Evaluation method of training simulation on biological models for cardiovascular surgery residents.

OBJECTIVES: The goal of this study was to describe and evaluate our simulation training program on biological models for the cardiovascular surgery residency program at our institution. MATERIAL AND METHODS: Since 2016, with the purpose to develop better practical performance and evaluate the improvement of resident's surgical skills, a simulation training program was implemented, composed of some elemental procedures in cardiovascular surgery. It was established with one wet lab session weekly lasting 2 h, coached by two expert cardiovascular surgeons. Bovine and porcine hearts were used as biological models. At the end of the hands-on program, an objective assessment consisting of two practical modules was applied and performance was rated by way of a 5-point scale. In addition, to provide a subjective assessment, each resident filled out a questionnaire consisting of three items reviewing the overall quality of the workshops on a 10-point scale. RESULTS: The objective evaluation applied at the end of the training program consisted of valve replacement and coronary artery bypass grafting (CABG) modules. The mean performance rating scores for the valve replacement module ranged from 4.2 to 4.79, and CABG, from 4.33 to 4.87. Regarding subjective assessment, all items evaluated, such as expert's didactics, simulation performance, and biological simulator fidelity, received high grades (above 9 on a 10-point scale). CONCLUSIONS: Simulator training on biological models for cardiac surgery medical residents is a simple and effective learning method of surgical skills.

17ß-Estradiol prevents mesenteric injury induced by occlusion of the proximal descending aorta in male rats.

OBJECTIVE: In surgical aortic repair or cardiac surgery with aorta occlusion, the occurrence of mesenteric ischemia and bowel injury has been associated with higher short-term mortality. The vascular protection of estrogens has been investigated and is mainly mediated by increasing the availability of nitric oxide (NO). Therefore, this study investigated the role of 17ß-estradiol on visceral ischemia-reperfusion (I/R) injury after descending aorta occlusion in male rats. METHODS: Mesenteric ischemia was induced in male Wistar rats by placing a 2F Fogarty arterial embolectomy catheter (Edwards Lifesciences, Irvine, Calif) in the descending aorta, which remained occluded for 15 minutes, followed by reperfusion for up to 2 hours. Rats were divided into four groups: (1) rats that underwent surgical manipulation only (sham, n = 22); (2) rats that underwent I/R injury (n = 22); (3) rats treated with intravenous 17ß-estradiol (280 µg/kg) 30 minutes before I/R (n = 22); (4) or at the beginning of reperfusion (n = 22). Intestinal histopathologic changes were evaluated by histomorphometry. Mesenteric microcirculatory alterations were assessed by laser Doppler flowmetry and intravital microscopy technique. Protein expression of intercellular adhesion molecule-1, P-selectin, endothelial NO synthase (eNOS), and endothelin-1 was evaluated by immunohistochemistry; in addition, eNOS and endothelin-1 gene expressions were quantified by real-time polymerase chain reaction. Serum cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: Relative to the sham group, the I/R group exhibited a highly pronounced loss of intestine mucosal thickness, a reduction in mesenteric blood flow (P = .0203), increased migrated leukocytes (P < .05), and high mortality rate (35%). Treatment with 17ß-estradiol before aorta occlusion preserved intestine mucosal thickness (P = .0437) and mesenteric blood flow (P = .0251), reduced the number of migrated leukocytes (P < .05), and prevented any fatal occurrence. Furthermore, 17ß-estradiol downregulated the expression of intercellular adhesion molecule-1 (P = .0001) and P-selectin (P < .0001) on the endothelium and increased the protein expression of eNOS (P < .0001). The gene expressions of eNOS and endothelin-1 did not differ between the groups. CONCLUSIONS: The prophylactic treatment with 17ß-estradiol showed better overall repercussions and was able to prevent any fatal occurrence, increase eNOS expression, thus preserving mesenteric perfusion and intestinal integrity, and reduce inflammation.

Myocardial gene expression of T-bet, GATA-3, Ror-γt, FoxP3, and hallmark cytokines in chronic Chagas disease cardiomyopathy: an essentially unopposed TH1-type response.

BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC), a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC). Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (TH1/TH2/TH17/Treg) in CCC, NIC, and heart donor myocardial samples. METHODS AND RESULTS: Quantitative PCR showed markedly upregulated expression of IFN-γ and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by TH2 cells (IL-4, IL-5, and IL-13) or associated with Treg (TGF-ß and IL-10) were not upregulated in CCC myocardium. Expression of TH1-related genes such as T-bet, IFN-γ, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. CONCLUSIONS: Results are consistent with a strong local TH1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3(+)CTLA4(+) Treg cell population, which is unable to completely curb IFN-γ production in CCC myocardium, therefore fueling inflammation.

