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Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation.
N Engl J Med 2016; 374(20):1932-41NEJM

Abstract

BACKGROUND

In a trial comparing coronary-artery bypass grafting (CABG) alone with CABG plus mitral-valve repair in patients with moderate ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI) or survival after 1 year. Concomitant mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation, but patients had more adverse events. We now report 2-year outcomes.

METHODS

We randomly assigned 301 patients to undergo either CABG alone or the combined procedure. Patients were followed for 2 years for clinical and echocardiographic outcomes.

RESULTS

At 2 years, the mean (±SD) LVESVI was 41.2±20.0 ml per square meter of body-surface area in the CABG-alone group and 43.2±20.6 ml per square meter in the combined-procedure group (mean improvement over baseline, -14.1 ml per square meter and -14.6 ml per square meter, respectively). The rate of death was 10.6% in the CABG-alone group and 10.0% in the combined-procedure group (hazard ratio in the combined-procedure group, 0.90; 95% confidence interval, 0.45 to 1.83; P=0.78). There was no significant between-group difference in the rank-based assessment of the LVESVI (including death) at 2 years (z score, 0.38; P=0.71). The 2-year rate of moderate or severe residual mitral regurgitation was higher in the CABG-alone group than in the combined-procedure group (32.3% vs. 11.2%, P<0.001). Overall rates of hospital readmission and serious adverse events were similar in the two groups, but neurologic events and supraventricular arrhythmias remained more frequent in the combined-procedure group.

CONCLUSIONS

In patients with moderate ischemic mitral regurgitation undergoing CABG, the addition of mitral-valve repair did not lead to significant differences in left ventricular reverse remodeling at 2 years. Mitral-valve repair provided a more durable correction of mitral regurgitation but did not significantly improve survival or reduce overall adverse events or readmissions and was associated with an early hazard of increased neurologic events and supraventricular arrhythmias. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

Authors+Show Affiliations

From the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical CentFrom the Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center-Albert Einstein College of Medicine (R.E.M., J.J.D.), the International Center for Health Outcomes and Innovation Research (InCHOIR), Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai (M.K.P., A.J.M., H.L.C., E.B., J.R.O., E.G.M., L.N.G., A.C.G.), the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University (M.A.), and the Department of Cardiac Surgery, Mount Sinai Health System (E.A.R., J.D.P.) - all in New York; the Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (P.K.S., C.A.M.); the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville (G.A., S.G.B.); the Clinical Research Unit, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta (V.T.); the Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia (M.A.A., P.A.); the Division of Cardiology, Massachusetts General Hospital (J.W.H.), and the Cardiovascular Division, Brigham and Women's Hospital (P.T.O.) - both in Boston; Montreal Heart Institute, University of Montreal, Montreal (L.P.P., I.E.-H.), Peter Munk Cardiac Centre and Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the Division of Cardiac Surgery, University of Toronto, Toronto (R.D.W.), and Institut Universitaire de Cardiologie de Québec, Hôpital Laval, Quebec, QC (F.D., P.V.) - all in Canada; the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland (A.M.G.); and the Division of Cardiovascular Sciences (M.A.M., W.C.T.-P.) and Office of Biostatistics Research (N.J.), National Heart, Lung, and Blood Institute, Bethesda, and the Department of Surgery, University of Maryland Medical Cent

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27040451

Citation

Michler, Robert E., et al. "Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation." The New England Journal of Medicine, vol. 374, no. 20, 2016, pp. 1932-41.
Michler RE, Smith PK, Parides MK, et al. Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation. N Engl J Med. 2016;374(20):1932-41.
Michler, R. E., Smith, P. K., Parides, M. K., Ailawadi, G., Thourani, V., Moskowitz, A. J., ... Gelijns, A. C. (2016). Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation. The New England Journal of Medicine, 374(20), pp. 1932-41. doi:10.1056/NEJMoa1602003.
Michler RE, et al. Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation. N Engl J Med. 2016 May 19;374(20):1932-41. PubMed PMID: 27040451.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation. AU - Michler,Robert E, AU - Smith,Peter K, AU - Parides,Michael K, AU - Ailawadi,Gorav, AU - Thourani,Vinod, AU - Moskowitz,Alan J, AU - Acker,Michael A, AU - Hung,Judy W, AU - Chang,Helena L, AU - Perrault,Louis P, AU - Gillinov,A Marc, AU - Argenziano,Michael, AU - Bagiella,Emilia, AU - Overbey,Jessica R, AU - Moquete,Ellen G, AU - Gupta,Lopa N, AU - Miller,Marissa A, AU - Taddei-Peters,Wendy C, AU - Jeffries,Neal, AU - Weisel,Richard D, AU - Rose,Eric A, AU - Gammie,James S, AU - DeRose,Joseph J,Jr AU - Puskas,John D, AU - Dagenais,François, AU - Burks,Sandra G, AU - El-Hamamsy,Ismail, AU - Milano,Carmelo A, AU - Atluri,Pavan, AU - Voisine,Pierre, AU - O'Gara,Patrick T, AU - Gelijns,Annetine C, AU - ,, Y1 - 2016/04/03/ PY - 2016/4/5/entrez PY - 2016/4/5/pubmed PY - 2016/6/4/medline SP - 1932 EP - 41 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 374 IS - 20 N2 - BACKGROUND: In a trial comparing coronary-artery bypass grafting (CABG) alone with CABG plus mitral-valve repair in patients with moderate ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI) or survival after 1 year. Concomitant mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation, but patients had more adverse events. We now report 2-year outcomes. METHODS: We randomly assigned 301 patients to undergo either CABG alone or the combined procedure. Patients were followed for 2 years for clinical and echocardiographic outcomes. RESULTS: At 2 years, the mean (±SD) LVESVI was 41.2±20.0 ml per square meter of body-surface area in the CABG-alone group and 43.2±20.6 ml per square meter in the combined-procedure group (mean improvement over baseline, -14.1 ml per square meter and -14.6 ml per square meter, respectively). The rate of death was 10.6% in the CABG-alone group and 10.0% in the combined-procedure group (hazard ratio in the combined-procedure group, 0.90; 95% confidence interval, 0.45 to 1.83; P=0.78). There was no significant between-group difference in the rank-based assessment of the LVESVI (including death) at 2 years (z score, 0.38; P=0.71). The 2-year rate of moderate or severe residual mitral regurgitation was higher in the CABG-alone group than in the combined-procedure group (32.3% vs. 11.2%, P<0.001). Overall rates of hospital readmission and serious adverse events were similar in the two groups, but neurologic events and supraventricular arrhythmias remained more frequent in the combined-procedure group. CONCLUSIONS: In patients with moderate ischemic mitral regurgitation undergoing CABG, the addition of mitral-valve repair did not lead to significant differences in left ventricular reverse remodeling at 2 years. Mitral-valve repair provided a more durable correction of mitral regurgitation but did not significantly improve survival or reduce overall adverse events or readmissions and was associated with an early hazard of increased neurologic events and supraventricular arrhythmias. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/27040451/Two_Year_Outcomes_of_Surgical_Treatment_of_Moderate_Ischemic_Mitral_Regurgitation_ L2 - http://www.nejm.org/doi/full/10.1056/NEJMoa1602003?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -