Critical evaluation of screening questionnaires for obstructive sleep apnea in patients undergoing coronary artery bypass grafting and abdominal surgery.

BACKGROUND: Obstructive sleep apnea (OSA) is an independent risk factor for complications after surgery. However, OSA remains largely under recognized, and questionnaires designed to detect OSA have shown inconsistent results. Patients with cardiovascular diseases may not present with the typical symptoms of OSA. We therefore sought to compare the performance of screening questionnaires of patients referred for coronary artery bypass grafting (CABG) versus abdominal surgery (Abd surgery). METHODS: We studied 40 consecutive patients referred for CABG [29 men; age 56 ± 7 years; body mass index (BMI) 30 ± 4 kg/m(2)], and 41 referred to Abd Surgery matched for age, gender, and BMI (28 men; age 56 ± 8 years; BMI 29 ± 5 kg/m(2)). All patients were evaluated with validated questionnaires to predict OSA (STOP-Bang and Berlin), Epworth sleepiness scale (ESS) and full overnight polysomnography. RESULTS: The prevalence of OSA (apnea-hypopnea index ≥15 events/hour) in the CABG and Abd surgery groups was similar (52 and 41 %, respectively, p = 0.32). The Berlin questionnaire showed similar sensitivity (67 vs. 82 %, p = 0.17) but lower specificity in the CABG group (26 vs. 62 %, p = 0.02). The STOP-BANG questionnaire had a high sensitivity (90 vs. 94 %, p = 0.42) but low specificity (5 vs. 13 %, p = 0.25) in the CABG and Abd surgery groups, respectively. Patients referred for CABG slept less (323 [285-376] vs. 378 [308-415] minutes, p = 0.04) but had lower levels of daytime sleepiness than Abd surgery patients had (ESS, 6 ± 4 vs. 9 ± 5; p = 0.01, respectively). CONCLUSIONS: Presenting clinical characteristics of OSA are modulated by the population evaluated and may affect the performance of screening questionnaires.

Five-year follow-up of a randomized comparison between off-pump and on-pump stable multivessel coronary artery bypass grafting. The MASS III Trial.

BACKGROUND: Coronary artery bypass graft surgery with cardiopulmonary bypass is a safe, routine procedure. Nevertheless, significant morbidity remains, mostly because of the body's response to the nonphysiological nature of cardiopulmonary bypass. Few data are available on the effects of off-pump coronary artery bypass graft surgery (OPCAB) on cardiac events and long-term clinical outcomes. METHODS AND RESULTS: In a single-center randomized trial, 308 patients undergoing coronary artery bypass graft surgery were randomly assigned: 155 to OPCAB and 153 to on-pump CAB (ONCAB). Primary composite end points were death, myocardial infarction, further revascularization (surgery or angioplasty), or stroke. After 5-year follow-up, the primary composite end point was not different between groups (hazard ratio 0.71, 95% CI 0.41 to 1.22; P=0.21). A statistical difference was found between OPCAB and ONCAB groups in the duration of surgery (240±65 versus 300±87.5 minutes; P<0.001), in the length of ICU stay (19.5±17.8 versus 43±17.0 hours; P<0.001), time to extubation (4.6±6.8 versus 9.3±5.7 hours; P<0.001), hospital stay (6±2 versus 9±2 days; P<0.001), higher incidence of atrial fibrillation (35 versus 4% of patients; P<0.001), and blood requirements (31 versus 61% of patients; P<0.001), respectively. The number of grafts per patient was higher in the ONCAB than the OPCAB group (2.97 versus 2.49 grafts/patient; P<0.001). CONCLUSIONS: No difference was found between groups in the primary composite end point at 5-years follow-up. Although OPCAB surgery was related to a lower number of grafts and higher episodes of atrial fibrillation, it had no significant implications related to long-term outcomes. Clinical Trial Registration-URL: http://www.controlled-trials.com. Unique identifier: ISRCTN66068876.

Clinical profile of patients enroled in a cell therapy trial for severe coronary artery disease.

