Early reduction of pulmonary arterial hypertension in patients using a long-term mechanical ventricular assistance device: a cross-sectional study

ABSTRACT BACKGROUND: Severe pulmonary arterial hypertension (PAH) is a contraindication for heart transplantation (HT). It has been correlated with increased early and late mortality, mainly associated with right ventricular failure. Ventricular assistance devices (VADs) can promote reduction of intracardiac pressures and consequent reduction of PAH over the medium and long terms, thus enabling future candidature for HT. The diminution of early pulmonary pressure within this scenario remains unclear. OBJECTIVE: To evaluate the reduction of PAH and correlate data from right catheterization with the earliness of this reduction. DESIGN AND SETTING: Cross-sectional study in a general hospital in São Paulo, Brazil. METHODS: This was a retrospective analysis on the medical records of patients undergoing VAD implantation in a single hospital. Patients for whom VAD had been indicated as a bridge to candidature for HT due to their condition of constant PAH were selected. RESULTS: Four patients with VADs had constantly severe PAH. Their mean pulmonary artery systolic pressure (PASP) before VAD implantation was 66 mmHg. Over the 30-day period after the procedure, all the patients evolved with a drop in PASP to below 60 mmHg. Their new average was 36 mmHg, which was a drop of close to 50% from baseline values. The one-year survival of this sample was 100%. CONCLUSION: VAD implantation can reduce PAH levels. Early reduction occurred in all patients. Thus, use of VAD is an important bridge tool for enabling candidature for HT among patients with constantly severe PAH.

Adherence to the cardiac surgery checklist decreased mortality at a teaching hospital: A retrospective cohort study

Abstract Objectives To evaluate the impact of adherence to the cardiac surgical checklist on mortality at the teaching hospital. Methods A retrospective cohort study after the implementation of the cardiac surgical safety checklist in a reference hospital in Latin America. All patients undergoing coronary artery bypass surgery and/or heart valve surgery from 2013 to 2019 were analyzed. After the implementation of the project InCor-Checklist "Five steps to safe cardiac surgery" in 2015, the correlation between adherence and completeness of this instrument with surgical mortality was assessed. The EuroSCORE II was used as a reference to assess the risk of expected mortality for patients. Cross-sectional questionnaires were during the implementation of the InCor-Checklist. To perform the correlation, Pearson's coefficient was calculated using R software. Results Since 2013, data from 8139 patients have been analyzed. The average annual mortality was 5.98%. In 2015, the instrument was used in only 58% of patients; in contrast, it was used in 100% of patients in 2019. There was a decrease in surgical mortality from 8.22% to 3.13% for the same group of procedures. The results indicate that the greater the checklist use, the lower the surgical mortality (r = 88.9%). In addition, the greater the InCor-Checklist completeness, the lower the surgical mortality (r = 94.1%). Conclusion In the formation of the surgical patient safety culture, the implementation and adherence to the InCor-Checklist "Five steps to safe cardiac surgery" was associated with decreased mortality after cardiac surgery. HIGHLIGHTS Checklists avoid human errors and are commonly used in high-reliability industries. The "InCor Checklist" was associated with decreased mortality over time. Adherence, completeness, and sustainability within public policies are necessary.

Autologous blood salvage in cardiac surgery: clinical evaluation, efficacy and levels of residual heparin

ABSTRACT Objective: Intraoperative blood salvage (cell saver technique) in cardiac surgery is universally used in surgical procedures with a marked risk of blood loss. The primary objectives of this study were to determine the concentration of residual heparin in the final product that is reinfused into the patient in the operating room and to evaluate the efficacy and safety of the cell saver technique. Method: Twelve patients undergoing elective cardiac surgery were enrolled in this study. Using the XTRA Autotransfusion System, blood samples were collected from the cardiotomy reservoir, both prior to blood processing (pre-sample) and after it, directly from the bag with processed product (post-sample). Hematocrit and hemoglobin levels, the protein, albumin and residual heparin concentrations, hemolysis index, and the platelet, erythrocyte and leukocyte counts were measured. Results: Hematocrit and hemoglobin levels and red blood cell counts were higher in post-processing samples, with a mean variation of 54.78%, 19.81 g/dl and 6.84 × 106/mm3, respectively (p < 0.001). The mean hematocrit of the processed bag was 63.49 g/dl (range: 57.2-67.5). The residual heparin levels were ≤0.1 IU/ml in all post-treatment analyses (p = 0.003). No related adverse events were observed. Conclusion: The reduced residual heparin values (≤0.1 IU/ml) in processed blood found in this study are extremely important, as they are consistent with the American Association of Blood Banks guidelines, which establish target values below 0.5 IU/ml. The procedure was effective, safe and compliant with legal requirements and the available international literature.

