Chronic subcutaneous brain natriuretic peptide therapy in asymptomatic systolic heart failure

Paul McKie, John A. Schirger, Sherry L. Benike, Lynn K. Harstad, Joshua P. Slusser, David O. Hodge, Margaret May Redfield, John C Jr. Burnett, Horng Haur Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Aims: We have previously reported that asymptomatic systolic heart failure (HF) is characterized by an impaired renal response to volume expansion due to lack of activation of urinary cGMP which is corrected by subcutaneous (SQ) BNP. In the current study, we sought to define the cardiorenal response to intravascular volume expansion after 12 weeks of SQ BNP therapy. Methods and results: We utilized a double-blinded, placebo-controlled study to compare 12 weeks of twice-daily SQ BNP 10μg/kg (n = 22) or placebo (n = 12) in asymptomatic systolic HF. Subjects underwent two study visits: baseline and after 12 weeks of therapy. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular volume expansion. The primary endpoint was change in urinary sodium excretion in response to volume expansion at 12 weeks, and we observed a greater increase in urinary sodium excretion [166 (77, 290) vs. 15 (-39, 72) mEq/min; P = 0.02] with SQ BNP treatment vs. placebo. Secondary endpoints included change in urine flow and glomerular filtration rate (GFR) in response to volume expansion at 12 weeks. We observed a significant increase in urine flow (P <0.01) and trend for differential response in GFR (P = 0.08) with SQ BNP treatment vs. placebo. Conclusion: Among patients with asymptomatic systolic HF, twice-daily SQ BNP therapy improved the cardiorenal response to volume expansion at 12-week follow-up. Further studies are warranted to determine if these beneficial physiological observations with chronic natriuretic peptide administration translate into a delay in the progression to symptomatic HF.

Original languageEnglish (US)
JournalEuropean Journal of Heart Failure
DOIs
StateAccepted/In press - 2016

Fingerprint

Systolic Heart Failure
Brain Natriuretic Peptide
Placebos
Glomerular Filtration Rate
Sodium
Urine
Kidney
Therapeutics
Natriuretic Peptides
Echocardiography
Heart Failure

Keywords

  • Asymptomatic
  • Heart failure
  • Natriuretic peptides
  • Renal

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Chronic subcutaneous brain natriuretic peptide therapy in asymptomatic systolic heart failure. / McKie, Paul; Schirger, John A.; Benike, Sherry L.; Harstad, Lynn K.; Slusser, Joshua P.; Hodge, David O.; Redfield, Margaret May; Burnett, John C Jr.; Chen, Horng Haur.

In: European Journal of Heart Failure, 2016.

Research output: Contribution to journalArticle

@article{2982d9866d584582a32b714bcd58b9c9,
title = "Chronic subcutaneous brain natriuretic peptide therapy in asymptomatic systolic heart failure",
abstract = "Aims: We have previously reported that asymptomatic systolic heart failure (HF) is characterized by an impaired renal response to volume expansion due to lack of activation of urinary cGMP which is corrected by subcutaneous (SQ) BNP. In the current study, we sought to define the cardiorenal response to intravascular volume expansion after 12 weeks of SQ BNP therapy. Methods and results: We utilized a double-blinded, placebo-controlled study to compare 12 weeks of twice-daily SQ BNP 10μg/kg (n = 22) or placebo (n = 12) in asymptomatic systolic HF. Subjects underwent two study visits: baseline and after 12 weeks of therapy. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular volume expansion. The primary endpoint was change in urinary sodium excretion in response to volume expansion at 12 weeks, and we observed a greater increase in urinary sodium excretion [166 (77, 290) vs. 15 (-39, 72) mEq/min; P = 0.02] with SQ BNP treatment vs. placebo. Secondary endpoints included change in urine flow and glomerular filtration rate (GFR) in response to volume expansion at 12 weeks. We observed a significant increase in urine flow (P <0.01) and trend for differential response in GFR (P = 0.08) with SQ BNP treatment vs. placebo. Conclusion: Among patients with asymptomatic systolic HF, twice-daily SQ BNP therapy improved the cardiorenal response to volume expansion at 12-week follow-up. Further studies are warranted to determine if these beneficial physiological observations with chronic natriuretic peptide administration translate into a delay in the progression to symptomatic HF.",
keywords = "Asymptomatic, Heart failure, Natriuretic peptides, Renal",
author = "Paul McKie and Schirger, {John A.} and Benike, {Sherry L.} and Harstad, {Lynn K.} and Slusser, {Joshua P.} and Hodge, {David O.} and Redfield, {Margaret May} and Burnett, {John C Jr.} and Chen, {Horng Haur}",
year = "2016",
doi = "10.1002/ejhf.468",
language = "English (US)",
journal = "European Journal of Heart Failure",
issn = "1388-9842",
publisher = "Oxford University Press",