AIMS AND OBJECTIVES: To compare the clinical profile of patients included in a clinical trial of autologous bone marrow cells as an adjunctive therapy to coronary artery bypass grafting with that of patients undergoing routine coronary artery bypass grafting. BACKGROUND: The therapeutic potential of autologous bone marrow cells has been explored in the treatment of severe coronary artery disease. There are few data regarding the clinical and socio-economic profile of patients included in clinical trials using bone marrow cell. DESIGN: Case-control study. METHOD: Sixty-seven patients (61 SD 9) years, 82% men) with multivessel coronary artery disease were divided into two groups: patients in the bone marrow cell group (n = 34) underwent incomplete coronary artery bypass grafting + intramyocardial injection of autologous bone marrow cells (lymphomonocytic fraction -2.0 (SD 0.2 x 10(8)) cells/patient) in the ischaemic, non-revascularised myocardium, whereas patients in the coronary artery bypass grafting group (n = 33) underwent routine bypass surgery. Demographics, socio-economic status, clinical and echocardiographic data were collected. Statistical analysis included the Fisher's exact test (categorical variables) and the Student's t-test (continuous variables). RESULTS: There were no significant differences between groups regarding age, gender, BMI, heart rate, blood pressure and echo data. There was a greater prevalence of obesity (65 vs. 33%; OR = 3.7 [1.3-10.1]), of previous myocardial infarction (68 vs. 39%; OR = 3.2 [1.2-8.8]) and prior revascularisation procedures (59 vs. 24%; OR = 4.5 [1.6-12.7]) in the autologous bone marrow cells group and of smokers in the coronary artery bypass grafting group (51 vs. 23%; OR = 3.5 [1.2-10.4]). CONCLUSIONS: Patients included in this clinical trial of autologous bone marrow cells for severe coronary artery disease presented a greater prevalence of myocardial revascularisation procedures, indicating a more severe clinical presentation of the disease. Fewer smokers in this group could be attributable to life style changes after previous cardiovascular events and/or interventions. RELEVANCE TO CLINICAL PRACTICE: The knowledge of the clinical profile of patients included in cell therapy trials may help researchers in the identification of patients that may be enroled in future clinical trials of this new therapeutic strategy.

Entendimento do termo de consentimento por pacientes partícipes em pesquisas com fármaco na cardiologia / Informed consent as viewed by patients participating in cardiology drug trial / La comprensión del formulario de consentimiento por los pacientes que forman parte de investigaciones con fármaco en la cardiología

Fundamento: Em ensaios clínicos, o Termo de Consentimento Livre e Esclarecido (TCLE) é fundamental para preservar a ética, mas pela sua complexidade ele pode não ser entendido completamente. Neste estudo, avaliamos o entendimento do TCLE pelo paciente. Objetivo: Abordamos a questão sobre o nível de compreensão dos pacientes em relação aos estudos baseados no Consentimento Informado. Métodos: Convidamos participantes de pesquisa ambulatorial fases II, III e IV, com fármacos, para responder um questionário estruturado com 29 questões, tais como: por que aceitou participar? Leu o TCLE antes de assinar? Ao assiná-lo, estava certo de tê-lo entendido? Oitenta indivíduos (20 mulheres e 60 homens) compareceram, num universo de 106 pacientes. As variáveis de cada questão foram consideradas por frequência de ocorrência. A comparação entre as médias entre os grupos foi realizada pelos testes t de Student ou Wilcoxon; e para associações, o Qui-quadrado ou Razão de Verossimilhança, ou teste exato de Fisher. Resultados: A média das idades foi de 58,7 ± 9,3 anos. Das motivações para participar da pesquisa, 66,2 por cento apontaram seu próprio benefício; 42,5 por cento, o bem da ciência; 25,0 por cento alegaram atender a um pedido de seu médico; 50 por cento não entenderam corretamente o TCLE; e 32,9 por cento sequer o leram, mas o assinaram. Dentre os que receberam placebo após a randomização (n = 47), 66,7 por cento não entenderam o significado deste termo. Houve forte correlação entre o não entender o significado de placebo com a escolaridade (p = 0,02), evidenciando que quanto menor o nível de instrução, menor este entendimento. Conclusão: O TCLE é pouco compreendido pelos pacientes e para alguns deles a confiança no médico teve impacto na decisão de participar do ensaio clínico com fármaco, havendo também influência do nível de instrução dos sujeitos no entendimento do termo "placebo".

