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Background: The clinical impact of heart rate (HR) in heart failure with preserved ejection fraction (HFpEF) is a matter of debate. Among those with HFpEF, chronotropic incompetence (CI) has emerged as a pathophysiological mechanism linked to the severity of the disease. In this study, we sought to evaluate whether admission heart rate in acute heart failure differs along left ventricular ejection fraction (LVEF)., Methods: We included retrospectively 3,712 consecutive patients admitted for acute heart failure (AHF) in the Cardiology department of a third level center. HR values were assessed at presentation. LVEF was assessed by transthoracic echocardiogram during the index admission and stratified into four categories: reduced ejection fraction ( ≤ 40%), mildly reduced ejection fraction (41-49%), preserved ejection fraction (50-64%) and supranormal ejection fraction ( ≥ 65%). The association between HR and LVEF was assessed by multivariate linear and multinomial regression analyses., Results: The mean age of the sample was 73,9 ± 11.3 years, 1,734 (47,4%) were women, and 1,214 (33,2%), 570 (15,6%), 1,229 (33,6%) and 648 (17,7%) patients showed LVEF ≤ 40%, 41-49%, 50-64%, and ≥65% respectively. The median HR at admission was 95 (IQR 78-120) beats per minute and 1,653 were on atrial fibrillation (45.2%). There was an inverse relationship between HR at admission and LVEF. Lower HR was significantly associated with a higher LVEF in the whole sample ( p  < 0,001). This inverse relationship was found in sinus rhythm but not in patients with atrial fibrillation., Conclusion: HR at admission for AHF is a predictor of LVEF but only in patients with sinus rhythm.

Aims: There is limited information on the sex-specific longitudinal changes of left ventricular ejection fraction (LVEF) after an acute heart failure (AHF) hospitalization. We aimed to investigate whether LVEF trajectories over time and their impact on mortality and AHF readmission rates differ between men and women., Methods and Results: We conducted a retrospective sex-specific analysis of longitudinal LVEF measurements (n = 9581) in 3383 patients with an index hospitalization for AHF in a single tertiary-level hospital. Statistical techniques suited for longitudinal data analysis were used. The mean age of the sample was 73.8 ± 11.2 years, and 47.9% were women. The mean LVEF was 49.4 ± 15.3%. At a median follow-up of 2.58 years (interquartile range 0.77-5.62), we registered 2197 deaths (64.9%) and 2597 AHF readmissions in 1302 (38.5%) patients. The longitudinal analysis showed that women had consistently higher LVEF values throughout the follow-up with both trajectories characterized by an early peak-approximately at 1 year-followed by decreasing values in men but a plateau in women. Multivariate between-sex comparisons across LVEF categories revealed that women had lower rates of AHF readmissions when LVEF ≤40%. On the contrary, women displayed an excess risk of AHF readmissions when LVEF >60%. A trend in the same direction was found for cardiovascular and all-cause mortality., Conclusion: Sex was a significant factor in determining the follow-up trajectory of LVEF and predicting differences in outcomes after an AHF admission. The findings suggest that women have a higher risk of AHF readmissions at higher LVEF values, while men have a higher risk at lower LVEF values. For all-cause and cardiovascular mortality, the same direction of the association was inferred but they were not significant., (© 2024 European Society of Cardiology.)

Introduction and Objectives: Noncardiovascular events represent a significant proportion of the morbidity and mortality burden in patients with heart failure (HF). However, the risk of these events appears to differ by left ventricular ejection fraction (LVEF) status. In this study, we sought to evaluate the risk of noncardiovascular death and recurrent noncardiovascular readmission by LVEF status following an admission for acute HF., Methods: We retrospectively assessed a cohort of 4595 patients discharged after acute HF in a multicenter registry. We evaluated LVEF as a continuum, stratified in 4 categories (LVEF ≤ 40%, 41%-49%, 50%-59%, and ≥ 60%). Study endpoints were the risks of noncardiovascular mortality and recurrent noncardiovascular admissions during follow-up., Results: At a median follow-up of 2.2 [interquartile range, 0.76-4.8] years, we registered 646 noncardiovascular deaths and 4014 noncardiovascular readmissions. After multivariable adjustment including cardiovascular events as a competing event, LVEF status was associated with the risk of noncardiovascular mortality and recurrent noncardiovascular admissions. When compared with patients with LVEF ≤ 40%, those with LVEF 51%-59%, and especially those with LVEF ≥ 60%, were at higher risk of noncardiovascular mortality (HR, 1.31; 95%CI, 1.02-1,68; P=.032; and HR, 1.47; 95%CI, 1.15-1.86; P=.002; respectively), and at higher risk of recurrent noncardiovascular admissions (IRR, 1.17; 95%CI, 1.02-1.35; P=.024; and IRR, 1.26; 95%CI, 1.11-1.45; P=.001; respectively)., Conclusions: Following an admission for HF, LVEF status was directly associated with the risk of noncardiovascular morbidity and mortality. Patients with HFpEF were at higher risk of noncardiovascular death and total noncardiovascular readmissions, especially those with LVEF ≥ 60%., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Patients with worsening heart failure (WHF) are frequently hospitalized. However, some of the patients with WHF are discharged from the emergency department without hospitalization. The factors influencing the decision of admission are heterogeneous and, in most cases, remain not well-defined. This study aimed to analyze whether left ventricular ejection fraction (LVEF) influences admission decisions following a visit to the emergency department for WHF., Patients and Methods: This is a retrospective analysis of 3168 patients discharged from a hospitalization for acute heart failure in a single-center in Spain. During follow-up, visits to the emergency department for WHF, including those hospitalized (WHF-readmissions) and episodes of WHF directly discharged without hospitalization in 24h (WHF-DDWH), were recorded. The association between the LVEF categories (<50% and ≥50%) and recurrent WHF-DDWH was evaluated by negative binomial regression. Estimates of risk were expressed as incidence rate ratios (IRR)., Results: The mean age (SD) of the study sample was 73.5 (11.2) years, and 1658 (52.3%) showed LVEF>50%. At a median (percentile 25% to percentile 75%) follow-up of 2.7 (1.0-5.8) years, 3341 episodes of WHF in 1439 patients were recorded. Of them, we registered 743 episodes of WHF-DDWH in 468 patients (22.2%). Compared to patients with LVEF<50%, those with LVEF≥50% exhibited an adjusted increased risk of recurrent WHF-DDWH (IRR: 1.36, CI 95%: 1.13-1.62, p=0.001)., Conclusions: Following an acute heart failure admission, patients with LVEF≥50% showed an increased risk of same-day discharge for WHF., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Background The mechanisms explaining the clinical benefits of ferric carboximaltose (FCM) in patients with heart failure, reduced or intermediate left ventricular ejection fraction, and iron deficiency remain not fully clarified. The Myocardial-IRON trial showed short-term cardiac magnetic resonance (CMR) changes suggesting myocardial iron repletion following administration of FCM but failed to find a significant increase in left ventricular ejection fraction in the whole sample. Conversely, the strain assessment could evaluate more specifically subtle changes in contractility. In this subanalysis, we aimed to evaluate the effect of FCM on the short-term left and right ventricular CMR feature tracking derived strain. Methods and Results This is a post hoc subanalysis of the double-blind, placebo-controlled, randomized clinical trial that enrolled 53 ambulatory patients with heart failure and left ventricular ejection fraction <50%, and iron deficiency [Myocardial-IRON trial (NCT03398681)]. Three-dimensional left and 2-dimensional right ventricular CMR tracking strain (longitudinal, circumferential, and radial) changes were evaluated before, 7 and 30 days after randomization using linear mixed-effect analysis. The median (interquartile range) age of the sample was 73 years (65-78), and 40 (75.5%) were men. At baseline, there were no significant differences in CMR feature tracking strain parameters across both treatment arms. At 7 days, the only global 3-dimensional left ventricular circumferential strain was significantly higher in the FCM treatment-arm (difference: -1.6%, P =0.001). At 30 days, and compared with placebo, global 3-dimensional left ventricular strain parameters significantly improved in those allocated to FCM treatment-arm [longitudinal (difference: -2.3%, P <0.001), circumferential (difference: -2.5%, P <0.001), and radial (difference: 4.2%, P =0.002)]. Likewise, significant improvements in global right ventricular strain parameters were found in the active arm at 30 days (longitudinal [difference: -3.3%, P =0.010], circumferential [difference: -4.5%, P <0.001], and radial [difference: 4.5%, P =0.027]). Conclusions In patients with stable heart failure, left ventricular ejection fraction <50%, and iron deficiency, treatment with FCM was associated with short-term improvements in left and right ventricular function assessed by CMR feature tracking derived strain parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03398681.

