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"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

Heart failure with preserved ejection fraction (HFpEF) follows other heart failure types in many ways, but with some unique challenges to diagnosis.

The "" of HF requires signs or symptoms caused by structural or functional cardiac abnormalities and either elevated natriuretic peptides or objective evidence of cardiogenic pulmonary or systemic congestion, or both.

For HFpEF, defined as a clinical diagnosis of HF with left ventricular ejection fraction (LVEF) ≥50%, there are lower levels of natriuretic peptides than with HF with reduced ejection fraction (HFrEF) at a given LV end-diastolic pressure.

Overweight and obesity, which are more common in HFpEF, are also associated with lower natriuretic peptide levels. While one European group recommends that a 50% reduction in natriuretic peptide cutoff values be used for the diagnosis of HF in individuals with obesity, "this approach has not been validated," according to the 2023 ACC for management of HFpEF.

Congestion in HFpEF

"Congestion represents the central, unifying feature of the otherwise heterogeneous syndrome" of HFpEF, notes a .

However, while overt congestion makes for a straightforward HFpEF diagnosis, ambulatory patients with exertional dyspnea present a challenge, as symptoms and hemodynamic abnormalities often manifest only during exertional activities, notes another .

While most HFpEF patients present with both dyspnea and overt congestion -- with clinical signs such as peripheral edema, ascites, jugular venous distention, S3 gallop sounds, and elevated cardiac filling pressures -- about 35% present with dyspnea on exertion but on physical examination. Such "unexplained dyspnea" requires further diagnostic testing.

Hemodynamics

Echocardiography done to assess ejection fraction also can point out diastolic dysfunction, along with atrial and ventricular size, ventricular wall thickness, valve disease, and wall motion abnormalities suggesting prior myocardial infarction.

But "HFpEF is not synonymous with diastolic dysfunction," cautioned the expert consensus decision pathway document. "In fact, the presence of diastolic dysfunction on echocardiogram is neither specific nor sufficient to make the diagnosis of HFpEF and, International Classification of Diseases-Tenth Revision (ICD-10) billing codes notwithstanding, 'diastolic heart failure' is not an accurate or appropriate term for the constellation of symptoms in individuals with HFpEF."

Rest and exercise hemodynamic assessment during right heart catheterization is the gold standard to definitively establish or refute the diagnosis, but isn't always available or accessible due to cost and requirement for expertise. Exercise stress echocardiography can be an alternative, although again is "often limited by the ability to acquire diagnostic quality imaging during stress and false-negative results as a number of patients with HFpEF may not display elevation in E/e' or other surrogate markers with exertion," the consensus decision pathway document noted.

"Many clinicians, when faced with the diagnostic option of diastolic stress testing or invasive hemodynamic measurements, may instead simply initiate GDMT [guideline-directed medical therapy] for HFpEF ... to assess for symptomatic improvement," it added. "A therapeutic trial of GDMT is a reasonable first step instead of more intensive testing to establish a HFpEF diagnosis if the latter is not readily available."

Alternatively, evidence of increased cardiac filling pressures requisite for HFpEF diagnosis can be inferred from physical examination, chest radiography, echocardiography, or natriuretic peptide assays or diagnostic scoring systems, like the H2FPEF score.

In a retrospective of patients with unexplained dyspnea, the H2FPEF score based on echocardiographic and clinical variables had an area under the curve of 0.845 compared with invasive testing. The false-negative rate was 7% with an H2FPEF score of 0 and 36% (15 of 42) with a score of 1; false-positive rates were low. The consensus decision pathway called it "the more practical system for use by clinicians."

"It is important to note that the H2FPEF score was derived and validated in patients with unexplained dyspnea," the 2023 on HFpEF added. "In patients with overt signs and symptoms of HF ... and elevated NPs, a low H2FPEF score does not exclude HFpEF, but may point to atypical causes of the HFpEF syndrome such as infiltrative cardiomyopathies."

HFpEF Mimickers

Other points of difference in the physical exam and history taking compared with HFrEF include the need to look for HFpEF mimickers, such as kidney failure or nephrotic syndrome, liver failure or cirrhosis, anemia, amyloidosis, hypertrophic cardiomyopathy, constrictive pericarditis, severe obesity with peripheral edema, lung disease with or without cor pulmonale, primary pulmonary hypertension, and chronic respiratory failure hypoventilation syndrome.

The HFpEF guidelines point out that definite HFpEF (based on high natriuretic peptides, high pulmonary capillary wedge pressure, HF hospitalization, or a combination thereof) with low H2FPEF score can be a clue to other conditions masquerading as HFpEF. Other clues include:

• Kussmaul's sign (increased jugular venous pressure when inhaling)

• Decreased voltage electrocardiogram relative to left ventricular hypertrophy without a history of hypertension

• Inability to up-titrate or initiate neurohormonal therapy

• Recently stopping all antihypertensive therapy

• Known risk factors for infiltrative or restrictive cardiomyopathy HFpEF in a patient under age 55, unless obese or diabetic

• Prominent musculoskeletal or neurologic features, like bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, and significant peripheral neuropathy

Thus, depending on the presenting symptoms, a patient might need urinalysis to assess for proteinuria, abdominal ultrasound to assess for cirrhosis, and pulmonary evaluation with imaging, spirometry, and arterial blood gas, the consensus decision pathway notes. "These mimics have distinct pathophysiological mechanisms, and failure to consider additional diagnoses may result in missed opportunities to institute effective disease-directed therapies."

Special Populations

While HFpEF presents challenges for diagnosis across the board, that's even more so for women, due to higher EFs and more preserved LV global longitudinal strain compared with men, the consensus decision pathway notes.

It recommended taking a careful history of pregnancy (which is prognostic) and preeclampsia (which is linked to higher HFpEF hospitalization risk). These are additive to the usual risk factors and "particularly noteworthy among populations with inadequate access to quality healthcare, such as individuals from under-represented racial and ethnic groups and those with lower socioeconomic status," the document pointed out.

Read previous installments of this series:

Part 1: Heart Failure: A Look at Low Ejection Fraction

Part 2: Exploring Heart Failure With Preserved Ejection Fraction

Part 3: Heart Failure With Reduced Ejection Fraction: Diagnosis and Evaluation

Part 4: Case Study: Lightheadedness, Fatigue in Man With Hypertension

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