USA: Recommendations for Heart Failure (HF)

Recommendations for heart failure (HF) are centred on the New York Heart Association (NYHA) classification, such that most seemingly asymptomatic patients are not appropriate for disease-modifying therapies. Its use as the primary criterion for treatment selection is questionable. A recent study by Luis E. Rohde and colleagues revealed that NYHA class might be an incomplete predictor of adverse outcomes. They addressed the question, "how does NYHA classification differ over time, and how does it relate to long-term prognosis in patients with mild HF with reduced ejection fraction?"

In a secondary analysis of the PARADIGM-HF Trial, the findings of which are published in JAMA Cardiology, the research team aimed to evaluate within-patient variation in the classification of NYHA over time, the association between NYHA class and an objective measure of HF severity that is N-NT-proBNP [terminal pro–B-type natriuretic peptide]), and their link with long-term prognosis in the PARADIGM-HF trial. At randomization, a comparison was drawn between patients categorized as NYHA class I, II, and III in PARADIGM-HF. For this purpose, all patients in PARADIGM-HF in the NYHA class II or higher at baseline were treated with sacubitril-valsartan during a 6- to 10-week run-in before randomization. Cardiovascular death or first heart failure hospitalization (primary outcome) was noted—the analysis comprised 8326 patients with known NYHA classification at randomization.

Findings

• Of 389 patients in NYHA class I, 58% changed functional class in the first year after randomization.
• The NT-proBNP level was a poor discriminator of NYHA classification: for NYHA class I vs II, the AUC was 0.51.
• For the NT-proBNP level, the estimated kernel density overlap was 93% between NYHA class I vs II, 79% between NYHA I vs III, and 83% between NYHA II vs III.
• Patients with the NYHA III classification showed a distinctively higher cardiovascular events rate (NYHA III vs I, hazard ratio [HR], 1.84; NYHA III vs II, HR, 1.49).
• Patients in NYHA classes I and II showed lower event rates (NYHA II vs I, HR, 1.24).
• Stratification by the level of NT-proBNP (<1600 pg/mL or ≥1600 pg/mL) identified subgroups with specific risk, such that NYHA class I patients with high NT-proBNP levels (n = 175) had a numerically higher event rate compared to patients with low NT-proBNP levels from any NYHA class (vs I, HR, 3.43; vs II, HR, 2.12; vs III, HR, 1.37).

"The findings showed that patients in NYHA class I and II overlapped considerably in objective measures and long-term prognosis," the authors wrote. "Physician-defined 'asymptomatic' functional class concealed patients at considerable risk for unfavourable results."

"Classification of NYHA might be limited to differentiate mild forms of heart failure," the authors concluded.

Reference

Rohde LE, Zimerman A, Vaduganathan M, et al. Associations Between New York Heart Association Classification, Objective Measures, and Long-term Prognosis in Mild Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial. JAMA Cardiol. Published online December 07, 2022. doi:10.1001/jamacardio.2022.4427.