title: Pathophysiology-based novel pharmacotherapy for heart failure with preserved ejection fraction.
abstract: Heart failure has become increasingly prevalent and poses a significant socioeconomic burden in the developed world. Approximately half of heart failure patients have preserved ejection fraction (HFpEF) and experience an increased morbidity and mortality attributed to the lack of effective therapies and to the presence of comorbidities. Suppression of neurohormonal activation by beta-blockers and renin-angiotensin-aldosterone system inhibitors is the cornerstone in the pharmacotherapy of heart failure with reduced ejection fraction (HFrEF). However, these medications are not associated with significant clinical benefit in HFpEF. In this review, we provide an in-depth pathophysiology-based update on novel pharmacotherapies of HFpEF. A deeper insight into the pathophysiologic mechanisms of HFpEF may create opportunities for novel pharmacological interventions.
authors.affiliation: First Department of Cardiology, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki, Greece; Heart Failure Care Group, The Royal Brompton Hospital, London Imperial College, London, UK.
authors.forename: Dimitrios M
authors.initials: DM
authors.lastname: Konstantinou
authors.forename: Yiannis S
authors.initials: YS
authors.lastname: Chatzizisis
authors.forename: George D
authors.initials: GD
authors.lastname: Giannoglou
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D013318:Stroke Volume
chemical_list: D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: ACEi; ANP; ARBs; BH4; BNP; DPP; Diastolic dysfunction; GC; GLP-1; HFpEF; HFrEF; Heart failure; Late I(Na); NCX; NO; NOS; Na(+)–Ca(2+) exchanger; PDE; PKA; PKG; Pathophysiology; Pharmacotherapy; RAAS; RyR2; SERCA2; TGF-β1; angiotensin II receptor blockers; angiotensin converting enzyme inhibitors; atrial natriuretic peptide; brain natriuretic peptide; cAMP; cGMP; cyclic adenosine monophosphate; cyclic guanosine monophosphate; dipeptidyl-peptidase; glucagon like peptide-1; guanylate cyclase; heart failure with preserved ejection fraction; heart failure with reduced ejection fraction; late Na(+) current; nitric oxide; nitric oxide synthase; phosphodiesterases; protein kinase A; protein kinase G; renin–angiotensin–aldosterone system; ryanodine receptor-2; sarcoplasmic reticulum Ca(++) ATPase-isoform 2; tetrahydrobiopterin; transforming growth factor-β1