Sean P Murphy1, Margaret F Prescott2, Alexander Camacho1, Seethalakshmi R Iyer3, Alan S Maisel4, G Michael Felker5, Javed Butler6, Ileana L Piña7, Nasrien E Ibrahim8, Cheryl Abbas2, John C Burnett3, Scott D Solomon9, James L Januzzi10. 1. Massachusetts General Hospital, Boston, Massachusetts, USA. 2. Novartis Pharmaceuticals, East Hanover, New Jersey, USA. 3. Mayo Clinic, Rochester, Minnesota, USA. 4. University of California, San Diego School of Medicine, San Diego, California, USA. 5. Duke University Medical Center and Duke Clinical Research Institute, Durham, North Carolina, USA. 6. University of Mississippi Medical Center, Jackson, Mississippi, USA. 7. Detroit Medical Center, Detroit, Michigan, USA. 8. Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA. 9. Harvard Medical School, Boston, Massachusetts, USA; Brigham and Women's Hospital, Boston, Massachusetts, USA. 10. Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA; Baim Institute for Clinical Research, Boston, Massachusetts, USA. Electronic address: JJanuzzi@partners.org.
Abstract
OBJECTIVES: This study sought to assess associations between longitudinal change in atrial natriuretic peptide (ANP) and reverse cardiac remodeling following initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). BACKGROUND: Neprilysin inhibition results in an increase of several vasoactive peptides that may mediate the beneficial effects of sacubitril/valsartan, including ANP. METHODS: In a prospective study of initiation and titration of sacubitril/valsartan in patients with HFrEF, blood was collected at scheduled time points into tubes containing protease inhibitors. This pre-specified exploratory analysis included patients in whom ANP was measured at baseline and serially through 12 months of treatment. RESULTS: Among 144 participants (mean age: 64.5 years; left ventricular ejection fraction: 30.8%), following initiation of sacubitril/valsartan, there was an early and significant increase in ANP, with the majority of rise from 99 pg/ml at baseline to 156 pg/ml at day 14 (p < 0.001). There was a further trend toward a second increase from day 30 to day 45 (p = 0.07). At maximal rise, ANP had doubled. In longitudinal analyses, early rise in ANP was followed by a subsequent increase in urinary cycle guanosine monophosphate. Larger early increase in ANP was associated with larger later improvements in left ventricular ejection fraction and left atrial volume index (p < 0.001 for both). CONCLUSIONS: Concentrations of ANP doubled after initiation of sacubitril/valsartan in patients with HFrEF. Larger early increases in ANP were associated with a greater magnitude of subsequent reverse cardiac remodeling. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).
OBJECTIVES: This study sought to assess associations between longitudinal change in atrial natriuretic peptide (ANP) and reverse cardiac remodeling following initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). BACKGROUND:Neprilysin inhibition results in an increase of several vasoactive peptides that may mediate the beneficial effects of sacubitril/valsartan, including ANP. METHODS: In a prospective study of initiation and titration of sacubitril/valsartan in patients with HFrEF, blood was collected at scheduled time points into tubes containing protease inhibitors. This pre-specified exploratory analysis included patients in whom ANP was measured at baseline and serially through 12 months of treatment. RESULTS: Among 144 participants (mean age: 64.5 years; left ventricular ejection fraction: 30.8%), following initiation of sacubitril/valsartan, there was an early and significant increase in ANP, with the majority of rise from 99 pg/ml at baseline to 156 pg/ml at day 14 (p < 0.001). There was a further trend toward a second increase from day 30 to day 45 (p = 0.07). At maximal rise, ANP had doubled. In longitudinal analyses, early rise in ANP was followed by a subsequent increase in urinary cycle guanosine monophosphate. Larger early increase in ANP was associated with larger later improvements in left ventricular ejection fraction and left atrial volume index (p < 0.001 for both). CONCLUSIONS: Concentrations of ANP doubled after initiation of sacubitril/valsartan in patients with HFrEF. Larger early increases in ANP were associated with a greater magnitude of subsequent reverse cardiac remodeling. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).
Authors: S Jeson Sangaralingham; Kanupriya Whig; Satyamaheshwar Peddibhotla; R Jason Kirby; Hampton E Sessions; Patrick R Maloney; Paul M Hershberger; Heather Mose-Yates; Becky L Hood; Stefan Vasile; Shuchong Pan; Ye Zheng; Siobhan Malany; John C Burnett Journal: Proc Natl Acad Sci U S A Date: 2021-12-28 Impact factor: 12.779
Authors: Erica M Dillon; Shouzuo D Wei; Deepak K Gupta; Hui Nian; Brooks S Rodibaugh; Katherine N Bachmann; Allen J Naftilan; Lynne W Stevenson; Nancy J Brown Journal: J Card Fail Date: 2021-06-13 Impact factor: 5.712