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS's DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.

Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients.

Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients' myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.

Transplantation for Chagas' disease: an overview of immunosuppression and reactivation in the last two decades.

Over the last 20 yr, the immunosuppression protocols in chagasic heart-transplanted patients have gone through three phases, and we have identified several changes and discoveries about Chagas' disease reactivation, mortality, and neoplasia development. The first phase was especially important because until that time, Chagas' disease was an absolute contraindication for transplantation. The second phase started when an adjustment was made to the immunosuppression protocol, a lower dosage being adopted to avoid adverse effects, especially neoplasias and reactivation episodes. Currently, strategies to change the immunosuppression, especially replacement of mycophenolate mofetil by azathioprine or low doses of mycophenolate in this special situation, have been shown to be effective in reducing Chagas' disease reactivation. Cardiac transplantation for Chagas' disease is a reality. Although patients with Chagas' disease may experience particular complications when undergoing transplantation compared with transplantation for other etiologies, these difficulties are well known, and treatment and preventive strategies are also better established. In other organs and tissues, transplantation in patients with Chagas' disease also has good outcomes. Blood monitoring for parasitemias is mandatory as is the institution of therapy in the case of a reactivation diagnosis. Acute Chagas' disease may occur in patients who received organs from donors with Chagas' disease.

Cardiac effects of postconditioning depend critically on the duration of reperfusion and reocclusion episodes.

OBJECTIVE: The objective of the present study was to evaluate the effects of ischemic postconditioning on left ventricular function in isolated rat hearts. METHODS: The hearts of 24 Wistar rats were were isolated, perfused immediately, and distributed into 3 groups: GI, control (n = 8); GII, three 10-second cycles of postconditioning (n = 8); and GIII, three 30-second cycles of postconditioning (n = 8). After a 15-minute stabilization period, all hearts underwent 20 minutes of global ischemia following 20 minutes of reperfusion. At times t0 (control), t5, t10, t15, and t20 (0, 5, 10, 15, and 20 minutes of reperfusion, respectively), we recorded the heart rate, coronary flow, systolic pressure, +(dP/dt)max (maximum speed of increase in the left ventricular pressure), and -(dP/dt)max (maximum speed of decrease in the left ventricular pressure). Data were analyzed by a 1-way analysis of variance, followed by the Tukey test; a P value <.05 was considered statistically significant. RESULTS: There were no significant differences among the analyzed groups with respect to heart rate, coronary flow, systolic pressure, and -(dP/dt)max (P > .05); however, statistically significant differences in +(dP/dt)max between GII and GI and between GII and GIII occurred at t20 (GI, 1409.0 +/- 415.1 mm Hg/s; GII, 1917.3 +/- 403.0 mm Hg/s; GIII, 1344.8 +/- 355.8 mm Hg/s) (GII versus GI, P = .04; GII versus GIII, P = .02). CONCLUSION: Ischemic postconditioning with three 10-second cycles of reperfusion/reocclusion was demonstrated effective for preserving +(dP/dt)max in isolated rat hearts that underwent 20 minutes of ischemia following 20 minutes of reperfusion.

Effects of clonidine and isoflurane on the myocardial contractility behavior of isolated rat hearts.

Isoflurane is chosen as an anesthesia drug for cardiac surgeries, and its effectiveness and safety have been proved in countless clinical studies. Clonidine, a central alpha-agonist, has recently been added to isoflurane to attenuate sympathetic hyperactivity by acting directly on its site of origin in the central nervous system. The ability of alpha2-adrenoceptor agonists to inhibit central sympathetic outflow may benefit patients at risk of myocardial damage by improving myocardial oxygen demand and the supply ratio and contributing to hemodynamic stability. We investigated the effects of clonidine and isoflurane, alone and in combination, on the myocardial contractility of isolated rat hearts and found that use of clonidine plus isoflurane decreased the systolic pressure somewhat, but use of the drugs separately did not exhibit this effect. Clonidine plus isoflurane did not affect +(dP/dt)max, but it did decrease -(dP/dt)max significantly compared with the use of isoflurane alone. These results indicate that clonidine and isoflurane have the capacity to interact with each other. The capacity of clonidine to decrease isoflurane's inotropic effect could theoretically contribute to improving the myocardial oxygen demand and the supply ratio, decreasing surgical stress, and benefiting patients at risk of myocardial damage.

Can tricuspid annuloplasty of the donor heart reduce valve insufficiency following cardiac transplantation with bicaval anastomosis?

