Custos comparativos entre a revascularização miocárdica com e sem circulação extracorpórea / Comparative costs between myocardial revascularization with or without extracorporeal circulation

FUNDAMENTO: Técnicas cirúrgicas de revascularização miocárdica sem o uso de circulação extracorpórea (CEC) projetaram esperanças de resultados operatórios com menor dano sistêmico, menor ocorrência de complicações clínicas e menor tempo de internação hospitalar, gerando expectativas de menor custo hospitalar. OBJETIVO: Avaliar o custo hospitalar em pacientes submetidos à cirurgia de revascularização miocárdica com e sem o uso de CEC, e em portadores de doença multiarterial coronariana estável com função ventricular preservada. MÉTODOS: Os custos hospitalares foram baseados na remuneração governamental vigente. Acrescentaram-se aos custos uso de órteses e próteses, complicações e intercorrências clínicas. Consideraram-se o tempo e os custos de permanência na UTI e de internação hospitalar. RESULTADOS: Entre janeiro de 2002 e agosto de 2006, foram randomizados 131 pacientes para cirurgia com CEC (CCEC) e 128 pacientes sem CEC (SCEC). As características basais foram semelhantes para os dois grupos. Os custos das intercorrências cirúrgicas foram significativamente menores (p < 0,001) para pacientes do grupo SCEC comparados ao grupo CCEC (606,00 ± 525,00 vs. 945,90 ± 440,00), bem como os custos na UTI: 432,20 ± 391,70 vs. 717,70 ± 257,70, respectivamente. Os tempos de permanência na sala cirúrgica foram (4,9 ± 1,1 h vs. 3,9 ± 1,0 h), (p < 0,001) na UTI (48,2 ± 17,2 h vs. 29,2 ± 26,1h) (p < 0,001), com tempo de entubação (9,2 ± 4,5 h vs. 6,4 ± 5,1h) (p < 0,001) para pacientes do grupo com e sem CEC, respectivamente. CONCLUSÃO: Os resultados permitem concluir que a cirurgia de revascularização miocárdica, sem circulação extracorpórea, proporciona diminuição de custos operacionais e de tempo de permanência em cada setor relacionado ao tratamento cirúrgico.

BACKGROUND: Surgical techniques of myocardial revascularization without the use of extracorporeal circulation (ECC) have raised hopes of attaining operative results with less systemic damage, lower occurrence of clinical complications and shorter hospital stay duration, generating expectations of lower hospital costs. OBJECTIVE: To evaluate the hospital costs in patients submitted to myocardial revascularization with and without ECC and in those with stable multiarterial coronary disease with preserved ventricular function. METHODS: The hospital costs were based on the existing governmental reimbursement. The costs included that of ortheses and prostheses and clinical complications. The time and costs of ICU stay and hospital stay duration were considered. RESULTS: Between January 2002 and August 2006, 131 patients were randomized to surgery with ECC (SECC), whereas 128 were randomized to surgery without ECC (WECC). The basal characteristics were similar for both groups. The costs of surgical complications were significantly lower (p < 0.001) in patients from the WECC when compared to the SECC group (606.00 ± 525.00 vs. 945.90 ± 440.00), as well as ICU costs: 432.20 ± 391.70 vs. 717.70 ± 257.70, respectively. The duration of the operating room stay were 4.9 ± 1.1 h vs. 3.9 ± 1.0 h, p < 0.001; at the ICU it was 48.2 ± 17.2 h vs. 29.2 ± 26.1h) (p < 0.001), with intubation time of 9.2 ± 4.5 h vs. 6.4 ± 5.1h, p < 0.001 for patients from the group with and without ECC, respectively. CONCLUSION: The present study allowed us to conclude that the myocardial revascularization surgery without extracorporeal circulation results in the decrease of operational costs and duration of the stay in each section related to the surgical treatment.

Quality of life after on-pump and off-pump coronary artery bypass grafting surgery.