Chronic thromboembolic pulmonary hypertension: the impact of advances in perioperative techniques in patient outcomes / Hipertensão pulmonar tromboembólica crônica: o impacto dos avanços nas técnicas perioperatórias nos resultados dos pacientes

ABSTRACT Objectives Pulmonary endarterectomy (PEA) is the gold standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed at reporting outcomes of CTEPH patients undergoing PEA within 10 years, focusing on advances in anesthetic and surgical techniques. Methods We evaluated 102 patients who underwent PEA between January 2007 and May 2016 at the Instituto do Coração do Hospital das Clínicas da Universidade de São Paulo. Changes in techniques included longer cardiopulmonary bypass, heating, and cooling times and mean time of deep hypothermic circulatory arrest and shortened reperfusion time. Patients were stratified according to temporal changes in anesthetic and surgical techniques: group 1 (January 2007-December 2012), group 2 (January 2013-March 2015), and group 3 (April 2015-May 2016). Clinical outcomes were any occurrence of complications during hospitalization. Results Groups 1, 2, and 3 included 38, 35, and 29 patients, respectively. Overall, 62.8% were women (mean age, 49.1 years), and 65.7% were in New York Heart Association functional class III-IV. Postoperative complications were less frequent in group 3 than in groups 1 and 2: surgical complications (10.3% vs. 34.2% vs. 31.4%, p=0.035), bleeding (10.3% vs. 31.5% vs. 25.7%, p=0.047), and stroke (0 vs. 13.2% vs. 0, p=0.01). Between 3 and 6 months post-discharge, 85% were in NYHA class I-II. Conclusion Improvements in anesthetic and surgical procedures were associated with better outcomes in CTEPH patients undergoing PEA during the 10-year period.

RESUMO Objetivo A endarterectomia pulmonar (EAP) é o tratamento padrão ouro para hipertensão pulmonar tromboembólica crônica (HPTEC). O objetivo deste estudo foi relatar a evolução de pacientes com HPTEC submetidos a EAP em 10 anos, com foco nos avanços nas técnicas anestésicas e cirúrgicas. Métodos Foram avaliados 102 pacientes submetidos à EAP entre janeiro de 2007 e maio de 2016 no Instituto do Coração do Hospital das Clínicas da Universidade de São Paulo. Mudanças nas técnicas incluíram circulação extracorpórea, tempos de aquecimento e resfriamento mais longos e tempo médio de hipotermia profunda com parada circulatória e tempo de reperfusão reduzido. Os pacientes foram estratificados de acordo com as mudanças temporais nas técnicas anestésicas e cirúrgicas: grupo 1 (janeiro de 2007 a dezembro de 2012), grupo 2 (janeiro de 2013 a março de 2015) e grupo 3 (abril de 2015 a maio de 2016). Os desfechos clínicos foram qualquer ocorrência de complicações durante a hospitalização. Resultados Os grupos 1, 2 e 3 incluíram 38, 35 e 29 pacientes, respectivamente. No geral, 62,8% eram mulheres (idade média, 49,1 anos) e 65,7% estavam em classe funcional III-IV da New York Heart Association. As complicações pós-operatórias foram menos frequentes no grupo 3 do que nos grupos 1 e 2: complicações cirúrgicas (10,3% vs. 34,2% vs. 31,4%, p=0,035), sangramento (10,3% vs. 31,5% vs. 25,7%, p=0,047) e acidente vascular cerebral (0 vs. 13,2% vs. 0, p=0,01). Entre 3 e 6 meses após a alta, 85% estavam na classe I-II da NYHA. Conclusão Melhorias nos procedimentos anestésicos e cirúrgicos foram associadas a melhores resultados em pacientes com HPTEC submetidos a EAP durante o período de 10 anos.