Background Following a heart failure (HF)-decompensation, there is scarce data about sex-related prognostic differences across left ventricular ejection fraction (LVEF) status. We sought to evaluate sex-related differences in 6-month mortality risk across LVEF following admission for acute HF. Methods and Results We retrospectively evaluated 4812 patients consecutively admitted for acute HF in a multicenter registry from 3 hospitals. Study end points were all-cause, cardiovascular, and HF-related mortality at 6-month follow-up. Multivariable Cox regression models were fitted to investigate sex-related differences across LVEF. A total of 2243 (46.6%) patients were women, 2569 (53.4%) were men, and 2608 (54.2%) showed LVEF≥50%. At 6-month follow-up, 645 patients died (13.4%), being 544 (11.3%) and 416 (8.6%) cardiovascular and HF-related deaths, respectively. LVEF was not independently associated with mortality (HR, 1.02; 95% CI 0.99-1.05; P =0.135). After multivariable adjustment, we found no sex-related differences in all-cause mortality ( P value for interaction=0.168). However, a significant interaction between sex and cardiovascular and HF mortality risks was found across LVEF ( P value for interaction=0.030 and 0.007, respectively). Compared with men, women had a significantly lower risk of cardiovascular and HF-mortality at LVEF<25% and <43%, respectively. On the contrary, women showed a higher risk of HF-mortality at the upper extreme of LVEF (>80%). Conclusions Following an admission for acute HF, no sex-related differences were found in all-cause mortality risk. However, when compared with men, women showed a lower risk of cardiovascular and HF-mortality at the lower extreme of LVEF. On the contrary, they showed a higher risk of HF death at the upper extreme.

Background: Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet β-blockers are commonly used in HFpEF despite the lack of robust evidence., Objectives: This study aimed to evaluate the effect of β-blocker withdrawal on peak oxygen consumption (peak Vo 2 ) in patients with HFpEF and chronotropic incompetence., Methods: This is a multicenter, randomized, investigator-blinded, crossover clinical trial consisting of 2 treatment periods of 2 weeks separated by a washout period of 2 weeks. Patients with stable HFpEF, New York Heart Association functional classes II and III, previous treatment with β-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n = 26) versus continuing (arm B: n = 26) β-blocker treatment and were then crossed over to receive the opposite intervention. Changes in peak Vo 2 and percentage of predicted peak Vo 2 (peak Vo 2 %) measured at the end of the trial were the primary outcome measures. To account for the paired-data nature of this crossover trial, linear mixed regression analysis was used., Results: The mean age was 72.6 ± 13.1 years, and most of the patients were women (59.6%) in New York Heart Association functional class II (66.7%). The mean peakVo 2 and peak Vo 2 % were 12.4 ± 2.9 mL/kg/min, and 72.4 ± 17.8%, respectively. No significant baseline differences were found across treatment arms. Peak Vo 2 and peak Vo 2 % increased significantly after β-blocker withdrawal (14.3 vs 12.2 mL/kg/min [Δ +2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [Δ +11.7%]; P < 0.001, respectively)., Conclusions: β-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. β-blocker use in HFpEF deserves profound re-evaluation. (β-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39)., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from the Spanish Ministry of Economy and Competitiveness through the Carlos III Health Institute: Fondos de Investigación Sanitaria (PI17/01426), and cofunded with European Regional Development Fund and Centro de Investigación Biomédica en Red Enfermedades Cardiovascular funds (16/11/00420 and 16/11/00403). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The optimal length of stay (LOS) in patients hospitalized for acute heart failure (AHF) remains controversial. Plasma antigen carbohydrate 125 (CA125) has emerged as a reliable proxy of congestion. We aimed to evaluate whether there is a differential impact of LOS on the risk of 6-month AHF readmission across CA125 levels., Methods: This is a retrospective study that included 1,387 patients discharged for AHF in two third-level centers. CA125 was measured 48±24 h after admission. The association between CA125 and LOS with the risk of subsequent AHF readmission at 6 months was analyzed by Cox regression analysis accounting for death as a competing event., Results: The median (IQR) age of the sample was 78 (69-83) years, 625 (41.1%) patients were women, and 832 (60%) exhibited preserved left ventricular ejection fraction. The median LOS and CA125 were 6 (4-9) days and 36 (17-83) U/mL, respectively. A total of 707 (51%) patients displayed high CA125 levels (≥35 U/mL). At 6 months, 87 deaths (6,3%) and 304 AHF readmissions (21,9%) were registered, respectively. A multivariate analysis revealed a differential effect of LOS on 6-month AHF readmission across CA125 levels (p-value for interaction=0.010). In those with CA125<35 U/mL, LOS≥7 days did not modify the risk (HR:1.31; 95% CI: 0.92-1.87, p=0.131). Conversely, in those with CA125≥35 U/mL, LOS≥7 days was associated with a lower risk of AHF readmission (HR:0.70; 95% CI: 0.51-0.98, p=0.036)., Conclusions: In patients with AHF, high CA125 levels may identify those patients that benefit from a more prolonged hospitalization in terms of reducing the risk of mid-term AHF readmissions., (Copyright © 2021. Published by Elsevier B.V.)

Background Cardiac magnetic resonance (CMR) permits robust risk stratification of discharged ST-segment-elevation myocardial infarction patients, but its indiscriminate use in all cases is not feasible. We evaluated the utility of left ventricular ejection fraction (LVEF) by echocardiography for a selective use of CMR after ST-segment-elevation myocardial infarction. Methods Echocardiography and CMR were performed in 1119 patients discharged for ST-segment-elevation myocardial infarction included in a multicenter registry. The prognostic power of CMR beyond echocardiography-LVEF was assessed using adjusted C statistic, net reclassification improvement index, and integrated discrimination improvement index. Results During a 4.8-year median follow-up, 136 (12%) first major adverse cardiac events (MACE) occurred (47 cardiovascular deaths and 89 readmissions for acute heart failure). In the entire group, CMR-LVEF (but not echocardiography-LVEF) independently predicted MACE occurrence. The MACE rate significantly increased only in patients with CMR-LVEF<40% (≥50%: 7%, 40%-49%: 9%, <40%: 27%, P <0.001). Most patients displayed echocardiography-LVEF≥50% (629, 56%), and they had a low MACE rate (57/629, 9%). In patients with echocardiography-LVEF<50% (n=490, 44%), the MACE rate was also low in those with CMR-LVEF≥40% (24/278, 9%) but significantly increased in patients with CMR-LVEF<40% (55/212, 26%; P <0.001). Compared with echocardiography-LVEF, CMR-LVEF significantly improved MACE prediction in the group of patients with echocardiography-LVEF<50% (C statistic, 0.80 versus 0.72; net reclassification improvement index, 0.73; integrated discrimination improvement index, 0.10) but not in those with echocardiography-LVEF≥50% (C statistic 0.66 versus 0.66; net reclassification improvement index, 0.17; integrated discrimination improvement index, 0.01). Conclusions A straightforward strategy based on a selective use of CMR for risk prediction in ST-segment-elevation myocardial infarction patients with echocardiography-LVEF<50% can provide insights into patient care. The cost-effectiveness of this approach, as well as the direct implications in clinical management, should be further explored.

