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.

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.

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.

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.

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.

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 ...

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

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.

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.

Comprometimento da função pulmonar em pacientes submetidos à cirurgia de rotação de retalho do músculo peitoral para correção de complicaçoes do esterno pós-cirurgia cardíaca / Worsening of Pulmonary Function in Patients Submitted to Muscle Flap Surgery for Treatment of Sternal Wound Complications After Heart Surgery

PURPOSE: To evaluate pulmonary function of patients submitted to muscle flap for treatment of mediastinitis. METHODS: Fifteen patients operated with the muscle flap technique were compared with 26 consecutive patients submitted to heart surgery with extracorporeal circulation, that did not present wound complications. Both groups were evaluated for age, sex, body weight, height, surgery, forced vital capacity (FVC), forced expiratory volume in first second (FEV1) and the relation (FEV1/FVC) in absolute and percentual values, espirometry conclusions and clinical evidences of lung disease. RESULTS: There was no statistical difference between preoperative and postoperative period for FVC (p = 0.98), FEV1 (p = 0.68) and FEV1/FVC (p = 0.30) in the group with no sternal complications. In the control group, the median of FVC was 3907 +/- 1053.25 and in the study group was 2818 +/- 766.86 in absolute values (p = 0.0015). The median of FEV1, in the control group, was 2995 +/- 855.68 and in the study group was 2232 +/- 617.68 in absolute values (p = 0.0046). There was statistical difference, between groups, in FVC (104.78 +/- 21.73 and 82.04 +/- 21.16) and FEV1 (99 +/- 22.67 and 79.04 +/- 19.17) in percentual (p = 0.0026 and 0.0067) values. There was no statistical difference for the ratio FEV1/FVC. The study group had five patients diagnosed as having restrictive ventilatory insufficiency by espirometry against none in the control group (p = 0.0031). CONCLUSION: Patients with infectious complications of sternum and mediastinum, treated surgically with muscle flap rotation may present restrictive pulmonary insufficiency in moderate degree, that must be considered in this situation.

Ventriculectomia parcial esquerda: ponte para transplante em pacientes com insuficiência cardíaca refratária e hipertensäo pulmonar / Partial left ventriculectomy: option to transplantation in patients with refractory heart failure and pulmonary hypertension

A insuficiência cardíaca congestiva refratária a tratamento clínico tem no transplante cardíaco ortotópico a sua melhor opçäo cirúrgica. Escassez de doadores, morbidade significativa associada com a terapêutica anti-rejeiçäo, aterosclerose coronária e custos consideráveis associados com o transplante säo fatores responsáveis pela sua limitada aplicaçäo. Para os que se encontram na lista para transplante, o período de espera de 6 meses a 1 ano pode levar à deterioraçäo hemodinâmica e expressivo número de mortos. A sobrevida, na lista de espera, pode ser de 46 por cento em 1 ano. Afora isso, um significativo número de pacientes tem contra-indicaçäo para transplante, por apresentar hipertensao e resistência pulmonar elevadas. A ventriculectomia parcial esquerda (VPE), restaurando o raio do ventrículo esquerdo e melhorando, assim, a relaçäo massa-volume e o desempenho sistólico, pode propiciar diminuiçäo da pressao e da resistência pulmonar, em alguns pacientes.

A síndrome de Holt-Oram revisitada: dois casos em uma mesma família / Holt-Oram syndrome revisited: two patients in the same family

Holt-Oram syndrome was first described in 1960 as an association of familial heart disease and musculoskeletal abnormalities. The most important findings include atrial septal defects, atrioventricular conduction abnormalities, vascular hypoplasia, and upper limb musculoskeletal deformities. We report two patients with this syndrome in the same family and discuss the variability of the musculoskeletal abnormalities and their association with the cardiac morphologic defects. Both patients in this study had associated eosinophilia, which has not been reported in the literature.

Estimulaçäo DDD com eletrodo único usando estimulaçäo atrial bifásica simultânea: primeiros resultados clínicos / Single lead DDD pacing with overlapping biphasing atrial stimulation: first clinical results

A estimulaçäo de dupla câmara (DDD) com eletrodo único usando eletrodo atrial flutuante está limitada em funçäo dos altos limiares encontrados para captura atrial. Avaliamos um sistema novo de cabo eletrodo para estimulaçao atrial que utiliza dois anéis atriais com pulsos de onda quadrada simultâneos unipolares lançados com polaridade oposta. O primeiro pulso é aplicado ao pólo distal do eletrodo e é positivo, o segundo pulso é aplicado ao pólo proximal do eletrodo e é negativo, ambos em relaçäo à carcaça do gerador. O atraso entre os dois pulsos é programável entre 0,0 ms e 1,0 ms. A distância entre os anéis a nível atrial é de 10 mm e a distância entre o pólo distal atrial e o eletrodo ventricular unipolar pode ser selecionado entre 11,13 e 15 cm. O posicionamento dos anéis a nével atrial é selecionado de acordo com a medida do limiar de estimulaçäo do pulso bifásico simultâneo, incluindo manobras respiratóris para confirmar a captura/sense contínuos. O gerador de pulso tem uma única conexäo para o eletrodo e a capacidade de aplicar os pulsos programáveis de onda quadrada com polaridade opostas, com atrasos programáveis de 0,0 a 1,0 ms. O gerador pode ser programado para a estimulaçäo VDD com eletrodo único. Este sistema foi implantado em 4 pacientes com bloqueio AV total e funçäo sinusal normal. Os limiares de estimulaçäo atrial e diafragmático foram medidos com várias configuraçöes do pulso, larguras e atrasos, intra e pós-operatórios. A porçäo média do átrio direito foi selecionada como a melhor posiçäo para os anéis atriais com captura contínua durante inspiraçäo profunda. Os pacientes tiveram alta com o gerador programado no modo VDD. A evoluçäo de 30 dias após o implante mostrou perda de captura atrial transitória durante inspiraçäo em 1 paciente, apesar da ausência de outras variaçöes no limiar, comparado com a evoluçäo de 48 horas pós implante. Em conclusäo, a estimulaçäo bifásica simultânea reduz o limiar de estimulaçäo atrial, ao mesmo tempo em que mantém o sense atrial adequado com uma margem de segurança em relaçäo à estimulaçäo diafragmática.

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