@article{3163274,
    title = "New strategies for heart failure with preserved ejection fraction: the
importance of targeted therapies for heart failure phenotypes",
    author = "Senni, Michele and Paulus, Walter J. and Gavazzi, Antonello and Fraser, and Alan G. and Diez, Javier and Solomon, Scott D. and Smiseth, Otto A. and and Guazzi, Marco and Lam, Carolyn S. P. and Maggioni, Aldo P. and Tschoepe, and Carsten and Metra, Marco and Hummel, Scott L. and Edelmann, Frank and and Ambrosio, Giuseppe and Coats, Andrew J. Stewart and Filippatos, and Gerasimos S. and Gheorghiade, Mihai and Anker, Stefan D. and Levy, and Daniel and Pfeffer, Marc A. and Stough, Wendy Gattis and Pieske, Burkert and M.",
    journal = "EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY",
    year = "2014",
    volume = "35",
    number = "40, SI",
    pages = "2797-2811",
    publisher = "Oxford University Press",
    doi = "10.1093/eurheartj/ehu204",
    keywords = "Heart failure, Diastolic; Clinical trial; Diabetes mellitus; Exercise
tolerance; Phenotype; Preserved ejection fraction",
    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."
}