Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. METHODS: DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov, NCT04350593. FINDINGS: Between April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58-1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97-1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52-1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo. INTERPRETATION: In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated. FUNDING: AstraZeneca.

Aortic Center: specialized care improves outcomes and decreases mortality / Centro de Tratamento da Aorta: a especialização reduz complicações e mortalidade

Objective: To compare in-hospital outcomes in aortic surgery in our cardiac surgery unit, before and after foundation of our Center for Aortic Surgery (CTA). Methods: Prospective cohort with non-concurrent control. Foundation of CTA required specialized training of surgical, anesthetic and intensive care unit teams, routine neurological monitoring, endovascular and hybrid facilities, training of the support personnel, improvement of the registry and adoption of specific protocols. We included 332 patients operated on between: January/2003 to December/2007 (before-CTA, n=157, 47.3%); and January/2008 to December/2010 (CTA, n=175, 52.7%). Baseline clinical and demographic data, operative variables, complications and in-hospital mortality were compared between both groups. Results: Mean age was 58±14 years, with 65% male. Group CTA was older, had higher rate of diabetes, lower rates of COPD and HF, more non-urgent surgeries, endovascular procedures, and aneurysms. In the univariate analysis, CTA had lower mortality (9.7 vs. 23.0%, P=0.008), which occurred consistently across different diseases and procedures. Other outcomes which were reduced in CTA included lower rates of reinterventions (5.7 vs 11%, P=0.046), major complications (20.6 vs. 33.1%, P=0.007), stroke (4.6 vs. 10.9%, P=0.045) and sepsis (1.7 vs. 9.6%, P=0.001), as compared to before-CTA. Multivariable analysis adjusted for potential counfounders revealed that CTA was independently associated with mortality reduction (OR=0.23, IC 95% 0.08 – 0.67, P=0.007). CTA independent mortality reduction was consistent in the multivariable analysis stratified by disease (aneurysm, OR=0.18, CI 95% 0.03 – 0.98, P=0.048; dissection, OR=0.31, CI 95% 0.09 – 0.99, P=0.049) and by procedure (hybrid, OR=0.07, CI 95% 0.007 – 0.72, P=0.026; Bentall, OR=0.18, CI 95% 0.038 – 0.904, P=0.037). Additional multivariable predictors of in-hospital mortality included creatinine ...

Objetivo: Comparar desfechos intrahospitalares em pacientes submetidos a cirurgia da aorta torácica e toracoabdominal, antes e após a constituição do Centro Especializado de Tratamento da Aorta (CTA). Métodos: Coorte prospectiva com controle não contemporâneo. A criação do CTA envolveu treinamento cirúrgico especializado, sala híbrida, monitorização neurológica, capacitação de pessoal de apoio, aperfeiçoamento dos registros e uso de protocolos específicos. Foram incluídos 332 pacientes operados em 2 períodos: janeiro/2003 a dezembro/2007 (pré-CTA, n=157, 47,3%); e janeiro/2008 a dezembro/2010 (CTA, n=175, 52,7%). As características demográficas, clínicas, dados cirúrgicos, complicações e mortalidade hospitalar foram comparados nos 2 grupos. Resultados: A idade média foi 58±14 anos, com 65% sexo masculino. O grupo CTA teve idade, prevalência de diabete (DM) e glicemia maiores; menor prevalência de doença pulmonar obstrutiva crônica e insuficiência cardíaca; maior proporção de aneurismas e cirurgias eletivas; e mais procedimentos endovasculares que o pré-CTA. Na análise univariada, o grupo CTA mostrou redução de mortalidade (9,7% x 23,0%, P=0,008), que foi consistente nos diferentes subgrupos estratificados por patologia e por procedimento. O grupo CTA teve também redução de reoperações (5,7% x 11%, P=0,046), complicações maiores (20,6% x 33,1%, P=0,007), acidente vascular cerebral (4,6% x 10,9%, P=0,045) e sepse (1,7% x 9,6%, P=0,001), comparado ao pré-CTA. Na análise multivariada, o CTA se associou de forma independente a redução de mortalidade hospitalar (OR=0,23, IC 95% 0,08 - 0,67, P=0,007). A redução de mortalidade do CTA também ocorreu na análise estratificada por patologia (cirurgias de aneurisma, OR=0,18, IC 95% 0,03 - 0,98, P=0,048; cirurgias de dissecção, OR=0,31, IC 95% 0,09 - 0,99, P=0,049) e por procedimento (híbridos, OR=0,07, IC 95% 0,007 - 0,72, P=0,026; Bentall, OR=0,18, IC 95% 0,038 – 0,904, P=0,037). Também foram ...

