Increased morbidity and mortality at normal natriuretic peptide levels in HFpEF

Heart failure with preserved ejection fraction in patients with normal natriuretic peptide levels is associated with increased morbidity and mortality

Literature - Verbrugge FH, Omote K, Reddy YNV et al. - Eur Heart J. 2022 Feb 9;ehab911. doi: 10.1093/eurheartj/ehab911.

Introduction and methods

Background and aim of the study

The pathophysiology of HFpEF with normal natriuretic peptide (NP) levels remains poorly described. This study investigated the cardiac morphology, cardiac function, hemodynamic parameters and clinical outcomes in patients with HFpEF with normal NP levels, patients with HFpEF with high NP levels and in controls with dyspnea due to non-cardiac causes.

Methods

A total of 581 patients with NYHA Class II-II dyspnea who underwent invasive cardiopulmonary exercise testing at rest and during exercise were included in this study. 161 individuals had dyspnea due to non-cardiac causes and 420 patients had HFpEF (defined as signs and symptoms of HF with LVEF ≥50% and pulmonary arterial wedge pressure (PAWP) ≥15 mmHg at rest and/or ≥25 mmHg during exercise). Among those with HFpEF, 157 had normal NP levels (NT-proBNP <125 or <375 ng/L in AF) and 263 had high NP levels (NT-proBNP ≥125 or ≥375 ng/L in AF).

Outcomes

The study compared cardiac morphology and function parameters as well as hemodynamic characteristics in rest and exercise, and outcomes (all-cause mortality or HF hospitalization) between the three study groups. The median follow-up for clinical outcomes was 32 months (IQR 8-54 months).

Main results

Cardiac morphology and function

Patients with HFpEF and normal NP had preserved right ventricular function, but higher left ventricular mass and worse diastolic function compared with controls with dyspnea due to non-cardiac causes.
Patients with HFpEF and high NP had higher left ventricular mass index, higher left atrial volume index, higher left ventricular filling pressures, more right ventricular remodeling and dysfunction and more secondary mitral and tricuspid valve regurgitation, compared with patients with HFpEF and normal NP.

Hemodynamics at rest and during exercise

Compared to controls, patients with HFpEF and normal NP levels had less cardiac output (CO) reserve during exercise. Patients with HFpEF and normal NP levels had higher left ventricular transmural pressure (LVTMP), higher PAWP, higher pulmonary vascular resistance (PVR) and lower stroke volume index compared with controls.
Patients with HFpEF and high NP levels displayed lower CO reserves, higher cardiac filling pressures and lower stroke volumes compared with patients with HFpEF and normal NP levels.

Clinical outcomes

Patients with HFpEF and normal NP levels had a lower risk for all-cause mortality or HF hospitalization compared with patients with HFpEF and high NP levels (HR: 0.41, 95% CI: 0.24-0.72, after adjustment for age, sex, and BMI). However, patients with HFpEF and normal NP levels had a significantly higher risk for all-cause mortality or HF hospitalization compared with controls with dyspnea due to non-cardiac causes (HR: 2.74, 95% CI: 1.02-7.32, after adjustment for age, sex, and BMI).

Conclusion

This study found that patients with HFpEF and normal NP levels display abnormalities in cardiac structure, cardiac function and hemodynamic parameters compared to controls with dyspnea due to non-cardiac causes. Moreover, Patients with HFpEF and normal NP levels had a significantly higher risk for all-cause mortality or HF hospitalization compared with controls.

Find this article online at Eur Heart J.