RESUMO
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.
Assuntos
Parada Cardíaca , Transplante de Coração , Obtenção de Tecidos e Órgãos , Morte , Coração , Humanos , Perfusão/métodos , Doadores de Tecidos , Isquemia QuenteRESUMO
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).
RESUMO
AIMS: There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients. METHODS AND RESULTS: Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.98; p = 0.048), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance [Correction added on 29 April 2024, after first online publication: In the preceding sentence, "95% CI 0.02 - 0.09" has been corrected to "95% CI 0.02 - 0.98; p = 0.048" in this version.]. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group. CONCLUSIONS: Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.
Assuntos
Biomarcadores , Insuficiência Cardíaca , Peptídeo Natriurético Encefálico , Alta do Paciente , Fragmentos de Peptídeos , Volume Sistólico , Humanos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Feminino , Masculino , Volume Sistólico/fisiologia , Idoso , Biomarcadores/sangue , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Readmissão do Paciente/estatística & dados numéricos , Monitorização Fisiológica/métodos , Hospitalização/estatística & dados numéricosRESUMO
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.
Assuntos
COVID-19 , Proteína 1 Semelhante a Receptor de Interleucina-1 , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Prognóstico , COVID-19/diagnóstico , SARS-CoV-2 , BiomarcadoresRESUMO
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.
Assuntos
COVID-19 , Pneumonia , Adulto , Idoso , Biomarcadores , Proteína C-Reativa , COVID-19/diagnóstico , Feminino , Fibrose , Humanos , Interleucina-6 , Masculino , Pessoa de Meia-Idade , Mucina-1 , Oxigênio , Prognóstico , Estudos Retrospectivos , SARS-CoV-2RESUMO
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.
Assuntos
Hematopoiese Clonal/genética , DNA (Citosina-5-)-Metiltransferases/genética , Proteínas de Ligação a DNA/genética , Insuficiência Cardíaca , Proteínas Proto-Oncogênicas/genética , Disfunção Ventricular Esquerda , Idoso , Causas de Morte , DNA Metiltransferase 3A , Dioxigenases , Progressão da Doença , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Mortalidade , Mutação , Prognóstico , Estudos Prospectivos , Espanha/epidemiologia , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
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.
RESUMO
BACKGROUND: Acute kidney injury (AKI) is a serious complication in patients hospitalized for decompensated heart failure (HF). Currently, AKI definitions consider creatinine levels at admission as reference of baseline renal function (RF). However, renal impairment may already be present at admission. We aimed to study the impact on AKI detection of considering outpatient RF as reference. METHODS: In a cohort of 458 patients hospitalized for decompensated HF, we studied the occurrence of AKI using the standardized KDIGO criteria and grading (stages: 1, 2, 3), and considering two different definitions according to the RF used as reference or baseline: the latest outpatient measurement prior to admission vs. the first measurement at admission. We compared the prevalence, timing and prognostic value for both AKI definitions. RESULTS: The definition based on outpatient RF was associated with an increase in overall AKI detection from 20.1% to 33.8% (p < 0.001), and from 3.1% to 5.0% for advanced stages (2-3) (p < 0.001); additionally, 12.5% of patients already had criteria of AKI at admission (36.8% of AKI cases). Both definitions were associated with longer hospital stay. However, only AKI already present at admission, as based on pre-hospital creatinine, was independently associated with all-cause death, in-hospital and after discharge, and death or HF readmission in the follow-up: 1 stage (HR 2.72, 95%CI 1.83-4.06, p < 0.001) and 2-3 stage (HR 7.29, 95%CI, 3.02-17.64, p < 0.001). CONCLUSIONS: Evaluation of AKI in patients admitted with HF should consider pre-hospital RF, since it improves early identification of AKI and has implications for risk assessment.
