title: Developing New Treatments for Heart Failure: Focus on the Heart.
abstract: Compared with heart failure (HF) care 20 to 30 years ago, there has been tremendous advancement in therapy for ambulatory HF with reduced ejection fraction with the use of agents that block maladaptive neurohormonal pathways. However, during the past decade, with few notable exceptions, the frequency of successful drug development programs has fallen as most novel therapies have failed to offer incremental benefit or raised safety concerns (ie, hypotension). Moreover, no therapy has been approved specifically for HF with preserved ejection fraction or for worsening chronic HF (including acutely decompensated HF). Across the spectrum of HF, preliminary results from many phase II trials have been promising but are frequently followed by unsuccessful phase III studies, highlighting a disconnect in the translational process between basic science discovery, early drug development, and definitive clinical testing in pivotal trials. A major unmet need in HF drug development is the ability to identify homogeneous subsets of patients whose underlying disease is driven by a specific mechanism that can be targeted using a new therapeutic agent. Drug development strategies should increasingly consider therapies that facilitate reverse remodeling by directly targeting the heart itself rather than strictly focusing on agents that unload the heart or target systemic neurohormones. Advancements in cardiac imaging may allow for more focused and direct assessment of drug effects on the heart early in the drug development process. To better understand and address the array of challenges facing current HF drug development, so that future efforts may have a better chance for success, the Food and Drug Administration facilitated a meeting on February 17, 2015, which was attended by clinicians, researchers, regulators, and industry representatives. The following discussion summarizes the key takeaway dialogue from this meeting.
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.). m-gheorghiade@northwestern.edu.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Larson
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Sanjiv J
authors.initials: SJ
authors.lastname: Shah
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Greene
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Colucci
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Preston
authors.initials: P
authors.lastname: Dunnmon
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Kim
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Norman
authors.initials: N
authors.lastname: Stockbridge
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: James
authors.initials: J
authors.lastname: Carr
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Wilfried
authors.initials: W
authors.lastname: Dinh
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Krahn
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Frank
authors.initials: F
authors.lastname: Kramer
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Karin
authors.initials: K
authors.lastname: Wahlander
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Deckelbaum
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: David
authors.initials: D
authors.lastname: Crandall
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Okada
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Michele
authors.initials: M
authors.lastname: Senni
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Sergey
authors.initials: S
authors.lastname: Sikora
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
authors.affiliation: From the Center for Cardiovascular Innovation (M.G.) and Division of Cardiology (S.J.S.), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, IL; Cardiovascular & Metabolic Diseases Drug Discovery Unit, Takeda Pharmaceuticals, Chicago, IL (C.J.L., S.O.); Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); National Heart & Lung Institute, Imperial College, London, United Kingdom (J.G.F.C.); Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, MA (W.S.C.); Division of Cardiovascular and Renal Products, the United States Food and Drug Administration, Silver Spring, MD (P.D., N.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington DC (S.E.E.); Psychiatry Department (R.V.P.) and Cardiology Division (J.B.), Stony Brook University, NY; Stealth Bio Therapeutics, Philadelphia, PA (J.C.); Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany (W.D., T.K., F.K.); Department of Cardiology, Witten University, Witten, Germany (W.D.); Astra Zeneca Research and Development, Gothenburg, Sweden (K.W.); CSL Behring, Philadelphia, PA (L.I.D.); Sunovion Pharmaceuticals Inc, Marlborough, MA (D.C.); Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovannni XXIII, Bergamo, Italy (M.S.); Cardiocell Inc, San Diego, CA (S.S.); and Cardiology Division, Henry Ford Hospital, Detroit, MI (H.N.S.).
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004059:Diffusion of Innovation; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D005544:Forecasting; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015415:Biomarkers; D002317:Cardiovascular Agents
keywords: United States Food and Drug Administration; clinical trial; growth and development; heart failure; pharmaceutical preparations