}

TY - JOUR

T1 - Chronic subcutaneous brain natriuretic peptide therapy in asymptomatic systolic heart failure

AU - McKie, Paul

AU - Schirger, John A.

AU - Benike, Sherry L.

AU - Harstad, Lynn K.

AU - Slusser, Joshua P.

AU - Hodge, David O.

AU - Redfield, Margaret May

AU - Burnett, John C Jr.

AU - Chen, Horng Haur

PY - 2016

Y1 - 2016

N2 - Aims: We have previously reported that asymptomatic systolic heart failure (HF) is characterized by an impaired renal response to volume expansion due to lack of activation of urinary cGMP which is corrected by subcutaneous (SQ) BNP. In the current study, we sought to define the cardiorenal response to intravascular volume expansion after 12 weeks of SQ BNP therapy. Methods and results: We utilized a double-blinded, placebo-controlled study to compare 12 weeks of twice-daily SQ BNP 10μg/kg (n = 22) or placebo (n = 12) in asymptomatic systolic HF. Subjects underwent two study visits: baseline and after 12 weeks of therapy. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular volume expansion. The primary endpoint was change in urinary sodium excretion in response to volume expansion at 12 weeks, and we observed a greater increase in urinary sodium excretion [166 (77, 290) vs. 15 (-39, 72) mEq/min; P = 0.02] with SQ BNP treatment vs. placebo. Secondary endpoints included change in urine flow and glomerular filtration rate (GFR) in response to volume expansion at 12 weeks. We observed a significant increase in urine flow (P <0.01) and trend for differential response in GFR (P = 0.08) with SQ BNP treatment vs. placebo. Conclusion: Among patients with asymptomatic systolic HF, twice-daily SQ BNP therapy improved the cardiorenal response to volume expansion at 12-week follow-up. Further studies are warranted to determine if these beneficial physiological observations with chronic natriuretic peptide administration translate into a delay in the progression to symptomatic HF.

AB - Aims: We have previously reported that asymptomatic systolic heart failure (HF) is characterized by an impaired renal response to volume expansion due to lack of activation of urinary cGMP which is corrected by subcutaneous (SQ) BNP. In the current study, we sought to define the cardiorenal response to intravascular volume expansion after 12 weeks of SQ BNP therapy. Methods and results: We utilized a double-blinded, placebo-controlled study to compare 12 weeks of twice-daily SQ BNP 10μg/kg (n = 22) or placebo (n = 12) in asymptomatic systolic HF. Subjects underwent two study visits: baseline and after 12 weeks of therapy. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular volume expansion. The primary endpoint was change in urinary sodium excretion in response to volume expansion at 12 weeks, and we observed a greater increase in urinary sodium excretion [166 (77, 290) vs. 15 (-39, 72) mEq/min; P = 0.02] with SQ BNP treatment vs. placebo. Secondary endpoints included change in urine flow and glomerular filtration rate (GFR) in response to volume expansion at 12 weeks. We observed a significant increase in urine flow (P <0.01) and trend for differential response in GFR (P = 0.08) with SQ BNP treatment vs. placebo. Conclusion: Among patients with asymptomatic systolic HF, twice-daily SQ BNP therapy improved the cardiorenal response to volume expansion at 12-week follow-up. Further studies are warranted to determine if these beneficial physiological observations with chronic natriuretic peptide administration translate into a delay in the progression to symptomatic HF.

KW - Asymptomatic

KW - Heart failure

KW - Natriuretic peptides

KW - Renal

UR - http://www.scopus.com/inward/record.url?scp=84956611096&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84956611096&partnerID=8YFLogxK

U2 - 10.1002/ejhf.468

DO - 10.1002/ejhf.468

M3 - Article

C2 - 26806605

AN - SCOPUS:84956611096

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

SN - 1388-9842

ER -