Phosphodiesterase inhibitor for heart failure with preserved ejection fraction: A systematic review and meta-analysis

Zhu Chen; Kaixuan Zhao; Changhu Xiao; Ziyu He; Sha Liu; Xuemei Wu; Shuting Shi; Yuan Guo

doi:10.1016/j.jsps.2022.05.012

Phosphodiesterase inhibitor for heart failure with preserved ejection fraction: A systematic review and meta-analysis

Saudi Pharm J. 2022 Aug;30(8):1079-1087. doi: 10.1016/j.jsps.2022.05.012. Epub 2022 Jun 1.

Authors

Zhu Chen^{1

2}, Kaixuan Zhao², Changhu Xiao², Ziyu He³, Sha Liu², Xuemei Wu², Shuting Shi², Yuan Guo^{1

2

4}

Affiliations

¹ Department of Cardiovascular Medicine, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 412007, Hunan, China.
² Hunan Key Laboratory of Biomedical Nanomaterials and Devices, Hunan University of Technology, Zhuzhou 412007, Hunan, China.
³ Department of Research Laboratory, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 412007, Hunan, China.
⁴ Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.

Abstract

Background: Although heart failure with preserved ejection fraction (HFpEF) is a serious disease, only limited options are available for its treatment. Recent studies have analyzed the effects of phosphodiesterase (PDE) inhibitors, especially PDE5 and PDE3 inhibitors, in patients with HFpEF, with mixed outcomes.

Methods: We searched PUBMED and EMBASE databases up to August 2021. Randomized controlled trials (RCTs) and clinical trials that tested the effects of PDE inhibitors on patients with HFpEF were included as eligible studies. Indicators of left ventricular (LV) function, pulmonary arterial pressure (PAP), right ventricular (RV) function, exercise capacity, and quality of life (QOL) were used to evaluate the efficacy of PDE inhibitors in HFpEF.

Results: Six RCTs that reported in 7 studies were included to evaluate the efficiency of PDE inhibitors on HFpEF patients. In the pooled analysis, PDE inhibitors showed insignificant changes in the ratio of early diastolic mitral inflow to annular velocities, left atrial volume index, pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), peak oxygen uptake, 6-minute walking test distance, as well as Kansas City Cardiomyopathy Questionnaire score. However, substantial improvement was observed in the tricuspid annular plane systolic excursion (TAPSE). Additionally, the regression analysis showed that PDE inhibitor administration time is a critical factor for the decrease in PASP.

Conclusions: PDE inhibitors did not effectively improve LV function, PAP, exercise capacity, and QOL in patients with HFpEF. However, they improved RV function with significant difference, suggesting that PDE inhibitors might be a promising option for HFpEF patients with RV dysfunction.

Keywords: 6MWT, 6-minute walking test; 95% CIs, 95% confidence intervals; BD, baseline data; CD, change data; E/e′, early diastolic mitral inflow to annular velocities; FD, final data; HFpEF, heart failure with preserved ejection fraction; Heart failure with preserved ejection fraction; KCCQ, Kansas City cardiomyopathy questionnaire; LAVI, left atrial volume index; LV, left ventricular; MeSH, Medical Subject Heading; Meta-analysis; NT-proBNP, N-terminal fragment of the precursor to brain-type natriuretic peptide; PAP, pulmonary arterial pressure; PASP, pulmonary artery systolic pressure; PDE, phosphodiesterase; PH, pulmonary hypertension; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PVR, pulmonary vascular resistance; Phosphodiesterase inhibitor; QOL, quality of life; RCTs, randomized controlled trials; RR, risk ratio; RV, right ventricular; Right ventricular dysfunction; SMD, standardized mean difference; TAPSE, tricuspid annular plane systolic excursion; VO2, oxygen uptake; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate.