Bypass Angioplasty Revascularization Investigation Research Articles

Abstract 172: Baseline Physical Activity and Clinical Outcomes in Patients with Diabetes Mellitus and Stable Ischemic Heart Disease: Analysis From BARI-2D Trial.

Introduction: We aimed to evaluate the differences in clinical outcomes among patients with DM and coronary heart disease according to their baseline physical activity status. Methods: We evaluated 2,343 patients with CHD and DM who underwent either prompt revascularization (PR) and intensive medical therapy (IMT) or IMT alone in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Patients were categorized according to their baseline physical activity status to sedentary, mild physical activity or moderate/strenuous activity. Primary end points were all cause mortality. Cox Regression analysis was used to evaluate the effects of baseline physical activity on all-cause-mortality. Results: Of 2,343 patients, 858 (37%) were able to achieve moderate/strenuous physical activity prior to randomization. Patients with sedentary life style and mild physical activity at baseline had worse survival compared to those with higher activity levels (Figure). In a Cox regression analysis, in patients randomized to IMT alone, there were no differences in mortality across physical activity levels. In the PR arm, sedentary and mild physical activity carried high risk of mortality compared to strenuous activity levels. Furthermore, patients in the low physical activity categories carried an increased risk of death if they were randomized to the insulin sensitizing arm of the trial. Conclusions: In this study, patients with DM and CHD, moderate/strenuous physical activity at baseline had improved survival compared to mild physical activity or sedentary life-style.

Patient selection for elective revascularization to reduce myocardial infarction and mortality: new lessons from randomized trials, coronary physiology, and statistics.

As stated in American College of Cardiology/American Heart Association Guidelines, randomized trials have not demonstrated that elective percutaneous coronary intervention (PCI) reduces myocardial infarction (MI) or mortality over medical treatment. Even the Fractional Flow Reserve Guided PCI Versus Medical Therapy in Stable Coronary Disease (FAME 2) trial showed no statistically significant benefit of PCI over the deferred group by traditional intention-to-treat, nonbenchmark analysis starting at randomization that includes procedure-related events. Benchmark analysis in FAME 2 beginning 1 week after PCI removed procedure-related events that counterbalanced subsequent reduced MI and mortality compared with the deferred group. Meta-analysis of the literature on risk of events related to fractional flow reserve (FFR), including FFR Versus Angiography in Multivessel Evaluation (FAME), and other physiological measures of severity reveal an underappreciated, powerful interdependence among physiological severity of stenosis, diffuse coronary artery disease (CAD), event rates, sample size, and statistical certainty of differences. This analytic review synthesizes an evidenced-based, quantitative hypothesis and potential solution to this issue based on hard data from the literature by coauthors of diverse cardiovascular disciplines in trial design, biostatistics, invasive procedures, coronary physiology, fluid dynamics, coronary pathology, and quantitative imaging. Our synthesis elucidates a dual hypothesis for failure of elective PCI in stable CAD to reduce MI or mortality and novel trial design for selecting patients for whom PCI will likely reduce these events. First, a large burden of global diffuse CAD carries a high risk of coronary events unmitigated by PCI of a focal stenosis. Second, focal stenosis severity in previous randomized revascularization trials has been too modest without objectively quantified sufficient severity to observe benefit of PCI. In previous trials, mixture of diffuse coronary disease and intermediate stenosis may not incur high enough risk for potential benefit by PCI for sample size of reported trials. Greater quantitative severity with …

Comparison of coronary artery bypass graft surgery and percutaneous coronary intervention in patients with diabetes.

The optimal revascularization strategy in patients with diabetes is controversial. The Bypass Angioplasty Revascularization Investigation (BARI) trial, done more than a decade ago, suggested a mortality benefit of coronary artery bypass graft surgery (CABG) when compared with percutaneous coronary intervention (PCI) (with plain old balloon angioplasty) in the subgroup of patients with diabetes. In addition, several observational studies and meta-analyses similarly suggest a benefit of CABG over PCI in patients with diabetes. However, most of these studies compared CABG with PCI using balloon angioplasty, bare metal stents, or first-generation drug-eluting stents. In this review, we critically examine the data for optimal revascularization strategy in patients with diabetes and ask the question whether the currently available data from randomized trials that used outdated stents are applicable to current day practice.

Analysis of the Bypass Angioplasty Revascularization Investigation Trial Using a Multistate Model of Clinical Outcomes

Current cardiovascular randomized trials typically use composite outcomes. We hypothesized that the Bypass Angioplasty Revascularization Investigation (BARI) outcomes and conclusions would differ using a multistate model relative to the intervention for the composite outcome of death (D) and nonfatal Q-wave myocardial infarction (MI). We used a multistate model which uses transition paths to simultaneously assess multiple end points. Using the 10-year follow-up BARI data, we post hoc analyzed outcomes according to 3 transition paths: (1) from intervention to MI; (2) from intervention to death; and (3) from MI to death. Of 1,829 patients randomized to the intervention of percutaneous transluminal coronary angioplasty or coronary artery bypass grafting (CABG), 700 (38%) experienced the composite event D/MI which included 230 (13%) nonfatal MI and 470 (26%) death without antecedent nonfatal MI, whereas 79 of 230 (34%) experienced death after nonfatal MI. Outcomes of the 3 individual transition paths were analyzed by a multistate model. In contrast to standard survival analyses, after adjustment for baseline clinical covariates, outcomes after percutaneous transluminal coronary angioplasty or CABG were not significantly different for intervention to MI (p = 0.33) or intervention to death (p = 0.23), but MI to death favored CABG (p = 0.02). Deconstruction of the BARI data using a multistate model identifies a significant difference in individual transition-stage outcomes and therefore trial conclusions in contrast to the standard methods of survival analysis. These observations suggest multistate models should be considered in the design and analysis of randomized cardiovascular trials which use composite outcomes.

A novel coronary angiography index (DILEMMA score) for prediction of functionally significant coronary artery stenoses assessed by fractional flow reserve: A novel coronary angiography index

Angiographic evaluation of diameter stenosis has modest predictive value for functionally significant coronary artery stenoses as assessed by fractional flow reserve (FFR). Lesion length and assessment of area of myocardium at risk (Bypass Angioplasty Revascularization Investigation [BARI] Myocardial Jeopardy Index [MJI]) subtended by the stenotic coronary arteries are also predictors of functionally significant coronary artery stenoses. We sort to assess the diagnostic accuracy of DILEMMA score, which combines minimal lumen diameter (MLD), lesion length, and BARI MJI in prediction of significantly reduced FFR (≤0.8). We assessed patients who underwent coronary angiography and FFR. Lesion length and MLD were assessed by quantitative coronary angiography. Estimation of area of myocardium at risk subtended by coronary stenoses was performed using the BARI MJI. A total of 296 patients (age 64 ± 10.6 years, 68% male, 497 vessels) were included. DILEMMA score was significantly higher in vessels with significant FFR, 6.09 ± 3.23 versus 3.84 ± 2.99 (P < .001). In the derivation cohort, the optimism-adjusted Harrell c statistic for DILEMMA score was 0.82 compared with 0.76 for BARI MJI, 0.75 for lesion length, and 0.7 for MLD. In the validation cohort, the c-statistic for DILEMMA score, BARI MJI, lesion length, and MLD was 0.88, 0.77, 0.81, and 0.72, respectively. The DILEMMA score was a better predictor of FFR ≤0.8 compared with MLD, lesion length, and BARI MJI individually (P < .001, P < .02, and P < .045, respectively) on Bonferroni-adjusted pairwise comparison. DILEMMA score, taking into account MLD, lesion length, and BARI MJI, may have incremental predictive value beyond the individual indices alone for detecting functionally significant coronary artery stenoses.