Impacto Atual da Circulação Extracorpórea na Cirurgia de Revascularização Miocárdica no Estado de São Paulo / Current Impact of Cardiopulmonary Bypass in Coronary Artery Bypass Grafting in São Paulo State

Resumo Fundamento Resultados prévios com o uso de circulação extracorpórea (CEC) geram dificuldades na escolha do melhor tratamento para cada paciente na cirurgia de revascularização miocárdica (CRM) no contexto atual. Objetivo Avaliar o impacto da CEC no cenário atual da CRM no estado de São Paulo. Métodos Foram analisados 2.905 pacientes submetidos à CRM de forma consecutiva em 11 centros do estado de São Paulo pertencentes ao Registro Paulista de Cirurgia Cardiovascular (REPLICCAR) I. Dados perioperatórios e de seguimento foram colocados via on-line por especialistas treinados e capacitados em cada hospital. Foram analisadas as associações das variáveis perioperatórias com o tipo de procedimento (com ou sem CEC) e com os desfechos. A mortalidade esperada foi calculada por meio do EuroSCORE II (ESII). Os valores de p menores de 5% foram considerados significativos. Resultados Não houve diferença significativa em relação à idade dos pacientes entre os grupos (p=0,081). Dentre os pacientes, 72,9% eram de sexo masculino; 542 pacientes foram operados sem CEC (18,7%). Das características pré-operatórias, pacientes com infarto agudo do miocárdio (IAM) prévio (p=0,005) e disfunção ventricular (p=0,031) foram operados com CEC; no entanto, pacientes de emergência ou em classe funcional New York Heart Association (NYHA) IV foram operados sem CEC (p<0,001). O valor do ESII foi semelhante para ambos os grupos (p=0,427). Na CRM sem CEC, houve preferência pelo uso do enxerto radial (p<0,001) e com CEC pela artéria mamária direita (p<0,001). No pós-operatório, o uso de CEC esteve associado com reoperação por sangramento (p=0,012). Conclusão Atualmente, no REPLICCAR, reoperação por sangramento foi o único desfecho associado ao uso da CEC na CRM. (Arq Bras Cardiol. 2020; 115(4):595-601)

Abstract Background Previous results on the use of cardiopulmonary bypass (CPB) have generated difficulties in choosing the best treatment for each patient undergoing myocardial revascularization surgery (CABG) in the current context. Objective Evaluate the current impact of CPB in CABG in São Paulo State. Methods A total of 2905 patients who underwent CABG were consecutively analyzed in 11 São Paulo State centers belonging to the São Paulo Registry of Cardiovascular Surgery (REPLICCAR) I. Perioperative and follow-up data were included online by trained specialists in each hospital. Associations of the perioperative variables with the type of procedure and with the outcomes were analyzed. The study outcomes were morbidity and operative mortality. The expected mortality was calculated using EuroSCORE II (ESII). The values of p <5% were considered significant. Results There were no significant differences concerning the patients' age between the groups (p=0.081). 72.9% of the patients were males. Of the patients, 542 underwent surgery without CPB (18.7%). Of the preoperative characteristics, patients with previous myocardial infarction (p=0.005) and ventricular dysfunction (p=0.031) underwent surgery with CPB. However, emergency or New York Heart Association (NYHA) class IV patients underwent surgery without CPB (p<0.001). The ESII value was similar in both groups (p=0.427). In CABG without CPB, the radial graft was preferred (p<0.001), and in CABG with CPB the right mammary artery was the preferred one (p<0.001). In the postoperative period, CPB use was associated with reoperation for bleeding (p=0.012). Conclusion Currently in the REPLICCAR, reoperation for bleeding was the only outcome associated with the use of CPB in CABG. (Arq Bras Cardiol. 2020; 115(4):595-601)

Analysis of >100. 000 Cardiovascular Surgeries Performed at the Heart Institute and a New Era of Outcomes / Análise de >100. 000 Cirurgias Cardiovasculares Realizadas no Instituto do Coração e a Nova Era com Foco nos Resultados

