PMID- 36477809 OWN - NLM STAT- MEDLINE DCOM- 20230211 LR - 20231212 IS - 2380-6591 (Electronic) IS - 2380-6583 (Print) VI - 8 IP - 2 DP - 2023 Feb 1 TI - 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. PG - 150-158 LID - 10.1001/jamacardio.2022.4427 [doi] AB - IMPORTANCE: Heart failure (HF) treatment recommendations are centered on New York Heart Association (NYHA) classification, such that most apparently asymptomatic patients are not eligible for disease-modifying therapies. OBJECTIVES: To assess within-patient variation in NYHA classification over time, the association between NYHA class and an objective measure of HF severity (N-terminal pro-B-type natriuretic peptide [NT-proBNP] level), and their association with long-term prognosis in the PARADIGM-HF trial. DESIGN, SETTING, AND PARTICIPANTS: All patients in PARADIGM-HF were in NYHA class II or higher at baseline and were treated with sacubitril-valsartan during a 6- to 10-week run-in period before randomization. Patients classified as NYHA class I, II, and III in PARADIGM-HF were compared at randomization. EXPOSURES: NYHA class at randomization after 6 to 10 weeks of the run-in period. MAIN OUTCOMES AND MEASURES: Primary outcome was cardiovascular death or first HF hospitalization. Logistic regression models, areas under the receiver operating characteristic curve (AUC), kernel density estimation overlaps, and Cox proportional hazards models were used. RESULTS: The analysis included 8326 patients with known NYHA classification at randomization. Of 389 patients in NYHA class I, 228 (58%) changed functional class during the first year after randomization. Level of NT-proBNP was a poor discriminator of NYHA classification: for NYHA class I vs II, the AUC was 0.51 (95% CI, 0.48-0.54). For NT-proBNP level, 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 classified as NYHA III displayed a distinctively higher rate of cardiovascular events (NYHA III vs I, hazard ratio [HR], 1.84; 95% CI, 1.44-2.37; NYHA III vs II, HR, 1.49; 95% CI, 1.35-1.64). Patients in NYHA class I and II revealed lower event rates (NYHA II vs I, HR, 1.24; 95% CI, 0.97-1.58). Stratification by NT-proBNP level (<1600 pg/mL or >/=1600 pg/mL) identified subgroups with distinctive risk, such that NYHA class I patients with high NT-proBNP levels (n = 175) had a numerically higher event rate than patients with low NT-proBNP levels 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). CONCLUSIONS AND RELEVANCE: In this study, patients in NYHA class I and II overlapped substantially in objective measures and long-term prognosis. Physician-defined "asymptomatic" functional class concealed patients who were at substantial risk for adverse outcomes. NYHA classification might be limited to differentiate mild forms of HF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01035255. FAU - Rohde, Luis E AU - Rohde LE AD - Postgraduate Program in Cardiology and Cardiovascular Sciences, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. AD - Cardiovascular Division, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. FAU - Zimerman, Andre AU - Zimerman A AD - Postgraduate Program in Cardiology and Cardiovascular Sciences, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. AD - Cardiovascular Division, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. FAU - Vaduganathan, Muthiah AU - Vaduganathan M AD - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Claggett, Brian L AU - Claggett BL AD - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Packer, Milton AU - Packer M AD - Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas. FAU - Desai, Akshay S AU - Desai AS AD - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Zile, Michael AU - Zile M AD - Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston. FAU - Rouleau, Jean AU - Rouleau J AD - Institut de Cardiologie de Montreal, Universite de Montreal, Montreal, Quebec, Canada. FAU - Swedberg, Karl