Coronary artery bypass grafting versus medical therapy in patients with stable coronary artery disease: An individual patient data pooled meta-analysis of randomized trials.

OBJECTIVES: It is unclear whether coronary artery bypass grafting (CABG) improves survival compared with medical therapy (MT) in patients with stable coronary artery disease (CAD). The aim of this analysis was to perform an individual-patient data-pooled meta-analysis of contemporary randomized controlled trials that compared CABG and MT in patients with stable CAD. METHODS: A systematic search was performed in January 2021 to identify randomized controlled trials enrolling adult patients with stable CAD, randomized to CABG or MT. Only trials using at least aspirin, beta-blockers, and statins in the MT arm were included. Individual patient data were obtained from all eligible studies and pooled. The primary outcome was all-cause mortality. RESULTS: Four trials involving 2523 patients (1261 CABG; 1262 MT) were included with a median follow-up of 5.6 (4.0-9.2) years. CABG was associated with increased risk of all-cause mortality within 30 days (hazard ratio [HR], 4.81; 95% confidence interval [CI], 1.95-11.83) but subsequent reduction in the long-term risk of death (HR, 0.79; 95% CI, 0.69-0.89). As such, the cumulative 10-year mortality rate was lower in patients treated with CABG compared with MT (45.1% vs 51.7%, respectively; odds ratio, 0.70; 95% CI, 0.58-0.85). Age and race were significant treatment effect modifier (interaction P = .003 for both). CONCLUSIONS: In patients with stable CAD, initial allocation to CABG was associated with greater periprocedural risk of death but improved long-term survival compared with MT. The survival advantage for CABG became significant after the fourth postoperative year and was particularly pronounced in younger and non-White patients.

Initial Invasive or Conservative Strategy for Stable Coronary Disease.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Cost-effectiveness of on-pump and off-pump coronary artery bypass grafting for patients with coronary artery disease: Results from the MASS III trial.

BACKGROUND: Recent trials have reported similar clinical outcomes between on-pump and off-pump coronary artery bypass graft (CABG). However, long-term cost-effectiveness of these strategies is unknown. METHODS: A prespecified economic study was performed based on the MASS III trial. Costs were estimated for all patients based on observed healthcare resource usage over a 5-year follow-up. Health state utilities were evaluated with the SF-6D questionnaire. Cost-effectiveness was assessed as cost per quality-adjusted life-year (QALY) gained using a Markov model. Probabilistic sensitivity analysis with the Monte-Carlo simulation and cost-effectiveness acceptability curve were used to address uncertainty. RESULTS: Quality of life improved significantly in both groups during follow-up compared with baseline. At 5 years, when comparing on-pump and off-pump CABG groups, no differences were found in cumulative life-years (4.851 and 4.766 years, P = .319) and QALY gained (4.150 and 4.105 QALYs, P = .332). Mean cost in US dollars per patient during the trial did not differ significantly between the on-pump and off-pump groups ($5890.29 and $5674.75, respectively, P = .409). Over a lifetime horizon, the incremental cost-effectiveness ratio of on-pump versus off-pump CABG was $12,576 per QALY gained, which is above the suggested cost-effectiveness threshold range (from $3210 to 10,122). In the sensitivity analysis, the probability that on-pump CABG is cost-effective compared to off-pump surgery for a willingness-to-pay threshold of $3212 per QALY gained was <1%. For the $10,122 per QALY threshold, the same probability was 35%. CONCLUSION: This decision-analytic model suggests that on-pump CABG is not cost-effective when compared to off-pump CABG from a public health system perspective.

Stroke Rates Following Surgical Versus Percutaneous Coronary Revascularization.

