Heart failure with preserved ejection fraction, often called HFpEF (pronounced “hef-pef”), is a type of heart failure where the heart pumps out a normal amount of blood with each beat but has become too stiff to fill properly between beats. It accounts for roughly half of all heart failure cases. Unlike the more widely recognized form of heart failure where the heart becomes weak and floppy, in HFpEF the heart muscle is often thickened and rigid, creating a backup of pressure that leads to fluid retention, shortness of breath, and severe limits on physical activity.
How HFpEF Differs From Other Heart Failure
Heart failure is classified by a measurement called ejection fraction: the percentage of blood the left ventricle pushes out with each contraction. In HFpEF, that number is 50% or higher, which looks normal on imaging. In heart failure with reduced ejection fraction (HFrEF), it drops to 40% or below, meaning the heart is clearly weakened as a pump. A middle category, called mildly reduced ejection fraction, covers the 41% to 49% range.
The distinction matters because these subtypes respond differently to treatment. Medications that dramatically improve survival in HFrEF have historically shown little benefit in HFpEF, which made it a much harder condition to manage for decades. The underlying problem is also fundamentally different. In HFrEF, the heart can’t squeeze hard enough. In HFpEF, it can’t relax enough to fill.
What Happens Inside the Heart
Nearly all HFpEF patients have what’s called diastolic dysfunction, meaning the heart’s relaxation phase is impaired. During a normal heartbeat, the left ventricle relaxes and expands like a flexible balloon, drawing blood in from the lungs. In HFpEF, the ventricle walls have become stiff, so they resist stretching. Less blood enters the chamber, and the pressure needed to fill it climbs. That elevated pressure backs up into the lungs and veins, causing congestion.
The stiffness traces to changes at the cellular level. A giant protein called titin, which acts like a molecular spring inside heart muscle cells, becomes less elastic. Chemical modifications that normally keep titin flexible are reduced, so each cell generates more resting tension. At the same time, the process of clearing calcium out of heart cells after each contraction slows down, which means the muscle doesn’t fully relax before the next beat. During even mild physical activity, when heart rate climbs above 100 to 110 beats per minute, this incomplete relaxation becomes measurable and symptomatic.
Most patients with HFpEF also have structural remodeling. The heart wall thickens (a response to years of high blood pressure), and the chamber itself may shrink relative to the wall. The great majority of HFpEF patients have a history of hypertension, and this long-standing pressure overload drives the thickening that ultimately makes the ventricle rigid.
Symptoms and Exercise Intolerance
The hallmark symptom of HFpEF is a dramatic loss of exercise capacity. Even when the condition is well controlled and fluid levels are stable, patients typically experience severe limitations during physical activity. Walking uphill, climbing stairs, or carrying groceries can provoke breathlessness and exhaustion far beyond what’s expected for someone’s age.
This isn’t purely a heart problem. Research shows that the reduced exercise tolerance involves the whole body. Heart rate often fails to rise appropriately during exertion, a phenomenon called chronotropic incompetence, which limits how much blood the heart can deliver. The tiny blood vessels that supply working muscles also show signs of dysfunction, impairing oxygen delivery at the tissue level. Studies using magnetic resonance imaging have found that large-artery blood flow to the legs may look relatively normal in HFpEF patients, but the microvascular network, the smallest capillaries, doesn’t function well, and this correlates directly with worse symptoms and lower exercise capacity.
Beyond exertion, common symptoms include swelling in the legs and ankles, sudden weight gain from fluid retention, fatigue, and difficulty breathing when lying flat. These overlap with other forms of heart failure, which is one reason HFpEF can be tricky to diagnose.
Who Gets HFpEF
HFpEF disproportionately affects older adults, women, and people with metabolic conditions. Roughly 80% of HFpEF patients are overweight or obese and show features of metabolic syndrome: high blood pressure, type 2 diabetes, and abnormal cholesterol levels. Women outnumber men about two to one in HFpEF hospitalizations. The lifetime risk of developing HFpEF is nearly double for women compared to their risk of developing the reduced ejection fraction type (10.7% versus 5.8%), while men face roughly equal risk of both subtypes.
