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Introduction and Objectives: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients., Methods: The REMOVE trial is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF >10% (provided the LVEF is <50%); b) a reduction in LVEF >10% accompanied by an increase >15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted., Conclusions: The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients. Registred at ClinicalTrials.gov (Identifier: NCT05151861)., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Soluble suppressor of tumorigenicity-2 (sST2) is a biomarker for heart failure and pulmonary injury. We hypothesize that sST2 could help predict severity of SARS-CoV-2 infections., Methods: sST2 was analyzed in patients consecutively admitted for SARS-CoV-2 pneumonia. Other prognostic markers were also measured. In-hospital complications were registered, including death, ICU admission, and respiratory support requirements., Results: 495 patients were studied (53% male, age: 57.6±17.6). At admission, median sST2 concentrations was 48.5ng/mL [IQR, 30.6-83.1ng/mL] and correlated with male gender, older age, comorbidities, other severity biomarkers, and respiratory support requirements. sST2 levels were higher in patients who died (n=45, 9.1%) (45.6 [28.0, 75.9]ng/mL vs. 144 [82.6, 319] ng/mL, p<0.001) and those admitted to ICU (n=46, 9.3%) (44.7 [27.5, 71.3] ng/mL vs. 125 [69.0, 262]ng/mL, p<0.001). sST2 levels>210ng/mL were a strong predictor of complicated in-hospital courses, with higher risk of death (OR, 39.3, CI95% 15.9, 103) and death/ICU (OR 38.3, CI95% 16.3-97.5) after adjusting for all other risk factors. The addition of sST2 enhanced the predictive capacity of mortality risk models., Conclusions: sST2 represents a robust severity predictor in COVID-19 and could be an important tool for identifying at-risk patients who may benefit from closer follow-up and specific therapies., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life-sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7-13 min; range: 4-19 min). Ten min after CA, phosphorylation of cAMP-dependent protein kinase-A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

The severity of lung involvement is the main prognostic factor in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Carbohydrate antigen 15-3 (CA 15-3), a marker of lung damage and fibrosis, could help predict the prognosis of SARS-CoV-2 pneumonia. This was a retrospective and observational study. CA 15-3 was analyzed in the blood samples of patients consecutively admitted for SARS-CoV-2 pneumonia and whose blood samples were available in the biobank. Other prognostic markers were also measured (interleukin 6 [IL6], C-reactive protein [CRP], D-dimer, troponin T, and NT-ProBNP). The occurrence of in-hospital complications was registered, including death, the need for medical intensive care, and oxygen therapy at discharge. In this study, 539 patients were recruited (54.9% men, mean age: 59.6 ± 16.4 years). At admission, the mean concentrations of CA 15-3 was 20.5 ± 15.8 U/mL, and the concentration was correlated with male sex, older age, and other severity markers of coronavirus disease of 2019 (COVID-19) (IL6, CRP, D-dimer, troponine T, and NT-ProBNP). CA 15-3 levels were higher in patients who died (n = 56, 10.4%) (35.33 ± 30.45 vs. 18.8 ± 12.11, p < 0.001), who required intensive medical support (n = 78, 14.4%; 31.17 ± 27.83 vs. 18.68 ± 11.83; p < 0.001), and who were discharged with supplemental oxygen (n = 64, 13.3%; 22.65 ± 14.41 vs. 18.2 ± 11.7; p = 0.011). Elevated CA 15-3 levels (above 34.5 U/mL) were a strong predictor of a complicated in-hospital course, in terms of a higher risk of death (adjusted odds ratio [OR] 3.74, 95% confidence interval [CI]: 1.22-11.9, p = 0.022) and need for intensive care (adjusted OR 4.56, 95% CI: 1.37-15.8) after adjusting for all other risk factors. The degree of lung damage and fibrosis evaluated in terms of CA 15-3 concentrations may allow early identification of the increased risk of complications in patients with SARS-CoV-2 pneumonia., (© 2022. The Author(s).)