Abstract 11726: Novel Non-Invasive Method to Estimate Myocardial Mass at Risk Calculated From Cardiac Computed Tomography Data: Validation Study Using Angiographic Myocardial Jeopardy Scores in Patients With Single Vessel Disease

Background: The myocardial mass at risk (MMAR), representing volume of myocardium distal to culprit lesion, is one of important factors for predicting adverse cardiac event in ischemic heart disease. However, current non-invasive cardiac imaging fails to quantify MMAR in patients with stable coronary artery disease. We have developed a new software calculating MMAR of any designated coronary artery by reconstructing the 3-dimensional-volume-data of cardiac computed tomography (CCT). The novel index, ratio of MMAR to whole left ventricular volume (%LV-MMAR), calculated with this software would be appealing to obtain MMAR objectively. This study aims to compare the %LV-MMAR with Bypass Angioplasty Revascularization Investigation (BARI) and modified Albert Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores, both of which are invasive angiographic methods widely used to estimate MMAR, in patients with single-vessel disease. Methods: Between April 2008 and March 2014, patients suspected of effort angina pectoris without history of previous myocardial infarction were assessed with CCT and invasive coronary angiography. Of those, 48 patients who were revealed single-vessel disease (left anterior descending artery (LAD): n=22, left circumflex artery (LCX): n=11 and right coronary artery (RCA): n=15) were included in this study. %LV-MMAR was calculated on the software. BARI and modified APPROACH score were calculated and compared with %LV-MMAR. Results: Mean %LV-MMAR was 27.6 [18.2-37.1] %. BARI and APPROACH scores showed a significant correlation (r=0.92, p&lt;0.0001). Also, a significant correlation was observed between %LV-MMAR versus BARI and %LV-MMAR versus APPROACH (r=0.95, p&lt;0.0001 and r=0.9, p&lt;0.0001, respectively). %LV-MMAR showed significant correlation with BARI and APPROACH scores in all vessels; LAD (r=0.95, p&lt;0.0001 and r=0.91, p&lt;0.0001, respectively), LCX (r=0.91, p=0.0001 and r=0.83, p=0.0002, respectively) and RCA (r=0.92, p&lt;0.0001 and r=0.85, p&lt;0.0001, respectively). Conclusions: This study revealed %LV-MMAR, calculated from CCT data on novel software, to be a promising index for estimating perfusion territory noninvasively in good agreement with BARI and modified APPROACH score.

Appropriate Revascularization in Stable Angina: Lessons From the BARI 2D Trial

BackgroundThe 2012 Guidelines for Diagnosis and Management of Patients with Stable Ischemic Heart Disease recommend intensive antianginal and risk factor treatment (optimal medical management [OMT]) before considering revascularization to relieve symptoms. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial randomized patients with ischemic heart disease and anatomy suitable to revascularization to (1) initial OMT with revascularization if needed or (2) initial revascularization plus OMT and found no difference in major cardiovascular events. Ultimately, however, 37.9% of the OMT group was revascularized during the 5-year follow-up period. MethodsData from the 1192 patients randomized to OMT were analyzed to identify subgroups in which the incidence of revascularization was so high that direct revascularization without a trial period could be justified. Multivariate logistic analysis, Cox regression models of baseline data, and a landmark analysis of participants who did not undergo revascularization at 6 months were constructed. ResultsThe models that used only data available at the time of study entry had limited predictive value for revascularization by 6 months or by 5 years; however, the model incorporating severity of angina during the first 6 months could better predict revascularization (C statistic = 0.789). ConclusionsWith the possible exception of patients with severe angina and proximal left anterior descending artery disease, this analysis supports the recommendation of the 2012 guidelines for a trial of OMT before revascularization. Patients could not be identified at the time of catheterization, but a short period of close follow-up during OMT identified the nearly 40% of patients who underwent revascularization.

Risk Factors for Incident Peripheral Arterial Disease in Type 2 Diabetes: Results From the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) Trial

