PMID- 37078691 OWN - NLM STAT- MEDLINE DCOM- 20230601 LR - 20230823 IS - 1532-2092 (Electronic) IS - 1099-5129 (Print) IS - 1099-5129 (Linking) VI - 25 IP - 5 DP - 2023 May 19 TI - Atrial Fibrillation can adversely impact Heart Failure with Preserved Ejection Fraction by its association with Heart Failure Progression and Mortality: A Post-Hoc Propensity Score-Matched Analysis of the TOPCAT Americas Trial. LID - 10.1093/europace/euad095 [doi] LID - euad095 AB - AIMS: Prevalent atrial fibrillation (AF) is associated with excess cardiovascular (CV) death (D) and hospitalizations (H) in heart failure (HF) with preserved ejection fraction (pEF). We evaluated if it had an independent role in excess CVD in HFpEF and studied its impact on cause-specific mortality and HF morbidity. METHODS AND RESULTS: We used propensity score-matched (PSM) cohorts from the TOPCAT Americas trial to account for confounding by other co-morbidities. Two prevalent AF presentations at study entry were compared: (i) subjects with Any AF event by history or on electrocardiogram (ECG) with PSM subjects without an AF event and (ii) subjects in AF on ECG with PSM subjects in sinus rhythm. We analyzed cause-specific modes of death and HF morbidity during a mean follow-up period of 2.9 years. A total of 584 subjects with Any AF event and 418 subjects in AF on ECG were matched. Any AF was associated with increased CVH [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11-1.61, P = 0.003], HFH (HR 1.44, 95% CI 1.12-1.86, P = 0.004), pump failure death (PFD) (HR 1.95, 95% CI 1.05-3.62, P = 0.035), and HF progression from New York Heart Association (NYHA) classes I/II to III/IV (HR 1.30, 95% CI 1.04-1.62, P = 0.02). Atrial fibrillation on ECG was associated with increased risk of CVD (HR 1.46, 95% CI 1.02-2.09, P = 0.039), PFD (HR 2.21, 95% CI 1.11-4.40, P = 0.024), and CVH and HFH (HR 1.37, 95% CI 1.09-1.72, P = 0.006 and HR 1.65, 95% CI 1.22-2.23, P = 0.001, respectively). Atrial fibrillation was not associated with risk of sudden death. Both Any AF and AF on ECG cohorts were associated with PFD in NYHA class III/IV HF. CONCLUSION: Prevalent AF can be an independent risk factor for adverse CV outcomes by its selective association with worsening HF, HFH, and PFD in HFpEF. Prevalent AF was not associated with excess sudden death risk in HFpEF. Atrial fibrillation was also associated with HF progression in early symptomatic HFpEF and PFD in advanced HFpEF. TRIAL REGISTRATION: TOPCAT trial is registered at www.clinicaltrials.gov:identifier NCT00094302. CI - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Saksena, Sanjeev AU - Saksena S AUID- ORCID: 0000-0001-6282-6420 AD - Electrophysiology Research Foundation, 161 Washington Valley Road, Suite 201, Warren, NJ 07059, USA. AD - Department of Medicine, Rutgers' Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901, USA. FAU - Slee, April AU - Slee A AUID- ORCID: 0000-0003-2469-3916 AD - Electrophysiology Research Foundation, 161 Washington Valley Road, Suite 201, Warren, NJ 07059, USA. FAU - Natale, Andrea AU - Natale A AUID- ORCID: 0000-0001-6601-944X AD - Texas Cardiac Arrhythmia Institute, St. David's Hospital and Department of Medicine, Univerisity of Texas at Austin, 919E 32nd Street, Austin, TX 78705, USA. FAU - Lakkireddy, Dhanunjaya R AU - Lakkireddy DR AD - Kansas City Heart Rhythm Institute, Overland Hospital, 5110 W 110st, Overland Park, Kansas City 66211, USA. FAU - Shah, Dipen AU - Shah D AUID- ORCID: 0000-0001-6839-2192 AD - Department of Cardiology, University Hospital, Rue Michet-Servet 1, 1206 Geneve, Switzerland. FAU - Di Biase, Luigi AU - Di Biase L AUID- ORCID: 0000-0001-6508-4047 AD - Department of Cardiology, Montefiore Medical Center, 111 East 201 Street, Bronx, NY 10467, USA. FAU - Lewalter, Thorsten AU - Lewalter T AUID- ORCID: 0000-0002-4056-6696 AD - Department of Medicine, Osypka Herzzentrum, Am Isarkanal 36, 81379 Munich, Germany. FAU - Nagarakanti, Rangadham AU - Nagarakanti R AUID- ORCID: 0000-0002-7235-3695 AD - Electrophysiology Research Foundation, 161 Washington Valley Road, Suite 201, Warren, NJ 07059, USA. AD - Department of Medicine, Rutgers' Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901, USA. FAU - Santangeli, Pasquale AU - Santangeli P AUID- ORCID: 0000-0002-0023-9666 AD - Department of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. LA - eng SI - ClinicalTrials.gov/NCT00094302 PT - Journal Article PL - England TA - Europace JT - Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology JID - 100883649 SB - IM MH - Humans MH - *Atrial Fibrillation/epidemiology MH - *Heart Failure MH - Stroke Volume/physiology MH - Propensity Score MH - Comorbidity MH - Prognosis PMC - PMC10228603 OTO - NOTNLM OT - Antiarrhythmic therapy OT - Arrhythmias OT - Atrial fibrillation OT - Cardiovascular mortality OT - Clinical trials OT - Heart failure with preserved ejection fraction OT - Outcomes research OT - Sudden death COIS- Conflict of interest: S.S. was a member of the Steering Committee of the TOPCAT trial. The Electrophysiology Research Foundation received a research grant as an investigational site for the TOPCAT trial. All remaining authors have declared no conflicts of interest with the subject of this manuscript. EDAT- 2023/04/20 13:41 MHDA- 2023/06/01 06:42 PMCR- 2023/04/20 CRDT- 2023/04/20 08:43 PHST- 2023/02/15 00:00 [received] PHST- 2023/03/27 00:00 [accepted] PHST- 2023/06/01 06:42 [medline] PHST- 2023/04/20 13:41 [pubmed] PHST- 2023/04/20 08:43 [entrez] PHST- 2023/04/20 00:00 [pmc-release] AID - 7132913 [pii] AID - euad095 [pii] AID - 10.1093/europace/euad095 [doi] PST - ppublish SO - Europace. 2023 May 19;25(5):euad095. doi: 10.1093/europace/euad095.