Author + information
- Received April 15, 2019
- Revision received August 28, 2019
- Accepted August 29, 2019
- Published online December 23, 2019.
- Siu-Hin Wan, MDa,b,
- Isabel Torres-Courchoud, MD, PhDc,
- Paul M. McKie, MDa,b,
- Joshua P. Slusser, BScd,
- Margaret M. Redfield, MDa,b,
- John C. Burnett Jr., MDa,b,
- David O. Hodge, MSd and
- Horng H. Chen, MBBCha,b,∗ ()
- aDepartment of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota
- bCardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota
- cHospital Reina Sofía, Tudela, Navarra, Spain
- dDepartment of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota
- ↵∗Address for correspondence:
Dr. Horng H. Chen, Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905.
• 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)
- B-type natriuretic peptide
- heart failure
- phosphodiesterase inhibition
- systolic dysfunction
This research was supported by grants from the National Institutes of Health (PO1 HL 76611, R01 HL 84155, HL136440) and NIH/NCRR Center for Translational Science Activities (grant number UL1 RR024150). Drs. Wan and Torres-Courchoud contributed equally to this work and are joint first authors. Drs. Chen and Burnett hold patents and licensed designer natriuretic peptides; and are co-founders of Zumbro Discovery. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received April 15, 2019.
- Revision received August 28, 2019.
- Accepted August 29, 2019.
- 2019 The Authors