Background: The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence (ChI) has emerged as a crucial pathophysiological mechanism. Beta-blockers, drugs with negative chronotropic effects, are commonly used in HFpEF, although current evidence does not support its routine use in these patients., Hypothesis: We postulate beta-blockers may have deleterious effects in HFpEF and ChI. This work aims to evaluate the short-term effect of beta-blockers withdrawal on functional capacity assessed by the maximal oxygen uptake (peakVO2) in patients with HFpEF and ChI., Methods: This is a prospective, crossover, randomized (1:1) and multicenter study. After randomization, the clinical and cardiac rhythm will be continuously registered for 30 days. PeakVO2 is assessed by cardiopulmonary exercise testing (CPET) at 15 and 30 days in both groups. Secondary endpoints include quality of life, cognitive, and safety assessment. Patients with stable HFpEF, functional class New York Heart Association (NYHA) II-III, chronic treatment with beta-blockers, and ChI will be enrolled. A sample size estimation [alfa: 0.05, power: 90%, a 20% loss rate, and delta change of mean peakVO2: +1.2 mL/kg/min (SD ± 2.0)] of 52 patients is necessary to test our hypothesis., Results: Patients started enrolling in October 2018. As January 14th, 2020, 28 patients have been enrolled. It is projected to enroll the last patient at the end of July 2020., Conclusions: Optimizing therapy that improves functional capacity remains an unmeet priority in HFpEF. Deprescribing beta-blockers in patients with HFpEF and ChI seems a plausible intervention to improve functional capacity. This trial is an attempt towards precision medicine in this complex syndrome., Trial Registration: ClinicalTrials.gov: NCT03871803., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Functional mitral regurgitation (FMR) is a common finding in patients with acute heart failure (AHF) and reduced left ventricular ejection fraction (heart failure and reduced ejection fraction [HFrEF]). However, its clinical impact remains unclear. We aimed to evaluate the association between the severity of FMR after clinical stabilization and short-term adverse outcomes after a hospitalization for AHF. We prospectively included 938 consecutive patients with HFrEF discharged after a hospitalization for AHF, after excluding those with organic valve disease, congenital heart disease, or aortic valve disease. FMR was assessed semiquantitatively by color Doppler analysis of the regurgitant jet area, and its severity was categorized as none or mild (grade 0 or 1), moderate (grade 2), or severe (grade 3 or 4). FMR was assessed at 120 ± 24 hours after admission. The primary end point was the composite of all-cause mortality and rehospitalization at 90 days. At discharge, 533 (56.8%), 253 (26.9%), and 152 (16.2%) patients showed none-mild, moderate, and severe FMR. At the 90-day follow-up, 161 patients (17.2%) either died (n = 49) or were readmitted (n = 112). Compared with patients with none or mild FMR, rates of the composite end point were higher for patients with moderate and severe FMRs (p <0.001). After the multivariable adjustment, those with moderate and severe FMRs had a significantly higher risk of reaching the end point (hazard ratio = 1.50, 95% confidence interval 1.04 to 2.17, p = 0.027; and hazard ratio = 1.63, 95% confidence interval 1.07 to 2.48, p = 0.023, respectively). In conclusion, FMR is a common finding in patients with HFrEF, and its presence, when moderate or severe, identifies a subgroup at higher risk of adverse clinical outcomes at short term., (Copyright © 2017 Elsevier Inc. All rights reserved.)