BACKGROUND: Coronary artery bypass grafting techniques without using cardiopulmonary bypass (off-pump CABG) result in less systemic damage, less clinical complications, less time spent in the intensive care unit, and shorter hospital stays, thereby raising the perspective of improved quality of life (QOL) for patients. OBJECTIVE: To assess quality of life in patients who underwent on-pump and off-pump CABG. METHODS: The Short-Form Health Survey (SF-36) Questionnaire was administered to patients with stable multivessel coronary artery disease (CAD) and preserved ventricular function before and at six and 12 months after surgery. RESULTS: Between January 2002 and December 2006, a total of 202 patients were randomized to either on-pump or off-pump CABG. Demographic, clinical, laboratory, and angiographic characteristics were similar in both groups. One hundred and five patients underwent off-pump CABG and 97 underwent on-pump CABG. In the postoperative course, 22 patients had myocardial infarction, 29 reported angina, one was reoperated, and three experienced stroke. No patient died. Quality of life, as measured by the SF-36 questionnaire, was shown to be similar in both groups regarding physical and mental components. However, male patients showed a significant improvement in physical functioning and role limitations due to physical problems. Also, a large number of patients in both groups returned to work. CONCLUSION: Progressive enhancement in quality of life and early return to work were observed for all patients, regardless of the surgical technique used. Save for a greater improvement in physical functioning and role limitations due to physical problems experienced by male patients, no statistically significant differences were found in the other domains between groups.

Qualidade de vida após revascularização cirúrgica do miocárdio com e sem circulação extracorpórea / Quality of life after on-pump and off-pump coronary artery bypass grafting surgery

FUNDAMENTO: Técnicas de cirurgia de revascularização miocárdica (RM) sem o uso de circulação extracorpórea (CEC) possibilitou resultados operatórios com menor dano sistêmico, menor ocorrência de complicações clínicas, menor permanência na sala de terapia intensiva e também no tempo de internação, gerando expectativas de melhor qualidade de vida (QV) dos pacientes. OBJETIVO: Avaliar a QV em pacientes submetidos à cirurgia de revascularização com e sem CEC. MÉTODOS: Em pacientes com doença multiarterial coronariana (DAC) estável e função ventricular preservada, aplicou-se o Short-Form Health Survey (SF-36) Questionnaire antes da cirurgia e depois de 6 e 12 meses. RESULTADOS: Entre janeiro de 2002 e dezembro de 2006, foram randomizados 202 pacientes para cirurgia de RM. As características demográficas clínicas laboratoriais e angiográficas foram semelhantes nos dois grupos. Desses pacientes, 105 foram operados sem CEC e 97 com CEC. Na evolução, 22 pacientes sofreram infarto, 29 relataram angina, um reoperou, 3 tiveram AVC e nenhum morreu. A avaliação da QV mostrou similaridade nos dois grupos em relação ao componente físico e mental. Todavia, encontrou-se significativa melhora da capacidade funcional e percepção do aspecto físico nos pacientes do sexo masculino. Além disso, um expressivo número de pacientes dos dois grupos retornou ao trabalho. CONCLUSÃO: Em todos os pacientes estudados, observaram-se melhora progressiva da qualidade de vida e retorno precoce ao trabalho, independentemente da técnica cirúrgica empregada. Exceto pela melhor percepção da capacidade funcional e do aspecto físico experimentado pelos homens, não houve diferença estatística nos resultados dos demais domínios alcançados pelos dois grupos estudados.

BACKGROUND: Coronary artery bypass grafting techniques without using cardiopulmonary bypass (off-pump CABG) result in less systemic damage, less clinical complications, less time spent in the intensive care unit, and shorter hospital stays, thereby raising the perspective of improved quality of life (QOL) for patients. OBJECTIVE: To assess quality of life in patients who underwent on-pump and off-pump CABG. METHODS: The Short-Form Health Survey (SF-36) Questionnaire was administered to patients with stable multivessel coronary artery disease (CAD) and preserved ventricular function before and at six and 12 months after surgery. RESULTS: Between January 2002 and December 2006, a total of 202 patients were randomized to either on-pump or off-pump CABG. Demographic, clinical, laboratory, and angiographic characteristics were similar in both groups. One hundred and five patients underwent off-pump CABG and 97 underwent on-pump CABG. In the postoperative course, 22 patients had myocardial infarction, 29 reported angina, one was reoperated, and three experienced stroke. No patient died. Quality of life, as measured by the SF-36 questionnaire, was shown to be similar in both groups regarding physical and mental components. However, male patients showed a significant improvement in physical functioning and role limitations due to physical problems. Also, a large number of patients in both groups returned to work. CONCLUSION: Progressive enhancement in quality of life and early return to work were observed for all patients, regardless of the surgical technique used. Save for a greater improvement in physical functioning and role limitations due to physical problems experienced by male patients, no statistically significant differences were found in the other domains between groups.