BACKGROUND: The aim of this study was to evaluate the degree of tricuspid valve insufficiency after orthotopic cardiac transplantation with bicaval anastomosis and prophylactic donor heart annuloplasty. METHODS: At present, our cardiac transplantation experience includes 478 cases. After January 2002, we included 30 consecutive patients in this study who had undergone orthotopic cardiac transplantation and survived >6 months. The patients were divided into 2 groups: group I, 15 patients who underwent transplantation with prophylactic tricuspid annuloplasty on the donor heart with the De Vega technique; and group II, 15 patients who underwent transplantation without this procedure. Their preoperative clinical characteristics were the same. During the late postoperative follow-up, the degree of tricuspid insufficiency was evaluated by transthoracic Doppler echocardiography and assessed according to the Simpson scale: 0, absent; 1, mild; 2, moderate; and 3, severe. Hemodynamic parameters were evaluated invasively by means of a Swan-Ganz catheter during routine endomyocardial biopsies. RESULTS: The mean follow-up time was 26.9 +/- 5.4 months (range, 12-36 months). In group I, 1 patient (6.6%) died from infection in the 18th month after the operation; the death was not related to the annuloplasty. In group II, 1 death (6.6%) occurred after 10 months because of rejection (P > .05). After the 24-month follow-up, the mean degree of tricuspid insufficiency was 0.4 +/- 0.5 in group I and 1.7 +/- 0.9 in group II (P < .05). Similarly, the 2 groups were significantly different with respect to the right atrium pressure, which was higher in group II. CONCLUSIONS: Prophylactic tricuspid annuloplasty on the donor heart was able to reduce significantly the degree of valvular insufficiency, even in cardiac transplantation with bicaval anastomosis; however, it did not modify significantly the hemodynamic performance of the allograft during the investigation period. It is very important to extend the observation period and casuistics to verify other benefits that this technique may offer.

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

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).

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).

Mitochondrial DNA haplogroups and variants predispose to chagas disease cardiomyopathy

Cardiomyopathies are major causes of heart failure. Chagas disease (CD) is caused by the parasite Trypanosoma cruzi, and it is endemic in Central and South America. Thirty percent of cases evolve into chronic chagas cardiomyopathy (CCC), which has worse prognosis as compared with other cardiomyopathies. In vivo bioenergetic analysis and ex vivo proteomic analysis of myocardial tissues highlighted worse mitochondrial dysfunction in CCC, and previous studies identified nuclear-encoded mitochondrial gene variants segregating with CCC. Here, we assessed the role of the mitochondrial genome through mtDNA copy number variations and mtDNA haplotyping and sequencing from heart or blood tissues of severe, moderate CCC and asymptomatic/indeterminate Chagas disease as well as healthy controls as an attempt to help decipher mitochondrial-intrinsic genetic involvement in Chagas disease development. We have found that the mtDNA copy number was significantly lower in CCC than in heart tissue from healthy individuals, while blood mtDNA content was similar among asymptomatic Chagas disease, moderate, and severe CCC patients. An MtDNA haplogrouping study has indicated that African haplogroups were over represented in the Chagas subject groups in comparison with healthy Brazilian individuals. The European lineage is associated with protection against cardiomyopathy and the macro haplogroup H is associated with increased risk towards CCC. Using mitochondria DNA sequencing, 84 mtDNA-encoded protein sequence pathogenic variants were associated with CCC. Among them, two variants were associated to left ventricular non-compaction and two to hypertrophic cardiomyopathy. The finding that mitochondrial protein-coding SNPs and mitochondrial haplogroups associate with risk of evolving to CCC is consistent with a key role of mitochondrial DNA in the development of chronic chagas disease cardiomyopathy.

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy

Abstract: Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS's DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.

[New concepts on the pathogenesis of chronic Chagas cardiomyopathy: myocardial gene and protein expression profiles]. / Novos conceitos em patogenia da cardiopatia chagáisica crônica: perfis de expressão gênica e proteica do miocárdio.

The pathogenesis of chronic Chagas cardiomyopathy (CCC) is still being unraveled. In the last decade, a role for inflammatory cytokines on tissue damage has been shown. The present review will address the molecular and immunological mechanisms of tissue damage on human CCC with a special focus on results obtained by our research group using genomic and proteomic approaches. The results suggest that direct modulation of myocardium gene and protein expression by inflammatory cytokines may be a new pathogenic mechanism in CCC, with therapeutic implications.

Complications after Surgical Procedures in Patients with Cardiac Implantable Electronic Devices: Results of a Prospective Registry.

