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

• Published in: JACC. Basic to translational science 2019-12, Vol.4 (8), p.962-972
• Main Authors: Wan, Siu-Hin, Torres-Courchoud, Isabel, McKie, Paul M., Slusser, Joshua P., Redfield, Margaret M., Burnett, John C., Hodge, David O., Chen, Horng H.
• Format: Article
• Language: English
• Subjects: B-type natriuretic peptide; cardiorenal; heart failure; nesiritide; phosphodiesterase inhibition; PRECLINICAL RESEARCH; systolic dysfunction
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2019.08.008

[Display omitted] •In preclinical systolic dysfunction, defined as left ventricular systolic dysfunction with no heart failure signs or symptoms, impairment in cardiorenal response to volume expansion may lead to symptomatic heart failure. Rescue of this impaired process in preclinical disease may prevent development of symptomatic heart failure.•In preclinical systolic dysfunction, inhibition of phosphodiesterase-V in combination with exogenous B-type natriuretic peptide administration results in improved cardiac function but worsened renal function in response to acute volume expansion.•Future studies are needed to further define the physiological effects and long-term outcomes of phosphodiesterase-V inhibition and exogenous BNP administration. Understanding the cardiorenal effects and outcomes of combination phosphodiesterase-V with exogenous B-type natriuretic peptide may affect the clinical management of patients with preclinical systolic dysfunction and renal dysfunction. 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)