Diagnosing heart failure with preserved ejection fraction requires a careful combination of clinical observation, blood tests, and imaging studies, as this condition often presents with symptoms similar to other diseases while the heart’s pumping function appears normal.
Introduction: Who Should Seek Diagnostic Testing
If you find yourself increasingly short of breath during everyday activities like climbing stairs or walking short distances, or if you wake up at night feeling breathless, these could be signs that warrant medical evaluation. Heart failure with preserved ejection fraction, also called HFpEF, affects millions of people worldwide and often develops gradually, making early symptoms easy to overlook or attribute to aging or being out of shape.[1]
You should consider seeking diagnostic testing if you experience typical heart failure symptoms such as fatigue, weakness, difficulty breathing, shortness of breath when lying flat, sudden breathlessness at night, or swelling in your ankles, legs, or abdomen. These symptoms can significantly impact your daily life and may indicate that your heart is not meeting your body’s needs.[3]
Certain groups of people are at higher risk and should be particularly attentive to these warning signs. Older adults, especially women, face increased risk of developing HFpEF. If you have high blood pressure, obesity, diabetes, kidney disease, or metabolic syndrome, you belong to a higher-risk category. In fact, between 80 and 90 percent of patients with HFpEF have hypertension, making it one of the strongest risk factors for this condition.[1]
The diagnosis of HFpEF can be challenging because symptoms often appear only during physical activity or stress, and the condition is quite complex and varied in how it affects different people. Many patients may have normal test results when resting, which can delay proper diagnosis. This is why it’s important not to dismiss persistent symptoms even if you’ve had normal test results in the past.[2]
Classic Diagnostic Methods
Clinical Examination and Medical History
The diagnostic process typically begins with a thorough medical history and physical examination. Your doctor will ask detailed questions about your symptoms, when they occur, what makes them better or worse, and how they affect your daily activities. They will also review your medical history, including any existing conditions like high blood pressure, diabetes, or heart disease, as these are important clues in diagnosing HFpEF.[3]
During the physical examination, your doctor will look for specific signs that suggest heart failure. These include listening for an S3 heart sound, which is an extra sound the heart makes when blood rushes into a stiff ventricle, checking for jugular venous distension (swelling of the neck veins that indicates increased pressure in the heart), and feeling for a displaced apical pulse, which is the heartbeat felt through the chest wall. Research has shown that the presence of jugular venous distension, an S3 heart sound, and a displaced apical impulse significantly increase the likelihood that a patient has heart failure.[3]
Blood Tests: Natriuretic Peptides
One of the most important blood tests in diagnosing HFpEF measures natriuretic peptides. These are hormones released by the heart when it is under stress or working harder than normal. The two main types measured are brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). Elevated levels of these markers suggest that the heart is struggling and support a diagnosis of heart failure.[3]
Measurement of natriuretic peptides is particularly useful in the outpatient setting when the diagnosis is uncertain. If you present with shortness of breath and other symptoms that could be caused by heart problems or lung problems, these blood tests can help your doctor determine which organ system is responsible. Physicians should obtain a BNP or NT-proBNP level for patients with possible heart failure if the diagnosis is uncertain.[3]
However, it’s important to understand that these blood tests are not perfect. Some patients with HFpEF have normal natriuretic peptide levels, especially when measured at rest. Additionally, these markers can be elevated in other conditions, so they must be interpreted in the context of your overall clinical picture.[7]
Echocardiography: The Key Imaging Test
The most important test for confirming HFpEF is an echocardiogram, also called a heart ultrasound. This non-invasive test uses sound waves to create moving images of your heart, allowing doctors to see how well your heart chambers are filling with blood and how effectively they are pumping it out. Patients with suspected heart failure should be referred for two-dimensional transthoracic echocardiography to confirm the diagnosis and identify whether the ejection fraction is preserved or reduced.[3]
Ejection fraction is a crucial measurement that tells doctors what percentage of blood in the left ventricle is pumped out with each heartbeat. A normal ejection fraction is more than 55 percent. HFpEF is diagnosed when the ejection fraction is 50 percent or greater, yet the patient still has signs and symptoms of heart failure. This means the heart’s pumping ability appears preserved, but other problems prevent it from working properly.[5]
The echocardiogram also evaluates diastolic function, which refers to how well the heart relaxes and fills with blood between beats. In HFpEF, the heart muscle becomes stiff and cannot relax properly, leading to impaired filling. The test measures various indicators of diastolic dysfunction, including an elevated ratio called E/e’ (E over e prime), increased left ventricular mass, and enlargement of the left atrium. The presence of an enlarged left atrium with preserved ejection fraction and normal mitral valve function should prompt consideration of HFpEF.[12]
Scoring Systems to Aid Diagnosis
Because diagnosing HFpEF can be challenging, researchers have developed scoring systems to help doctors identify patients who are more likely to have this condition. Two widely recognized scoring systems are the H2FPEF score developed in 2018 and the HFA-PEFF algorithm created in 2020.[11]
The H2FPEF score combines clinical and echocardiographic characteristics to calculate the probability that a patient’s shortness of breath is due to HFpEF. This validated screening tool can help guide doctors in deciding which patients should be referred for more advanced testing. Although these scoring systems represent a significant step forward in accurate diagnosis, they still leave some cases in an “uncertainty area” where the diagnosis remains unclear.[11]
Additional Diagnostic Tests
