Comparison of New York Heart Association Class and Patient-Reported Outcomes for Heart Failure With Reduced Ejection Fraction

Abstract

Importance: It is unclear how New York Heart Association (NYHA) functional class compares with patient-reported outcomes among patients with heart failure (HF) in contemporary US clinical practice.

Objective: To characterize longitudinal changes and concordance between NYHA class and the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS), and their associations with clinical outcomes.

Design, setting, and participants: This cohort study included 2872 US outpatients with chronic HF with reduced ejection fraction across 145 practices enrolled in the CHAMP-HF registry between December 2015 and October 2017. All patients had complete NYHA class and KCCQ-OS data at baseline and 12 months. Longitudinal changes and correlations between the 2 measure were examined. Multivariable models landmarked at 12 months evaluated associations between improvement in NYHA and KCCQ-OS from baseline to 12 months with clinical outcomes occurring from months 12 through 24. Statistical analyses were performed from March to August 2020.

Exposure: Change in health status, as defined by 12-month change in NYHA class or KCCQ-OS.

Main outcomes and measures: All-cause mortality, HF hospitalization, and mortality or HF hospitalization.

Results: In total, 2872 patients were included in this analysis (median [interquartile range] age, 68 [59-75] years; 872 [30.4%] were women; and 2156 [75.1%] were of White race). At baseline, 312 patients (10.9%) were NYHA class I, 1710 patients (59.5%) were class II, 804 patients (28.0%) were class III, and 46 patients (1.6%) were class IV. For KCCQ-OS, 1131 patients (39.4%) scored 75 to 100 (best health status), 967 patients (33.7%) scored 50 to 74, 612 patients (21.3%) scored 25 to 49, and 162 patients (5.6%) scored 0 to 24 (worst health status). At 12 months, 1002 patients (34.9%) had a change in NYHA class (599 [20.9%] with improvement; 403 [14.0%] with worsening) and 2158 patients (75.1%) had a change of 5 or more points in KCCQ-OS (1388 [48.3%] with improvement; 770 [26.8%] with worsening). The most common trajectory for NYHA class was no change (1870 [65.1%]), and the most common trajectory for KCCQ-OS was an improvement of at least 10 points (1047 [36.5%]). After adjustment, improvement in NYHA class was not associated with subsequent clinical outcomes, whereas an improvement of 5 or more points in KCCQ-OS was independently associated with decreased mortality (hazard ratio, 0.59; 95% CI, 0.44-0.80; P < .001) and mortality or HF hospitalization (hazard ratio, 0.73; 95% CI, 0.59-0.89; P = .002).

Conclusions and relevance: Findings of this cohort study suggest that, in contemporary US clinical practice, compared with NYHA class, KCCQ-OS is more sensitive to clinically meaningful changes in health status over time. Changes in KCCQ-OS may have more prognostic value than changes in NYHA class.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Greene reported receiving research support from the American Heart Association; Amgen; AstraZeneca; Bristol Myers Squibb; Merck & Co; the National Heart, Lung, and Blood Institute (NHLBI); and Novartis and receiving personal fees from Amgen, Cytokinetics, and Merck & Co. Dr Butler reported receiving personal fees from Abbott, Adrenomed, Amgen, Applied Therapeutics, Arena Pharma, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, CVRx, Eli Lilly, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck & Co, Novartis, Novo Nordisk, Relypsa, Sequana Medical, V-Wave Limited, and Vifor outside the submitted work. Dr Spertus reported receiving personal fees from Novartis during the conduct of the study; receiving personal fees from Amgen, AstraZeneca, Bayer, Blue Cross Blue Shield of Kansas City, Janssen, Merck & Co, Myokardia, and United Healthcare outside the submitted work; receiving royalties for copyright of SAQ, Kansas City Cardiomyopathy Questionnaire, and PAQ; and having equity in Health Outcomes Sciences. Ms Hellkamp reported receiving grants from Novartis during the conduct of the study. Dr Vaduganathan reported receiving research grant support or personal fees from American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, and Relypsa; and participating on committees for studies sponsored by Galmed, the National Institutes of Health, and Novartis. Dr DeVore reported receiving grants from Novartis and personal fees from Novartis during the conduct of the study; receiving grants from American Heart Association, Amgen, AstraZeneca, Bayer, Intra-Cellular Therapies, American Regent Inc, the NHLBI, Novartis, and PCORI; receiving personal fees from Amgen, AstraZeneca, Bayer, CareDx, InnaMed, LivaNova, Mardil Medical, Procyrion, scPharmaceuticals, Story Health, and Zoll Consulting; and receiving nonfinancial support from Abbott outside the submitted work. Dr Albert reported receiving personal fees from Novartis during the conduct of the study; receiving personal fees from Amgen and AstraZeneca outside the submitted work; and receiving nonfinancial support from Boston Scientific. Dr Duffy reported being an employee of Novartis Pharmaceutical Corporation with minimal stock options outside the submitted work. Dr Patterson reported receiving personal fees from Novartis during the conduct of the study; receiving personal fees from Alnylam outside the submitted work; and receiving research funding from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Merck, Novartis, and Otsuka. Dr Hernandez reported receiving grants from American Regent, AstraZeneca, Boehringer Ingelheim, Merck & Co, Novartis, and Verily during the conduct of the study; receiving research support from AstraZeneca, GlaxoSmithKline, Luitpold, Merck & Co, and Novartis; and receiving personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Merck & Co, Myokardia, Novartis, and Sanofi outside the submitted work. Dr Fonarow reported receiving grants from the National Institutes of Health; receiving personal fees from Novartis during the conduct of the study; and receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards, Janssen, Medtronic, Merck & Co, and Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Change From Baseline to 12-Month Follow-up in New York Heart Association (NYHA) Class and Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS)

Data reflect the proportion of patients with a change in NYHA class or meaningful change in KCCQ-OS of 5 or more points from baseline to 12-month follow-up.

Figure 2.. Associations Between Change in New York Heart Association (NYHA) Class and Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) With Clinical Outcomes Among Patients With Heart Failure (HF) With Reduced Ejection in Contemporary US Outpatient Practice

Unadjusted and adjusted hazard ratios indicating the risk of adverse clinical outcomes associated with improvement in NYHA class and improvement in KCCQ-OS. Adjusted models include age, sex, race/ethnicity, total household income, body mass index, systolic blood pressure, heart rate, ejection fraction, glomerular filtration rate, atrial fibrillation, coronary artery disease, diabetes, chronic obstructive pulmonary disease, prior heart failure hospitalization, cardiac resynchronization therapy, implantable cardioverter-defibrillator, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, sacubitril/valsartan, evidence-based β-blocker, and mineralocorticoid receptor antagonist.