BACKGROUND: Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are used for coronary revascularization in patients with multivessel and left main coronary artery disease. Stroke is among the most feared complications of revascularization. Due to its infrequency, studies with large numbers of patients are required to detect differences in stroke rates between CABG and PCI. OBJECTIVES: This study sought to compare rates of stroke after CABG and PCI and the impact of procedural stroke on long-term mortality. METHODS: We performed a collaborative individual patient-data pooled analysis of 11 randomized clinical trials comparing CABG with PCI using stents; ERACI II (Argentine Randomized Study: Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease) (n = 450), ARTS (Arterial Revascularization Therapy Study) (n = 1,205), MASS II (Medicine, Angioplasty, or Surgery Study) (n = 408), SoS (Stent or Surgery) trial (n = 988), SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial (n = 1,800), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease) trial (n = 600), FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900), VA CARDS (Coronary Artery Revascularization in Diabetes) (n = 198), BEST (Bypass Surgery Versus Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease) (n = 880), NOBLE (Percutaneous Coronary Angioplasty Versus Coronary Artery Bypass Grafting in Treatment of Unprotected Left Main Stenosis) trial (n = 1,184), and EXCEL (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial (n = 1,905). The 30-day and 5-year stroke rates were compared between CABG and PCI using a random effects Cox proportional hazards model, stratified by trial. The impact of stroke on 5-year mortality was explored. RESULTS: The analysis included 11,518 patients randomly assigned to PCI (n = 5,753) or CABG (n = 5,765) with a mean follow-up of 3.8 ± 1.4 years during which a total of 293 strokes occurred. At 30 days, the rate of stroke was 0.4% after PCI and 1.1% after CABG (hazard ratio [HR]: 0.33; 95% confidence interval [CI]: 0.20 to 0.53; p < 0.001). At 5-year follow-up, stroke remained significantly lower after PCI than after CABG (2.6% vs. 3.2%; HR: 0.77; 95% CI: 0.61 to 0.97; p = 0.027). Rates of stroke between 31 days and 5 years were comparable: 2.2% after PCI versus 2.1% after CABG (HR: 1.05; 95% CI: 0.80 to 1.38; p = 0.72). No significant interactions between treatment and baseline clinical or angiographic variables for the 5-year rate of stroke were present, except for diabetic patients (PCI: 2.6% vs. CABG: 4.9%) and nondiabetic patients (PCI: 2.6% vs. CABG: 2.4%) (p for interaction = 0.004). Patients who experienced a stroke within 30 days of the procedure had significantly higher 5-year mortality versus those without a stroke, both after PCI (45.7% vs. 11.1%, p < 0.001) and CABG (41.5% vs. 8.9%, p < 0.001). CONCLUSIONS: This individual patient-data pooled analysis demonstrates that 5-year stroke rates are significantly lower after PCI compared with CABG, driven by a reduced risk of stroke in the 30-day post-procedural period but a similar risk of stroke between 31 days and 5 years. The greater risk of stroke after CABG compared with PCI was confined to patients with multivessel disease and diabetes. Five-year mortality was markedly higher for patients experiencing a stroke within 30 days after revascularization.

Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data.

