Heart failure with preserved ejection fraction is a complex condition affecting millions of people worldwide, where the heart muscle remains strong enough to pump but becomes too stiff to fill properly with blood, leaving patients struggling with breathlessness, fatigue, and fluid buildup despite a seemingly normal heart function.
Epidemiology
Heart failure with preserved ejection fraction, often abbreviated as HFpEF, represents a significant and growing health challenge across the globe. This condition affects approximately three million people in the United States alone and up to thirty-two million people worldwide. The scale of this problem becomes even more apparent when we consider that HFpEF comprises at least half of all heart failure diagnoses, making it one of the most common forms of heart failure today.[2][11]
The prevalence of HFpEF continues to increase in developed countries, a trend that appears closely linked to the aging of populations and the rising rates of conditions that put people at risk for this disease. In the United States, approximately five million people have been diagnosed with heart failure overall, with more than six hundred and fifty thousand new diagnoses occurring each year. Almost half of these patients have heart failure with preserved ejection fraction.[3][9]
This condition shows distinct patterns across different demographic groups. HFpEF is notably more common among older individuals, affecting patients who tend to be older than those with other forms of heart failure. The disease also shows a clear gender preference, occurring more frequently in women compared to men. Additionally, patients with preserved ejection fraction are more likely to be obese and to have multiple other health conditions compared to those with reduced heart pumping function.[3][12]
The burden of HFpEF extends beyond individual health to create substantial challenges for healthcare systems. Patients with this condition are hospitalized approximately one point four times per year, and the disease carries a mortality rate of approximately fifteen percent per year. Heart failure overall is the leading cause of hospitalization in people older than sixty-five years of age, with HFpEF accounting for a significant portion of these admissions.[2][11]
Causes
Heart failure with preserved ejection fraction develops when various conditions and diseases impair the heart’s structure or function over time. Unlike other forms of heart failure where the heart’s pumping ability is damaged, HFpEF occurs when the heart muscle becomes stiff and loses its ability to relax properly, even though it can still squeeze and pump fairly normally.[5]
One of the most fundamental causes of HFpEF is the natural effect of aging on the heart. As people grow older, the heart muscle tends to stiffen naturally. This stiffening prevents the heart from filling with blood properly during the relaxation phase of the heartbeat, known as diastole. When the heart cannot fill adequately, less blood is available to pump out to the body, even if the pumping action itself remains strong.[5]
Coronary artery disease represents another major cause of HFpEF. This condition occurs when the arteries that supply blood to the heart muscle become narrowed or blocked. The resulting low blood flow to the heart muscle, called ischemia, can prevent the heart from relaxing properly and filling with blood as it should. When heart muscle doesn’t receive enough oxygen and nutrients, it cannot function optimally, contributing to the development of heart failure.[5]
High blood pressure, or hypertension, stands as one of the most important causes of HFpEF. When blood pressure remains elevated over time, the heart must work harder to pump blood against this increased pressure. In response, the heart muscle can thicken, a process called hypertrophy. While this thickening initially helps the heart pump against high pressure, the thickened muscle becomes stiff and limits the heart’s ability to relax and fill with blood properly.[5]
Additional causes of HFpEF include various heart conditions present from birth, known as congenital heart disease, as well as diseases that affect the heart muscle directly, called cardiomyopathy. Diabetes and kidney disease can also contribute to the development of HFpEF by affecting the heart’s structure and function over time. These conditions often interact with each other, creating a complex web of factors that ultimately lead to the heart becoming too stiff to fill properly.[5]
Risk Factors
Several factors substantially increase a person’s likelihood of developing heart failure with preserved ejection fraction. Understanding these risk factors helps identify individuals who may benefit from closer monitoring and preventive measures. The risk factors for HFpEF span demographic characteristics, medical conditions, and lifestyle choices.[1]
