Functional Status, Pulmonary Artery Pressure, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction

Abstract

Background: Patients with heart failure with preserved ejection fraction have functional impairment resulting in reduced quality of life. Specific pathological mechanisms underlying symptoms have not yet been defined.

Objectives: The aim of this study was to identify hemodynamic and other patient-related variables that are associated with New York Heart Association (NYHA) functional class and to analyze functional class in perspective with other clinical, laboratory, imaging, and hemodynamic parameters with respect to its influence on outcomes.

Methods: Between January 2011 and February 2015, 193 patients with confirmed heart failure with preserved ejection fraction were enrolled.

Results: Those in more advanced NYHA functional classes (III and IV; n = 136) were older (p = 0.008), had higher body mass indexes (p = 0.004), and had higher levels of N-terminal pro-brain natriuretic peptide (p = 0.001) compared with less symptomatic patients (NYHA class II; n = 57). Furthermore, parameters reflecting left ventricular diastolic dysfunction were more pronounced in advanced NYHA classes (early mitral inflow velocity/early diastolic mitral annular velocity; p = 0.023) as well as parameters reflecting right ventricular afterload (diastolic pulmonary artery pressure; p < 0.001). By multivariate regression analysis, age (p = 0.007), body mass index (p = 0.002), N-terminal pro-brain natriuretic peptide (p < 0.001), early mitral inflow velocity/mitral peak velocity of late filling (p = 0.031), and diastolic pulmonary artery pressure (p < 0.001) were independently associated with advanced NYHA class. After 21.9 months of follow-up, 64 patients (33.2%) reached the combined endpoint, defined as hospitalization for heart failure and/or cardiac death. By multivariate Cox analysis, NYHA functional class was independently associated with outcome (hazard ratio: 2.133; p = 0.040), as well as N-terminal pro-brain natriuretic peptide (hazard ratio: 1.655; p < 0.001) and impaired right ventricular function (hazard ratio: 2.360; p = 0.001).

Conclusions: Symptoms of breathlessness in patients with heart failure with preserved ejection fraction are multifactorial and largely related to body mass index, left ventricular diastolic function, and the pulmonary vasculature. Clinically meaningful therapeutic interventions should target body weight, left ventricular stiffness, and concomitant pulmonary vascular disease.

Keywords: functional capacity; heart failure; outcome.