BACKGROUND: Numerous randomised trials have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for patients with coronary artery disease. However, no studies have been powered to detect a difference in mortality between the revascularisation strategies. METHODS: We did a systematic review up to July 19, 2017, to identify randomised clinical trials comparing CABG with PCI using stents. Eligible studies included patients with multivessel or left main coronary artery disease who did not present with acute myocardial infarction, did PCI with stents (bare-metal or drug-eluting), and had more than 1 year of follow-up for all-cause mortality. In a collaborative, pooled analysis of individual patient data from the identified trials, we estimated all-cause mortality up to 5 years using Kaplan-Meier analyses and compared PCI with CABG using a random-effects Cox proportional-hazards model stratified by trial. Consistency of treatment effect was explored in subgroup analyses, with subgroups defined according to baseline clinical and anatomical characteristics. FINDINGS: We included 11 randomised trials involving 11 518 patients selected by heart teams who were assigned to PCI (n=5753) or to CABG (n=5765). 976 patients died over a mean follow-up of 3·8 years (SD 1·4). Mean Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score was 26·0 (SD 9·5), with 1798 (22·1%) of 8138 patients having a SYNTAX score of 33 or higher. 5 year all-cause mortality was 11·2% after PCI and 9·2% after CABG (hazard ratio [HR] 1·20, 95% CI 1·06-1·37; p=0·0038). 5 year all-cause mortality was significantly different between the interventions in patients with multivessel disease (11·5% after PCI vs 8·9% after CABG; HR 1·28, 95% CI 1·09-1·49; p=0·0019), including in those with diabetes (15·5% vs 10·0%; 1·48, 1·19-1·84; p=0·0004), but not in those without diabetes (8·7% vs 8·0%; 1·08, 0·86-1·36; p=0·49). SYNTAX score had a significant effect on the difference between the interventions in multivessel disease. 5 year all-cause mortality was similar between the interventions in patients with left main disease (10·7% after PCI vs 10·5% after CABG; 1·07, 0·87-1·33; p=0·52), regardless of diabetes status and SYNTAX score. INTERPRETATION: CABG had a mortality benefit over PCI in patients with multivessel disease, particularly those with diabetes and higher coronary complexity. No benefit for CABG over PCI was seen in patients with left main disease. Longer follow-up is needed to better define mortality differences between the revascularisation strategies. FUNDING: None.

Alterations in lipid transfers to HDL associated with the presence of coronary artery disease in patients with type 2 diabetes mellitus.

BACKGROUND: We previously showed that unesterified-cholesterol transfer to high-density lipoprotein (HDL), a crucial step in cholesterol esterification and role in reverse cholesterol transport, was diminished in non-diabetic patients with coronary artery disease (CAD). The aim was to investigate whether, in patients with type 2 diabetes mellitus (T2DM), the occurrence of CAD was also associated with alterations in lipid transfers and other parameters of plasma lipid metabolism. METHODS: Seventy-nine T2DM with CAD and 76 T2DM without CAD, confirmed by cineangiography, paired for sex, age (40-80 years), BMI and without statin use, were studied. In vitro transfer of four lipids to HDL was performed by incubating plasma of each patient with a donor emulsion containing radioactive lipids during 1 h at 37 °C. Lipids transferred to HDL were measured after chemical precipitation of non-HDL fractions and the emulsion. Results are expressed as % of total radioactivity of each lipid in HDL. RESULTS: In T2DM + CAD, LDL-cholesterol and apo B were higher than in T2DM. T2DM + CAD also showed diminished transfer to HDL of unesterified cholesterol (T2DM + CAD = 7.6 ± 1.2; T2DM = 8.2 ± 1.5%, p < 0.01) and of cholesteryl-esters (4.0 ± 0.6 vs 4.3 ± 0.7, p < 0.01). Unesterified cholesterol in the non-HDL serum fraction was higher in T2DM + CAD (0.93 ± 0.20 vs 0.85 ± 0.15, p = 0.02) and CETP concentration was diminished (2.1 ± 1.0 vs 2.5 ± 1.1, p = 0.02). Lecithin-cholesterol acyltransferase activity, HDL size and lipid composition were equal. CONCLUSION: Reduction in T2DM + CAD of cholesterol transfer to HDL may impair cholesterol esterification and reverse cholesterol transport and altogether with simultaneous increased plasma unesterified cholesterol may facilitate CAD development in T2DM.

Association between UCP2 A55V polymorphism and risk of cardiovascular events in patients with multi-vessel coronary arterial disease.