OBJECTIVEThe aim of this article was to define risk factors for incidence of peripheral arterial disease (PAD) in a large cohort of patients with type 2 diabetes mellitus (T2DM), overall and within the context of differing glycemic control strategies.RESEARCH DESIGN AND METHODSThe Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) randomized controlled trial assigned participants to insulin-sensitizing (IS) therapy versus insulin-providing (IP) therapy. A total of 1,479 participants with normal ankle-brachial index (ABI) at study entry were eligible for analysis. PAD outcomes included new ABI ≤0.9 with decrease at least 0.1 from baseline, lower extremity revascularization, or lower extremity amputation. Baseline risk factors within the overall cohort and time-varying risk factors within each assigned glycemic control arm were assessed using Cox proportional hazards models.RESULTSDuring an average 4.6 years of follow-up, 303 participants (20.5%) experienced an incident case of PAD. Age, sex, race, and baseline smoking status were all significantly associated with incident PAD in the BARI 2D cohort. Additional baseline risk factors included pulse pressure, HbA1c, and albumin-to-creatinine ratio (P < 0.05 for each). In stratified analyses of time-varying covariates, changes in BMI, LDL, HDL, systolic blood pressure, and pulse pressure were most predictive among IS patients, while change in HbA1c was most predictive among IP patients.CONCLUSIONSAmong patients with T2DM, traditional cardiovascular risk factors were the main predictors of incident PAD cases. Stratified analyses showed different risk factors were predictive for patients treated with IS medications versus those treated with IP medications.

Select Articles Published on the Topic of Coronary Heart Disease in 2013

Select Articles Published on the Topic of Coronary Heart Disease in 2013

Coronary artery bypass in patients with type 2 diabetes: Experience from the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial

Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) was a study of management strategies for diabetic patients with myocardial ischemia and coronary artery disease. In a 2×2 design, early revascularization versus medical management with or without late revascularization and insulin sensitization versus insulin provision were examined. No advantage for either strategy was seen, except in the group undergoing early coronary artery bypass grafting (CABG). In that group, a reduction in subsequent myocardial infarction was noted. The purpose of our report was to characterize the conduct and short-term outcomes for CABG that led to this result. Data from the BARI 2D CABG stratum were collected, including the baseline demographic and cardiovascular characteristics, technical details of the operation, and perioperative morbidity and mortality, and analyzed. A total of 347 patients were studied. The average cardiac function was normal, and most had multivessel disease. Almost all had undergone CABG by way of a median sternotomy using an internal mammary artery, and one third were off pump. The perioperative morbidity and mortality were low and compared well with larger outcomes databases. BARI 2D showed that early CABG in patients with type 2 diabetes and myocardial ischemia and multivessel disease reduced the subsequent myocardial infarction rates. The present results have demonstrated that this was achieved using off-pump surgery in certain cases, standard myocardial protection, and routine use of the internal mammary artery or other arterial grafts.

Change in Albuminuria and eGFR Following Insulin Sensitization Therapy Versus Insulin Provision Therapy in the BARI 2D Study

In the Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial, glycemic control with insulin-sensitization therapy was compared with insulin-provision therapy in patients with type 2 diabetes and coronary artery disease. This study examined differences in albumin excretion and renal function in the insulin-sensitization group versus the insulin-provision group over 5 years. In total, 1799 patients with measurements of creatinine and urine albumin/creatinine ratio at baseline and at least two follow-up visits were included. Management of BP, lipids, and lifestyle counseling was uniform. Progression of albuminuria was defined as doubling of baseline albumin/creatinine ratio to at least 100 mg/g or worsening of albumin/creatinine ratio status on two or more visits. Worsening renal function was defined as >25% decline in estimated GFR and annualized decline of >3 ml/min per 1.73 m(2) per year. By 6 months and thereafter, the mean glycated hemoglobin levels were lower in the insulin-sensitization group compared with the insulin-provision group (P<0.002 for each time point; absolute difference=0.4%). Albumin/creatinine ratio increased over time in the insulin-sensitization group (P value for trend<0.001) and was stable in the insulin-provision group. Risk for progression of albumin/creatinine ratio was higher in the insulin-sensitization group compared with the insulin-provision group (odds ratio, 1.59; 95% confidence interval, 1.25 to 2.02; P=0.02). Over 5 years, albumin/creatinine ratio increased from 11.5 (interquartile range=5.0-46.7) to 15.7 mg/g (interquartile range=6.2-55.4) in the insulin-sensitization group (P<0.001) and from 12.1 (interquartile range=5.3-41.3) to 12.4 mg/g (interquartile range=5.8-50.6) in the insulin-provision group (P=0.21). Estimated GFR declined from 75.0±20.6 to 66.3±22.6 ml/min per 1.73 m(2) in the insulin-sensitization group (P<0.001) and from 76.1±29.5 to 66.8±22.1 ml/min per 1.73 m(2) in the insulin-provision group (P<0.001). Over 5 years, despite lower glycated hemoglobin levels, the insulin-sensitization treatment group had greater progression of albumin/creatinine ratio compared with the insulin-provision treatment group. Decline in estimated GFR was similar.

