Breathlessness With a Preserved EF
Lisa Zahakos, RPA-C · Authorized synthetic narration

Her ejection fraction is sixty-three percent. She still cannot finish the walk she used to enjoy. A reassuring number has not explained what changed.

Welcome to HEART RESERVE Clinical Conversations. I’m Lisa Zahakos, a physician assistant and founder of HEART RESERVE.

In this episode, we’ll follow Renee with unexplained breathlessness, Angela with a treatment decision, and Teresa after a hospitalization. These are fictional teaching cases for clinicians.

You can listen straight through, or use the chapters to return to a case. I’ll ask you to consider a few decisions and then walk through the reasoning. The activity page has the objectives, references and online questions.

This episode focuses on heart failure with preserved ejection fraction. The syndrome requires more than a pumping percentage: symptoms or signs must be connected to objective cardiac evidence. Ejection fraction categories, trial entry criteria and product indications are related but are not interchangeable. Under the 2022 U S guideline and historical trial terminology, heart failure with preserved ejection fraction refers to a left ventricular ejection fraction of at least 50 percent; heart failure with mildly reduced ejection fraction refers to 41 to 49 percent. The 2026 European Society of Cardiology guideline instead uses reduced ejection fraction for values below 50 percent and preserved ejection fraction for values of at least 50 percent, removing the separate mildly reduced category. Identify the guideline framework. These naming changes do not alter completed trials or U S product-label boundaries. Several trials and the finerenone heart-failure indication include left ventricular ejection fraction of at least 40 percent. Always read the actual study or label boundary.

The women’s-health focus is a reason to ask a fuller history and examine care gaps. It is not a claim that every woman has the same phenotype or that a medicine works better simply because the patient is a woman. Pregnancy history, blood pressure, metabolic disease, kidney health, function and access belong in one clinical story.

Let’s begin with Renee.

Renee used to walk the school track while her daughter practiced. Over six months she has begun stopping after one lap. The report says left ventricular ejection fraction 63 percent. She was told the result was reassuring. She wants to know why activity has become harder.

Presentation. Stable exertional dyspnea; no new chest pain, syncope or breathlessness at rest.

Context. body mass index 37 kilograms per square meter; hypertension; remote severe preeclampsia.

Available tests. left ventricular ejection fraction 63 percent; N T pro B N P 88 picograms per milliliter; full echo parameters not yet reviewed.

Clinical task. Keep the differential open and obtain the evidence needed to explain the symptom.

Begin with the change in her life.

Ask Renee to describe a usual day before and after the symptoms began. A comparison with her own baseline is more useful than asking only whether she can exercise. How far does she walk? Does she stop because of breathlessness, fatigue, chest discomfort, pain or fear of falling? Is the limitation reproducible? Has the pace of decline changed? Establish the timeline before interpreting any single result.

Then separate a stable outpatient problem from a potentially unstable one. New breathlessness at rest, chest pressure, syncope, severe hypoxemia or rapidly progressive symptoms require urgent assessment according to the presentation. The reassuring wording on an old echocardiogram must not override a new concerning symptom. Renee’s initial presentation is stable; that permits a structured evaluation, not a dismissal.

Ask about orthopnea, waking breathless, edema, weight change, palpitations, sleep-disordered breathing and exertional chest symptoms. Reconcile prescribed and nonprescribed medicines. Review blood pressure history, atrial fibrillation, kidney disease, diabetes, valve disease and previous cardiovascular testing. A description such as 'deconditioned' may eventually be reasonable, but it should not replace the assessment needed to support it.

What a preserved ejection fraction can, and cannot, tell you.

Ejection fraction is the proportion of end-diastolic ventricular volume ejected with a beat. It does not directly measure filling pressure, reserve during exercise or the total burden of a multisystem illness. A woman can have preserved left ventricular ejection fraction and still have a clinically important limitation in filling, vascular function or the response to exertion. Conversely, an ejection fraction of 63 percent is not evidence by itself that heart failure with preserved ejection fraction is present.

Read the entire echocardiogram in clinical context. Review chamber size, left atrial volume, wall thickness, tissue Doppler measurements, estimated filling-pressure indices, right-sided findings and valve assessment. Image quality and rhythm matter. A report of 'diastolic dysfunction' does not automatically establish symptomatic heart failure; an apparently normal resting study does not necessarily explain exertional symptoms.

Do not calculate a diagnostic score with missing inputs. Renee’s ejection fraction and N T pro B N P do not supply the information required for a complete H2FPEF or HFA-PEFF assessment. A score can organize uncertainty when used in the population and context for which it was designed. Its output should help decide the next step, not substitute for reasoning.

Here is the decision. Which information would most help determine whether Renee’s evaluation is on the right track?

Pause here if you would like a moment to think it through.

The best next step in this case is: Review the symptom trajectory, examination, full echo findings and competing causes.

These findings connect her functional change to a focused diagnostic plan.

Use biomarkers without letting them close the case.

Natriuretic peptides are useful, but obesity can lower their concentrations. An unflagged value is therefore less reassuring when the clinical question is heart failure with preserved ejection fraction in a woman with obesity and exertional symptoms. Other conditions, including atrial fibrillation and kidney dysfunction, can also alter interpretation. Use the actual value, units, assay and context rather than the laboratory flag alone.

A selected 2024 research cohort illustrates this problem. Among 78 volunteers with obesity and dyspnea, 65 percent were women. Forty qualified for invasive exercise testing; 24 were found to have heart failure with preserved ejection fraction. That is 60 percent of those tested and 31 percent of the full sample. Resting N T pro B N P and echocardiographic measures did not clearly separate the groups. These findings support a diagnostic concern; they are not a population prevalence estimate for all women with obesity.

