Discordance between N-terminal pro-B-type natriuretic peptide and left ventricular end-diastolic pressure in suspected heart failure with a preserved ejection fraction: implications for diagnosis and prognosis.

Abstract

Diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging, as natriuretic peptides and resting haemodynamic measurements reflect complementary but incomplete aspects of myocardial stress and filling pressure. In this prospective all-comer cohort (UKSH-Trial registration number AZ-D412-/21), adults undergoing elective left heart catheterisation underwent simultaneous invasive left ventricular end-diastolic pressure (LVEDP) measurement and N-terminal pro-B-type natriuretic peptide (NT-proBNP) sampling. The H₂FPEF score was calculated in patients with preserved ejection fraction (≥50%), and those with intermediate or high probability were included. Patients were classified using guideline-recommended NT-proBNP thresholds and LVEDP ≥16 mm Hg into four groups: normal (Group 1), isolated LVEDP elevation (Group 2), isolated NT-proBNP elevation (Group 3) and combined elevation (Group 4). The primary endpoint was all-cause mortality, analysed using multivariable Cox models, including age, sex, renal dysfunction and H2FPEF risk category. Among 514 participants (mean age 70 years, 49% women), group distribution was 29%, 14%, 28% and 29%. Discordance was common (42%). Clinical profiles aligned more closely with NT-proBNP than LVEDP. Compared with Group 1, adjusted mortality was not significantly higher in Group 2 (HR 1.34, 95% CI 0.45 to 4.02), whereas it was significantly higher in Group 3 (HR 2.26, 95% CI 1.02 to 5.01) and Group 4 (HR 3.33, 95% CI 1.54 to 7.20). NT-proBNP and LVEDP are frequently discordant and provide complementary prognostic information in suspected HFpEF. Mortality risk was highest when both were elevated and was also increased with isolated NT-proBNP elevation, whereas isolated LVEDP elevation was not associated with excess mortality. These findings support integrated biomarker-haemodynamic assessment and warrant prospective validation.