A randomized comparative study of patients undergoing myocardial revascularization with or without cardiopulmonary bypass surgery: The MASS III Trial.

UNLABELLED: The MASS III Trial is a large project from a single institution, The Heart Institute of the University of Sao Paulo, Brazil (InCor), enrolling patients with coronary artery disease and preserved ventricular function. The aim of the MASS III Trial is to compare medical effectiveness, cerebral injury, quality of life, and the cost-effectiveness of coronary surgery with and without of cardiopulmonary bypass in patients with multivessel coronary disease referred for both strategies. The primary endpoint should be a composite of cardiovascular mortality, cerebrovascular accident, nonfatal myocardial infarction, and refractory angina requiring revascularization. The secondary end points in this trial include noncardiac mortality, presence and severity of angina, quality of life based on the SF-36 Questionnaire, and cost-effectiveness at discharge and at 5-year follow-up. In this scenario, we will analyze the cost of the initial procedure, hospital length of stay, resource utilization, repeat hospitalization, and repeat revascularization events during the follow-up. Exercise capacity will be assessed at 6-months, 12-months, and the end of follow-up. A neurocognitive evaluation will be assessed in a subset of subjects using the Brain Resource Center computerized neurocognitive battery. Furthermore, magnetic resonance imaging will be made to detect any cerebral injury before and after procedures in patients who undergo coronary artery surgery with and without cardiopulmonary bypass. TRIALS REGISTRATION: Clinical Trial registration information ISRCTN59539154 Off-pump vs. on-pump surgery in patients with Stable CAD MASS III.

Comparative costs between myocardial revascularization with or without extracorporeal circulation.

BACKGROUND: Surgical techniques of myocardial revascularization without the use of extracorporeal circulation (ECC) have raised hopes of attaining operative results with less systemic damage, lower occurrence of clinical complications and shorter hospital stay duration, generating expectations of lower hospital costs. OBJECTIVE: To evaluate the hospital costs in patients submitted to myocardial revascularization with and without ECC and in those with stable multiarterial coronary disease with preserved ventricular function. METHODS: The hospital costs were based on the existing governmental reimbursement. The costs included that of ortheses and prostheses and clinical complications. The time and costs of ICU stay and hospital stay duration were considered. RESULTS: Between January 2002 and August 2006, 131 patients were randomized to surgery with ECC (SECC), whereas 128 were randomized to surgery without ECC (WECC). The basal characteristics were similar for both groups. The costs of surgical complications were significantly lower (p < 0.001) in patients from the WECC when compared to the SECC group (606.00 +/- 525.00 vs. 945.90 +/- 440.00), as well as ICU costs: 432.20 +/- 391.70 vs. 717.70 +/- 257.70, respectively. The duration of the operating room stay were 4.9 +/- 1.1 h vs. 3.9 +/- 1.0 h, p < 0.001; at the ICU it was 48.2 +/- 17.2 h vs. 29.2 +/- 26.1h) (p < 0.001), with intubation time of 9.2 +/- 4.5 h vs. 6.4 +/- 5.1h, p < 0.001 for patients from the group with and without ECC, respectively. CONCLUSION: The present study allowed us to conclude that the myocardial revascularization surgery without extracorporeal circulation results in the decrease of operational costs and duration of the stay in each section related to the surgical treatment.

Dynamic regulation of MTHFR mRNA expression and C677T genotype modulate mortality in coronary artery disease patients after revascularization.