Assuntos
Injúria Renal Aguda , Insuficiência Cardíaca , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Creatinina , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Hospitais , Humanos , Estudos Retrospectivos , Fatores de RiscoRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have shown to prevent heart failure progression, although the mechanisms remain poorly understood. Here we evaluated the effect of empagliflozin (EMPA, SGLT2i) in cardiac remodeling after myocardial infarction, the interplay with diabetes status and the role of cardiac GTP enzyme cyclohydrolase 1 (cGCH1). A rat model of diabetes (50 mg/kg streptozotocin, i.p.) was subjected to myocardial infarction and left ventricular systolic dysfunction, by ligation of the left anterior descending coronary artery. EMPA therapy significantly improved cardiac remodeling parameters and ameliorated processes of fibrosis and hypertrophy, in both non-diabetic and diabetic rats. This cardioprotective effect related with a significant increase in myocardial expression levels of cGCH1, which led to activation of nNOS and eNOS, and inhibition of iNOS, and subsequently resulted in increasing of NO levels and decreasing O2.- and nitrotyrosine levels. These effects were replicated in a cardiomyocyte biomechanical stretching diabetic model, where silencing cGCH1 blocked the preventive effect of EMPA. The beneficial effects were observed irrespective of diabetes status, although the magnitude was greater in presence of diabetes. Empagliflozin improves myocardial remodeling after myocardial infarction through overexpression of cGCH1, and irrespective of diabetes status.
Assuntos
Compostos Benzidrílicos/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , GTP Cicloidrolase/metabolismo , Glucosídeos/farmacologia , Infarto do Miocárdio/complicações , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Disfunção Ventricular Esquerda/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Animais , GTP Cicloidrolase/genética , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Ratos , Ratos Wistar , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/patologiaRESUMO
BACKGROUND: Soluble ST2 (sST2), which is the soluble form of interleukin (IL)-1 receptor-like 1, identifies risk in acutely decompensated heart failure (ADHF). IL-1ß is an inflammatory cytokine that has deleterious effects in myocardial remodeling and function. IL-1ß inhibition has beneficial effects after acute myocardial infarction. However, the role of IL-1ß in ADHF and its relationship to ST2 remain unclear. OBJECTIVES: This study sought to investigate the relationship between IL-1ß and sST2, and the prognostic impact of such a relationship in patients with ADHF. METHODS: This study examined 316 consecutive patients who were hospitalized with ADHF (72 ± 12 years of age, 57% male, and left ventricular ejection fraction 45 ± 17%). Blood samples were collected at presentation, and IL-1ß and sST2 levels were measured. All-cause mortality was obtained for all patients at 1 year. RESULTS: The IL-1ß concentration at presentation was associated with prior HF hospitalizations, functional impairment, and higher N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T concentrations. IL-1ß was higher in patients who died during the year after hospitalization (n = 52, 16.5%) (p = 0.005), and the optimal threshold was identified with levels over 49.1 pg/ml (hazard ratio: 2.5; 95% confidence interval: 1.43 to 4.49; p = 0.0014). Circulating IL-1ß positively correlated with sST2 (ρ = 0.65; p < 0.001). Considering the prognostic thresholds of IL-1ß (≥49.1 pg/ml) and sST2 (≥35.0 ng/ml) concentrations: all patients with low sST2 also presented with low IL-1ß; among patients with high sST2, only those with also high IL-1ß had a significantly higher risk of death (30% vs. 14%; hazard ratio: 2.52; 95% confidence interval: 1.40 to 4.56; p = 0.002). CONCLUSIONS: Circulating IL-1ß concentrations are clinically meaningful in ADHF patients and interplay with the predictive ability of sST2. IL-1 axis-related inflammation signaling may represent a therapeutic target in ADHF.
Assuntos
Insuficiência Cardíaca/sangue , Interleucina-1/sangue , Sistema de Registros , Medição de Risco/métodos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Doença Aguda , Idoso , Biomarcadores/sangue , Causas de Morte/tendências , Ensaio de Imunoadsorção Enzimática , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Curva ROC , Fatores de Risco , Espanha/epidemiologia , Taxa de Sobrevida/tendênciasRESUMO
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.
Assuntos
Insuficiência Cardíaca/epidemiologia , Hospitalização/tendências , Vigilância da População/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Insuficiência Cardíaca/terapia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/tendências , Estudos Retrospectivos , Espanha/epidemiologia , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
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 individualsâ¯≥â¯75â¯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⯱â¯4.1â¯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 patientsâ¯≥â¯75â¯years (2.78%) showed cardiac uptake; compared with those without uptake, these patients were older (85⯱â¯5 vs. 80⯱â¯4, pâ¯<â¯0.001) and predominantly males (90% vs. 64%, pâ¯=â¯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≥85â¯years (2.7% among females). The estimated prevalence for the European standard populationâ¯≥â¯75â¯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 (pâ¯=â¯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, pâ¯=â¯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.