BACKGROUND: UCP2 (uncoupling protein 2) plays an important role in cardiovascular diseases and recent studies have suggested that the A55V polymorphism can cause UCP2 dysfunction. The main aim was to investigate the association of A55V polymorphism with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease and preserved left ventricular function. METHODS: The participants of the MASS II were genotyped for the A55V polymorphism using allele-specific PCR assay. Survival curves were calculated with the Kaplan-Meier method and evaluated with the log-rank statistic. The relationship between baseline variables and the composite end-point of cardiac death, acute myocardial infarction (AMI), refractory angina requiring revascularization and cerebrovascular accident were assessed using a Cox proportional hazards survival model. RESULTS: There were no significant differences for baseline variables according genotypes. After 2 years of follow-up, dysglycemic patients harboring the VV genotype had higher occurrence of AMI (p=0.026), Death+AMI (p=0.033), new revascularization intervention (p=0.009) and combined events (p=0.037) as compared with patients carrying other genotypes. This association was not evident in normoglycemic patients. CONCLUSIONS: These findings support the hypothesis that A55V polymorphism is associated with UCP2 functional alterations that increase the risk of cardiovascular events in patients with previous coronary artery disease and dysglycemia.

The effect of age on outcomes of coronary artery bypass surgery compared with balloon angioplasty or bare-metal stent implantation among patients with multivessel coronary disease. A collaborative analysis of individual patient data from 10 randomized trials.

OBJECTIVES: This study sought to assess whether patient age modifies the comparative effectiveness of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI). BACKGROUND: Increasingly, CABG and PCI are performed in older patients to treat multivessel disease, but their comparative effectiveness is uncertain. METHODS: Individual data from 7,812 patients randomized in 1 of 10 clinical trials of CABG or PCI were pooled. Age was analyzed as a continuous variable in the primary analysis and was divided into tertiles for descriptive purposes (≤56.2 years, 56.3 to 65.1 years, ≥65.2 years). The outcomes assessed were death, myocardial infarction and repeat revascularization over complete follow-up, and angina at 1 year. RESULTS: Older patients were more likely to have hypertension, diabetes, and 3-vessel disease compared with younger patients (p < 0.001 for trend). Over a median follow-up of 5.9 years, the effect of CABG versus PCI on mortality varied according to age (interaction p < 0.01), with adjusted CABG-to-PCI hazard ratios and 95% confidence intervals (CI) of 1.23 (95% CI: 0.95 to 1.59) in the youngest tertile; 0.89 (95% CI: 0.73 to 1.10) in the middle tertile; and 0.79 (95% CI: 0.67 to 0.94) in the oldest tertile. The CABG-to-PCI hazard ratio of less than 1 for patients 59 years of age and older. A similar interaction of age with treatment was present for the composite outcome of death or myocardial infarction. In contrast, patient age did not alter the comparative effectiveness of CABG and PCI on the outcomes of repeat revascularization or angina. CONCLUSIONS: Patient age modifies the comparative effectiveness of CABG and PCI on hard cardiac events, with CABG favored at older ages and PCI favored at younger ages.

Preoperative B-type natriuretic peptide, and not the inflammation status, predicts an adverse outcome for patients undergoing heart surgery.

OBJECTIVES: B-type natriuretic peptide (BNP) and inflammatory markers are implicated in the pathophysiology of both ischemic cardiomyopathy and complications after cardiac surgery with cardiopulmonary bypass (CPB). The purpose of this study was to assess preoperative and postoperative levels of BNP, interleukin-6 (IL-6), interleukin-8 (IL-8), P-selectin, intercellular adhesion molecule (ICAM), C-reactive protein (CRP) in patients undergoing cardiac surgery with CPB and investigate their variation and ability to correlate with immediate outcome. METHODS: Plasma levels of these markers were measured preoperatively, 6 and 24 h after CBP in 62 patients. Main endpoints were requirements for intra-aortic balloon pump, intensive care unit (ICU) stay longer than five days, ventilator dependence >24 h, requirement for dobutamine, hospital stay >10 days, clinical complications (infection, myocardial infarction, renal failure, stroke and ventricular arrhythmias) and in-hospital mortality. RESULTS: Preoperative BNP levels correlate with longer ICU stay (P = 0.003), longer ventilator use (P = 0.018) and duration of dobutamine use (P < 0.001). The receiver-operating characteristic curve demonstrated BNP levels >190 pg/ml as predictor of ICU >5 days and BNP levels >20.5 pg/ml correlated with dobutamine use, with areas under the curve of 0.712 and 0.842, respectively. Preoperative levels of ICAM-1 were associated with in-hospital mortality (P = 0.042). In the postoperative period, was found association between CRP, IL-6 and P-selectin with ventilation duration (P = 0.013, P = 0.006, P < 0.001, respectively) and P-selectin with ICU stay (P = 0.009). CONCLUSIONS: BNP correlates with clinical endpoints more than inflammatory markers and can be used as a predictor of early outcome after heart surgery.