INTRODUCTION: A large body of evidence links plasma homocysteine (Hcy) concentrations and cardiovascular disease. A common MTHFR polymorphism (C677T) leads to a variant with reduced activity and associated with increased Hcy levels. Coronary surgery precipitates a significant and sustained increase in the blood concentrations of Hcy and elevated levels of plasma Hcy have been associated to saphenous vein (SV) graft disease after CABG. However, the effects of MTHFR genotypes in the incidence of cardiovascular events after CABG have not been investigated prospectively. Here, we investigate whether MTHFR gene variants are associated with an increased cardiovascular risk in individuals submitted to CABG. We also propose a molecular mechanism to explain our findings. METHODS: We performed MTHFR C677T genotypes in 558 patients with two or three vessel-disease and normal left ventricular function prospectively followed in the MASS II Trial, a randomized study to compare treatments for multivessel CAD and preserved left ventricle function. Follow-up time was 5 years. Survival curves were calculated with the Kaplan-Meier method, and evaluated with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, myocardial infarction and refractory angina using a Cox proportional hazards survival model. Finally, using an ex-vivo organ culture we have reproduced the arterialization of SV implants by culturing human SV either under venous hemodynamic condition (flow: 5 mL/min; no pressure) or arterial hemodynamic condition (flow: 50 mL/min; pressure: 80 mm Hg) for 1 day. MTHFR gene expression was quantified by real time RT-PCR in 15 SV from different individuals in both experimental conditions. RESULTS: There were no significant differences among individuals within each genotype group for baseline clinical characteristics. A statistically significant association between the TT genotype, associated with increased serum levels of Hcy, and cardiovascular mortality after 5 years was verified (p=0.007) in individuals submitted to CABG surgery. In addition, MTHFR TT genotype was still significantly associated with a 4.4 fold increased risk in cardiovascular outcomes (p=0.01) even after adjustment of a Cox multivariate model for age, sex, hypertension, diabetes, LDL, HDL, triglycerides, and number of diseased vessels in this population. Finally, a significant reduction in MTHFR gene expression was demonstrated in human SV when submitted to an arterial hemodynamic condition (p=0.02). CONCLUSIONS: There is a dynamic regulation of MTHFR gene expression during the arterialization process of human saphenous vein grafts resulting in lower levels of gene expression when in an arterial hemodynamic condition. In addition, the C677T MTHFR functional variant is associated with a worse outcome in individuals submitted to CABG. Taken together, these data suggest an important role of Hcy metabolism in individuals after CABG.

Clinical judgment and treatment options in stable multivessel coronary artery disease: results from the one-year follow-up of the MASS II (Medicine, Angioplasty, or Surgery Study II).

OBJECTIVES: This study examined the predictive power of clinical judgment in the incidence of cardiovascular end points in a group of individuals with multivessel coronary artery disease (CAD) followed up in the MASS II (Medicine, Angioplasty, or Surgery Study II). BACKGROUND: There is still no consensus on the best treatment for patients with stable multivessel CAD and preserved left ventricular function. METHODS: Preferred treatment allocation was recorded for each of the 611 randomized patients in the MASS II trial before randomization. We have divided our sample according to physician-guided decision and randomization result into two categories: concordant or discordant. The incidence of the points of cardiac death, myocardial infarction, and refractory angina was compared between concordant and discordant patients. RESULTS: The number of concordant individuals was 292 (48.2%), and this number was not different between the three studied treatments (p = 0.11). A significant difference (p = 0.02) was disclosed because of an increased incidence of combined end point events in discordant patients. In the multivariate Cox hazard model, clinical judgment was a powerful predictor of outcome (p = 0.01) even after adjustment for other covariates. The main subgroup explaining this difference was a significant shift toward a worse outcome in the subgroup of discordant patients who underwent percutaneous coronary intervention (PCI) (p = 0.003). CONCLUSIONS: Angiographic variables were more often used in making clinical decisions regarding PCI than clinical variables, and the only independent predictor of concordance status in the PCI group was the number of diseased vessels (p = 0.01). Our data are a reminder that physician judgment remains an important predictor of outcomes.

Effect of glycoprotein IIIa PlA2 polymorphism on outcome of patients with stable coronary artery disease and effect of smoking.