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Impact of Glycemic Control Strategies on the Progression of Diabetic Peripheral Neuropathy in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Cohort

OBJECTIVEThe Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial demonstrated similar long-term clinical effectiveness of insulin-sensitizing (IS) versus insulin-providing (IP) treatments for type 2 diabetes on cardiovascular outcomes in a cohort with documented coronary artery disease. We evaluated the effects of randomized glycemic control strategy (IS vs. IP) on the prevalence and incidence of diabetic peripheral neuropathy (DPN).RESEARCH DESIGN AND METHODSDPN (defined as Michigan Neuropathy Screening Instrument [MNSI] clinical examination score >2) was assessed at baseline and yearly for 4 years. DPN prevalence and incidence were compared by intention-to-treat modeling by logistic generalized estimating equation models for prevalence and Kaplan-Meier estimates and Cox regression models for incidence rates.RESULTSResults are reported for 2,159 BARI 2D participants (70% males) with valid baseline and at least one follow-up MNSI score (mean age 62 ± 9 years, mean HbA1c 7.7 ± 1.6%, diabetes duration 10 ± 9 years). There were no differences in the prevalence of DPN between the IS and the IP groups throughout the 4 years of follow-up. In 1,075 BARI 2D participants with no DPN at baseline, the 4-year cumulative incidence rate of DPN was significantly lower in the IS (66%) than in the IP (72%) strategy group (P = 0.02), which remained significant after adjusting for the in-trial HbA1c (P = 0.04). In subgroup analyses, IS strategy had a greater benefit in men (hazard ratio 0.75 [99% CI 0.58–0.99], P < 0.01).CONCLUSIONSAmong patients with type 2 diabetes followed for up to 4 years during BARI 2D, a glycemic control therapy with IS significantly reduced the incidence of DPN compared with IP therapy and may add further benefit for men.

Favorable Effects of Insulin Sensitizers Pertinent to Peripheral Arterial Disease in Type 2 Diabetes

OBJECTIVEThe aim of this manuscript was to report the risk of incident peripheral arterial disease (PAD) in a large randomized clinical trial that enrolled participants with stable coronary artery disease and type 2 diabetes and compare the risk between assigned treatment arms.RESEARCH DESIGN AND METHODSThe Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial randomly assigned participants to insulin sensitization (IS) therapy versus insulin-providing (IP) therapy for glycemic control. Results showed similar 5-year mortality in the two glycemic treatment arms. In secondary analyses reported here, we examine the effects of treatment assignment on the incidence of PAD. A total of 1,479 BARI 2D participants with normal ankle-brachial index (ABI) (0.91–1.30) were eligible for analysis. The following PAD-related outcomes are evaluated in this article: new low ABI ≤0.9, a lower-extremity revascularization, lower-extremity amputation, and a composite of the three outcomes.RESULTSDuring an average 4.6 years of follow-up, 303 participants experienced one or more of the outcomes listed above. Incidence of the composite outcome was significantly lower among participants assigned to IS therapy than those assigned to IP therapy (16.9 vs. 24.1%; P < 0.001). The difference was significant in time-to-event analysis (hazard ratio 0.66 [95% CI 0.51–0.83], P < 0.001) and remained significant after adjustment for in-trial HbA1c (0.76 [0.59–0.96], P = 0.02).CONCLUSIONSIn participants with type 2 diabetes who are free from PAD, a glycemic control strategy of insulin sensitization may be the preferred therapeutic strategy to reduce the incidence of PAD and subsequent outcomes.

