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• W3181023598 abstract "HomeCirculation: Heart FailureVol. 14, No. 7Early Reduction in Ambulatory Pulmonary Artery Pressures After Initiation of Sacubitril/Valsartan Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBEarly Reduction in Ambulatory Pulmonary Artery Pressures After Initiation of Sacubitril/Valsartan Akshay S. Desai, MD, MPH, J. Thomas Heywood, MD, Lisa Rathman, CRNP, William T. Abraham, MD, Philip Adamson, MD, Marie-Elena Brett, PhD, Maria R. Costanzo, MD, Sumant Lamba, MD, Nirav Raval, MD, David Shavelle, MD, Poornima Sood, MD and Lynne W. Stevenson, MD Akshay S. DesaiAkshay S. Desai Correspondence to: Akshay S. Desai, MD, MPH, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115. Email E-mail Address: [email protected] https://orcid.org/0000-0002-1443-0701 Brigham and Women’s Hospital, Boston, MA (A.S.D.). Search for more papers by this author , J. Thomas HeywoodJ. Thomas Heywood Scripps Clinic, La Jolla, CA (J.T.H.). Search for more papers by this author , Lisa RathmanLisa Rathman The Heart Group of Lancaster General Health, Lancaster, PA (L.R.). Search for more papers by this author , William T. AbrahamWilliam T. Abraham https://orcid.org/0000-0003-4805-1037 Ohio State University, Columbus (W.T.A.). Search for more papers by this author , Philip AdamsonPhilip Adamson https://orcid.org/0000-0002-8974-9004 Abbott Labs, Austin, TX (P.A., M.-E.B., P.S.). Search for more papers by this author , Marie-Elena BrettMarie-Elena Brett https://orcid.org/0000-0001-5545-7209 Abbott Labs, Austin, TX (P.A., M.-E.B., P.S.). Search for more papers by this author , Maria R. CostanzoMaria R. Costanzo https://orcid.org/0000-0001-6995-7538 Advocate Medical Group, Downers Grove, IL (M.R.C.). Search for more papers by this author , Sumant LambaSumant Lamba First Coast Cardiovascular Institute, Jacksonville, FL (S.L.). Search for more papers by this author , Nirav RavalNirav Raval Advent Health Transplant Institute, Orlando, FL (N.R.). Search for more papers by this author , David ShavelleDavid Shavelle https://orcid.org/0000-0002-9209-9807 University of Southern California, Los Angeles, CA (D.S.). *Current affiliation: MemorialCare Heart and Vascular Institute, Long Beach Medical Center, Long Beach, CA Search for more papers by this author , Poornima SoodPoornima Sood Abbott Labs, Austin, TX (P.A., M.-E.B., P.S.). Search for more papers by this author and Lynne W. StevensonLynne W. Stevenson https://orcid.org/0000-0002-8626-5258 Vanderbilt University Medical Center, Nashville, TN (L.W.S.). Search for more papers by this author Originally published12 Jul 2021https://doi.org/10.1161/CIRCHEARTFAILURE.120.008212Circulation: Heart Failure. 2021;14Guidelines recommend use of ARNIs (angiotensin receptor neprilysin inhibitors) for many patients with symptomatic heart failure and reduced ejection fraction (HFrEF) to reduce morbidity and mortality.1 Early reductions in natriuretic peptides and atrial and ventricular volumes with sacubitril/valsartan compared with enalapril suggest a possible impact of neprilysin inhibition on intracardiac filling pressures.2,3 We used data from the CardioMEMS PAS (Post-Approval Study) to evaluate the impact of ARNI initiation on ambulatory pulmonary artery pressures (PAP) in chronic HF.The PAS was a longitudinal cohort study of 1200 patients with chronic HF, New York Heart Association class III symptoms, and prior HF hospitalization receiving an implantable PAP sensor for ambulatory hemodynamic monitoring.4 The study was approved by the institutional review board at each participating site, and all subjects provided informed consent. We examined changes in PAP from baseline to 30 days among PAS patients newly initiated on ARNI (sacubitril/valsartan) at median 168 (interquartile range, 41–313) days after device implantation. Differences were calculated between pressures averaged during the week before ARNI initiation and those during the last week of the 30-day period after drug initiation. A comparator group was defined from patients with HFrEF who were eligible but not initiated on ARNI within a matched 30-day period (days, 163–170 to days, 194–200 postsensor implantation). The data that support the findings of this study are available from the corresponding author upon reasonable request.Patients newly initiated on ARNI (n=96) were generally well-matched with the comparator group (n=406), but were more commonly female or black, and tended to have higher blood pressure, estimated glomerular filtration rate, EF, and background use of guideline-directed medical therapy at study entry. Mean PAP (mPAP) was 32.8±10.5 mm Hg immediately before start of sacubitril/valsartan and decreased to 29.9±9.4 mm Hg after 30 days (difference, −2.9 mm Hg [95% CI, −4.1 to −1.8 mm Hg], P<0.001, Figure [A]). Reduction in mPAP occurred principally in patients with baseline mPAP ≥30 mm Hg (n=60; difference, −4.2 mm Hg [95% CI, −5.7 to −2.6 mm Hg], P<0.0001), with little change occurring in those with baseline mPAP <30 mm Hg (n=36; difference, −0.9 mm Hg [95% CI, −2.1 to 0.3 mm Hg], P=0.14, Figure [B]). PA pressure reduction at 30 days was greater in those initiated on ARNI than in HFrEF patients not initiated on sacubitril/valsartan analyzed during the temporally matched interval (Figure [C]). There was no difference between