NYHA Functional Class Independently Associated With HFpEF Outcomes

Patients with more advanced NYHA functional classes tended to be older, had higher BMIs, and had higher levels of N-terminal pro-brain natriuretic peptide.

Patients with heart failure with preserved ejection fraction (HFpEF) experience symptoms of breathlessness that were found to be multi-factorial and related to BMI, left ventricular diastolic function, and pulmonary vasculature.

Daniel Dalos, MD, of the Division of Cardiology at the Medical University of Vienna, and colleagues sought to identify the hemodynamic and other patient-related variables associated with New York Heart Association (NYHA) functional class and to assess NYHA class in relation to other clinical parameters. Their findings were published in the Journal of the American College of Cardiology.

A total of 193 patients with confirmed HFpEF were included in the study between January 2011 and February 2015. Patients with more advanced NYHA functional classes (III and IV; n=136) tended to be older, had higher BMIs, and had higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP; P=.008; .004, and .001; respectively) compared with patients with less advanced NYHA classes (II; n=57). More often, these patients had arterial hypertension (P=.002) and were taking diuretic agents (P<.001) compared with patients who with less severe NYHA classes.

Lower hemoglobin levels and glomerular filtration rates were also observed in patients with more advanced NYHA functional classes (P=.006 and .008, respectively). Left ventricular diastolic dysfunction was also more severe in patients with advanced NYHA classes (E/Eʹ ratio; P=.023) as well as larger right ventricular end-diastolic diameters (P=.019).

The authors identified the following variables independently associated with NYHA functional class, with respect to each parameter cluster: “clinical: advanced age, higher BMI, previous heart failure hospitalizations; laboratory: higher NT-proBNP serum levels; transthoracic echocardiography: higher E/A ratio; and invasive hemodynamic parameters: higher diastolic pulmonary artery pressure.”

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After nearly 22 months of follow-up, 64 patients (33.2%) reached the combined end point, defined as hospitalization for heart failure and/or cardiac death. NYHA functional class was independently associated with outcome, by multivariate Cox analysis (hazard ratio [HR]: 2.133; P=.040), as well as NT-proBNP (HR: 1.655; P<.001) and impaired right ventricular function (HR: 2.360; P=.001).

“Interestingly, the diastolic pressure gradient, which has been recently introduced as the most reliable parameter for the assessment of pulmonary vascular disease and has been related with outcomes in this specific patient population, was not associated with functional impairment in our cohort,” researchers pointed out.

“The present study shows the prognostic importance of NYHA functional class on outcomes in patients with HFpEF,” they concluded. “Furthermore, it clearly delineates that in addition to advanced age and higher BMI, distinct hemodynamic parameters reflecting both LV filling impairment and pulmonary vascular disease underlie the cardinal symptom of HFpEF.”

They encouraged future studies to target body weight, left ventricular diastolic dysfunction, and pulmonary vasculature, because these treating these factors will improve clinical outcomes in patients with HFpEF.


Dalos D, Mascherbauer J, Zotter-Tufaro C, et al. Functional status, pulmonary artery pressure, and clinical outcomes in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2016;68(2):189-199. doi: 10.1016/j.jacc.2016.04.052.