Erberto Carluccio1, Frank L Dini2, Roberto Bitto3, Michele Ciccarelli4, Michele Correale5, Andreina D'Agostino2, Giuseppe Dattilo3, Marco Ferretti6, Arianna Grelli7, Stefania Guida7, Francesca Jacoangeli8, Laura Lupi9, Lorenzo Luschi10, Daniele Masarone11, Valentina Mercurio12, Giuseppe Pacileo11, Nicola Riccardo Pugliese2, Antonella Rispoli4, Laura Scelsi7, Carlo Gabriele Tocchetti12, Natale Daniele Brunetti5, Alberto Palazzuoli10, Massimo Piepoli13, Savina Nodari9, Giuseppe Ambrosio14. 1. Cardiology and Cardiovascular Pathophysiology, University of Perugia, Italy. Electronic address: erberto.carluccio@unipg.it. 2. Cardiac, Thoracic and Vascular Department, University of Pisa, Italy. 3. Dpt. of Clinical and Experimental Medicine Section of Cardiology, University of Messina, Italy. 4. Chair of Cardiology, Dept. of Medicine, Surgery and Dentistry, University of Salerno, Italy. 5. Department of Cardiology, University Hospital Foggia, Italy. 6. Department of Cardiology, University Hospital of Parma, Parma, Italy. 7. Division of Cardiology, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy. 8. Cardiology and Cardiovascular Pathophysiology, University of Perugia, Italy. 9. Department of Cardiology, University of Brescia and ASST Spedali Civili di Brescia, Italy. 10. Cardiovascular Diseases Unit, Department of Internal Medicine, University of Siena, Italy. 11. Heart Failure Unit, AORN dei Colli, Monaldi Hospital, Naples, Italy. 12. Department of Translational Medical Sciences, Federico II University, Naples, Italy. 13. Heart Failure Unit, Cardiology Department, Guglielmo da Saliceto Hospital, AUSL, Piacenza, Italy. 14. Cardiology and Cardiovascular Pathophysiology, University of Perugia, Italy; CERICLET-Centro Ricerca Clinica e Traslazionale, University of Perugia, Italy.
Abstract
BACKGROUND: Sacubitril/valsartan improves outcome in patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF, HFrEF). However, little is known about possible mechanisms underlying this favourable effect. PURPOSE: To assess changes in echocardiographically-derived hemodynamic profiles induced by sacubitril/valsartan and their impact on outcome. METHODS: In this multicenter, open-label study, 727 HFrEF outpatients underwent comprehensive echocardiography at baseline (before starting sacubitril/valsartan) and after 12 months. Estimated LV filling pressure (E/e') and cardiac index (CI, l/min/m2) were combined to determine 4 hemodynamic profiles: profile-A (normal-flow/normal-pressure); profile-B (low-flow/normal-pressure); profile-C: (normal-flow/high-pressure); profile-D: (low-flow/high-pressure). Changes among categories were recorded, and their associations with rates of the composite of death/HF-hospitalization were assessed by multivariable Cox analysis. RESULTS: At baseline, 29% had profile-A, 15% had profile-B, 32% profile-C, and 24% profile-D. After 12 months, the hemodynamic profile improved in 53% of patients (all profile-A achievers, or profile-D patients achieving either C or B profile), while it remained unchanged in 39% patients and worsened in 9%. Prevalence of improved profile progressively increased with increasing dose of sacubitril/valsartan (P < 0.0001). After the second echocardiography, patients were followed up 12.6 ± 7.6 months: event-rate was lower in patients with improved profile (12.3%, 95%CI: 9.4-16.1) compared to patients in whom hemodynamic profile remained unchanged (29.9%, 24.0-37.3) or worsened (31.2%, 20.7-46.9, P < 0.0001). Improved hemodynamic profile was associated with favourable outcome independent of LVEF and other covariates (HR 0.65, 95%CI: 0.45-0.95, P < 0.05). CONCLUSION: In HFrEF patients, the beneficial prognostic effects of sacubitril/valsartan are associated with improvement in hemodynamic conditions.
BACKGROUND: Sacubitril/valsartan improves outcome in patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF, HFrEF). However, little is known about possible mechanisms underlying this favourable effect. PURPOSE: To assess changes in echocardiographically-derived hemodynamic profiles induced by sacubitril/valsartan and their impact on outcome. METHODS: In this multicenter, open-label study, 727 HFrEF outpatients underwent comprehensive echocardiography at baseline (before starting sacubitril/valsartan) and after 12 months. Estimated LV filling pressure (E/e') and cardiac index (CI, l/min/m2) were combined to determine 4 hemodynamic profiles: profile-A (normal-flow/normal-pressure); profile-B (low-flow/normal-pressure); profile-C: (normal-flow/high-pressure); profile-D: (low-flow/high-pressure). Changes among categories were recorded, and their associations with rates of the composite of death/HF-hospitalization were assessed by multivariable Cox analysis. RESULTS: At baseline, 29% had profile-A, 15% had profile-B, 32% profile-C, and 24% profile-D. After 12 months, the hemodynamic profile improved in 53% of patients (all profile-A achievers, or profile-D patients achieving either C or B profile), while it remained unchanged in 39% patients and worsened in 9%. Prevalence of improved profile progressively increased with increasing dose of sacubitril/valsartan (P < 0.0001). After the second echocardiography, patients were followed up 12.6 ± 7.6 months: event-rate was lower in patients with improved profile (12.3%, 95%CI: 9.4-16.1) compared to patients in whom hemodynamic profile remained unchanged (29.9%, 24.0-37.3) or worsened (31.2%, 20.7-46.9, P < 0.0001). Improved hemodynamic profile was associated with favourable outcome independent of LVEF and other covariates (HR 0.65, 95%CI: 0.45-0.95, P < 0.05). CONCLUSION: In HFrEF patients, the beneficial prognostic effects of sacubitril/valsartan are associated with improvement in hemodynamic conditions.