Genetic variants of diabetes risk and incident cardiovascular events in chronic coronary artery disease.

OBJECTIVE: To determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence. METHODS: From the about 30 known genes associated with diabetes, we genotyped single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve. RESULTS: Genetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610). CONCLUSIONS: Combined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease. CLINICAL TRIAL REGISTRATION INFORMATION: Medicine, Angioplasty, or Surgery Study (MASS II). Unique identifier: ISRCTN66068876 URL.

The effect of internal thoracic artery grafts on long-term clinical outcomes after coronary bypass surgery.

OBJECTIVES: We sought to compare long-term outcomes after coronary bypass surgery with and without an internal thoracic artery graft. METHODS: We analyzed clinical outcomes over a median follow-up of 6.7 years among 3,087 patients who received coronary bypass surgery as participants in one of 8 clinical trials comparing surgical intervention with angioplasty. We used 2 statistical methods (covariate adjustment and propensity score matching) to adjust for the nonrandomized selection of internal thoracic artery grafts. RESULTS: Internal thoracic artery grafting was associated with lower mortality, with hazard ratios of 0.77 (confidence interval, 0.62-0.97; P = .02) for covariate adjustment and 0.77 (confidence interval, 0.57-1.05; P = .10) for propensity score matching. The composite end point of death or myocardial infarction was reduced to a similar extent, with hazard ratios of 0.83 (confidence interval, 0.69-1.00; P = .05) for covariate adjustment to 0.78 (confidence interval, 0.61-1.00; P = .05) for propensity score matching. There was a trend toward less angina at 1 year, with odds ratios of 0.81 (confidence interval, 0.61-1.09; P = .16) in the covariate-adjusted model and 0.81 (confidence interval, 0.55-1.19; P = .28) in the propensity score-adjusted model. CONCLUSIONS: Use of an internal thoracic artery graft during coronary bypass surgery seems to improve long-term clinical outcomes.

Efficacy of aneurysmectomy in patients with severe left ventricular dysfunction: favorable short-and long-term results in ischemic cardiomyopathy.

INTRODUCTION: The purpose of this study was to (1) identify the functional results after aneurysm surgery in patients with ischemic cardiomyopathy and (2) identify predictors of favorable outcomes. METHODS AND MATERIAL: Patients (n = 169) with angiographic left ventricular ejection fraction of 22 ± 5% underwent aneurysm surgery and were prospectively followed for three years. Prior to surgery, 40% and 60% of the patients were in congestive heart failure NYHA class I/II and III/IV, respectively. Concomitant revascularization was performed on 95% of the patients. RESULTS: Cumulative in-hospital and 36-month mortalities were 7% and 15%, respectively. These respective rates varied according to preoperative parameters: CHF class I-II, 4% and 13%; CHF class III-IV, 8% and 16%; LVEF,20%, 12% and 26%; LVEF 21-30%, 2% and 6%; gated LVEF exercise/rest .5%, ,1% and 4%; and gated LVEF exercise/rest #5%, 17% and 38%. Higher LVEF ex/rest ratio (p = 0.01), male sex (p = 0.05), and a higher number of grafts (p = 0.01) were predictive of improvement in CHF class at follow-up based on the results of a multivariate analysis. After three years of follow-up, 84% of the patients were in class I/II, LVEF was 45 ± 7%, and gated LVEF ex/rest ratio was 13% higher (p,0.01) compared to the beginning of the study. CONCLUSIONS: These data suggest that aneurysmectomy among patients with severe LV dysfunction result in short and long-term favorable functional outcome and survival. Selection of appropriate surgical candidates may substantially improve survival rates among these patients.