The female predominance appears to accelerate after menopause. Estrogen helps regulate inflammation, blood vessel function, and the signaling molecules that keep heart muscle flexible. When estrogen levels drop, the cardiovascular system becomes more vulnerable to the stiffening and microvascular dysfunction that drive HFpEF. Pregnancy-related conditions like preeclampsia and gestational diabetes also increase long-term risk.
The Role of Obesity and Inflammation
Obesity isn’t just a risk factor for HFpEF. It’s increasingly recognized as a core driver of the disease through a cascade of inflammatory damage. When fat tissue expands, particularly the visceral fat around organs, it shifts from a relatively quiet storage depot to an active source of inflammatory signals. Fat deposits directly on and around the heart secrete molecules that damage heart muscle cells, impair their energy production, and reduce the density of tiny blood vessels feeding the heart wall.
This inflammation isn’t a side effect of heart failure getting worse. It appears to be one of the primary mechanisms that causes HFpEF in the first place. The combination of sodium retention, hormonal disruption, toxic fat buildup in heart cells, and chronic low-grade inflammation creates a self-reinforcing cycle. This understanding has reshaped how researchers think about treating HFpEF, moving attention toward therapies that target weight loss and metabolic health rather than just heart function alone.
How HFpEF Is Diagnosed
Diagnosing HFpEF requires putting together several pieces. A doctor first looks for typical heart failure symptoms: shortness of breath, fluid retention, and exercise limitation. An echocardiogram (ultrasound of the heart) then confirms that the ejection fraction is 50% or above while showing signs of impaired relaxation, such as thickened walls or abnormal filling patterns.
Blood tests for a protein called NT-proBNP help when the clinical picture is unclear. Levels at or above 125 pg/mL suggest elevated pressure inside the heart and warrant further evaluation. One of the challenges with HFpEF is that some patients look relatively normal at rest, and the abnormal pressure only appears during physical activity. Exercise stress testing, sometimes with specialized catheter measurements, can unmask the condition in borderline cases.
Treatment Options
For years, HFpEF had no proven disease-modifying therapy, which set it apart from other forms of heart failure. That changed with a class of medications originally developed for type 2 diabetes called SGLT2 inhibitors. These drugs reduce the risk of hospitalization for heart failure or death from cardiovascular causes by roughly 25% across clinical trials, with consistent benefits regardless of whether the patient has diabetes. The effect holds across the full range of ejection fractions studied, making these the first medications to meaningfully alter the course of HFpEF.
Beyond medication, managing the conditions that fuel HFpEF is central to treatment. Controlling blood pressure reduces the stimulus for heart wall thickening. Weight loss in obese patients improves symptoms, exercise capacity, and the inflammatory profile that drives the disease. Diuretics help manage fluid overload and reduce congestion symptoms, though they treat the consequences rather than the cause. Regular physical activity, even at modest intensity, has been shown to improve exercise tolerance and quality of life.
Long-Term Outlook
HFpEF carries a serious prognosis. In one study following patients after an acute episode of decompensated HFpEF, roughly two-thirds died within five years. What makes HFpEF particularly complex is that only about half of those deaths are from cardiovascular causes. The other half result from the web of coexisting conditions, including kidney disease, diabetes complications, and cancer, that tend to cluster in HFpEF patients. This pattern underscores that HFpEF is not simply a heart disease but a systemic condition rooted in metabolic and inflammatory dysfunction across multiple organs.
Prognosis varies widely depending on how many comorbidities are present, how early the condition is identified, and how effectively those comorbidities are managed. The arrival of SGLT2 inhibitors and the growing focus on obesity-targeted therapies represent the first meaningful shift in a condition that was largely untreatable for decades.