Author + information
- Received September 1, 2015
- Revision received December 16, 2015
- Accepted December 16, 2015
- Published online July 1, 2016.
- Siu-Hin Wan, MDa,b,
- Paul M. McKie, MDa,b,
- John A. Schirger, MDa,b,
- Joshua P. Slusser, BSc,
- David O. Hodge, MSc,
- Margaret M. Redfield, MDa,b,
- John C. Burnett Jr., MDa,b and
- Horng H. Chen, MBBCha,b,∗ ()
- aDivision of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota
- bCardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota
- cDepartment of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota
- ↵∗Reprint requests and correspondence:
Dr. Horng H. Chen, Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.
Objectives This study determined whether there is development of tachyphylaxis to enhancement of cardiorenal response to acute volume loading (AVL) with B-type natriuretic peptide (BNP) after 12-week, twice-daily subcutaneous BNP administration in patients with preclinical diastolic dysfunction (PDD).
Background PDD is characterized by normal systolic function and moderate or severe diastolic dysfunction but no symptoms of heart failure (HF). Impairment in cardiorenal endocrine response to stress by AVL exists in PDD and is corrected by acute administration of subcutaneous BNP.
Methods A double-blinded, placebo-controlled proof-of-concept study was conducted to compare 12 weeks of twice daily subcutaneous BNP, 10 μg/kg (n = 24), versus placebo (n = 12) in PDD. Subjects underwent 2 study visits, at baseline and after 12 weeks. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular AVL.
Results Among those with PDD, there was a statistically significant improvement in diastolic function after 12 weeks of BNP, as measured by a decrease in the Doppler E/e′ ratio (where E is early mitral inflow velocity and e′ is mitral annulus early diastolic motion) (p = 0.004) and improvement of diastolic dysfunction grade (p = 0.008). After 12 weeks, there was statistically significantly greater sodium excretion, urine flow, and urinary cyclic guanosine monophosphate excretion to AVL (all p < 0.001), as well as a trend toward greater glomerular filtration rate (p = 0.050) in the BNP group as compared to the placebo group.
Conclusions In subjects with PDD, chronic BNP administration resulted in sustained improvement in diastolic function without development of tachyphylaxis to the enhancement of cardiorenal response to volume expansion with BNP. (Human Brain Natriuretic Peptide [BNP] [or Nesiritide] to Help Heart, Kidney and Humoral Function; NCT00405548)
- B-type natriuretic peptide
- cardiorenal syndrome
- diastolic dysfunction
- heart failure with preserved ejection fraction
This research was supported by National Institutes of Health (NIH) grants PO1HL76611 and R01HL84155; NIH/National Center for Research Resources Clinical and Translational Science Awards grant UL1 RR024150; and the Mayo Foundation. Scios Inc. supplied the study drug. Drs. Burnett and Chen have patented and licensed chrimeric natriuretic peptides and receive royalties from Capricor Therapeutics, Anexon, and Up-to-Date, and are cofounders of Zumbro Discovery. All other authors report that they have no relationships relevant to the contents of this paper to disclose.
- Received September 1, 2015.
- Revision received December 16, 2015.
- Accepted December 16, 2015.
- 2016 American College of Cardiology Foundation