Five-year follow-up of angiographic disease progression after medicine, angioplasty, or surgery.

BACKGROUND: Progression of atherosclerosis in coronary artery disease is observed through consecutive angiograms. Prognosis of this progression in patients randomized to different treatments has not been established. This study compared progression of coronary artery disease in native coronary arteries in patients undergoing surgery, angioplasty, or medical treatment. METHODS: Patients (611) with stable multivessel coronary artery disease and preserved ventricular function were randomly assigned to CABG, PCI, or medical treatment alone (MT). After 5-year follow-up, 392 patients (64%) underwent new angiography. Progression was considered a new stenosis of ≥ 50% in an arterial segment previously considered normal or an increased grade of previous stenosis > 20% in nontreated vessels. RESULTS: Of the 392 patients, 136 underwent CABG, 146 PCI, and 110 MT. Baseline characteristics were similar among treatment groups, except for more smokers and statin users in the MT group, more hypertensives and lower LDL-cholesterol levels in the CABG group, and more angina in the PCI group at study entry. Analysis showed greater progression in at least one native vessel in PCI patients (84%) compared with CABG (57%) and MT (74%) patients (p < 0.001). LAD coronary territory had higher progression compared with LCX and RCA (P < 0.001). PCI treatment, hypertension, male sex, and previous MI were independent risk factors for progression. No statistical difference existed between coronary events and the development of progression. CONCLUSION: The angioplasty treatment conferred greater progression in native coronary arteries, especially in the left anterior descending territories and treated vessels. The progression was independently associated with hypertension, male sex, and previous myocardial infarction.

Reduced expression of systemic proinflammatory and myocardial biomarkers after off-pump versus on-pump coronary artery bypass surgery: a prospective randomized study.

BACKGROUND: The effects of off-pump (OffPCABG) and on-pump (OnPCABG) coronary artery bypass grafting (CABG) on myocardium and inflammation are unclear. OBJECTIVE: Compare the inflammatory response and myocardial injury from patients (pts) submitted to OffPCABG with those that undergo OnPCABG. METHODS: Patients with normal left ventricular function were assigned to OffPCABG (n = 40) and OnPCABG (n = 41). Blood samples were collected before and 24 hours after surgery for determination of creatine kinase (CK)-MB (CK-MB), troponin I (cTnI), interleukin (IL)-6, IL-8, P-selectin, intercellular adhesion molecule (ICAM)-1 and C-reactive protein (CRP). Mortalities were registered at 12 months. RESULTS: Preoperative CK-MB and cTnI levels were 3.1 +/- 0.6 IU and 1.2 +/- 0.5 ng/mL for OffPCABG and 3.0 +/- 0.5 IU and 1.0 +/- 0.2 ng/mL for OnPCABG pts. Postoperative CK-MB and cTnI levels were 13.9 +/- 6.5 IU and 19.0 +/- 9.0 ng/mL for OffPCABG vs 29.5 +/- 11.0 IU and 31.5 +/- 10.1 ng/mL for OnPCABG (P < .01). OffPCABG and OnPCABG pts had similar preoperative IL-6 (10 +/- 7 and 9 +/- 13 pg/mL), IL-8 (19 +/- 7 and 17 +/- 7 pg/mL), soluble P-selectin (70 +/- 21 and 76 +/- 23 pg/mL), soluble ICAM-1 (117 +/- 50 and 127 +/- 52 ng/mL), and CRP (0.09 +/- 0.05 and 0.11 +/- 0.07 mg/L). At 24 hours, for OffPCABG and OnPCABG: IL-6 was 37 +/- 38 and 42 +/- 41 g/mL; IL-8, 33 +/- 31 and 60 +/- 15 pg/mL; soluble P-selectin, 99 +/- 26 and 172 +/- 30 pg/mL; soluble ICAM-1, 227 +/- 47 and 236 +/- 87 ng/mL; and CRP, 10 +/- 11 and 14 +/- 13 mg/L (P < .01 vs preoperation; P < .01 vs OffPCABG). Increased 24-hour postoperative CRP levels was the only marker to have significant positive correlations with events and occurred just for the OnPCABG pts. In-hospital and 1-year mortalities for the OnPCABG and OffPCABG pts were 2.0% and 2.2% (P = .1) and 2.7% and 4.7% (P = .06), respectively. CONCLUSIONS: Thus, the absence of CPB during CABG preserves better the myocardium and attenuates inflammation-however, without improving survival.