Aortic Center: specialized care improves outcomes and decreases mortality.

OBJECTIVE: To compare in-hospital outcomes in aortic surgery in our cardiac surgery unit, before and after foundation of our Center for Aortic Surgery (CTA). METHODS: Prospective cohort with non-concurrent control. Foundation of CTA required specialized training of surgical, anesthetic and intensive care unit teams, routine neurological monitoring, endovascular and hybrid facilities, training of the support personnel, improvement of the registry and adoption of specific protocols. We included 332 patients operated on between: January/2003 to December/2007 (before-CTA, n=157, 47.3%); and January/2008 to December/2010 (CTA, n=175, 52.7%). Baseline clinical and demographic data, operative variables, complications and in-hospital mortality were compared between both groups. RESULTS: Mean age was 58±14 years, with 65% male. Group CTA was older, had higher rate of diabetes, lower rates of COPD and HF, more non-urgent surgeries, endovascular procedures, and aneurysms. In the univariate analysis, CTA had lower mortality (9.7 vs. 23.0%, P=0.008), which occurred consistently across different diseases and procedures. Other outcomes which were reduced in CTA included lower rates of reinterventions (5.7 vs 11%, P=0.046), major complications (20.6 vs. 33.1%, P=0.007), stroke (4.6 vs. 10.9%, P=0.045) and sepsis (1.7 vs. 9.6%, P=0.001), as compared to before-CTA. Multivariable analysis adjusted for potential confounders revealed that CTA was independently associated with mortality reduction (OR=0.23, IC 95% 0.08 - 0.67, P=0.007). CTA independent mortality reduction was consistent in the multivariable analysis stratified by disease (aneurysm, OR=0.18, CI 95% 0.03 - 0.98, P=0.048; dissection, OR=0.31, CI 95% 0.09 - 0.99, P=0.049) and by procedure (hybrid, OR=0.07, CI 95% 0.007 - 0.72, P=0.026; Bentall, OR=0.18, CI 95% 0.038 - 0.904, P=0.037). Additional multivariable predictors of in-hospital mortality included creatinine (OR=1.7 [1.1-2.6], P=0.008), urgent surgery (OR=5.0 [1.5-16.7], P=0.008) and thoracoabdominal aneurysm (OR=24.6 [3.1-194.1], P=0.002). CONCLUSION: Thoracic aorta surgery in specialized center was associated with lower incidence of complications and all-cause mortality as compared to usual care.

Effectiveness of metoprolol in preventing atrial fibrillation and flutter in the postoperative period of coronary artery bypass graft surgery.

OBJECTIVE: To assess the effectiveness of metoprolol in preventing clinically detectable atrial fibrillation (AF) and flutter after coronary artery bypass graft (CABG) surgery. METHODS: An open, randomized study was carried out to treat 200 patients who had undergone isolated CABG surgery with extracorporeal circulation. The patients were randomized to either receive metoprolol orally or not to receive the medication in the postoperative period. The outcomes were the detection of sustained atrial AF and flutter, which were symptomatic or required treatment. The patients with the following characteristics were excluded from the study: baseline left ventricular ejection fraction < 35%; previous AF; history of bronchospasm; second- and third-degree atrioventricular blocks, low cardiac output, and heart failure. RESULTS: Arrhythmias occurred in 11 out of 100 patients in the metoprolol group and in 24 out of 100 patients in the control group (P=0.02). The relative risk (RR) was 0.46 (95% CI = 0.24-0.88), and the number necessary to treat (NNT) and avoid the outcome was 8 patients. AF was the arrhythmia most frequently observed (30/35). In 38 patients aged 70 years or more, the arrhythmias occurred in 2 out of 19 patients in the metoprolol group and in 10 out of 19 patients in the control group (c2 Yates: P=0.01). The relative risk was 0.20 (95% CI = 0.05-0.79) and the number necessary to treat was 2 patients. CONCLUSION: Metoprolol is effective in preventing AF and flutter in the postoperative period of CABG surgery, and this effect was more evident in the group of elderly patients.

