Cardiac Versus Renal Response to Volume Expansion in Preclinical Systolic Dysfunction With PDEV Inhibition and BNP

Siu-Hin Wan; Isabel Torres-Courchoud; Paul M McKie; Joshua P Slusser; Margaret M Redfield; John C Burnett Jr; David O Hodge; Horng H Chen

doi:10.1016/j.jacbts.2019.08.008

Cardiac Versus Renal Response to Volume Expansion in Preclinical Systolic Dysfunction With PDEV Inhibition and BNP

JACC Basic Transl Sci. 2019 Dec 23;4(8):962-972. doi: 10.1016/j.jacbts.2019.08.008. eCollection 2019 Dec.

Authors

Siu-Hin Wan^{1

2}, Isabel Torres-Courchoud³, Paul M McKie^{1

2}, Joshua P Slusser⁴, Margaret M Redfield^{1

2}, John C Burnett Jr^{1

2}, David O Hodge⁴, Horng H Chen^{1

2}

Affiliations

¹ Department of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota.
² Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota.
³ Hospital Reina Sofía, Tudela, Navarra, Spain.
⁴ Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota.

Abstract

Impaired cardiorenal response to acute saline volume expansion in preclinical systolic dysfunction (PSD) may lead to symptomatic heart failure. The objective was to determine if combination phosphodiesterase-V inhibition and exogenous B-type natriuretic peptide (BNP) administration may enhance cardiorenal response. A randomized double-blinded, placebo-controlled study was conducted in 21 subjects with PSD and renal dysfunction. Pre-treatment with tadalafil and subcutaneous BNP resulted in improved cardiac function, as evidenced by improvement in ejection fraction, left atrial volume index, and left ventricular end-diastolic volume. However, there was reduced renal response with reduction in renal plasma flow, glomerular filtration rate, and urine flow. (Tadalafil and Nesiritide as Therapy in Pre-clinical Heart Failure; NCT01544998).

Keywords: ACC, American College of Cardiology; AHA, American Heart Association; ANP, atrial natriuretic peptide; B-type natriuretic peptide; BNP, B-type natriuretic peptide; GFR, glomerular filtration rate; HF, heart failure; LAVI, left atrial volume index; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; NP, natriuretic peptide; PDEV, type V phosphodiesterase; PSD, preclinical systolic dysfunction; RPF, renal plasma flow; SC, subcutaneous; VE, acute saline volume expansion; cGMP, cyclic guanosine monophosphate; cardiorenal; heart failure; nesiritide; phosphodiesterase inhibition; systolic dysfunction.

Associated data

ClinicalTrials.gov/NCT01544998

Abstract

Associated data

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