Author + information
- Received July 5, 2018
- Revision received November 27, 2018
- Accepted December 5, 2018
- Published online March 18, 2019.
- Nasrien E. Ibrahim, MDa,b,
- Cian P. McCarthy, MB BCh, BAOa,
- Shreya Shrestha, MDa,
- Hanna K. Gaggin, MD, MPHa,b,
- Renata Mukai, BAa,
- Jackie Szymonifka, MAc,
- Fred S. Apple, PhDd,
- John C. Burnett Jr., MDe,
- Seethalakshmi Iyer, MS Pharme and
- James L. Januzzi Jr., MDa,b,f,∗ (, )@JJheart_doc
- aCardiology Division, Massachusetts General Hospital, Boston, Massachusetts
- bHarvard Medical School, Boston, Massachusetts
- cNew York University Langone Medical Center, New York, New York
- dLaboratory Medicine & Pathology, Hennepin County Medical Center & University of Minnesota, Minneapolis, Minnesota
- eMayo Clinic, Rochester, Minnesota
- fBaim Institute for Clinical Research, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. James L. Januzzi, Jr., Massachusetts General Hospital, 32 Fruit Street, Yawkey 5984, Boston, Massachusetts 02114.
Background With sacubitril/valsartan treatment, B-type natriuretic peptide (BNP) concentrations increase; it remains unclear whether change in BNP concentrations is similar across all assays for its measurement. Effects of sacubitril/valsartan on atrial natriuretic peptide (ANP) concentrations in patients are unknown. Lastly, the impact of neprilysin inhibition on mid-regional pro-ANP (MR-proANP), N-terminal pro-BNP (NT-proBNP), proBNP1-108, or C-type natriuretic peptide (CNP) is not well understood.
Objectives This study sought to examine the effects of sacubitril/valsartan on results from different natriuretic peptide assays.
Methods Twenty-three consecutive stable patients with heart failure and reduced ejection fraction were initiated and titrated on sacubitril/valsartan. Change in ANP, MR-proANP, BNP (using 5 assays), NT-proBNP (3 assays), proBNP1-108, and CNP were measured over 3 visits.
Results Average time to 3 follow-up visits was 22, 46, and 84 days. ANP rapidly and substantially increased with initiation and titration of sacubitril/valsartan, more than doubling by the first follow-up visit (+105.8%). Magnitude of ANP increase was greatest in those with concentrations above the median at baseline (+188%) compared with those with lower baseline concentrations (+44%); ANP increases were sustained. Treatment with sacubitril/valsartan led to inconsistent changes in BNP, which varied across methods assessed. Concentrations of MR-proANP, NT-proBNP, and proBNP1-108 variably declined after treatment; whereas CNP concentrations showed no consistent change.
Conclusions Initiation and titration of sacubitril/valsartan led to variable changes in concentrations of multiple natriuretic peptides. These results provide important insights into the effects of sacubitril/valsartan treatment on individual patient results, and further suggest the benefit of neprilysin inhibition may be partially mediated by increased ANP concentrations.
This work was sponsored by a grant from Abbott, Inc. Dr. Ibrahim is supported in part by the Dennis and Marilyn Barry Fellowship in Cardiology (Boston, Massachusetts). Dr. Gaggin is supported in part by the Clark Fund for Cardiac Research Innovation (Boston, Massachusetts). Dr. Januzzi is supported in part by the Hutter Family Professorship (Boston, Massachusetts). Dr. Ibrahim has received speaker fees from Novartis. Dr. Gaggin has received grant support from Roche Diagnostics and Jana Care; has received consulting income from Roche Diagnostics; and has participated in clinical endpoint committees/data safety monitoring boards for Radiometer. Dr. Apple has received consulting income from Metanomics Healthcare; is on the board of directors for HyTest Ltd; is on the advisory board for Instrumentation Laboratory, LumiraDx, and Banyan Biomarkers; is an associate editor of Clinical Chemistry; and has received honoraria for speaking from Siemens Healthcare. Dr. Burnett has received consulting income from Novartis. Dr. Januzzi has received grant support from Alere, Siemens, Roche Diagnostics, Abbott, Singulex, and Prevencio; has received consulting income from Roche Diagnostics, Abbott, Critical Diagnostics, Janssen, and Novartis; and has participated in clinical endpoint committees/data safety monitoring boards for Novartis, Amgen, Pfizer, Janssen, AbbVie, and Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received July 5, 2018.
- Revision received November 27, 2018.
- Accepted December 5, 2018.
- 2019 American College of Cardiology Foundation
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