Change in enrollment patterns, patient selection, and clinical outcomes with the availability of drug-eluting stents in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial

In the BARI 2D trial, patients with type 2 diabetes and stable coronary artery disease were randomized to prompt revascularization versus intensive medical therapy (IMT). This analysis sought to evaluate how the availability of drug-eluting stents (DESs) has changed practice and outcomes. In BARI 2D, 1,605 patients were in the percutaneous coronary intervention (PCI)-intended stratum. As DES became available midway through recruitment, we report clinical outcomes among patients who underwent IMT versus prompt PCI with bare-metal stents (BMSs) or DES up to 4 years. In North America, after DES became available, selection for the PCI-intended stratum increased from 73% to 79% (P = .003). Fewer BMS than DES patients had total occlusions treated or underwent rotational atherectomy (5.6% vs 9.7%, P = .02, and 1.2% vs 3.7%, P < .01, respectively). Subsequent revascularization (IMT 39%, BMS 29%, DES 21%, P < .01) and target vessel revascularization (BMS 16.1% vs DES 9.6%, P = .03) were lower with DES. Angina at 2 years tended to be less common with DES (IMT 39%, BMS 37%, DES 29%, P = .04, for 3 groups, P = .07 for DES vs BMS). The composite of death, myocardial infarction, or stroke was IMT 16.0%, BMS 20.5%, DES 17.5%; P = .80. When DES became available in North America, patients were more likely to be selected into the PCI-intended stratum. Compared with patients receiving BMS, those receiving DES tended to have less target vessel revascularization and angina.

Race/Ethnic Disparities in Risk Factor Control and Survival in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

This study sought to evaluate the impact of race/ethnicity on cardiovascular risk factor control and on clinical outcomes in a setting of comparable access to medical care. The BARI 2D trial enrolled 1,750 participants from the United States and Canada that self-reported either White non-Hispanic (n = 1,189), Black non-Hispanic (n = 349), or Hispanic (n = 212) race/ethnicity. Participants had type 2 diabetes and coronary artery disease and were randomized to cardiac and glycemic treatment strategies. All patients received intensive target-based medical treatment for cardiac risk factors. Average follow-up was 5.3 years. Kaplan-Meier survival curves and Cox proportional hazards regression models were constructed to assess potential differences in mortality and cardiovascular outcomes across racial/ethnic groups. Long-term risk of death and death/myocardial infarction/stroke did not vary significantly by race/ethnicity (5-year death: 11.0% Whites, 13.7% Blacks, 8.7% Hispanics, p = 0.19; adjusted hazard ratio 1.18 Black versus White, 95% confidence interval 0.84 to 1.67, p = 0.33 and 0.82 Hispanic versus White, 95% confidence interval 0.51 to 1.34, p = 0.43). Among the 1,168 patients with suboptimal risk factor control at baseline, the ability to attain better risk factor control during the trial was associated with higher 5-year survival (71%, 86% and 95% for patients with 0 or 1, 2, and 3 factors in control, respectively, p <0.001); this pattern was observed within each race/ethnic group. In conclusion, significant race/ethnic differences in cardiac risk profiles that persisted during follow-up did not translate into significant differences in 5-year death or death/MI/stroke.

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Rosiglitazone and outcomes for patients with diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