Background: In clinical tests, the Informed Consent is critical to preserve the ethics, but due to its high complexity level, it cannot be fully understood. This study assesses the Informed Consent as viewed by patients. Objective: We addressed the issue of what do patients understand about the studies based on the IC. Methods: We invited participants of outpatient clinical drug trials phase II, III and IV to answer a questionnaire with 29 questions, such as: why have you accepted to participate? Did you read the Informed Consent before signing it? By signing it, were you sure you have fully understood it? Eighty individuals (20 women and 60 men) showed up, from 106 patients. The variables of each question were considered as often as they appeared. The comparison of the averages among the groups was made by t tests of Student or Wilcoxon; and for associations, Chi-square or Likelihood Ratio, or Fisher's exact test. Results: Ages averaged 58.7 ± 9.3 years. Concerning their reasons to taking part in the survey, 66.2 percent pointed out their own benefit; 42.5 percent, for science's sake; 25.0 percent claimed they were doing so at their doctor's request; 50 percent did not understand the Informed Consent properly; and 32.9 percent did not read it, but signed it. Among those who were administered placebo after randomization (n = 47), 66.7 percent did not understand the meaning of the informed consent. A strong correlation between failure to understand the meaning of placebo with literacy level (p = 0,02) was verified, which is an evidence that the smaller is the literacy level, the smaller is the understanding level. Conclusion: The Informed Consent is poorly understood by patients and for some of them, trusting a doctor affected their decision in taking part in the clinical trial with drugs. Their literacy level also influenced their understanding of the term "placebo".

Fundamento: En ensayos clínicos, el Formulario de Consentimiento Informado (FCI) es fundamental para que se preserve la ética, sin embargo por su complexidad él puede no comprenderse completamente. En este estudio, evaluamos la comprensión del FCI por parte del paciente. Objetivo: Abordamos la cuestión sobre el nivel de comprensión de los pacientes respecto a los estudios basados en el Consentimiento Informado. Métodos: Invitamos a los participantes de investigación clínica fase II, III y IV con fármacos para responder un cuestionario estructurado con 29 cuestiones, tales como: ¿Por qué aceptó participar?¿Leyó el FCI antes de firmarlo?¿Al firmarlo estaba seguro de haberlo entendido? Ochenta individuos (20 mujeres y 60 varones) comparecieron, en un total de 106 pacientes. Las variables de cada cuestión se llevaron a cabo por frecuencia de ocurrencia. La comparación entre los promedios entre los grupos se realizó mediante las pruebas t de Student o Wilcoxon; y para asociaciones, el Chi-cuadrado o Razón de Verosimilitud, o prueba exacta de Fisher. Resultados: El promedio de las edades fue de 58,7 ± 9,3 años. De las motivaciones para participar en la investigación, el 66,2 por ciento señaló su propio beneficio; un 42,5 por ciento, el bien de la ciencia; un 25,0 por ciento alegó atender a una petición de su médico; el 50 por ciento no comprendió correctamente el FCI; y un 32,9 por ciento tampoco leyó el formulario, pero lo firmó. Entre los que recibieron placebo tras la randomización (n = 47), un 66,7 por ciento no entendió el significado de este término. Hubo una fuerte correlación entre las personas que no entendían el significado de placebo con la escolaridad (p = 0,02), evidenciando que cuanto menor era el nivel de instrucción, menor era la comprensión. Conclusión: EL FCI es poco comprendido por los pacientes y para algunos de ellos la confianza en el médico tuvo impacto en la decisión de participar en el ensayo clínico con fármaco, habiendo...

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.

Head-to-head comparison of dobutamine and adenosine stress real-time myocardial perfusion echocardiography for the detection of coronary artery disease.

We sought to determine the value of dobutamine versus adenosine real-time myocardial perfusion (MP) echocardiography for detecting coronary artery disease and the value of quantitative analysis of MP over electrocardiography, wall motion, and qualitative MP. We studied 54 patients by real-time MP echocardiography and coronary angiography. Replenishment velocity (beta) and an index of myocardial blood flow (A(n)xbeta) were derived from quantitative MP. During dobutamine stress, beta (1.7 +/- 0.7 vs 2.7 +/- 1.2; P < .001) and A(n)xbeta (2.2 +/- 1.0 vs 3.5 +/- 1.6; P < .001) reserves were lower in patients with coronary artery disease. The same was observed with adenosine for beta (1.7 +/- 0.8 vs 2.5 +/- 1.1; P < .001) and A(n)xbeta (1.9 +/- 0.7 vs 3.2 +/- 1.4; P < .001) reserves. Accuracy of electrocardiography, wall motion, qualitative MP, and quantitative MP were 61%, 76%, 76%, and 80% for dobutamine and 70%, 70%, 76%, and 80% for adenosine, respectively. Quantitative MP had incremental diagnostic value over other variables during dobutamine (chi(2) 23.7-38.4; P < .001) and adenosine (chi(2) 26.7-59.4; P < .001). In conclusion, dobutamine and adenosine real-time MP echocardiography hold similar accuracy for detecting coronary artery disease. Quantitative MP provides incremental diagnostic information over other variables.

