Natriuretic peptide responses to exercise in HFpEF diagnosis: a pilot study

Diagnosing heart failure with preserved ejection fraction (HFpEF) can be challenging because natriuretic peptide (NP) plasma levels and diastolic function parameters during rest echocardiography may be normal or marginally abnormal in patients displaying exercise-induced symptoms suggestive of HF. In these patients exercise echocardiography is recommended.We wanted to assess whether directly measured NP levels post-exercise had added diagnostic value beyond rest plasma N-terminal pro-brain NP (NT-proBNP) levels for diagnosing HFpEF.

Participants with left ventricular diastolic dysfunction (LVDD), who could not be classified as HFpEF by a panel of experts more than 4 years ago, were prospectively enrolled in the HELPFulUP observational study from August 2021 to October 2022. All participants in the HELPFulUP study underwent clinical assessment, rest and exercise-echocardiography and measurements of plasma NT-proBNP before and directly after exercise. An expert panel, blinded to exercise NT-proBNP results, but with knowledge of signs, symptoms and all other diagnostic parameters including baseline values of NT-proBNP adjudicated HFpEF status. We calculated the area under the receiver operating characteristic curve (area under the curve (AUC)) for HFpEF for rest and post-exercise NT-proBNP levels and the delta NT-proBNP.

Of the 112 LVDD participants (59 women), 11 were diagnosed with HFpEF by the expert panel based on the additional information retrieved from exercise echocardiography, and 101 remained classified as LVDD. Rest (AUC=0.78 (95% CI 0.66 to 0.90) and exercise values of NT-proBNP (AUC=0.77 (95% CI 0.65 to 0.90) had similar discriminatory value. The delta NT-proBNP AUC was 0.53 (95% CI 0.31 to 0.75).

In this pilot study, the diagnostic performance of the change with exercise in NP levels to detect incident HFpEF, beyond measurements in rest, did not point to a strong diagnostic value.