Association between ADAMTS13 polymorphisms and risk of cardiovascular events in chronic coronary disease.

INTRODUCTION: Association between ADAMTS13 levels and cardiovascular events has been described recently. However, no genetic study of ADAMTS13 in coronary patients has been described. MATERIALS AND METHODS: Based on related populations frequencies and functional studies, we tested three ADAMTS13 polymorphisms: C1342G (Q448E), C1852G (P618A) and C2699T (A900V) in a group of 560 patients enrolled in the Medical, Angioplasty, or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. The incidence of the 5-year end-points of death and death from cardiac causes, myocardial infarction, refractory angina requiring revascularization and cerebrovascular accident was determined for each polymorphim's allele, genotype and haplotype. Risk was assessed with the use of logistic regression and Cox proportional-hazards model and multivariable adjustment was employed for possible confounders. RESULTS: Clinical characteristics and received treatment of each genotype group were similar at baseline. In an adjusted model for cardiovascular risk variables, we were able to observe a significant association between ADAMTS13 900V variant and an increased risk of death (OR: 1,92 CI: 1,14-3,23, p=0,015) or death from cardiac cause (OR:2,67, CI: 1,59-4,49, p=0,0009). No association between events and ADAMTS13 Q448E or P618A was observed. CONCLUSIONS: This first report studying the association between ADAMTS13 genotypes and cardiovascular events provides evidence for the association between ADAMTS13 900V variant and an increased risk of death in a population with multi-vessel CAD.

Efficacy of aneurysmectomy in patients with severe left ventricular dysfunction: favorable short-and long-term results in ischemic cardiomyopathy

INTRODUCTION: The purpose of this study was to (1) identify the functional results after aneurysm surgery in patients with ischemic cardiomyopathy and (2) identify predictors of favorable outcomes. METHODS AND MATERIAL: Patients (n = 169) with angiographic left ventricular ejection fraction of 22±5 percent underwent aneurysm surgery and were prospectively followed for three years. Prior to surgery, 40 percent and 60 percent of the patients were in congestive heart failure NYHA class I/II and III/IV, respectively. Concomitant revascularization was performed on 95 percent of the patients. RESULTS: Cumulative in-hospital and 36-month mortalities were 7 percent and 15 percent, respectively. These respective rates varied according to preoperative parameters: CHF class I-II, 4 percent and 13 percent; CHF class III-IV, 8 percent and 16 percent; LVEF,20 percent, 12 percent and 26 percent; LVEF 21-30 percent, 2 percent and 6 percent; gated LVEF exercise/rest .5 percent, ,1 percent and 4 percent; and gated LVEF exercise/rest #5 percent, 17 percent and 38 percent. Higher LVEF ex/rest ratio (p = 0.01), male sex (p = 0.05), and a higher number of grafts (p = 0.01) were predictive of improvement in CHF class at follow-up based on the results of a multivariate analysis. After three years of follow-up, 84 percent of the patients were in class I/II, LVEF was 45±7 percent, and gated LVEF ex/rest ratio was 13 percent higher (p,0.01) compared to the beginning of the study. CONCLUSIONS: These data suggest that aneurysmectomy among patients with severe LV dysfunction result in shortand long-term favorable functional outcome and survival. Selection of appropriate surgical candidates may substantially improve survival rates among these patients.

