Santiago Jimenez-Marrero1, Pedro Moliner2, Iris Rodríguez-Costoya3, Cristina Enjuanes4, Lidia Alcoberro1, Sergi Yun5, Jose Gonzalez-Costello6, Alberto Garay1, Marta Tajes7, Esther Calero4, Encarnación Hidalgo4, Carmen Guerrero8, Elena García-Romero9, Carles Díez-López6, Miguel Cainzos-Achirica10, Josep Comin-Colet11. 1. Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Cardio-Oncology Unit, Cardiology Department, Bellvitge University Hospital-Catalan Institute of Oncology (ICO), L'Hospital de Llobregat, Barcelona, Spain. 2. Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Cardio-Oncology Unit, Cardiology Department, Bellvitge University Hospital-Catalan Institute of Oncology (ICO), L'Hospital de Llobregat, Barcelona, Spain. Electronic address: pmoliner@bellvitgehospital.cat. 3. Department of Cardiology, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain; Heart Diseases Biomedical Research Group, Research Programme in Inflammatory and Cardiovascular Disorders, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. 4. Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. 5. Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Department of Internal Medicine, Bellvitge University Hospital, L' Hospitalet de Llobregat, Barcelona, Spain. 6. Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Advanced Heart Failure and Heart Transplant Unit, Department ion Cardiology, Bellvitge University Hospital, Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain. 7. Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. 8. Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain. 9. Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Advanced Heart Failure and Heart Transplant Unit, Department ion Cardiology, Bellvitge University Hospital, Hospitalet de Llobregat, Barcelona, Spain. 10. Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore MD, United States; Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist Hospital, Houston TX, United States. 11. Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain. Electronic address: josepcomin@gmail.com.
Abstract
BACKGROUND: Sympathetic activity (SA) is increased in patients with heart failure and reduced ejection fraction (HFrEF) and is associated with poor outcomes. However, its clinical implications are less understood in HF with mid-range (HFmrEF) and preserved ejection fraction (HFpEF). We aimed to study SA across left ventricle ejection fraction (LVEF) groups and its association with clinical outcomes. METHODS AND RESULTS: SA estimated by norepinephrine (NE) levels was determined in 742 consecutive outpatients with chronic HF: 348 (47%) with HFrEF, 116 (16%) HFmrEF, and 278 (37%) HFpEF. After a mean follow-up of 15 months, 17% died. Adjusted analyses showed that patients with HFpEF and HFmrEF had lower estimated marginal means of NE levels compared to HFrEF (278 and 116 pg/mL, respectively, vs. 348 pg/mL; p-value=0.005). Adjusted Cox regression analyses showed that high norepinephrine levels independently predicted all-cause mortality (ACM) in all 3 groups. The strongest associations between high NE levels and cardiovascular mortality (CVM) were observed in HFmrEF (HR: 4.7 [1.33-16.68]), while the weakest association was in HFpEF (HR: 2.62 [1.08-6.35]). CONCLUSIONS: Adjusted analyses showed that HFpEF and HFmrEF were associated with lower SA compared to HFrEF. Nevertheless, increasing NE levels were independently associated with ACM and CVM in all three LVEF groups. The strongest association between high NE levels and CVM was present in HFmrEF patients, while the weakest was seen in HFpEF. These findings could explain why the response to neurohormonal therapies in patients with HFmrEF is similar to that of patients with HFrEF rather than with HFpEF.
BACKGROUND: Sympathetic activity (SA) is increased in patients with heart failure and reduced ejection fraction (HFrEF) and is associated with poor outcomes. However, its clinical implications are less understood in HF with mid-range (HFmrEF) and preserved ejection fraction (HFpEF). We aimed to study SA across left ventricle ejection fraction (LVEF) groups and its association with clinical outcomes. METHODS AND RESULTS:SA estimated by norepinephrine (NE) levels was determined in 742 consecutive outpatients with chronic HF: 348 (47%) with HFrEF, 116 (16%) HFmrEF, and 278 (37%) HFpEF. After a mean follow-up of 15 months, 17% died. Adjusted analyses showed that patients with HFpEF and HFmrEF had lower estimated marginal means of NE levels compared to HFrEF (278 and 116 pg/mL, respectively, vs. 348 pg/mL; p-value=0.005). Adjusted Cox regression analyses showed that high norepinephrine levels independently predicted all-cause mortality (ACM) in all 3 groups. The strongest associations between high NE levels and cardiovascular mortality (CVM) were observed in HFmrEF (HR: 4.7 [1.33-16.68]), while the weakest association was in HFpEF (HR: 2.62 [1.08-6.35]). CONCLUSIONS: Adjusted analyses showed that HFpEF and HFmrEF were associated with lower SA compared to HFrEF. Nevertheless, increasing NE levels were independently associated with ACM and CVM in all three LVEF groups. The strongest association between high NE levels and CVM was present in HFmrEF patients, while the weakest was seen in HFpEF. These findings could explain why the response to neurohormonal therapies in patients with HFmrEF is similar to that of patients with HFrEF rather than with HFpEF.
Authors: Matthew J Singleton; M Benjamin Nelson; T Jake Samuel; Dalane W Kitzman; Peter Brubaker; Mark J Haykowsky; Bharathi Upadhya; Haiying Chen; Michael D Nelson Journal: J Card Fail Date: 2021-11-10 Impact factor: 6.592