Abstract Background: The current challenge of cardiovascular surgery (CVS) is to improve the outcomes in increasingly severe patients. In this respect, continuous quality improvement (CQI) programs have had an impact on outcomes. Objective: To assess the evolution of the incidence and mortality due to CVS, as well as the current outcomes of the Hospital das Clínicas Heart Institute of the University of São Paulo Medical School (InCor-HCFMUSP). Methods: An outcome analysis of CVSs performed at the InCor, between January 1984 and June 2019. We observed the surgical volume and mortality rates in 5 time periods: 1st (1984-1989), 2nd (1990-1999), 3rd (2000-2007), 4th (2008-2015) and 5th (2016-2019). The CQI program was implemented between 2015 and 2016. The analysis included the total number of surgeries and the evolution of the most frequent procedures. Results: A total of 105,599 CCVs were performed, with an annual mean of 2,964 procedures and mortality of 5,63%. When comparing the 4th and the 5th periods, the average global volume of surgeries was increased from 2,943 to 3,139 (p = 0.368), bypass graft (CABG), from 638 to 597 (p = 0.214), heart valve surgery, from 372 to 465 (p = 0.201), and congenital heart disease surgery, from 530 to 615 (p = 0.125). The average global mortality went from 7.8% to 5% (p < 0.0001); in CABG surgery, from 5.8% to 3.1% (p < 0.0001); in heart valve surgery, from 14% to 7.5% (p < 0.0001) and in congenital heart disease surgery, from 12.1% to 9.6% (p < 0.0001). Conclusion: In spite of a recent trend towards increased surgical volume, there was a significant decrease in operative mortality in the groups studied. After the implementation of the CQI program, the mortality rates were closer to international standards.

Resumo Fundamento: O desafio atual da cirurgia cardiovascular (CCV) é melhorar resultados em pacientes cada vez mais graves. Nesse sentido, Programas de Melhoria Contínua da Qualidade (PMCQ) tem impactado os resultados. Objetivo: Avaliar a evolução da incidência e mortalidade das CCV, assim como os resultados atuais do Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (InCor). Métodos: Análise dos resultados das CCV realizadas no InCor entre jan-1984 e jun-2019. Foram observadas as tendências dos volumes cirúrgicos e da mortalidade em 5 períodos 1º (1984-1989), 2º (1990-1999), 3º (2000-2007), 4º (2008-2015) e 5º (2016-2019). O PMCQ foi estabelecido entre 2015-2016. A análise incluiu o total de cirurgias e a evolução dos procedimentos mais frequentes. Resultados: Foram realizadas 105.599 CCV, com uma média anual de 2.964 procedimentos e mortalidade de 5,63%. Comparando o 4º com o 5º período, o volume global médio de cirurgias foi de 2.943 para 3.139 (p = 0,368), cirurgias de revascularização miocárdica (CRM) de 638 para 597 (p = 0,214), valvas cardíacas de 372 para 465 (p = 0,201) e cardiopatias congênitas de 530 para 615 (p = 0,125). A mortalidade média global passou de 7,8% para 5% (p < 0,0001), nas cirurgias de revascularização miocárdica de 5,8% para 3,1% (p < 0,0001), nas cirurgias valvares de 14% para 7,5% (p < 0,0001) e nas cirurgias de cardiopatias congênitas de 12,1% para 9,6% (p < 0,0001). Conclusão: Embora haja uma tendência recente ao aumento dos volumes cirúrgicos, houve uma diminuição significativa da mortalidade cirúrgica nos grupos analisados. Após o estabelecimento do PMCQ, as taxas de mortalidade se aproximaram a dos padrões internacionais.

Valve heart surgery in Brazil - the bypass registry analysis

Abstract Objective: To analyze the profile and outcomes of patients who underwent valve heart surgery in Brazil, using information retrieved from the Brazilian Registry of Cardiovascular Surgeries in Adults (BYPASS Registry) database. Methods: This is a multicenter cohort study, evaluating 920 patients submitted to heart valve surgery. Demographics and postoperative clinical outcomes were assessed and compared to estimate mortality risk using the European System for Cardiac Operative Risk Evaluation (EuroSCORE). Results: Isolated aortic valve replacement was the most frequently performed surgery (34%), followed by isolated mitral valve replacement (24.9%). Valve repair was performed in 21% of mitral procedures. Minimally invasive access was performed in 1.6% and the most frequent postoperative complications were arrhythmias (22.6%), infections (5.7%), and low-output syndrome (5.1%). Operations covered by the public health system accounted for 80.8% and the hospital mortality rate was 7.3%. Conclusion: The most frequent isolated valve surgery in Brazil is the aortic valve replacement by conventional open access and the rheumatic disease is still the main etiology for valve surgery. The BYPASS Registry has a fundamental role to provide information on the profile of patients with valve heart disease in our country in order to delineate adequate strategies for health promotion and resource allocation for cardiac surgery.