BACKGROUND:: Complications after surgical procedures in patients with cardiac implantable electronic devices (CIED) are an emerging problem due to an increasing number of such procedures and aging of the population, which consequently increases the frequency of comorbidities. OBJECTIVE:: To identify the rates of postoperative complications, mortality, and hospital readmissions, and evaluate the risk factors for the occurrence of these events. METHODS:: Prospective and unicentric study that included all individuals undergoing CIED surgical procedures from February to August 2011. The patients were distributed by type of procedure into the following groups: initial implantations (cohort 1), generator exchange (cohort 2), and lead-related procedures (cohort 3). The outcomes were evaluated by an independent committee. Univariate and multivariate analyses assessed the risk factors, and the Kaplan-Meier method was used for survival analysis. RESULTS:: A total of 713 patients were included in the study and distributed as follows: 333 in cohort 1, 304 in cohort 2, and 76 in cohort 3. Postoperative complications were detected in 7.5%, 1.6%, and 11.8% of the patients in cohorts 1, 2, and 3, respectively (p = 0.014). During a 6-month follow-up, there were 58 (8.1%) deaths and 75 (10.5%) hospital readmissions. Predictors of hospital readmission included the use of implantable cardioverter-defibrillators (odds ratio [OR] = 4.2), functional class III--IV (OR = 1.8), and warfarin administration (OR = 1.9). Predictors of mortality included age over 80 years (OR = 2.4), ventricular dysfunction (OR = 2.2), functional class III-IV (OR = 3.3), and warfarin administration (OR = 2.3). CONCLUSIONS:: Postoperative complications, hospital readmissions, and deaths occurred frequently and were strongly related to the type of procedure performed, type of CIED, and severity of the patient's underlying heart disease. FUNDAMENTO:: Complicações após procedimentos cirúrgicos em portadores de dispositivos cardíacos eletrônicos implantáveis (DCEI) são um problema emergente devido ao aumento crescente na taxa destes procedimentos e ao envelhecimento da população, com consequente aumento de comorbidades. OBJETIVOS:: Identificar as taxas de complicações pós-operatórias, mortalidade e readmissão hospitalar, e pesquisar fatores de risco para a ocorrência desses eventos. MÉTODOS:: Registro prospectivo e unicêntrico que incluiu todos os indivíduos submetidos a procedimentos cirúrgicos em DCEI no período de fevereiro a agosto de 2011. Os pacientes foram distribuídos por tipos de procedimento nos seguintes grupos: implantes iniciais (coorte 1), troca de gerador (coorte 2) e procedimentos em cabos-eletrodos (coorte 3). Os desfechos foram avaliados por um comitê independente. Empregou-se a análise univariada e multivariada para a pesquisa de fatores de risco e o método de Kaplan-Meier para análise de sobrevida. RESULTADOS:: Foram incluídos 713 pacientes, sendo 333, 304 e 76 distribuídos nas coortes 1, 2 e 3, respectivamente. Complicações pós-operatórias foram detectadas em 7,5%, 1,6% e 11,8% dos pacientes nas coortes 1, 2 e 3, respectivamente (p = 0,014). Durante os 6 meses de seguimento, houve 58 (8,1%) óbitos e 75 (10,5%) readmissões hospitalares. Preditores de readmissão hospitalar incluíram o uso de cardioversor-desfibrilador implantável ( odds ratio [OR] = 4,2), classe funcional III-IV (OR = 1,8) e uso de warfarina (OR = 1,9). Preditores de mortalidade incluíram idade acima de 80 anos (OR = 2,4), disfunção ventricular (OR = 2,2), classe funcional III-IV (OR = 3,3) e uso de warfarina (OR = 2,3). CONCLUSÕES:: Complicações pós-operatórias, readmissões hospitalares e óbitos foram frequentes. Esses eventos estiveram fortemente relacionados ao tipo de procedimento realizado, tipo de DCEI e gravidade da doença cardíaca do paciente.

Polymerase chain reaction in endomyocardial biopsies for monitoring reactivation of Chagas' disease in heart transplantation: a case report and review of the literature.

Polymerase chain reaction (PCR) has been used to detect microbiological agent recurrence after heart transplantation of viral-induced cardiomyopathies. We report a case of reactivation of Chagas' disease after heart transplantation in which parasites could be detected in the endomyocardial biopsy using hematoxylin-eosin-stained sections, immunohistochemistry, and PCR for Trypanosoma cruzi DNA. Interestingly, PCR results remained positive in the endomyocardial biopsy 53 days after the beginning of successful treatment, pointing to the possibility of chronic persistence of parasites in the myocardium after the reactivation of Chagas' disease.