TCF7L2 polymorphism rs7903146 is associated with coronary artery disease severity and mortality.

BACKGROUND: TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. METHODS AND RESULTS: two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR = 2.32 95%CI 1.27-4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). CONCLUSIONS: rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets. CLINICAL TRIAL REGISTRATION INFORMATION: MEDICINE, ANGIOPLASTY, OR SURGERY STUDY (MASS II): Unique identifier: ISRCTN66068876.

In vitro simultaneous transfer of lipids to HDL in coronary artery disease and in statin treatment.

The exchange of lipids with cells and other lipoproteins is a crucial process in HDL metabolism and for HDL antiatherogenic function. Here, we tested a practical method to quantify the simultaneous transfer to HDL of phospholipids, free-cholesterol, esterified cholesterol and triacylglycerols and to verify the lipid transfer in patients with coronary artery disease (CAD) or undergoing statin treatment. Twenty-eight control subjects without CAD, 27 with CAD and 25 CAD patients under simvastatin treatment were studied. Plasma samples were incubated with a donor nanoemulsion prepared by ultrasonication of the constituent lipids and labeled with radioactive lipids; % lipids transferred to HDL were quantified in the HDL-containing supernatant after chemical precipitation of non-HDL fractions and the nanoemulsion. The assay was precise and reproducible. Increase of temperature (4-37 degrees C), of incubation period (5 min to 2 h), of HDL-cholesterol concentration (33-244 mg/dL) and of mass of nanoemulsion lipids (0.075-0.3 mg/microL) resulted in increased lipid transfer from the nanoemulsion to HDL. In contrast, increasing pH (6.5-8.5) and albumin concentration (3.5-7.0 g/dL) did not affect lipid transfer. There was no difference between CAD and control non-CAD with regard to the lipid transfer, but statin treatment reduced the transfer to HDL of all four lipids. The test herein described is a valid and practical tool for exploring an important aspect of HDL metabolism.

Factors related to the selection of surgical versus percutaneous revascularization in diabetic patients with multivessel coronary artery disease in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial.

OBJECTIVES: We evaluated demographic, clinical, and angiographic factors influencing the selection of coronary artery bypass graft (CABG) surgery versus percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary artery disease (CAD) in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial. BACKGROUND: Factors guiding selection of mode of revascularization for patients with diabetes mellitus and multivessel CAD are not clearly defined. METHODS: In the BARI 2D trial, the selected revascularization strategy, CABG or PCI, was based on physician discretion, declared independent of randomization to either immediate or deferred revascularization if clinically warranted. We analyzed factors favoring selection of CABG versus PCI in 1,593 diabetic patients with multivessel CAD enrolled between 2001 and 2005. RESULTS: Selection of CABG over PCI was declared in 44% of patients and was driven by angiographic factors including triple vessel disease (odds ratio [OR]: 4.43), left anterior descending stenosis >or=70% (OR: 2.86), proximal left anterior descending stenosis >or=50% (OR: 1.78), total occlusion (OR: 2.35), and multiple class C lesions (OR: 2.06) (all p < 0.005). Nonangiographic predictors of CABG included age >or=65 years (OR: 1.43, p = 0.011) and non-U.S. region (OR: 2.89, p = 0.017). Absence of prior PCI (OR: 0.45, p < 0.001) and the availability of drug-eluting stents conferred a lower probability of choosing CABG (OR: 0.60, p = 0.003). CONCLUSIONS: The majority of diabetic patients with multivessel disease were selected for PCI rather than CABG. Preference for CABG over PCI was largely based on angiographic features related to the extent, location, and nature of CAD, as well as geographic, demographic, and clinical factors. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305).