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Eur Heart J. 2014 Oct 21;35(40):2797-815. doi: 10.1093/eurheartj/ehu204. Epub 2014 Aug 7.

New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes.

Author information

1
Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy.
2
Institute for Cardiovascular Research, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
3
Wales Heart Research Institute, Cardiff University, Cardiff, UK.
4
Division of Cardiovascular Sciences Centre for Applied Medical Research and Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, University of Navarra, Pamplona, Spain.
5
Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
6
Institute for Surgical Research, Department of Cardiology, and Center for Cardiological Innovation, University of Oslo, Oslo, Norway.
7
Heart Failure Unit, Department of Biomedical Sciences for Health, IRCCS Policlinico San Donato, University of Milano, Milan, Italy.
8
National University Health System, Singapore, Singapore.
9
ANMCO Research Center, Florence, Italy.
10
Department of Cardiology and Pneumology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Germany.
11
Cardiology, Department of Experimental and Applied Medicine, University of Brescia, Brescia, Italy.
12
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA Section of Cardiology, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, MI, USA.
13
Department of Cardiology and Pneumology, University of Göttingen, Göttingen, Germany.
14
Division of Cardiology, University of Perugia School of Medicine, Perugia, Italy.
15
Monash University, Melbourne, Australia University of Warwick, Conventry, UK.
16
Athens University Hospital Attikon, Athens, Greece.
17
Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
18
Department of Innovative Clinical Trials, University Medical Centre Gottingen, Gottingen, Germany Applied Cachexia Research, Department of Cardiology, Charite, Campus CVK, Berlin, Germany.
19
Framingham Heart Study, Framingham, MA, USA Division of Cardiology, Boston University School of Medicine, Boston, MA, USA Center for Population Studies, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
20
Department of Clinical Research, Campbell University College of Pharmacy and Health Sciences, North Carolina, USA.
21
Department of Cardiology, Medical University Graz, Ludwig-Boltzmann-Institute for Heart Failure Research, Auenbruggerplatz 15, 8010 Graz, Austria burkert.pieske@medunigraz.at.

Abstract

The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.

KEYWORDS:

Clinical trial; Diabetes mellitus; Exercise tolerance; Heart failure, Diastolic; Phenotype; Preserved ejection fraction

PMID:
25104786
PMCID:
PMC4204003
DOI:
10.1093/eurheartj/ehu204
[Indexed for MEDLINE]
Free PMC Article

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