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)

Infectious agents and inflammation in donated hearts and dilated cardiomyopathies related to cardiovascular diseases, Chagas' heart disease, primary and secondary dilated cardiomyopathies.

BACKGROUND: Clinical and experimental conflicting data have questioned the relationship between infectious agents, inflammation and dilated cardiomyopathy (DCM). OBJECTIVES: The aim of this study was to determine the frequency of infectious agents and inflammation in endomyocardial biopsy (EMB) specimens from patients with idiopathic DCM, explanted hearts from different etiologies, including Chagas' disease, compared to donated hearts. METHODS: From 2008 to 2011, myocardial samples from 29 heart donors and 55 patients with DCMs from different etiologies were studied (32 idiopathic, 9 chagasic, 6 ischemic and 8 other specific etiologies). Inflammation was investigated by immunohistochemistry and infectious agents by immunohistochemistry, molecular biology, in situ hybridization and electron microscopy. RESULTS: There were no differences regarding the presence of macrophages, expression of HLA class II and ICAM-I in donors and DCM. Inflammation in Chagas' disease was predominant. By immunohistochemistry, in donors, there was a higher expression of antigens of enterovirus and Borrelia, hepatitis B and C in DCMs. By molecular biology, in all groups, the positivity was elevated to microorganisms, including co-infections, with a higher positivity to adenovirus and HHV6 in donors towards DCMs. This study was the first to demonstrate the presence of virus in the heart tissue of chagasic DCM. CONCLUSIONS: The presence of inflammation and infectious agents is frequent in donated hearts, in the myocardium of patients with idiopathic DCM, myocardial dysfunction related to cardiovascular diseases, and primary and secondary cardiomyopathies, including Chagas' disease. The role of co-infection in Chagas' heart disease physiopathology deserves to be investigated in future studies.

Dobutamine stress echocardiography predicts cardiac events or death in asymptomatic patients long-term after heart transplantation: 4-year prospective evaluation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the major cause of death after cardiac transplantation during long-term follow-up. Nevertheless, annual angiographic evaluation is difficult to perform routinely. We evaluated the value of clinical risk factors and non-invasive testing for cardiac allograft vasculopathy in predicting cardiac events or death in asymptomatic patients with normal ventricular function during long-term follow-up after heart transplantation. METHODS: We studied 39 patients, mean aged 48 +/- 13 years, at 86 +/- 31 months after heart transplantation. Patients underwent thallium scintigraphy, treadmill stress testing, dobutamine stress echocardiography, and angiography to detect CAV. We prospectively observed all patients an additional 4 years for acute myocardial infarction, congestive heart failure, or death. RESULTS: Angiography detected CAV in 15 patients (38%). Three patients had acute myocardial infarction and another 7 had congestive heart failure, representing 25% of cardiac events during the study period. Nine deaths (23%) occurred during the same observation time. Univariate analysis showed that increased body mass index, positive dobutamine stress echocardiography results, and positive angiography results were associated significantly with cardiac events or death during follow-up. In the absence of coronary angiography, stepwise logistic regression identified positive dobutamine echocardiography results as the unique independent predictor of cardiac events (p = 0.001) or death (p = 0.002). CONCLUSION: Cardiac events and death after heart transplantation increased during long-term follow-up of this population. However, dobutamine stress echocardiography is well tolerated and, in the absence of routine angiographic evaluation, may be a strong predictor of these events.

Leukocyte depletion during CPB: effects on inflammation and lung function.

Cardiopulmonary bypass (CPB) is related to inflammatory response and pulmonary dysfunction. The aim of this study was to evaluate the effects of CPB leukocyte filtration on inflammation and lung function after coronary artery bypass grafting (CABG). A prospective randomized study was performed to compare CABG patients undergoing CPB leukocyte filtration (n = 9) or standard CPB (n = 11). Computed tomography, oxygenation, leukocyte count, hemodynamic data, PaO2/FiO2, shunt fraction, interleukins, elastase, and myeloperoxidase were evaluated. Data were analyzed using two-factor ANOVA for repeated measurements. The filtered group showed lower neutrophil counts up to 50 min of CPB, lower shunt fraction up to 6 h after surgery, and lower levels of IL-10 at the end of surgery (p < 0.05). There was no statistically significant difference between groups related to other parameters. Leukodepletion during CPB results in neutrophil sequestration by a short time, decreased IL-10 serum levels, and lower worsening of lung function only temporarily.