NYHA Class Alone Fails to Accurately Discern Risk Among Heart Failure Patients

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A new analysis from the PARADIGM-HF study suggests substantial overlap exists in regard to the objective measures and long-term prognosis of patients with NYHA Class I and II heart failure.

Using data from the PARADIGM-HF trial, investigators produced results they suggest underline the potential limitations of using NYHA classification to differentiate mild forms of heart failure.

“In a large contemporary [heart failure] trial with systematic data collection and blinded adjudicated end points, time-honored NYHA classification could discriminate subgroups of increased risk but was incomplete to characterize critical aspects related to [heart failure], particularly for patients with mild functional limitation,” wrote investigators. “Across different NYHA classes, we observed considerable overlap in objective measures of [heart failure].”

As knowledge and technology advances, the need to identify objective measures for optimal classification of heart failure patients has become a focal point of many research endeavors. Among the long-time staples which have seen their utility questioned recently are ejection fraction and, now, NYHA class.

In the current study, investigators designed their secondary analysis with the specific intent of assessing within-patient variation in NYHA classification over time, the association between NYHA class and an objective measure of heart failure severity NT-proBNP level, and their association with long-term prognosis in the PARADIGM-HF trial. To do so, investigators leveraged data from those in classified as NYHA class I, II, and III at randomization after the 6–10-week run-in period from within the parallel-design, double-blind PARADIGM-HF trial.

Investigators obtained data from 8326 patients with known NYHA classification at randomization from the trial. Of these 389 were classified as NYHA class I, 5919 were classified as NYHA class II, and 2018 were classified as NYHA class III. compared with NYHA class II and III, those classified as NYHA class I at randomization were younger, were more frequently men, and had fewer comorbidities.

Among the 389 patients classified as having NYHA class I heart failure at randomization, 58% changed functional class during the first year following randomization. Results of the investigators’ analysis indicated levels of NT-proBNP were a poor discriminator of NYHA classification, with an AUC of 0.51 (95% CI, 0.48-0.54) for NYHA class I versus class II. Additionally, for NT-proBNP level, investigators determined the estimated kernel density overlap was 93% between NYHA class I and class II, 79% between NYHA class I and class III, and 83% between NYHA class II and III.

Further analysis indicated those classified as having NYHA class III heart failure had a greater rate of cardiovascular events compared to those with NYHA class I (HR, 1.84 [95% CI, 1.44-2.37]) or class II heart failure (HR, 1.49 [95% CI, 1.35-1.64]). Those in NYHA class I had a lower rate of events than those in NYHA class II (HR, 1.24 [95% CI, 0.97-1.58]). Before concluding, investigators pointed out stratification into subgroups defined by NT-proBNP levels identified subgroups of patients with distinctive cardiovascular risk. Underlining this distinctive risk, investigators highlighted results suggesting patients with NYHA class I heart failure with high NT-proBNP levels had a numerically higher event rate than patients with low NT-proBNP from any NYHA class (vs I, HR, 3.43 [95% CI, 2.03-5.87]; vs II, HR, 2.12 [95% CI, 1.58-2.86]; vs III, HR, 1.37 [95% CI, 1.00-1.88]).

“NYHA classification dynamically changed over time and was an incomplete predictor of adverse outcomes, particularly in patients with mild [heart failure],” investigators concluded. “These findings challenge the use of NYHA class as the leading criteria to enroll patients in [heart failure] trials and to select therapeutic strategies in clinical guidelines.”

This study, “Associations Between New York Heart Association Classification, Objective Measures, and Long-term Prognosis in Mild Heart Failure,” was published in JAMA Cardiology.