Heart Failure With Preserved Versus Reduced Ejection Fraction

The short answer

Heart failure is not one disease. The 2022 American Heart Association, American College of Cardiology, and Heart Failure Society of America guideline sorts it by ejection fraction, the share of blood the left ventricle pumps out with each beat. When that fraction sits at 40 percent or below, the label is heart failure with reduced ejection fraction (HFrEF). At 50 percent or above, it is heart failure with preserved ejection fraction (HFpEF). The band in between, 41 to 49 percent, is called mildly reduced (HFmrEF). This distinction matters because the reduced form has a well-tested set of medicines that lengthen life, while the preserved form is both harder to diagnose and, until recently, had almost nothing with strong outcome evidence behind it.

What the ejection fraction bands actually mean

Ejection fraction is a percentage. A healthy left ventricle typically ejects somewhere around 55 to 70 percent of its blood volume per beat. The 2022 guideline uses four categories built on that number. HFrEF is an ejection fraction of 40 percent or lower. HFmrEF spans 41 to 49 percent. HFpEF is 50 percent or higher, paired with objective evidence of elevated filling pressures inside the heart. A fourth category, heart failure with improved ejection fraction (HFimpEF), describes someone whose fraction was once 40 percent or below and has since risen above 40 percent on treatment. That last group is a reminder that these bands are not permanent addresses; people move between them.

The key conceptual split is mechanical. In HFrEF, the ventricle is weak and cannot contract forcefully enough, a problem of systolic function. In HFpEF, the ventricle squeezes normally but is stiff and does not relax and fill properly, a problem of diastolic function. Same syndrome of breathlessness, fluid retention, and fatigue, but two different underlying failures of the pump.

Why HFpEF is harder to diagnose

A low ejection fraction is easy to see on an echocardiogram, so HFrEF often announces itself. HFpEF is subtler. The ejection fraction looks normal, and the heart may show no obvious structural abnormality at rest, so the diagnosis rests on proving that filling pressures are elevated despite a normal-looking squeeze.

Blood tests do not always settle it. Natriuretic peptides, the hormones the heart releases when stretched, tend to run lower in HFpEF than in HFrEF. In people with obesity, a common HFpEF trait, these peptides can fall below the usual diagnostic threshold even when invasively measured pressures inside the heart are clearly high. A normal blood test, in other words, does not rule the condition out.

To close that gap, clinicians lean on structured probability tools such as the H2FPEF score, which weighs factors like body mass index, hypertension, atrial fibrillation, age, and Doppler measures of filling pressure. When the estimate lands in an intermediate range, the more definitive step is hemodynamic exercise testing, sometimes with a catheter, because filling pressures that look acceptable at rest can climb sharply with exertion. That is a heavier diagnostic lift than measuring an ejection fraction once, and it partly explains why HFpEF is underdiagnosed.

Why the evidence base and drug benefits diverge

Here is the part that surprises many people. For HFrEF, decades of trials converged on what cardiologists call the four pillars of guideline-directed medical therapy: beta blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Each class works through the neurohormonal pathways that drive a weak heart to remodel and deteriorate, and each carries an independent survival benefit. Used together, they substantially reduce mortality and hospitalization.

For HFpEF, that same neurohormonal playbook largely failed. Drugs that clearly extended life in reduced ejection fraction did not reproduce those mortality gains when the ejection fraction was preserved. The 2022 guideline reflects that gap in the strength of its recommendations. SGLT2 inhibitors earned a Class 2a recommendation in HFpEF, the strongest of the preserved-EF options, on the strength of trials like EMPEROR-Preserved, which showed empagliflozin cut the combined risk of cardiovascular death or heart failure hospitalization, driven mainly by fewer hospitalizations. Mineralocorticoid receptor antagonists and angiotensin receptor-neprilysin inhibitors received weaker Class 2b recommendations. Notably, even the SGLT2 benefit in preserved EF has centered on keeping people out of the hospital rather than delivering the robust all-cause mortality reduction seen across the four pillars in HFrEF.

Why the divergence? HFpEF is biologically heterogeneous. It overlaps with obesity, hypertension, kidney disease, and inflammation, and a single mechanism does not capture it the way neurohormonal overdrive captures much of HFrEF. A treatment that helps one HFpEF phenotype may do little for another, which dilutes the average result in a broad trial. The reduced-EF population is more mechanistically uniform, and trials there could target a shared pathway with reproducible success.

What this means for a patient

The ejection fraction band is not a bureaucratic label. It tells you which evidence applies to you. If your fraction is reduced, there is a defined, life-extending regimen worth optimizing fully. If it is preserved, the diagnosis itself may take more work, treatable drivers like blood pressure and weight carry more weight, and SGLT2 inhibitors have become the best-supported medication, even though the field is still catching up to the depth of evidence that reduced ejection fraction enjoys. Knowing your number, and which side of the divide you fall on, is the starting point for an informed conversation with your cardiologist.

This article is educational and not a substitute for individual medical advice.