Brazilian Thoracic Society recommendations for the diagnosis and treatment of chronic thromboembolic pulmonary hypertension / Recomendações para o diagnóstico e tratamento da hipertensão pulmonar tromboembólica crônica da Sociedade Brasileira de Pneumologia e Tisiologia

ABSTRACT Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious and debilitating disease caused by occlusion of the pulmonary arterial bed by hematic emboli and by the resulting fibrous material. Such occlusion increases vascular resistance and, consequently, the pressure in the region of the pulmonary artery, which is the definition of pulmonary hypertension. The increased load imposed on the right ventricle leads to its progressive dysfunction and, finally, to death. However, CTEPH has a highly significant feature that distinguishes it from other forms of pulmonary hypertension: the fact that it can be cured through treatment with pulmonary thromboendarterectomy. Therefore, the primary objective of the management of CTEPH should be the assessment of patient fitness for surgery at a referral center, given that not all patients are good candidates. For the patients who are not good candidates for pulmonary thromboendarterectomy, the viable therapeutic alternatives include pulmonary artery angioplasty and pharmacological treatment. In these recommendations, the pathophysiological bases for the onset of CTEPH, such as acute pulmonary embolism and the clinical condition of the patient, will be discussed, as will the diagnostic algorithm to be followed and the therapeutic alternatives currently available.

RESUMO A hipertensão pulmonar tromboembólica crônica (HPTEC) é uma doença grave e debilitante, causada pela oclusão do leito arterial pulmonar por êmbolos hemáticos e por material fibroso induzido pela presença desses êmbolos. Essa oclusão eleva a resistência vascular e, por consequência, a pressão do território arterial pulmonar, caracterizando a presença de hipertensão pulmonar. Esse aumento da carga imposta ao ventrículo direito leva a progressiva insuficiência do mesmo e, finalmente, ao óbito. No entanto, ao contrário das outras formas de hipertensão pulmonar, a HPTEC possui uma particularidade muito significativa: a existência de tratamento potencialmente curativo através da tromboendarterectomia pulmonar. Dessa forma, o objetivo primordial do manejo deve ser a avaliação do potencial cirúrgico do paciente em um centro de referência em HPTEC. Entretanto, nem todos os pacientes podem ser submetidos à cirurgia. Para esses pacientes outras alternativas terapêuticas viáveis são a angioplastia de artérias pulmonares e o tratamento farmacológico. Nestas recomendações, discutir-se-ão as bases fisiopatológicas para o surgimento de HPTEC, a partir da embolia pulmonar aguda, bem como o quadro clínico apresentado pelo paciente, o algoritmo diagnóstico a ser seguido e as alternativas terapêuticas disponíveis.

Procedimentos cardiovasculares híbridos / Hybrid cardiovascular procedures

O desenvolvimento das salas cirúrgicas híbridas permitiu que operações de abordagem cirúrgica convencional pudessem ser realizadas e complementadas com a abordagem percutânea e endovascular, criando uma nova forma de tratar os pacientes por meio de cirurgias híbridas. Os procedimentos híbridos permitem que cirurgiões e cardiologistas intervencionistas possam associar suas expertises para tratar, da melhor forma possível, os pacientes com doenças cada vez mais complexas e avançadas, com melhores resultados, reduzindo a morbidade e mortalidade perioperatória e permitindo recuperação mais rápida

The development of hybrid operating rooms allowed that conventional surgical approach operations could be performed and complemented with the percutaneous and endovascular approach, creating a new way of treating patients through hybrid surgeries. Hybrid procedures allow surgeons and interventional cardiologists to combine their expertise to best treat patients with increasingly complex and advanced diseases, with better outcomes, reducing perioperative morbidity and mortality and allowing faster recovery

Does methylene blue attenuate inflammation in nonischemic lungs after lung transplantation? / O azul de metileno atenua a inflamação em pulmões não isquêmicos após transplante pulmonar?