Rosiglitazone improves glycemic control for patients with type 2 diabetes mellitus, but there remains controversy regarding an observed association with cardiovascular hazard. The cardiovascular effects of rosiglitazone for patients with coronary artery disease remain unknown. To examine any association between rosiglitazone use and cardiovascular events among patients with diabetes mellitus and coronary artery disease, we analyzed events among 2368 patients with type 2 diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Total mortality, composite death, myocardial infarction, and stroke, and the individual incidence of death, myocardial infarction, stroke, congestive heart failure, and fractures, were compared during 4.5 years of follow-up among patients treated with rosiglitazone versus patients not receiving a thiazolidinedione by use of Cox proportional hazards and Kaplan-Meier analyses that included propensity matching. After multivariable adjustment, among patients treated with rosiglitazone, mortality was similar (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.58-1.18), whereas there was a lower incidence of composite death, myocardial infarction, and stroke (HR, 0.72; 95% CI, 0.55-0.93) and stroke (HR, 0.36; 95% CI, 0.16-0.86) and a higher incidence of fractures (HR, 1.62; 95% CI, 1.05-2.51); the incidence of myocardial infarction (HR, 0.77; 95% CI, 0.54-1.10) and congestive heart failure (HR, 1.22; 95% CI, 0.84-1.82) did not differ significantly. Among propensity-matched patients, rates of major ischemic cardiovascular events and congestive heart failure were not significantly different. Among patients with type 2 diabetes mellitus and coronary artery disease in the BARI 2D trial, neither on-treatment nor propensity-matched analysis supported an association of rosiglitazone treatment with an increase in major ischemic cardiovascular events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Endothelial Progenitor Cells, Microvascular Obstruction, and Left Ventricular Remodeling in Patients With ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Endothelial progenitor cells (EPCs) are released from the bone marrow during cardiac ischemic events, potentially influencing vascular and myocardial repair. We assessed the clinical and angiographic correlates of EPC mobilization at the time of primary percutaneous coronary intervention in 78 patients with ST elevation myocardial infarction and the impact of both baseline and follow-up EPC levels on left ventricular (LV) remodeling. Blood samples were drawn from the aorta and the culprit coronary artery for cytofluorimetric EPC detection (CD34+CD45dimKDR+ cells, in percentage of cytofluorimetric counts). Area at risk was assessed by Bypass Angioplasty Revascularization Investigation myocardial jeopardy index, thrombotic burden as thrombus score and microvascular obstruction (MVO) as a combination of ST segment resolution and myocardial blush grade. Echocardiographic evaluation of LV remodeling was performed at 1-year follow-up in 54 patients, whereas peripheral EPC levels were reassessed in 40 patients. EPC levels during primary percutaneous coronary intervention were significantly higher in intracoronary than in aortic blood (0.043% vs 0.0006%, p <0.001). Both intracoronary and aortic EPC were related to area at risk extent, to intracoronary thrombus score (p <0.001), and inversely to MVO (p = 0.001). Peripheral EPC levels at 1-year follow-up were lower in patients with LV remodeling than in those without (0.001% [0.001 to 0.002] vs 0.003% [0.002 to 0.010]; p = 0.01) and independently predicted absence of remodeling at multivariate analysis. In conclusion, a rapid intracoronary EPC recruitment takes place in the early phases of ST elevation myocardial infarction, possibly reflecting an attempted reparative response. The extent of this mobilization seems to be correlated to the area at risk and to the amount of MVO. Persistently low levels of EPC are associated to LV remodeling.

Residual Ischemia After Revascularization in Multivessel Coronary Artery Disease

Revascularization strategies for multivessel coronary artery disease include percutaneous coronary intervention and coronary artery bypass grafting. In this study, we compared the completeness of revascularization as assessed by coronary angiography and by quantitative serial perfusion imaging using cardiovascular magnetic resonance. Patients with multivessel coronary disease were recruited into a randomized trial of treatment with either coronary artery bypass grafting or percutaneous coronary intervention. Angiographic disease burden was determined by the Bypass Angioplasty Revascularization Investigation (BARI) myocardial jeopardy index. Cardiovascular magnetic resonance first-pass perfusion imaging was performed before and 5 to 6 months after revascularization. Using model-independent deconvolution, hyperemic myocardial blood flow was evaluated, and ischemic burden was quantified. Sixty-seven patients completed follow-up (33 coronary artery bypass grafting and 34 percutaneous coronary intervention). The myocardial jeopardy index was 80.7±15.2% at baseline and 6.9±11.3% after revascularization (P<0.0001), with revascularization deemed complete in 62.7% of patients. Relative to cardiovascular magnetic resonance, angiographic assessment overestimated disease burden at baseline (80.7±15.2% versus 49.9±29.2% [P<0.0001]), but underestimated it postprocedure (6.9±11.3% versus 28.1±33.4% [P<0.0001]). Fewer patients achieved complete revascularization based on functional criteria than on angiographic assessment (38.8% versus 62.7%; P=0.015). After revascularization, hyperemic myocardial blood flow was significantly higher in segments supplied by arterial bypass grafts than those supplied by venous grafts (2.04±0.82 mL/min per gram versus 1.89±0.81 mL/min per gram, respectively; P=0.04). Angiographic assessment may overestimate disease burden before revascularization, and underestimate residual ischemia after revascularization. Functional data demonstrate that a significant burden of ischemia remains even after angiographically defined successful revascularization.