The Prognostic Significance of Cardiac Structure and Function in Atrial Fibrillation: The ENGAGE AF-TIMI 48 Echocardiographic Substudy.
Atrial fibrillation (AF) is associated with increased risk for thromboembolism and death; however, the relationships between cardiac structure and function and adverse outcomes among individuals with AF are incompletely understood.



The Effective Anticoagulation with Factor Xa Next Generation in AF-Thrombolysis in Myocardial Infarction 48 study tested the once-daily oral factor Xa inhibitor edoxaban in comparison with warfarin for the prevention of stroke (ischemic or hemorrhagic) or systemic embolism in 21,105 subjects with nonvalvular AF and increased risk for thromboembolic events (CHADS2 score ≥ 2). In a prospective substudy of 971 subjects who underwent transthoracic echocardiography at baseline, Cox proportional hazards models were used to evaluate associations between cardiac structure and function and the risks for death and thromboembolism (ischemic stroke, transient ischemic attack, or systemic embolism).



Over a median follow-up period of 2.5 years, 89 deaths (9.2%) and 48 incident thromboembolic events (4.9%) occurred in 971 subjects. In models adjusted for CHADS2 score, aspirin use, and randomized treatment, larger left ventricular (LV) end-diastolic volume index (hazard ratio per 1 SD [12.9 mL/m(2)], 1.49; 95% CI, 1.16-1.91) and higher LV filling pressures measured by E/e' ratio (hazard ratio per 1 SD [4.6], 1.32; 95% CI, 1.08-1.61) were independently associated with increased risks for death. E/e' ratio > 13 significantly improved the prediction of death beyond clinical factors alone. No features of cardiac structure and function were independently associated with thromboembolism in this population. Findings were similar when adjusted for CHA2DS2-VASc score in place of CHADS2 score.



In a contemporary population of patients with AF at increased risk for thromboembolic events, larger LV size and higher filling pressures were significantly associated with increased risk for death, but neither left atrial nor LV measures were associated with thromboembolic risk. LV size and filling pressures may help identify patients with AF at increased risk for death.
Vanderbilt Heart and Vascular Institute, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: d.gupta@vanderbilt.edu.
Deepak K
DK
Gupta
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Robert P
RP
Giugliano
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Christian T
CT
Ruff
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Brian
B
Claggett
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Sabina
S
Murphy
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Elliott
E
Antman
Daiichi Sankyo Pharma Development, Edison, New Jersey.
Michele F
MF
Mercuri
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Eugene
E
Braunwald
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Scott D
SD
Solomon
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000000981:diagnostic imaging* / Q000401:mortality* / Q000628:therapy; D015984:Causality; D015897:Comorbidity; D004311:Double-Blind Method; D004452:Echocardiography / Q000706:statistics & numerical data*; D006801:Humans; D038622:Internationality; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D013318:Stroke Volume; D015996:Survival Rate; D013923:Thromboembolism / Q000000981:diagnostic imaging* / Q000401:mortality* / Q000517:prevention & control
D000925:Anticoagulants
Atrial fibrillation; Death; ENGAGE AF–TIMI 48; Echocardiography; Stroke; Thromboembolism