Incident HFpEF and time-dependent changes in markers of LVDD severity in women and men with preclinical LVDD.

Background: The progression of left ventricular diastolic dysfunction (LVDD) over time may lead to the development of heart failure with preserved ejection fraction (HFpEF). HFpEF is twice as common in women compared with men; however, the sex-specific progression from LVDD towards HFpEF is poorly described. Therefore, we aim to evaluate changes over time in markers of LVDD severity and HFpEF in women and men with preclinical LVDD.

Methods and results: We reassessed 146 participants from the HELPFul study (58% women and 42% men) with preclinical LVDD after a median follow-up of 4.3 (IQR: 3.9-4.7) years. The follow-up measurements mirrored baseline measurements, encompassing clinical examination, blood draw for biomarkers and echocardiography. We determined HFpEF incidence and report changes over time in echocardiography. Additionally, we studied how blood pressure and kidney function affected LVDD progression, including plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, using generalised mixed models. All analyses were performed for women and men combined, and sex stratified. Out of 146 participants, 15 (10%) developed HF of whom 13 had HFpEF (9 women and 4 men). Over time, mean kidney function (estimated glomerular filtration rate, eGFR) declined from 89±14.4 to 81±16.9 mL/min/1.73 m² and median NT-proBNP plasma levels increased from 71 (IQR: 44-120) to 100 (IQR: 51-157) pg/mL. In women, a higher systolic and in men a higher diastolic blood pressure were associated with an increase in NT-proBNP plasma levels over time. Lower eGFR levels were related to increased NT-proBNP plasma levels over time in both men and women.

Conclusions: Our study demonstrates that only a small proportion of women and men with preclinical LVDD develop incident HF over a roughly 5-year follow-up period. High blood pressure and decreased kidney function were associated with higher levels of NT-proBNP. This highlights the need to further explore cardiorenal protection as a method to prevent HFpEF.