For Renee, the practical response is to obtain the missing information and reconsider the competing explanations. It is not to diagnose heart failure with preserved ejection fraction from body mass index, start every heart failure medicine empirically, or reassure her solely because the laboratory result was not flagged.

Make the differential explicit.

heart failure with preserved ejection fraction is one explanation for breathlessness, not the only one. The first evaluation commonly includes a focused examination, ECG, appropriate laboratory testing and review of imaging. Testing should be selected to answer the clinical question: anemia, pulmonary disease, rhythm disturbance, ischemia, significant valve disease and other causes may need consideration. Obesity can coexist with each of these conditions.

Some disorders can resemble heart failure with preserved ejection fraction yet require a different diagnostic and treatment pathway. Clues to infiltrative cardiomyopathy, constrictive physiology or important valve disease should prompt directed evaluation. Do not label every thickened ventricle as ordinary hypertensive remodeling. Equally, do not send every patient with dyspnea for every advanced test; use the history and first-line findings to choose what will resolve the uncertainty.

Document both the leading hypothesis and the reason it remains uncertain. 'Possible heart failure with preserved ejection fraction; full echo and alternate causes under review' is more useful than a premature definitive diagnosis. That distinction also protects later treatment decisions from being based on a diagnosis that was never confirmed.

When resting data leave an intermediate probability.

The HFA-PEFF framework uses clinical assessment, echocardiographic and natriuretic-peptide evidence, functional testing when uncertainty remains, and a final search for the underlying cause. The H2FPEF approach estimates diagnostic likelihood from clinical and echocardiographic features. These tools answer related questions with different inputs; disagreement or an intermediate result is a reason to review the evidence, not average the scores.

In a symptomatic patient whose resting findings do not resolve the question, specialist assessment may lead to exercise echocardiography or invasive exercise hemodynamics. The choice depends on the remaining uncertainty, local expertise, feasibility and the patient’s circumstances. A normal resting pressure cannot necessarily answer what happens during the activity that produces symptoms.

Explain the purpose of the referral in the order: 'Persistent exertional dyspnea with obesity and hypertension, preserved ejection fraction, nondiagnostic resting assessment; please evaluate for heart failure with preserved ejection fraction and mimics.' Include the actual tests, symptom trajectory and question. This gives the receiving clinician a starting point and makes it easier to recognize whether the referral has answered the question.

Bring the history forward without overinterpreting it.

Renee remembers severe preeclampsia but has never been asked about it in a general medical visit. Record the condition and timing as part of her cardiovascular history. It may strengthen the prevention conversation, but it cannot establish the cause of her current dyspnea. Pregnancy complications are not interchangeable with a past diagnosis of peripartum cardiomyopathy, and neither should be inferred without evidence.

Ask what she understood from the earlier test: 'When you heard that the pumping percentage was normal, did you think that meant there could not be a heart problem?' Then correct the misunderstanding without creating unnecessary certainty: 'The pumping percentage is preserved. We still need to understand why activity has become harder. We are checking heart and nonheart causes.'

Close with a concrete plan: the next test or consultation, who tracks it, how she receives the result and which new symptoms change the urgency. If transportation or cost makes the planned test unrealistic, address that before ending the visit. The outcome of this encounter is an explained next step, not simply a referral entered in the chart.

Here is the decision. After reviewing the resting data, uncertainty remains. Which referral best communicates the clinical need?

Pause here if you would like a moment to think it through.

The best next step in this case is: Describe persistent exertional symptoms, available findings, alternatives and the question of exercise evaluation.

A focused referral makes the uncertainty and desired next decision clear.

The takeaway: Preserved ejection fraction and a low natriuretic peptide do not end the evaluation of persistent exertional symptoms. Confirm the syndrome, examine alternatives and track the next diagnostic step.

Before we move on, let’s apply that reasoning in more detail.

Test the reassurance: a worked diagnostic reveal.

Return to Renee after the complete resting evaluation. There is no major valve lesion, no clear anemia and no sustained tachyarrhythmia. A complete H F A peff assessment is intermediate. This does not turn a nondiagnostic study into a negative study. Her symptom occurs during exertion; a resting measurement may not reproduce the physiology causing it. The next question is which functional assessment can resolve the uncertainty and change management.

If specialist exercise echocardiography remains inconclusive or is not feasible, invasive exercise hemodynamics may be appropriate in a center with the required expertise. Explain what the additional test will answer, its burdens and the alternatives. Do not assume that everyone with obesity needs catheterization; persistent symptoms, the probability of disease and the consequences of the result drive the decision.

A 2025 study using selected outpatient diagnostic cohorts found that the usual N T pro B N P threshold of 125 picograms per milliliter had sensitivity of 82 percent when body mass index was below 35 and 67 percent when body mass index was at least 35. This supports caution about a low value in Renee. It does not establish a new universal threshold or a screening test for asymptomatic people. Atrial fibrillation and kidney dysfunction can raise concentrations, while obesity can lower them. A single laboratory flag cannot resolve those competing influences.

Before referral, state one sentence that states the clinical uncertainty and one that states the functional loss. Then attach the actual echo measurements, rhythm, biomarker value, blood pressure history and relevant testing. Ask the receiving team to report both the diagnostic conclusion and the next treatment or follow-up responsibility. A referral succeeds when its answer returns to the clinician and patient who need it.