AU - Swedberg K AD - Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. FAU - Lefkowitz, Martin AU - Lefkowitz M AD - Novartis, East Hanover, New Jersey. FAU - Shi, Victor AU - Shi V AD - Novartis, East Hanover, New Jersey. FAU - McMurray, John J V AU - McMurray JJV AD - BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. FAU - Solomon, Scott D AU - Solomon SD AD - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts. LA - eng SI - ClinicalTrials.gov/NCT01035255 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Cardiol JT - JAMA cardiology JID - 101676033 RN - 0 (Biomarkers) SB - IM CIN - JAMA Cardiol. 2023 Aug 1;8(8):793. PMID: 37342034 MH - Humans MH - Biomarkers MH - *Heart Failure/drug therapy MH - New York MH - Prognosis MH - Stroke Volume PMC - PMC9857149 COIS- Conflict of Interest Disclosures: Dr Rohde reported having been a consultant or served on advisory board for Amgen, AstraZeneca, Bayer, Merck, Novartis, and Servier. Dr Vaduganathan reported having been a consultant or having served on advisory boards for American Regent, Amgen, AstraZeneca, Baxter HealthCare, Bayer, Boehringer Ingelheim, Cytokinetics, Galmed, Impulse Dynamics, Lexicon Pharmaceuticals, Novartis, Occlutech, Relypsa, Roche Diagnostics, and Tricog Health. Dr Claggett reported having been a consultant for Amgen, AO Biome, Biogen, Boehringer Ingelheim, Cardurion, Corvia, Gilead, Myokardia, and Novartis. Dr Packer reported having received personal fees from Akcea Therapeutics, Altimmune, Amarin, Ardelyx, AstraZeneca, Amgen, Actavis, AbbVie, Bayer, Boehringer Ingelheim, Caladrius, Cardiorentis, Casana, CSL Behring, Cytokinetics, Daiichi Sankyo, Imara, Johnson & Johnson, Lilly, Moderna, Novo Nordisk, Novartis, Reata, Pfizer, Relypsa, Salamandra, Sanofi, Synthetic Biologics, and Theravance. Dr Desai reported grants and/or consulting fees from Abbott, Alnylam, AstraZeneca, Avidity Biopharma, Axon Therapeutics, Bayer, Boehringer Ingelheim, Biofourmis, Boston Scientific, Corvidia, Cytokinetics, DalCor Pharma, GlaxoSmithKline, Medpace, Merck, Novartis, Parexel, Regeneron, Relypsa, Roche, and Verily. Dr Zile reported having received research funding from Novartis and having been a consultant for Novartis, Abbott, Boston Scientific, CVRx, EBR, Endotronics, Ironwood, Merck, Medtronic, and Myokardia V Wave. Dr Rouleau reported grants and/or consulting fees from Novartis, Bristol Myers Squibb, AstraZeneca, and Bayer during the conduct of the study. Dr Swedberg reported consulting fees from Novartis during the conduct of the study and from AstraZeneca and Boehringer Ingelheim outside the submitted work. Dr Lefkowitz reported being a full-time employee of Novartis during the conduct of the study. Dr McMurray reported having received consulting and/or other payments through Glasgow University from Bayer, Cardiorentis, Amgen, Theracos, AbbVie, DalCor Pharmaceuticals, Pfizer, Merck, AstraZeneca, GlaxoSmithKline, Bristol Myers Squibb, Vifor-Fresenius, Kidney Research UK, Novartis, Servier, Cytokinetics, Alnylam, Cardurion, Ionis Pharmaceuticals, Boehringer Ingelheim, Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, Medscape/Heart.org, ProAdWise Communications, Radcliffe Cardiology, and The Corpus; all payments were made through a consultancy with Glasgow University and were not personal payments. Dr Solomon reported having received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI and having consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health outside the submitted work. No other disclosures were reported. EDAT- 2022/12/09 06:00 MHDA- 2023/02/11 06:00 PMCR- 2023/12/07 CRDT- 2022/12/08 12:19 PHST- 2022/12/09 06:00 [pubmed] PHST- 2023/02/11 06:00 [medline] PHST- 2022/12/08 12:19 [entrez] PHST- 2023/12/07 00:00 [pmc-release] AID - 2799381 [pii] AID - hoi220075 [pii] AID - 10.1001/jamacardio.2022.4427 [doi] PST - ppublish SO - JAMA Cardiol. 2023 Feb 1;8(2):150-158. doi: 10.1001/jamacardio.2022.4427.