Age represents one of the most significant risk factors for HFpEF. The risk of developing heart failure increases progressively with advancing age, and HFpEF specifically affects older patients more commonly than younger ones. The natural stiffening of heart muscle that occurs with aging contributes to this increased risk. Being older than sixty-five years places individuals in a particularly high-risk category for developing this condition.[1][2]
Gender plays an important role in HFpEF risk, with female sex identified as a significant risk factor. Women develop HFpEF more frequently than men, and this gender difference distinguishes HFpEF from other forms of heart failure. The reasons for this difference are not entirely understood but may relate to how women’s hearts respond to aging and other stresses differently than men’s hearts.[1]
Metabolic syndrome, a cluster of conditions that includes high blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol levels, significantly increases the risk of HFpEF. Obesity in particular has been identified as an important risk factor, with higher body mass index directly associated with increased likelihood of developing the condition. The relationship between obesity and HFpEF likely involves multiple mechanisms, including increased strain on the heart and inflammation.[1]
Diabetes and kidney dysfunction represent additional metabolic risk factors that contribute substantially to HFpEF development. These conditions affect the heart’s structure and function through various pathways, including changes in how the heart muscle cells work and increases in inflammation throughout the body. People with chronic kidney disease face elevated risk for developing HFpEF as their kidney function declines.[1][7]
Lifestyle factors also influence HFpEF risk significantly. Using tobacco products, cocaine, or alcohol increases the likelihood of developing the condition. Leading an inactive or sedentary lifestyle without regular physical activity raises risk, as does consuming foods high in salt and fat. A history of heart attack or existing coronary artery disease substantially elevates the probability of developing HFpEF. Family history matters too, with having relatives who experienced heart failure increasing individual risk.[18]
Symptoms
Heart failure with preserved ejection fraction produces symptoms that result from the heart’s inability to pump enough blood to meet the body’s needs and from the backup of blood and fluid that occurs when the stiff heart cannot fill properly. These symptoms can significantly impact a person’s daily life and ability to perform routine activities.[2]
Shortness of breath, medically termed dyspnea, stands as one of the most common and troubling symptoms of HFpEF. This breathlessness typically worsens with physical activity or exertion, a pattern called exertional dyspnea. Patients may find themselves becoming short of breath when climbing stairs, walking distances, or performing household tasks that previously caused no difficulty. As the condition progresses, breathlessness may occur with less and less activity, eventually affecting even simple movements.[3][9]
Many people with HFpEF experience breathing difficulties that worsen when lying flat, a symptom called orthopnea. This occurs because lying down allows fluid that has accumulated in the legs during the day to redistribute toward the chest and lungs, making breathing more difficult. Patients often need to sleep propped up on multiple pillows or in a reclining chair to breathe comfortably. Some individuals wake suddenly at night gasping for air, a frightening experience known as paroxysmal nocturnal dyspnea.[3][9]
Fatigue and weakness represent another major symptom cluster in HFpEF. Because the heart cannot pump sufficient blood to meet the body’s needs, muscles and organs receive less oxygen and nutrients than required for optimal function. This leads to a persistent sense of tiredness that doesn’t improve with rest. People with HFpEF often describe feeling exhausted after minimal exertion and lacking the energy to complete their normal daily activities.[3][9]
Fluid accumulation, or edema, commonly affects patients with HFpEF. The increased pressure inside the stiff heart transmits backward through the circulatory system, causing fluid to leak out of blood vessels into surrounding tissues. This typically produces swelling in the ankles, legs, and feet, which may worsen throughout the day and improve somewhat overnight when legs are elevated. In more severe cases, fluid can accumulate in the abdomen, creating a bloated or hard feeling in the belly. Weight gain often accompanies this fluid retention.[3][9]
