonary hypertension.
As of 2025, no medical treatment has been proven to reduce mortality in HFpEF; however, some medications improve mortality in patients with HFpEF and obesity. Other medications reduce hospitalizations due to HFpEF and improve symptoms.
There is controversy regarding the relationship between diastolic heart failure and HFpEF.
Signs and symptoms Clinical manifestations of HFpEF are similar to those observed in HFrEF and include shortness of breath including exercise induced dyspnea, paroxysmal nocturnal dyspnea and orthopnea, exercise intolerance, fatigue, elevated jugular venous pressure, and edema.
Patients with HFpEF poorly tolerate stress, particularly hemodynamic alterations of ventricular loading or increased diastolic pressures. In many patients with HFpEF, symptoms are predominantly characterized by exertional dyspnea related to increases in filling pressures during stress, rather than by primary fluid accumulation. Often there is a more dramatic elevation in systolic blood pressure in HFpEF than is typical of HFrEF.
Risk factors Diverse mechanisms contribute to the development of HFpEF, many of which are under-investigated and remain obscure. Despite this, there are clear risk factors that contribute to the development of HFpEF.
Hypertension, obesity, metabolic syndrome, diabetes and sedentary lifestyle have been identified as important risk factors for diverse types of heart disease including HFpEF.
Hypertension Conditions, such as hypertension, that encourage increased left ventricular afterload can lead to structural changes in the heart on a gross, as well as a microscopic level. It is thought that increased pressure, in concert with a pro-inflammatory state (insulin resistance, obesity), encourage ventricular stiffening and remodeling that lead to poor cardiac output seen in HFpEF. There changes are a result of left ventricular muscle hypertrophy caused by the high pressure, leading to the left ventricle becoming stiff. However the role of the "hypertensive heart disease" as a direct cause of heart failure with preserved ejection fraction remains a matter of debate. Some authors have noted that the link between hypertensive remodeling and the development of clinically overt heart failure has not been consistently demonstrated in longitudinal studies, suggesting that this relationship may reflect an association rather than a direct causal pathway.
A similar condition of increased afterload is exemplified by aortic stenosis. Aortic stenosis (narrowing of the aortic valve, which separates the left ventricle from the aorta) may cause the ventricular muscle to be hypertrophied, stiff, as a result of the increased pressure needed to pump across a narrowed valve. This can lead to HFpEF. In this setting, impaired diastolic function is primarily related to the increased afterload imposed by the valvular obstruction rather than to intrinsic myocardial disease. Improvement in diastolic function following relief of the obstruction has been documented, suggesting that the observed abnormalities are largely dependent on loading conditions rather than reflecting a primary cardiomyopathic process. In this setting, diastolic dysfunction is primarily driven by the markedly increased afterload imposed by the valvular obstruction, rather than by intrinsic stiffness of the hypertrophied myocardium.
Ischemia Ischemia, or inadequate oxygenation of the heart muscle (myocardium), is observed in a high proportion of HFpEF patients. This ischemia may be secondary to coronary artery disease, or a result of the previously described changes in microvasculature. Ischemia can result in impaired relaxation of the heart; when myocytes fail to relax appropriately, myosin cross bridges remain intact and generate tension throughout diastole and thus increase stress on the heart. This is termed partial persistent systole. Ischemia may manifest in distinct ways, either as a result of increasing tissue oxygen demand, or diminished ability of the heart to supply oxygen to the tissue. The former is the result of stress, such as exercise, while the latter is the result of reduced coronary flow.
Aging Cardiac senescence, or cellular deterioration that occurs as part of normal aging, closely resembles the manifestations of HFpEF. Specifically, loss of cardiac reserve, diminished vascular compliance, and diastolic dysfunction are characteristic of both processes. It has been suggestedLam, C. S., Donal, E., Kraigher‐Krainer, E., & Vasan, R. S. (2011). Epidemiology and clinical course of heart failure with preserved ejection fraction. European journal of heart failure, 13(1), 18-28. that HFpEF merely represents an acceleration of a normal aging process.
