{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:34:54Z","timestamp":1791506094176,"version":"4.3.4"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T00:00:00Z","timestamp":1550620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background. Sacubitril\/valsartan in heart failure (HF) with reduced ejection fraction (HFrEF) was shown to be superior to enalapril in reducing the risk of death and hospitalization for HF. Our aim was to evaluate the cardiopulmonary effects of sacubitril\/valsartan in patients with HFrEF. Methods. We conducted an observational study. Ninety-nine ambulatory patients with HFrEF underwent serial cardiopulmonary exercise tests (CPET) after initiation of sacubitril\/valsartan in addition to recommended therapy. Results. At baseline, 37% of patients had New York Heart Association (NYHA) class III. After a median follow-up of 6.2 months (range 3\u201314.9 months) systolic blood pressure decreased from 117 \u00b1 14 to 101 \u00b1 12 mmHg (p &lt; 0.0001), left ventricular ejection fraction (LVEF) increased from 27 \u00b1 6 to 29.7 \u00b1 7% (p &lt; 0.0001), peak oxygen consumption (VO2) improved from 14.6 \u00b1 3.3 (% of predicted = 53.8 \u00b1 14.1) to 17.2 \u00b1 4.7 mL\/kg\/min (% of predicted = 64.7 \u00b1 17.8) (p &lt; 0.0001), minute ventilation\/carbon dioxide production relationship (VE\/VCO2 Slope) decreased from 34.1 \u00b1 6.3 to 31.7 \u00b1 6.1 (p = 0.006), VO2 at anaerobic threshold increased from 11.3 \u00b1 2.6 to 12.6 \u00b1 3.5 mL\/kg\/min (p = 0.007), oxygen pulse increased from 11.5 \u00b1 3.0 to 13.4 \u00b1 4.3 mL\/kg\/min (p &lt; 0.0001), and \u2206VO2\/\u2206Work increased from 9.2 \u00b1 1.5 to 10.1 \u00b1 1.8 mL\/min\/watt (p = 0.0002). Conclusion. Sacubitril\/valsartan improved exercise tolerance, LVEF, peak VO2, and ventilatory efficiency at 6.2 months follow-up. Further studies are necessary to better clarify underlying mechanisms of this functional improvement.<\/jats:p>","DOI":"10.3390\/jcm8020262","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T11:45:39Z","timestamp":1550663139000},"page":"262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Early Effects of Sacubitril\/Valsartan on Exercise Tolerance in Patients with Heart Failure with Reduced Ejection Fraction"],"prefix":"10.3390","volume":"8","author":[{"given":"Giuseppe","family":"Vitale","sequence":"first","affiliation":[{"name":"Cardiovascular Rehabilitation Unit, Buccheri La Ferla Fatebenefratelli Hospital, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Romano","sequence":"additional","affiliation":[{"name":"Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation IRCCS \u2013 ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Di Franco","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppa","family":"Caccamo","sequence":"additional","affiliation":[{"name":"Cardiovascular Rehabilitation Unit, Buccheri La Ferla Fatebenefratelli Hospital, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9415-2360","authenticated-orcid":false,"given":"Cinzia","family":"Nugara","sequence":"additional","affiliation":[{"name":"Cardiovascular Rehabilitation Unit, Buccheri La Ferla Fatebenefratelli Hospital, 90123 Palermo, Italy"},{"name":"Biomedical Department of Internal Medicine and Specialities (DIBIMIS), University of Palermo \u2013 IRCSS Bonino Pulejo, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ajello","sequence":"additional","affiliation":[{"name":"Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation IRCCS \u2013 ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvo","family":"Storniolo","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital, Policlinico Paolo Giaccone, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Sarullo","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital, Policlinico Paolo Giaccone, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0548-0926","authenticated-orcid":false,"given":"Valentina","family":"Agnese","sequence":"additional","affiliation":[{"name":"Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation IRCCS \u2013 ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4119-9397","authenticated-orcid":false,"given":"Francesco","family":"Giallauria","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Division of Internal Medicine, Metabolic and Cardiac Rehabilitation Unit, Federico II University, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Novo","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital, Policlinico Paolo Giaccone, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8099-568X","authenticated-orcid":false,"given":"Francesco","family":"Clemenza","sequence":"additional","affiliation":[{"name":"Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation IRCCS \u2013 ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2046-8316","authenticated-orcid":false,"given":"Filippo","family":"Sarullo","sequence":"additional","affiliation":[{"name":"Cardiovascular Rehabilitation Unit, Buccheri La Ferla Fatebenefratelli Hospital, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1056\/NEJMoa1409077","article-title":"PARADIGM-HF Investigators and Committees. 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