{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:34:58Z","timestamp":1791506098229,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T00:00:00Z","timestamp":1592352000000},"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: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril\/valsartan (S\/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S\/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. Methods: Patients with HFrEF admitted to outpatients\u2019 services were screened out for study inclusion. S\/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. Results: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 \u00b1 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% \u00b1 5.8% to 31.8% \u00b1 7.3%, p &lt; 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 \u00b1 3.7 to 17.8 \u00b1 4.2 mL\/kg\/min, p &lt; 0.0001), the slope of increase in ventilation over carbon dioxide output (VE\/VCO2 slope )(from 33.4 \u00b1 6.2 to 30.3 \u00b1 6.5, p &lt; 0.0001), and HRR (from 11.4 \u00b1 9.5 to 17.4 \u00b1 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE\/VCO2slope (r = \u22120.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE\/VCO2slope (Beta (B) = \u22120.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = \u22120.304, p = 0.009). S\/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p &lt; 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = \u22122.065, SE = 0.354, p &lt; 0.001). Conclusions: In HFrEF patients, S\/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.<\/jats:p>","DOI":"10.3390\/jcm9061897","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T11:00:56Z","timestamp":1592478056000},"page":"1897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Sacubitril\/Valsartan Improves Autonomic Function and Cardiopulmonary Parameters in Patients with Heart Failure with Reduced Ejection Fraction"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4119-9397","authenticated-orcid":false,"given":"Francesco","family":"Giallauria","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-6550","authenticated-orcid":false,"given":"Giuseppe","family":"Vitale","sequence":"additional","affiliation":[{"name":"Cardiovascular Rehabilitation Unit, Buccheri La Ferla Fatebenefratelli Hospital, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6330-1738","authenticated-orcid":false,"given":"Mario","family":"Pacileo","sequence":"additional","affiliation":[{"name":"Unit of Cardiology and Intensive Care, \u201cUmberto I\u201d Hospital, Viale San Francesco, 84014 Nocera Inferiore (SA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Di Lorenzo","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Oliviero","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Passaro","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Calce","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Parlato","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8360-5173","authenticated-orcid":false,"given":"Crescenzo","family":"Testa","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-2949","authenticated-orcid":false,"given":"Giuseppe","family":"Romano","sequence":"additional","affiliation":[{"name":"Cardiology Unit and Research Office, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation IRCCS-ISMETT, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Clemenza","sequence":"additional","affiliation":[{"name":"Cardiology Unit and Research Office, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation IRCCS-ISMETT, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Sarullo","sequence":"additional","affiliation":[{"name":"Cardiovascular Rehabilitation Unit, Buccheri La Ferla Fatebenefratelli Hospital, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7223-7574","authenticated-orcid":false,"given":"Elio","family":"Venturini","sequence":"additional","affiliation":[{"name":"Cardiac Rehabilitation Unit, Azienda USL Toscana Nord-Ovest, Cecina Civil Hospital, 57023 Cecina (LI), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3744-6375","authenticated-orcid":false,"given":"Marco","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, 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":"IRCCS Centro Neurolesi Bonino Pulejo Messina, University of Palermo, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Iannuzzo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9698-9145","authenticated-orcid":false,"given":"Antonello","family":"D\u2019Andrea","sequence":"additional","affiliation":[{"name":"Unit of Cardiology and Intensive Care, \u201cUmberto I\u201d Hospital, Viale San Francesco, 84014 Nocera Inferiore (SA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Vigorito","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2046-8316","authenticated-orcid":false,"given":"Filippo M.","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":[[2020,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/cpf.12102","article-title":"Heart rate recovery: Autonomic determinants, methods of assessment and association with mortality and cardiovascular diseases","volume":"34","author":"Forjaz","year":"2014","journal-title":"Clin. 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