Efetividade do metoprolol na prevenção de fibrilação e flutter atrial no pós-operatório de cirurgia de revascularização miocárdica / Effectiveness of metoprolol in preventing atrial fibrillation and flutter in the postoperative period of coronary artery bypass graft surgery

OBJETIVO: Avaliar a efetividade do metoprolol na prevenção de fibrilação e flutter atrial clinicamente detectáveis após cirurgia de revascularização miocárdica. MÉTODOS: Ensaio clínico, randomizado e aberto, para tratar 200 pacientes submetidos à cirurgia de revascularização miocárdica isolada com circulação extracorpórea, randomizados para receber metoprolol, por via oral, ou para não receber a medicação no pós-operatório. Os desfechos de interesse eram a detecção de fibrilação e flutter atrial sustentados, sintomáticos ou que requeressem tratamento. Excluídos do estudo os pacientes com fração de ejeção basal do ventrículo esquerdo < 35 por cento, fibrilação atrial prévia, história de broncoespasmo, bloqueios atrioventriculares de 2º e 3º grau, baixo débito cardíaco e insuficiência cardíaca. RESULTADOS: Arritmias ocorreram em 11 de 100 pacientes do grupo metoprolol e em 24 de 100 pacientes do grupo controle (p=0,02). O risco relativo (RR) foi 0,46 (IC de 95 por cento= 0,24-0,88) e o número necessário para tratar (NNT) e evitar o desfecho foi de 8 pacientes. A fibrilação atrial foi a arritmia mais freqüentemente observada (30/35). Em 38 pacientes com idade > 70 anos, as arritmias ocorreram em 2 de 19 pacientes do grupo metoprolol e em 10 de 19 do grupo controle (c2 Yates: p=0,01). O risco relativo foi 0,20 (IC de 95 por cento= 0,05-0,79) e o número necessário para tratar foi de 2 pacientes. CONCLUSÃO: O metoprolol é efetivo na prevenção de fibrilação e flutter atrial no PO de cirurgia de revascularização miocárdica, sendo esse efeito mais marcante no grupo de pacientes idosos.

Lymphocyte's activation and apoptosis after coronary artery bypass graft: a comparative study of two membrane oxygenators--one with and another without a venous-arterial shunt.

Newer oxygenators with the latest technologies are designed to attenuate the immune response, including lymphopenia, prompted by cardiopulmonary bypass (CPB) in cardiac surgery. We evaluated the effect of CPB, comparing an oxygenator with a venous-arterial shunt and a conventional oxygenator with regard to lymphocyte's early activation and apoptosis induction and its implications in post-CPB lymphopenia. Patients undergoing coronary artery bypass graft surgery with CPB, using either a conventional oxygenator or one with a venous-arterial shunt, had blood samples drawn at anesthetic induction (baseline); the beginning and end of the CPB; and at 6, 12, and 24 hours after surgery. Analysis by flow cytometry was undertaken to assess the expression of lymphocyte surface markers (CD3+, CD25+, CD26+, CD69+) and apoptosis (annexin V). Twenty patients were studied; 10 used a conventional oxygenator, and 10 used an oxygenator with venous-arterial shunt. Postoperative lymphopenia (50% decrease), 35% increased expression of CD69+, and 56% decrease in annexin V were significant comparing baseline to 24 hour value, similarly in both groups. Early activation (expression of CD69+) and degree of apoptosis (expression of annexin V) of lymphocytes after CBP in cardiac surgery was similarly observed in both types of oxygenators. The observed lymphopenia after CPB does not appear to be secondary to apoptosis.