ABSTRACT Objective: To evaluate whether methylene blue (MB) could minimize the effects of ischemia-reperfusion injury in the nonischemic lung on a lung transplantation rodent model. Methods: Forty female Sprague-Dawley rats were divided into 20 donors and 20 recipients. The 20 recipient rats were divided into two groups (n = 10) according to the treatment (0.9% saline vs. 1% MB solutions). All animals underwent unilateral lung transplantation. Recipients received 2 mL of saline or MB intraperitoneally prior to transplantation. After 2 h of reperfusion, the animals were euthanized and histopathological and immunohistochemical analyses were performed in the nonischemic lung. Results: There was a significant decrease in inflammation-neutrophil count and intercellular adhesion molecule-1 (ICAM-1) expression in lung parenchyma were higher in the saline group in comparison with the MB group-and in apoptosis-caspase-3 expression was higher in the saline group and Bcl-2 expression was higher in MB group. Conclusions: MB is an effective drug for the protection of nonischemic lungs against inflammation and apoptosis following unilateral lung transplantation in rats.

RESUMO Objetivo: Avaliar se o azul de metileno (AM) pode minimizar os efeitos da lesão de isquemia-reperfusão sobre o pulmão não isquêmico em um modelo de transplante pulmonar em roedores. Métodos: Quarenta ratas Sprague-Dawley foram divididas em 20 doadoras e 20 receptoras. As 20 ratas receptoras foram divididas em dois grupos (n = 10) de acordo com o tratamento (solução salina a 0,9% vs. AM a 1%). Todos os animais foram submetidos a transplante pulmonar unilateral. As receptoras receberam 2 ml de solução salina ou de AM por via intraperitoneal antes do transplante. Após 2 h de reperfusão, os animais foram sacrificados, e foram realizadas análises histopatológicas e imuno-histoquímicas no pulmão não isquêmico. Resultados: Houve diminuição significativa da inflamação - a contagem de neutrófilos e a expressão de intercellular adhesion molecule-1 (ICAM-1, molécula de adesão intercelular-1) foram maiores no grupo salina em comparação com o grupo AM - e da apoptose - a expressão de caspase-3 foi maior no grupo salina, e a expressão de Bcl-2 foi maior no grupo AM. Conclusões: O AM é uma droga eficaz para a proteção de pulmões não isquêmicos contra inflamação e apoptose após transplante pulmonar unilateral em ratos.

Off-pump versus on-pump coronary artery bypass grafting in frail patients: study protocol for the fragile multicenter randomized controlled trial

Abstract Introduction: Advances in modern medicine have led to people living longer and healthier lives. Frailty is an emerging concept in medicine yet to be explored as a risk factor in cardiac surgery. When it comes to CABG surgery, randomized controlled clinical trials have primarily focused on low-risk (ROOBY, CORONARY), elevated-risk (GOPCABE) or high-risk patients (BBS), but not on frail patients. Therefore, we believe that off-pump CABG could be an important technique in patients with limited functional capacity to respond to surgical stress. In this study, the authors introduce the new national, multicenter, randomized, controlled trial "FRAGILE", to be developed in the main cardiac surgery centers of Brazil, to clarify the potential benefit of off-pump CABG in frail patients. Methods: FRAGILE is a two-arm, parallel-group, multicentre, individually randomized (1:1) controlled trial which will enroll 630 patients with blinded outcome assessment (at 30 days, 6 months, 1 year, 2 years and 3 years), which aims to compare adverse cardiac and cerebrovascular events after off-pump versus on-pump CABG in pre-frail and frail patients. Primary outcomes will be all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke, and coronary reintervention. Secondary outcomes will be major adverse cardiac and cerebrovascular events, operative time, mechanical ventilation time, hyperdynamic shock, new onset of atrial fibrillation, renal replacement therapy, reoperation for bleeding, pneumonia, length of stay in intensive care unit, length of stay in hospital, number of units of blood transfused, graft patency, rate of complete revascularization, neurobehavioral outcomes after cardiac surgery, quality of life after cardiac surgery and costs. Discussion: FRAGILE trial will determine whether off-pump CABG is superior to conventional on-pump CABG in the surgical treatment of pre-frail and frail patients. Trial registration: ClinicalTrials.gov, ID: NCT02338947. Registered on August 29th 2014; last updated on March 21st 2016.