Background: Colchicine has been proposed as a potential therapy in coronavirus disease 2019 (COVID-19) due to their anti-inflammatory actions., Methods: The COL-COVID study was a prospective, randomized, controlled and open-label clinical trial that compared colchicine added to standard treatment vs standard treatment in hospitalized COVID-19 patients that do not need mechanical ventilatory support. Colchicine was initiated within the first 48 hours of admission at a 1.5 mg loading dose, followed by 0.5 mg b.i.d. for one week and 0.5 mg per day for 28 days. The study endpoints were clinical status (7-points WHO ordinal scale) and inflammatory biomarkers (IL-6 and CRP)., Results: A total of 103 patients (51±12 years, 52% male) were randomly allocated to colchicine arm (n=52) and control arm (n=51). At day 28, all patients in the colchicine group were alive and discharged, whereas in the control group, two patients died in-hospital and one patient remained hospitalized. Clinical improvement in terms of changes on WHO scale at day 14 and 28 and time to 1-point clinical improvement did not differ between the two groups. Clinical deterioration (increase of at least 1-point in WHO scale) was observed in a higher proportion of cases in colchicine group (13.8%) vs control group (5.8%) (p=0.303); after adjustment by baseline risk factors and concomitant therapies, colchicine therapy was associated with a lower risk of clinical deterioration (p=0.030). Inflammatory biomarkers CRP and IL-6 concentrations course did not differ between the two arms., Conclusion: In hospitalized COVID-19 patients, colchicine treatment neither improved the clinical status, nor the inflammatory response, over the standard treatment. Nevertheless, a preventive effect for further clinical deterioration might be possible., Trial Registration: NCT04350320., Competing Interests: The authors declare no conflicts of interest in this work., (© 2021 Pascual-Figal et al.)

Background: Clonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown., Objectives: The purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology., Methods: The study cohort comprised 62 patients with HF and LVEF <45% (age 74 ± 7 years, 74% men, 52% nonischemic, and LVEF 30 ± 8%). Deep sequencing was used to detect CHIP mutations with a variant allelic fraction >2% in 54 genes. Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization., Results: CHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mortality (p = 0.151). After adjusting for risk factors, patients with mutations in either DNA methyltransferase 3 alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) exhibited accelerated HF progression in terms of death (hazard ratio [HR]: 2.79; 95% confidence interval [CI]: 1.31 to 5.92; p = 0.008), death or HF hospitalization (HR: 3.84; 95% CI: 1.84 to 8.04; p < 0.001) and HF-related death or HF hospitalization (HR: 4.41; 95% CI: 2.15 to 9.03; p < 0.001). In single gene-specific analyses, somatic mutations in DNMT3A or TET2 retained prognostic significance with regard to HF-related death or HF hospitalization (HR: 4.50; 95% CI: 2.07 to 9.74; p < 0.001, for DNMT3A mutations; HR: 3.18; 95% CI: 1.52 to 6.66; p = 0.002, for TET2 mutations). This association remained significant irrespective of ischemic/nonischemic etiology., Conclusions: Somatic mutations that drive clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology., Competing Interests: Funding Support and Author Disclosures This work has been supported by 2 grants from Instituto de Salud Carlos III (PI14/01637, PI17/01742); 2 grants from the Ministerio de Ciencia e Innovación (RYC-2016-20026, RTI2018-093554-A-I00); and a grant from Fundación Séneca de Ciencia y Tecnología de la Región de Murcia (PI14/19334). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Dr. Pascual-Figal has served on the advisory board for and/or received speaker honoraria from Novartis, Servier, AstraZeneca, Vifor, Pfizer, Abbott, and Roche. Dr. Bayes-Genis has received speaker fees from Novartis, Roche, and Critical Diagnostics. Dr. Fuster is a member of the Leducq Foundation Transatlantic Network on Clonal Hematopoiesis and Atherosclerosis (TNE-18CVD04); and is supported by a 2019 Leonardo Grant for Researchers and Cultural Creators from the BBVA Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Introduction and Objectives: Disease progression in patients after a first hospitalization for heart failure (HF), in particular the interaction between survival and rehospitalizations, is not well established., Methods: We studied all patients with a first hospitalization and main diagnosis of HF from 2009 to 2013 by analyzing the Minimum Data Set of the Region of Murcia. Both incident and recurrent patients were studied, and the trend in hospitalization rates was calculated by joinpoint regression. Patients were followed-up through their health cards until the end of 2015. Mortality and readmissions, including causes and chronology in relation to the time of death, were assessed., Results: A total of 8258 incident patients were identified, with annual rates increasing (+2.3%, P <.05) up to 1.24 patients per 1000 inhabitants, representing 71% of hospitalized individuals and 57% of total discharges due to HF. In the first year, 22% were readmitted due to HF, 31% due to cardiovascular causes, and 54% due to any cause. Five-year survival was 40%, which was significantly lower than age- and sex-adjusted expected survival for the general population (76%) (P <.001). Among patients who died during follow-up, readmissions (1.5 per patient/y, 0.4 due to HF) showed a "J" pattern, with 48% of rehospitalizations being concentrated in the last 3 deciles of survival prior to death., Conclusions: Rates of first hospitalization due to HF continue to increase, with high mortality and rehospitalizations during follow-up, which are concentrated mainly in the period prior to death., (Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: In decompensated heart failure (HF), both acute kidney injury (AKI) and high Galectina-3 (Gal-3) levels have been associated with poorer outcomes. Plasma Gal-3 levels are affected by renal function; however, the potential role of Gal-3 as a predictor of AKI has not been established., Methods: We measured Gal-3 concentrations at admission for 175 patients hospitalised for HF and recorded the onset of AKI according to the Risk, Injury, Failure, Loss and End-stage kidney disease (RIFLE) analytical criteria., Results: During hospitalisation, 44 patients (25.1%) developed AKI, although only 14 (8%) corresponded to more advanced stages. These 14 patients had significantly higher Gal-3 levels at admission, which remained a predictor of AKI after the multivariate adjustment by other predictors and by baseline renal function., Conclusions: High Gal-3 levels at admission are associated with a higher risk of AKI during hospitalisation for decompensated HF., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Background: Myocardial uptake of bone tracers has emerged as useful tool for the early detection of transthyretin amyloidosis (ATTR). The prevalence of wild-type ATTR (ATTRwt) in individuals remains to be established., Methods: All whole body bone scans performed in individuals ≥ 75 years with no previous clinical suspicion of ATTR were revised in a population-based university hospital over a 7-year period (1509 studies corresponding to 1114 patients; 80.5 ± 4.1 years, 65% males). Positive cardiac uptake was defined according to Perugini score as grade 2 or 3. Heart failure (HF) hospitalizations during the follow-up were obtained from regional administrative databases., Results: Thirty-one patients ≥ 75 years (2.78%) showed cardiac uptake; compared with those without uptake, these patients were older (85 ± 5 vs. 80 ± 4, p < 0.001) and predominantly males (90% vs. 64%, p = 0.005). The prevalence of cardiac uptake was 3.88% in males and 0.77% in females, and increased with age, reaching 13.9% in males≥85 years (2.7% among females). The estimated prevalence for the European standard population ≥ 75 years was 4.15% in males, 1.03% in females and 2.59% in the general population. HF hospitalizations rates were 14% in patients without uptake and 29% in those with cardiac uptake (p = 0.034). After adjusting for age and gender, cardiac uptake was associated with a higher risk of HF hospitalization (OR 2.60, 95%CI 1.09-5.74, p = 0.022)., Conclusions: Myocardial uptake in bone scan is very prevalent with ageing, mainly affects males and is associated with an increased risk of HF hospitalization. These findings reinforce ATTRwt as a relevant cause of HF in the elderly., (Copyright © 2018 Elsevier B.V. All rights reserved.)