Your doctor may order other tests to rule out different conditions or to better understand your heart’s function. An electrocardiogram (ECG or EKG) records the electrical activity of your heart and can detect rhythm problems, evidence of previous heart attacks, or signs of heart enlargement. A chest X-ray can show if your heart is enlarged or if there is fluid in your lungs, which would indicate congestion.[2]
Blood tests beyond natriuretic peptides may be ordered to check your kidney function, blood sugar levels, cholesterol, thyroid function, and blood counts. These tests help identify contributing factors or comorbidities that may be affecting your heart or overall health.[2]
Advanced Testing When Diagnosis Remains Uncertain
When the diagnosis remains unclear after initial testing, more advanced procedures may be necessary. Exercise stress testing combined with echocardiography can reveal abnormalities that only appear when the heart is working harder. During this test, images of your heart are taken both at rest and after exercise to see how your heart responds to increased demand.[12]
In some cases, cardiac catheterization with measurement of pressures inside the heart may be recommended. This invasive test involves threading a thin tube through blood vessels into the heart to directly measure the pressures in the heart chambers. Right heart catheterization at rest and during exercise is considered the gold standard for accurately diagnosing HFpEF, as it can directly confirm increased filling pressures. A key finding is a pulmonary capillary wedge pressure of 15 mmHg or higher at rest, or 25 mmHg or higher after exercise, or a left ventricular end-diastolic pressure of 16 mmHg or higher at rest.[11]
However, direct measurement of heart pressures during exercise is not widely available, is invasive, and is typically reserved for very select cases where the diagnosis has major implications for treatment decisions or when other tests have been inconclusive.[11]
Ruling Out Other Conditions
An important part of diagnosing HFpEF is excluding other conditions that can cause similar symptoms. Your doctor will want to rule out infiltrative cardiomyopathies, which are diseases where abnormal substances accumulate in the heart muscle. Approximately 13 percent of patients initially thought to have HFpEF actually have cardiac amyloidosis, a condition where abnormal proteins build up in the heart. Patients with significantly thickened heart walls, low blood flow velocities on testing, early-onset carpal tunnel syndrome in both wrists, and other systemic signs should undergo more detailed evaluation for amyloidosis.[12]
Both cardiac MRI (magnetic resonance imaging) and nuclear imaging studies provide non-invasive methods to diagnose conditions like amyloidosis. These advanced imaging techniques can show specific patterns in the heart muscle that indicate infiltrative diseases rather than typical HFpEF.[12]
Diagnostics for Clinical Trial Qualification
If you are considering participating in a clinical trial for HFpEF, you will need to undergo specific diagnostic tests to determine if you meet the study’s entry criteria. Clinical trials have standardized requirements to ensure that all participants truly have the condition being studied and that the results will be meaningful and applicable to similar patients.[2]
The fundamental requirement for most HFpEF clinical trials is confirmation that your left ventricular ejection fraction is 50 percent or greater. This is typically verified through echocardiography, though some trials may also accept cardiac MRI measurements. The ejection fraction measurement must have been performed relatively recently, often within a few months of trial enrollment, to ensure it reflects your current heart function.[2]
Clinical trials also require evidence of elevated filling pressures in the heart. This can be demonstrated through elevated natriuretic peptide levels (BNP or NT-proBNP) measured in your blood. The specific threshold values vary between studies, but generally, elevated levels are needed to confirm that you have active heart failure at the time of potential enrollment.[7]
Many trials require echocardiographic evidence of structural or functional abnormalities consistent with HFpEF. These might include measurements of diastolic dysfunction parameters, left atrial enlargement, increased left ventricular mass, or abnormal filling patterns. The specific echocardiographic criteria can be quite detailed and technical, reflecting researchers’ efforts to ensure they are studying a relatively homogeneous group of patients.[7]
Trials typically require documentation of heart failure symptoms and their severity. This is often assessed using the New York Heart Association (NYHA) functional classification system, which categorizes patients from Class I (no limitation of physical activity) to Class IV (symptoms at rest). Most HFpEF trials enroll patients in NYHA Class II or III, meaning they have mild to moderate limitations in their physical activities.[2]
Additional testing may be required to assess your exercise capacity objectively. A six-minute walk test measures how far you can walk in six minutes at your own pace. This simple test provides valuable information about your functional capacity and is often used as both an entry criterion and an outcome measure in clinical trials. Some trials may require more sophisticated exercise testing, such as cardiopulmonary exercise testing, which measures how your heart and lungs work together during physical activity.[3]
Laboratory tests beyond natriuretic peptides are typically required to ensure you don’t have other conditions that would make trial participation unsafe or that might confound the study results. These usually include complete blood counts, kidney function tests (creatinine and estimated glomerular filtration rate), liver function tests, electrolytes, and sometimes thyroid function tests. Specific trials testing drugs that affect particular organ systems may have additional laboratory requirements.[2]
Some trials require cardiac catheterization to directly confirm elevated filling pressures, though this is becoming less common as researchers develop better non-invasive methods of confirming HFpEF. When required, the catheterization might need to demonstrate specific pressure measurements both at rest and during exercise to definitively establish the diagnosis.[11]
Finally, trials have extensive exclusion criteria based on other health conditions or medications you may have. You’ll need to provide a complete medical history, and certain conditions like severe kidney disease, liver disease, recent heart attacks, uncontrolled blood pressure, or other types of heart disease may disqualify you from participation. The diagnostic workup for trial eligibility often includes tests to rule out these conditions.[2]