Peptídeo natriurético tipo-B e doenças cardiovasculares / B-type natriuretic peptide and cardiovascular disease

A descoberta de uma ligação endocrinológica entre o coração e os rins baseia-se em achados de microscopia eletrônica em que células de músculo estriado dos átrios de mamíferos se diferenciam tanto em células contráteis como em células endócrinas. O fator natriurético atrial (FNA), um peptídeo circulante com propriedades natriuréticas, diuréticas e vasodilatadoras, foi descoberto em 1980 por A. J. de Bold, e considerado, na ocasião, como a ligação hormonal entre o coração e os rins. Desde então, um imenso número de investigações multidisciplinares tem sido conduzido para esclarecer o real papel deste peptídeo na patogênese das doenças cardiovasculares, na regulação da pressão arterial e na excreção de sal e água. Essas investigações acabaram se tornando um excelente exemplo de pesquisa evoluída da bancada do laboratório à beira do leito do paciente. Hoje, o peptídeo natriurético tipo-B (PNB) vem gradual e lentamente se estabelecendo na área clínica. O objetivo deste artigo é prover o clínico de uma revisão atualizada dos progressos ocorridos até o momento, a fim de incluir o peptídeo natriurético tipo-B na prática clínica diária.

Primary cardiac angiosarcoma. A therapeutical dilemma.

Cardiac angiosarcomas are malignant tumors that almost invariably have a short and fatal evolution. The therapeutic approach includes surgery, chemotherapy, and radiation therapy, alone or in combination. Heart transplantation is an attractive option in nonresectable tumors, even though the current experience is still limited. However, in most patients, the diagnosis is still established late, and survival is only slightly altered by the proposed treatments, mainly due to previously existing and undetected metastases. We report a case that illustrates the therapeutic dilemma faced with this neoplasia, and we discuss the case based on a literature review.

Angiossarcoma cardíaco primário: um dilema terapêutico

Cardiac angiosarcomas are malignant tumors that almost invariably have a short and fatal evolution. The therapeutic approach includes surgery, chemotherapy, and radiation therapy, alone or in combination. Heart transplantation is an attractive option in nonresectable tumors, even though the current experience is still limited. However, in most patients, the diagnosis is still established late, and survival is only slightly altered by the proposed treatments, mainly due to previously existing and undetected metastases. We report a case that illustrates the therapeutic dilemma faced with this neoplasia, and we discuss the case based on a literature review

Fasceíte necrotizante do tórax em pós-operatório de cirurgia cardíaca / Postoperative necrotizing fasciitis of the thorax in cardiac surgery

Necrotizing fasciitis is a rare soft tissue infection and a life-threatening emergency, often fatal. Its incidence and management are described plentifully in the medical literature regarding the most common anatomical sites involved like the abdomen, lower and upper limbs, and perineum. However, available data and case reports of chest wall necrotizing fasciitis after thoracic procedures are scarce, mainly after major cardiac operations. We report and discuss a case of necrotizing fasciitis of the chest wall occurring in the immediate postoperative period of a cardiac procedure, and include a brief review of the concepts, pathophysiology, and treatment reported in the medical literature. We emphasize the need for early diagnosis and urgent and effective surgical debridement. Of importance is the fact that we have not found any references in the literature to cases similar or equal to the one we describe here, which occurred in the postoperative period of a cardiac procedure

Ventriculectomia parcial esquerda: ponte para transplante? / Partial left ventriculectomy: bridge to transplantation?

OBJETIVO: Analisar os resultados e a viabilidade da ventriculectomia parcial esquerda (VPE) como ponte para transplante cardíaco (TX). DELINEAMENTO: Estudo de coorte histórica e prospectivo. CASUISTICA E MÉTODOS: Cinquenta e três pacientes (pts) foram submetidos a VPE em um período de 5 anos. Destes, 7 pts com contra-indicação inicial ao TX, idades variando de 37 a 64 anos, 5 homens e 2 mulheres, com miocardiopatia dilatada, foram subseqüentemente relistados e transplantados. Foram analisados a fração de ejeção (FE), o diâmetro diastólico final do ventrículo esquerdo (DDFVE), a CF da NYHA, o consumo máximo de oxigênio (VO2 máx) e os escores de qualidade de vida (QV) antes da VPE, aos 3 e 6 meses, e pré-transplante...