Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity.

Autor: Kosiborod MN; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Abildstrøm SZ; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Borlaug BA; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Butler J; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Rasmussen S; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Davies M; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Hovingh GK; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Kitzman DW; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Lindegaard ML; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Møller DV; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Shah SJ; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Treppendahl MB; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Verma S; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Abhayaratna W; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Ahmed FZ; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Chopra V; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Ezekowitz J; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Fu M; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Ito H; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Lelonek M; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Melenovsky V; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Merkely B; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Núñez J; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Perna E; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Schou M; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Senni M; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Sharma K; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Van der Meer P; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., von Lewinski D; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Wolf D; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.)., Petrie MC; From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.).
Jazyk: angličtina
Zdroj: The New England journal of medicine [N Engl J Med] 2023 Sep 21; Vol. 389 (12), pp. 1069-1084. Date of Electronic Publication: 2023 Aug 25.
DOI: 10.1056/NEJMoa2306963
Abstrakt: Background: Heart failure with preserved ejection fraction is increasing in prevalence and is associated with a high symptom burden and functional impairment, especially in persons with obesity. No therapies have been approved to target obesity-related heart failure with preserved ejection fraction.
Methods: We randomly assigned 529 patients who had heart failure with preserved ejection fraction and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The dual primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in the 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level.
Results: The mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P<0.001), and the mean percentage change in body weight was -13.3% with semaglutide and -2.6% with placebo (estimated difference, -10.7 percentage points; 95% CI, -11.9 to -9.4; P<0.001). The mean change in the 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m; 95% CI, 8.6 to 32.1; P<0.001). In the analysis of the hierarchical composite end point, semaglutide produced more wins than placebo (win ratio, 1.72; 95% CI, 1.37 to 2.15; P<0.001). The mean percentage change in the CRP level was -43.5% with semaglutide and -7.3% with placebo (estimated treatment ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). Serious adverse events were reported in 35 participants (13.3%) in the semaglutide group and 71 (26.7%) in the placebo group.
Conclusions: In patients with heart failure with preserved ejection fraction and obesity, treatment with semaglutide (2.4 mg) led to larger reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss than placebo. (Funded by Novo Nordisk; STEP-HFpEF ClinicalTrials.gov number, NCT04788511.).
(Copyright © 2023 Massachusetts Medical Society.)
Databáze: MEDLINE