groups in the frequency of changes in other cardiovascular medicines (including loop diuretics) recorded during the 30-day interval.Download figureDownload PowerPointFigure. Observed changes in pulmonary artery pressures during study follow up. A, Longitudinal trends in systolic, diastolic, and mean pulmonary artery pressure (PAP) from initiation of sacubitril/valsartan to 30 days for all patients newly initiated on sacubitril/valsartan (N=96) and (B) according to PAP at study enrollment (<30 versus ≥30 mm Hg). C, Absolute changes in PAP from baseline to 30 days following sacubitril/valsartan vs temporally matched heart failure and reduced ejection fraction patients not initiated on sacubitril/valsartan (P<0.001 for all between-group comparisons).In summary, among patients implanted with a PAP sensor in clinical practice, those initiated on sacubitril/valsartan experienced greater decline in PA pressures at 30 days than a comparable population of patients with HFrEF not initiated on sacubitril/valsartan analyzed over a similar interval. These reductions were most pronounced in those with elevated mPAP and suggest an early impact of ARNI to reduce elevated filling pressures perhaps through potentiation of vasoactive peptides that decrease systemic vascular resistance, increase venous capacitance, and promote natriuresis.5 Despite important limitations including small sample size, potential confounding by patient differences in this nonrandomized comparison, and selection bias introduced by the decision to initiate ARNI, these data provide mechanistic support for early benefit of ARNI on remodeling and clinical outcomes in HFrEF.Nonstandard Abbreviations and AcronymsARNIangiotensin receptor neprilysin inhibitorHFrEFheart failure and reduced ejection fractionmPAPmean PAPPAPpulmonary artery pressurePASPost-Approval StudySources of FundingThe study (NCT No. 02279888) was funded by Abbott. The funder (Abbott) actively participated in the design and conduct of the study, including data collection, data management, data analysis, and interpretation of the data; and review of the article. This analysis was investigator-initiated and the funder had no role in article preparation or the decision to submit the article for publication.Disclosures Dr Desai reports consulting fees from Abbott, Alnylam, AstraZeneca, Amgen, Boston Scientific, Boehringer-Ingelheim, Biofourmis, Corvidia, DalCor Pharma, Novartis, Relypsa, and Regeneron as well as research support from Abbott, Alnylam, AstraZeneca and Novartis; Dr Heywood and L. Rathman report research support and speaker honoraria from Abbott; Drs Abraham, Raval, Shavelle, and Stevenson report research support from Abbott; Dr Costanzo reports research support from Abbott related to the CardioMEMS US PAS and GUIDE-HF trials and research support from Novartis related to the PARAGLIDE Trial; Drs Sood and Brett are Abbott employees; Dr Adamson is an Abbott employee and stockholder. The other author reports no conflicts.Footnotes*Current affiliation: MemorialCare Heart and Vascular Institute, Long Beach Medical Center, Long Beach, CAFor Sources of Funding and Disclosures, see page 821.Correspondence to: Akshay S. Desai, MD, MPH, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115. Email [email protected]harvard.eduReferences1. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, et al.. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.Circulation. 2017; 136:e137–e161. doi: 10.1161/CIR.0000000000000509LinkGoogle Scholar2. Desai AS, Solomon SD, Shah AM, Claggett BL, Fang JC, Izzo J, McCague K, Abbas CA, Rocha R, Mitchell GF; EVALUATE-HF Investigators. Effect of sacubitril-valsartan vs enalapril on aortic stiffness in patients with heart failure and reduced ejection fraction: a randomized clinical trial.JAMA. 2019; 322:1077–1084. doi: 10.1001/jama.2019.12843CrossrefMedlineGoogle Scholar3. Januzzi JL, Prescott MF, Butler J, Felker GM, Maisel AS, McCague K, Camacho A, Piña IL, Rocha RA, Shah AM, et al.; PROVE-HF Investigators. Association of change in N-Terminal Pro-B-type natriuretic peptide following initiation of sacubitril-valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction.JAMA. 2019; 322:1085–1095. doi: 10.1001/jama.2019.12821CrossrefMedlineGoogle Scholar4. Shavelle D, Desai AS, Abraham WT, Bourge RC, Raval N, Rathman LD, Heywood JT, Jermyn RA, Pelzel J, Jonsson OT, et al.; for the CardioMEMS Post-Approval Study Investigators. Reduction in annual hospitalizations during pulmonary artery pressure-guided therapy for ambulatory heart failure: 1-year outcomes from the CardioMEMS Post-Approval Study.Circ Heart Fail. 2020; 13:e006863. doi: 10.1161/CIRCHEARTFAILURE.119.006863LinkGoogle Scholar5. Vardeny O, Claggett B, Kachadourian J, Desai AS, Packer M, Rouleau J, Zile MR, Swedberg K, Lefkowitz M, Shi V, et al.. Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial.Eur J Heart Fail. 2019; 21:337–341. doi: 10.1002/ejhf.1402CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails July 2021Vol 14, Issue 7Article InformationMetrics Download: 412 © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCHEARTFAILURE.120.008212PMID: 34247518 Originally publishedJuly 12, 2021 Keywordsneprilysinpulmonary arteryhemodynamic monitoringenalaprilheart failurePDF download SubjectsHeart Failure" @default.
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