A polymorphism of glycoprotein IIb/IIIa has been associated with myocardial infarction and restenosis after percutaneous coronary intervention. The influence on outcome and the interaction of the Pl(A1) genotype with classic risk factors for coronary artery disease (CAD) were characterized in patients with chronic CAD followed prospectively for 3 years. Pl(A1) genotypes were assessed in 592 patients enrolled in the Medical, Angioplasty, or Surgery Study II, a randomized trial comparing treatments for patients with CAD and preserved left ventricular function. The incidence of the composite end point of cardiac death, myocardial infarction, and refractory angina requiring revascularization were determined in each genotype group. Risk was assessed with the Cox proportional-hazards model. The clinical characteristics and treatment of each genotype were similar. Although the composite end point tended to be more common in patients with the Pl(A2) allele, only smokers with the Pl(A2) allele had a significantly increased incidence of the composite end point (p = 0.01). Moreover, a 2.2-fold increased risk was apparent in smokers with the Pl(A2) allele (p = 0.03). Thus, taken together, these data provide support for the interaction effect between smoking and the Pl(A1) gene variant. Smokers with the Pl(A2) polymorphism of platelet glycoprotein IIIa are at greater risk for subsequent cardiac events in stable coronary disease.

Mac-1 and Fas activities are concurrently required for execution of smooth muscle cell death by M-CSF-stimulated macrophages.

OBJECTIVE: We have previously shown that macrophage colony stimulating factor (M-CSF), a potent survival and mitogenic factor for monocytes/macrophages (MM), enables MM to induce vascular smooth muscle cell (VSMC) apoptosis. The killing requires the binding of MM to VSMC via Mac-1 (CD11b/CD18) on MM and intracellular adhesion molecule-1 (ICAM-1) on VSMC. We hypothesized that, in addition to Mac-1 binding, the killing process requires the activation of the Fas-death receptor pathway, which can be blocked at the level of Fas-Fas ligand interaction. METHODS AND RESULTS: Human peripheral blood monocytes and VSMC were isolated and cultured as previously described. Soluble Fas (sFas) was overexpressed in VSMC by transduction using adenovirus specifying soluble Fas (Ad3hsFas). M-CSF markedly increased the expression of ICAM-1 in VSMC, resulting in enhanced clustering of MM on the surface of VSMC (>/=3 MM per VSMC). MM, but not VSMC, expressed Fas-ligand (FasL), and VSMC apoptosis was inhibited by secretion of sFas by VSMC upon Ad3sFas transduction. CONCLUSIONS: MM and M-CSF-induced VSMC killing requires MM binding to VSMC mediated by Mac-1 and ICAM-1, and Fas-FasL interaction.

Rac-dependent monocyte chemoattractant protein-1 production is induced by nutrient deprivation.

Under ischemic conditions, the vessel wall recruits inflammatory cells. Human aortic endothelial cells (HAECs) exposed to hypoxia followed by reoxygenation produce monocyte chemoattractant protein-1 (MCP-1); however, most experiments have been performed in the presence of nutrient deprivation (ND). We hypothesized that ND rather than hypoxia mediates endothelial MCP-1 production during ischemia, and that the small GTP-binding protein Rac1 and reactive oxygen species (ROS) are involved in this process. ND was generated by shifting HAECs from 10% to 1% FBS. Superoxide production by HAECs was increased 6 to 24 hours after ND, peaking at 18 hours. MCP-1 production was increased over a similar time frame, but peaked later at 24 hours. These effects were blocked by treatment with antioxidants such as superoxide dismutase mimetic and N-acetylcysteine (NAC), or NADPH oxidase inhibitors, DPI and gp91ds-tat. Superoxide and MCP-1 production were enhanced by RacV12 (constitutively active) in the absence of ND, and were inhibited by RacN17 (dominant-negative) adenoviral transduction under ND, suggesting that the small G-protein Rac1 is required. In conclusion, ND, an important component of ischemia, is sufficient to induce MCP-1 production by HAECs, and such production requires a functional Rac1, redox-dependent pathway.