Senile systemic amyloidosis, resulting from accumulation of aggregated wild-type transthyretin as part of the degenerative aging process, is emerging as an important and underdiagnosed contributor to HFpEF with age.
Menopause The decline in estrogen levels that occurs with menopause has been hypothesized to contribute to the increase in HFpEF observed amongst post-menopausal women. Animal studies show that even at a young age, a decline in estrogen leads to changes in expression of fibrosis related genes in the heart.
Pathophysiology
Gross structural abnormalities Structural changes that occur with HFpEF are often radically different from those associated with heart failure with reduced ejection fraction (HFrEF). Many patients experience increased thickening of the ventricular wall in comparison to chamber size, termed concentric hypertrophy. This leads to increased left ventricular mass and is typically accompanied by a normal, or slightly reduced, end diastolic filling volume. Conversely, HFrEF is typically associated with eccentric hypertrophy, characterized by an increase in cardiac chamber size without an accompanying increase in wall thickness. This leads to a corresponding increase in left ventricular end diastolic volume.However, the presence of concentric hypertrophy is not specific to HFpEF and is frequently observed in individuals with hypertension without clinical evidence of heart failure, epidemiological association does not necessarily imply a direct causal relationship, particularly as most studies have been conducted in populations with multiple coexisting cardiovascular conditions rather than in patients with isolated hypertension. In such patients, elevated filling pressures are not consistently present, indicating that structural remodeling alone may be insufficient to explain the development of heart failure symptoms.
In the setting of acute decompensation with preserved ejection fraction, several studies have reported a frequent coexistence of alternative cardiac conditions, such as severe valvular disease, recapillary pulmonary hypertension or cardiomyopathies, which may represent important drivers of the clinical presentation.
Cellular abnormalities Cellular changes generally underlie alterations in cardiac structure. In HFpEF cardiomyocytes have been demonstrated to show increased diameter without an increase in length; this is consistent with observed concentric ventricular hypertrophy and increased left ventricular mass. HFrEF cardiomyocytes exhibit the opposite morphology; increased length without increased cellular diameter. This too is consistent with eccentric hypertrophy seen in this condition.
Changes in the extracellular environment are of significant importance in heart disease. Particularly, regulation of genes that alter fibrosis contribute to the development and progression of HFrEF. This regulation is dynamic and involves changes in fibrillar collagens through increased deposition as well as inhibition of enzymes that break down extracellular matrix components (matrix metalloproteinases, collagenases). While early stage HFrEF is associated with a significant disruption of extracellular matrix proteins initially, as it progresses fibrotic replacement of myocardium may occur, leading to scarring and increased interstitial collagen. Fibrotic changes in HFpEF are more variable. Though there is typically an increased amount of collagen observed in these patients it is usually not dramatically different from healthy individuals.
A pro-inflammatory state may contribute to HFpEF. This induces changes in the vascular endothelium of the heart. Specifically, by reducing availability of nitric oxide, an important vasodilator and regulator of protein kinase G activity. As protein kinase G activity diminishes, cardiomyocytes undergo hypertrophic changes. Endothelial cells also are responsible for the production of E-selectin, which recruits lymphocytes into the tissue beneath the endothelium that subsequently release transforming growth factor beta, encouraging fibrosis and thus ventricular stiffening. Cardiac macrophages are thought to play an important role in the development of fibrosis as they are increased in HFpEF and release pro-fibrotic cytokines, such as IL-10. Further investigation of the role of inflammation in HFpEF is needed.
Diastolic dysfunction
Diastolic alterations in HFpEF are the predominating factor in impaired cardiac function and subsequent clinical presentation. Diastolic dysfunction is multifaceted, and a given patient may express diverse combinations of the following: incomplete myocardial relaxation, impaired rate of ventricular filling, increased left atrial pressure in filling, increased passive stiffness and decreased distensibility of the ventricle, limited ability to exploit the Frank-Starling mechanism with increased output demands, increased diastolic left heart or pulmonary venous pressure.