Additional symptoms of HFpEF include irregular or rapid heartbeats, called palpitations, which patients may feel as fluttering or pounding in the chest. Some people develop chest pain or discomfort. A dry, hacking cough may develop, particularly when lying down, as fluid accumulates in the lungs. Changes in urination patterns commonly occur, with patients needing to urinate frequently at night. Loss of appetite and nausea can develop as fluid accumulates in the digestive system.[18]
Prevention
Because pharmacological treatments for heart failure with preserved ejection fraction have historically shown limited success in improving outcomes, prevention takes on exceptional importance for this condition. The emphasis on prevention focuses on controlling the risk factors and medical conditions that lead to HFpEF development. A comprehensive approach to prevention can significantly reduce the likelihood of developing this challenging disease.[16]
Blood pressure control stands as perhaps the most critical preventive measure for HFpEF. Given that eighty to ninety percent of people with HFpEF have hypertension, maintaining blood pressure within healthy ranges through lifestyle modifications and medications when necessary represents a cornerstone of prevention. Regular blood pressure monitoring and working closely with healthcare providers to adjust treatment as needed helps protect the heart from the stiffening and thickening that high blood pressure causes over time.[1][3]
Maintaining a healthy diet provides substantial benefits for HFpEF prevention. A balanced eating pattern should include plenty of fruits and vegetables, with an aim for at least five portions daily. Meals should be based on starchy foods like potatoes, bread, rice, or pasta, and should include moderate amounts of dairy products or alternatives. Including beans, pulses, fish, eggs, meat, and other protein sources helps ensure adequate nutrition. Critically important for heart health is limiting saturated fat, salt, and sugar intake. Reducing salt consumption specifically helps control blood pressure and reduce fluid retention.[15]
Regular physical activity represents another vital component of HFpEF prevention. Exercise helps control weight, lower blood pressure, improve blood sugar control, and strengthen the cardiovascular system. Both endurance activities like walking, swimming, or cycling and resistance training with weights or bands provide benefits. Even moderate physical activity, accumulated throughout the day, contributes to heart health and reduces the risk of developing heart failure.[16]
Weight management plays an important role in prevention, particularly given obesity’s status as a significant risk factor for HFpEF. Achieving and maintaining a healthy body mass index through balanced eating and regular physical activity reduces strain on the heart and helps control other risk factors like high blood pressure, diabetes, and high cholesterol. For individuals who are overweight or obese, even modest weight loss can provide meaningful health benefits.[16]
Smoking cessation is essential for anyone who uses tobacco products. Smoking damages blood vessels, raises blood pressure, reduces oxygen delivery to tissues, and increases the risk of heart disease through multiple mechanisms. Quitting smoking at any age provides health benefits and reduces the risk of developing heart failure. Healthcare providers can offer support and medications to help people successfully quit.[15]
Controlling blood sugar levels is crucial for people with diabetes or prediabetes. High blood sugar damages blood vessels and the heart muscle over time, contributing to heart failure risk. Working with healthcare providers to maintain blood sugar within target ranges through diet, exercise, and medications when needed helps protect the heart. Similarly, managing cholesterol levels through healthy eating, exercise, and medications if prescribed helps prevent coronary artery disease, which can lead to HFpEF.[16]
Limiting alcohol consumption represents another important preventive measure. While moderate alcohol intake may be acceptable for some people, excessive drinking can damage the heart and should be avoided. Current recommendations suggest not exceeding fourteen alcohol units per week. For individuals whose heart problems relate directly to alcohol use, complete abstinence may be necessary.[15]
Vaccination plays a role in HFpEF prevention by protecting against infections that can stress the heart. Annual flu vaccination and the pneumococcal vaccination help prevent respiratory infections that could trigger heart failure in vulnerable individuals or worsen existing heart conditions. These vaccines are particularly important for older adults and people with chronic health conditions.[15]
Pathophysiology
Understanding how heart failure with preserved ejection fraction develops at a physiological level helps explain why patients experience their symptoms and why the condition proves challenging to treat. HFpEF involves complex changes in how the heart muscle works, how blood flows through the heart and circulation, and how different parts of the cardiovascular system respond to stress.[1]
