Clinical Diagnostic Tools May Misclassify HFpEF in Dyspnea Patients

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Two clinical tools have recently been proposed for diagnosing heart failure with preserved ejection fraction (HFpEF): the HFA-PEFF algorithm published in the European Heart Journal in 2019 and the H2FPEF score described in Circulation in 2018. Because there is no gold-standard definition of HFpEF, these scores have not been validated in external populations.

Timothy W. Churchill, MD, cardiologist in the Division of Cardiology, Shawn X. Li, MD, MBA, internal medicine resident, Gregory D. Lewis, MD, Heart Failure section head and medical director of Heart Failure and Transplant Program, and Jennifer E. Ho, MD, cardiologist in the Heart Failure and Transplant Program and the Cardiovascular Research Center at Massachusetts General Hospital, and colleagues recently became the first to compare scores on these tools against invasive hemodynamic criteria. In a research letter published in Circulation, they highlight that the HFA-PEFF and the H₂FPEFF tools generally perform well but note that misclassification is possible, particularly at low scores.

Study Methods

The team identified 156 patients with chronic dyspnea and preserved left ventricular ejection fraction (LVEF ≥50%) who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring between 2006 and 2017 and underwent echocardiography within one year of exercise testing with sufficient data for calculation of both scores. The average age was 59, and 67% were women.

Based on their previous work, the researchers set the diagnostic criteria for invasive HFpEF (HFpEF-inv) as:

• Elevated pulmonary capillary wedge pressure (PCWP, ≥15 mmHg) at rest or during exercise; plus
• Abnormally steep change in PCWP relative to cardiac output (ΔPCWP/Δcardiac output >2.0 mmHg/L/min)

HFA-PEFF Algorithm

Noninvasive score:

• Rule-out scores (0 to 1 point): 44 patients, of whom 11 met the criteria for HFpEF-inv
• Rule-in scores (≥5 points): 22 patients, of whom four did not have HFpEF-inv
• Thus, the number misclassified was 15/66 (23%)

After the addition of the algorithm's invasive criteria, there was agreement with HFpEF-inv for 126/156 patients (81%) and total misclassification of 30 patients (19%).

For the full algorithm:

• Sensitivity: 72%
• Specificity: 91%
• Positive predictive value (the probability that patients with rule-in scores truly have HFpEF): 89%
• Negative predictive value (the probability that patients with rule-out scores truly don't have HFpEF): 75%

H₂FPEF Score

• Rule-out scores (0 to 1 points, n=50): 28% had HFpEF-inv
• Intermediate scores (2–5 points, n=95): 60% had HFpEF-inv
• "High confidence" scores (6–9 points, n=11): 91% had HFpEF-inv
• Using a cutpoint of ≥5:
  • Sensitivity: 31%
  • Specificity: 92%
  • Positive predictive value: 81%
  • Negative predictive value: 55%

Exercise Capacity

Exercise capacity was markedly impaired across the entire cohort (average peak oxygen consumption, 16.1 mL/kg/min). Importantly, both scores effectively stratified patients on the basis of exercise capacity as well as other important hemodynamic parameters (peak exercise heart rate and PCWP).

Applying the Results

The most important limitation of both the HFA-PEFF algorithm and the H₂FPEF score is the potential inability to rule out HFpEF in patients with dyspnea. HFpEF in patients with dyspnea is largely exertional in nature, and exercise may serve as an important diagnostic probe to unmask abnormal physiology in this clinical setting, particularly when resting evaluation is unrevealing.

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