César Caraballo1, Nihar R. Desai1, Hillary Mulder2, Brooke Alhanti2, F. Perry Wilson3, Mona Fiuzat2, G. Michael Felker2, Ileana L. Piña4, Christopher M. O’Connor5, J. Lindenfeld6, James L. Januzzi7, Lawrence S. Cohen3, Tariq Ahmad1
1Section of Cardiovascular Medicine Center for Outcomes Research Evaluation (CORE) Yale University School of Medicine New Haven CT
2Duke Clinical Research Institute, Durham, NC
3Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT
4Detroit Medical Center, Detroit, MI
5Inova Heart and Vascular Institute, Fairfax, Va
6Vanderbilt University Medical Center, Nashville, TN
7Massachusetts General Hospital and Baim Institute for Clinical Research Boston MA.
Tóm tắt
Background
The New York Heart Association (
NYHA
) classification has served as a fundamental tool for risk stratification of heart failure (
HF
) and determines clinical trial eligibility and candidacy for drugs and devices. However, its ability to adequately stratify risk is unclear.
Methods and Results
To compare
NYHA
class with objective assessments and survival in patients with
HF
, we performed secondary analyses of 4 multicenter National Institutes of Health–funded
HF
clinical trials that included patients classified as
NYHA
class
II
or III: TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), DIG (The Effect of Digoxin on Mortality and Morbidity in Patients With Heart Failure), HF‐ACTION (Efficacy and Safety of Exercise Training in Patients With Chronic Heart Failure), and GUIDE‐IT (Guiding Evidence‐Based Therapy Using Biomarker Intensified Treatment in Heart Failure). Twenty‐month cumulative survival was compared between classes using Kaplan–Meier curves and the log rank test.
NT
‐proBNP (N‐terminal pro–B‐type natriuretic peptide), Kansas City Cardiomyopathy Questionnaire (
KCCQ
) scores, 6‐minute walk distances, left ventricular ejection fraction, and cardiopulmonary test parameters were compared using Wilcoxon rank sum tests and percentage overlap using kernel density estimations. Cumulative mortality varied significantly across
NYHA
classes and
HF
clinical trials (likelihood ratio,
P
<0.001). Mortality at 20 months for
NYHA
class
II
ranged from 7% for patients in
HF
‐
ACTION
to 15% in
GUIDE
‐
IT
, whereas mortality for
NYHA
class
III
ranged from 12% in
TOPCAT
to 26% in
GUIDE
‐
IT
. There was substantial percentage overlap in values for
NT
‐pro
BNP
levels (79% and 69%),
KCCQ
scores (63% and 54%), 6‐minute walk distances (63% and 54%), and left ventricular ejection fraction (88% and 83%). Similarly, there was substantial overall in values for minute ventilation–carbon dioxide production relationship (71%), maximal oxygen uptake (54%), and exercise duration (53%).
Conclusions
The
NYHA
system poorly discriminates
HF
patients across the spectrum of functional impairment. These findings raise important questions about the need for improved phenotyping of these patients to facilitate risk stratification and response to interventions.
