Heart failure with preserved ejection fraction

Emerging drug strategies

Fouad A. Zouein, Lisandra E. De Castro Brás, Danielle V. Da Costa, Merry L Lindsey, Mazen Kurdi, George W. Booz

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Approximately half of heart failure patients have a normal ejection fraction, a condition designated as heart failure with preserved ejection fraction (HFpEF). This heart failure subtype disproportionately affects women and the elderly and is commonly associated with other cardiovascular comorbidities, such as hypertension and diabetes. HFpEF is increasing at a steady rate and is predicted to become the leading cause of heart failure within a decade. HFpEF is characterized by impaired diastolic function, thought to be due to concentric remodeling of the heart along with increased stiffness of both the extracellular matrix and myofilaments. In addition, oxidative stress and inflammation are thought to have a role in HFpEF progression, along with endothelial dysfunction and impaired nitric oxide-cyclic guanosine monophosphate-protein kinase G signaling. Surprisingly a number of clinical studies have failed to demonstrate any benefit of drugs effective in heart failure with systolic dysfunction in HFpEF patients. Thus, HFpEF is one of the largest unmet needs in cardiovascular medicine, and there is a substantial need for new therapeutic approaches and strategies that target mechanisms specific for HFpEF. This conclusion is underscored by the recently reported disappointing results of the RELAX trial, which assessed the use of phosphodiesterase-5 inhibitor sildenafil for treating HFpEF. In animal models, endothelial nitric oxide synthase activators and If current inhibitors have shown benefit in improving diastolic function, and there is a rationale for assessing matrix metalloproteinase 9 inhibitors and nitroxyl donors. LCZ696, a combination drug of angiotensin II receptor blocker and neprilysin inhibitor, and the aldosterone receptor antagonist spironolactone are currently in clinical trial for treating HFpEF. Here we present an overview of the etiology and diagnosis of HFpEF that segues into a discussion of new therapeutic approaches emerging from basic research and drugs currently in clinical trial that primarily target diastolic dysfunction or imbalanced ventricular-arterial coupling.

Original languageEnglish (US)
Pages (from-to)13-21
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume62
Issue number1
DOIs
StatePublished - Jul 1 2013

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Heart Failure
Pharmaceutical Preparations
Guanylate Kinases
Clinical Trials
Systolic Heart Failure
Mineralocorticoid Receptor Antagonists
Phosphodiesterase 5 Inhibitors
Cyclic GMP-Dependent Protein Kinases
Neprilysin
Spironolactone
Matrix Metalloproteinase Inhibitors
Myofibrils
Nitric Oxide Synthase Type III
Angiotensin Receptor Antagonists
Matrix Metalloproteinase 9
Drug Combinations
Extracellular Matrix
Comorbidity
Nitric Oxide
Oxidative Stress

Keywords

  • cardiac remodeling
  • cardiomyocyte stiffness
  • diastolic dysfunction
  • extracellular matrix
  • heart failure
  • hypertension
  • preserved ejection fraction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Heart failure with preserved ejection fraction : Emerging drug strategies. / Zouein, Fouad A.; De Castro Brás, Lisandra E.; Da Costa, Danielle V.; Lindsey, Merry L; Kurdi, Mazen; Booz, George W.

In: Journal of Cardiovascular Pharmacology, Vol. 62, No. 1, 01.07.2013, p. 13-21.

Research output: Contribution to journalArticle

Zouein, Fouad A. ; De Castro Brás, Lisandra E. ; Da Costa, Danielle V. ; Lindsey, Merry L ; Kurdi, Mazen ; Booz, George W. / Heart failure with preserved ejection fraction : Emerging drug strategies. In: Journal of Cardiovascular Pharmacology. 2013 ; Vol. 62, No. 1. pp. 13-21.
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