The fundamental problem in HFpEF involves abnormalities in how the heart’s lower left chamber, the left ventricle, fills with blood during diastole. Unlike in healthy hearts where the ventricle relaxes easily and fills readily with blood, the left ventricle in HFpEF becomes stiff and rigid. This stiffness results from abnormalities in both active ventricular relaxation and passive ventricular compliance. When the ventricle cannot relax properly or stretch to accommodate blood, it fills incompletely, leaving less blood available to pump out to the body with each heartbeat.[3][9]
At the cellular level, profound changes occur in the heart muscle of patients with HFpEF. The individual heart muscle cells, called cardiac myocytes, become thicker and shorter than normal myocytes. Additionally, the amount of collagen, a structural protein that provides rigidity, increases significantly in the heart tissue. These changes make the heart muscle stiffer and less able to relax, contributing directly to the filling problems that characterize HFpEF. Research has also shown reductions in the number of small blood vessels, called capillaries, that supply the heart muscle itself.[1]
The stiffness of the ventricle leads to elevated pressures inside the heart chamber during the filling phase. Because the stiff ventricle resists filling, higher pressures are required to push blood into it. These elevated pressures don’t remain confined to the left ventricle but transmit backward through the heart’s upper left chamber, the left atrium, and into the blood vessels of the lungs, known as the pulmonary veins. This backward transmission of pressure causes fluid to leak from the lung blood vessels into the air spaces of the lungs, reducing lung compliance and creating the sensation of breathlessness that plagues patients with HFpEF.[3][9]
The pathophysiology of HFpEF extends beyond simple problems with the heart muscle’s stiffness and relaxation. Recent investigations have revealed a more complex and heterogeneous disease process than previously recognized. Multiple abnormalities contribute to the syndrome, including impairments in both diastolic and systolic reserve, meaning the heart cannot respond adequately when stressed by exercise or other demands. Chronotropic incompetence, an inability to increase heart rate appropriately with exercise, limits cardiac output. Dysfunction of the left atrium impairs its ability to help fill the ventricle. Pulmonary hypertension, or high blood pressure in the lung arteries, commonly develops. Impaired vasodilation and endothelial dysfunction, meaning the blood vessels cannot dilate properly, limit blood flow to muscles and organs.[1]
Importantly, many of these abnormalities appear only when the circulatory system faces stress from exercise or other demands. At rest, the heart may function reasonably well, which is why the ejection fraction, the percentage of blood pumped out with each heartbeat, remains preserved or normal in this condition. A normal ejection fraction is more than fifty-five percent, meaning that more than fifty-five percent of the blood in the left ventricle is pumped out with each heartbeat. In HFpEF, the ejection fraction typically measures fifty percent or higher, indicating that the ventricle can squeeze and pump effectively. However, because less blood fills the stiff ventricle in the first place, even a normal ejection fraction results in less total blood being pumped out to the body.[4][5]
The combination of decreased lung compliance from fluid accumulation and reduced cardiac output from inadequate filling creates the symptoms that patients experience. When the heart cannot deliver enough oxygen-rich blood to meet the body’s needs, especially during activity, patients feel short of breath and fatigued. Physiologic stressors, such as a hypertensive crisis or infection, can overwhelm the heart’s limited compensatory mechanisms and result in sudden, severe pulmonary edema, where the lungs fill rapidly with fluid.[3][9]
HFpEF increasingly is recognized as a highly heterogeneous disease with different patterns or phenotypes driven by various cardiac and non-cardiac conditions. The specific combination of abnormalities and contributing factors varies considerably among patients, which likely explains why clinical trials testing single medications have generally failed to show strong benefits across all patients with HFpEF. Some patients may have predominantly problems with heart muscle stiffness, while others have more significant issues with blood vessel function, lung disease, kidney dysfunction, or obesity-related complications. This heterogeneity makes both diagnosis and treatment of HFpEF particularly challenging.[1][11]