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.

The medicine, angioplasty, or surgery study (MASS-II): a randomized, controlled clinical trial of three therapeutic strategies for multivessel coronary artery disease: one-year results.

OBJECTIVES: We sought to evaluate the relative efficacies of three possible therapeutic strategies for patients with multivessel coronary artery disease (CAD), stable angina, and preserved ventricular function. BACKGROUND: Despite routine use of coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI), there is no conclusive evidence that either one is superior to medical therapy (MT) alone for the treatment of multivessel CAD. METHODS: The primary end point was defined as cardiac mortality, Q-wave myocardial infarction (MI), or refractory angina requiring revascularization. All data were analyzed according to the intention-to-treat principle. RESULTS: A total of 611 patients were randomly assigned to either a CABG (n = 203), PCI (n = 205), or MT (n = 203) group. The one-year survival rates were 96.0% for CABG, 95.6% for PCI, and 98.5% for MT. The rates for one-year survival free of Q-wave MI were 98% for CABG, 92% for PCI, and 97% for MT. After one-year follow-up, 8.3% of MT patients and 13.3% of PCI patients underwent to additional interventions, compared with only 0.5% of CABG patients. At one-year follow-up, 88% of the patients in the CABG group, 79% in the PCI group, and 46% in the MT group were free of angina (p < 0.0001). CONCLUSIONS: Medical therapy for multivessel CAD was associated with a lower incidence of short-term events and a reduced need for additional revascularization, compared with PCI. In addition, CABG was superior to MT for eliminating anginal symptoms. All three therapeutic regimens yielded relatively low rates of cardiac-related deaths.

Relative cost comparison of treatments for coronary artery disease: the First Year Follow-Up of MASS II Study.

BACKGROUND: Prior comparisons of costs following CABG and PTCA have demonstrated higher initial costs after CABG but following PTCA, recurrent symptoms and repeat revascularization result in increased late costs and over time their costs equilibrate. The MASS II trial provides an opportunity to compare the costs of CABG and PTCA in addition to a strategy of medical therapy. METHODS: We studied the 611 patients of MASS II [Medical (203), Angioplasty (205), or Surgery (203) Study], a randomized study to compare treatments for multivessel CAD and preserved left ventricle function. The costs were: CABG 10,650.00 US dollars; PTCA 6400.00 US dollars; new AMI hospitalization AMI 2550 US dollars; angiography not followed-up of PTCA 1900.00 US dollars; and medication 1200.00 US dollars for medical, and 1000.00 US dollars for the other groups. We did adjustment for average event-free time, and angina-free proportion. The statistical analysis carried out was chi-square, t test, and analysis of variance. RESULTS: After 1 year, 49% Medical, 79% PTCA, and 88% CABG became angina-free; P<0.0001. There were 26 coronary angiograms (5 medical, 17 PTCA, and 4 CABG), 23 AMI (8 medical, 17 PTCA, and 6 CABG; P=0.03); PTCA was performed in 7 Medical, 17 PTCA, and 1 CABG, (P=0.0003), CABG was performed in 15 Medical, 8 PTCA, and zero CABG; P=0.002. The event-free and event and angina-free-costs in the first year were 2453.50 US dollars and 5006.32 US dollars for Medical; 10348,43 US dollars; and 13,099.31 US dollars for PTCA; and 12,404.21 US dollars and 14,095.09 US dollars for CABG group. An increase from expected costs of 317%, 77%, and 21%, respectively. CONCLUSIONS: PTCA effective costs were similar to CAGB costs, Medical treatment presented the lowest cost, and however, the greatest increment, and CABG presented the most stable costs.