Editor's Choice - Risk of Rupture and All Cause Mortality of Abdominal Aortic Ectasia: A Systematic Review and Meta-Analysis.

OBJECTIVE: To clarify the natural history of abdominal aortic ectasia (AAE) measuring 25 - 29 mm in maximum diameter, and to determine the optimal follow up based on the growth, risk of rupture, and overall mortality of AAE. DATA SOURCES: MEDLINE, Web of Science Core Collection, and Google Scholar. REVIEW METHODS: This was a systematic review and meta-analysis of AAE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Web of Science Core Collection, and Google Scholar were searched, with the help of a health sciences librarian, up to 11 August 2021. Studies with longitudinal outcomes of AAE (prevalence, annual growth rate, aneurysmal enlargement, rupture, aneurysm related death, and all cause mortality) were included. Meta-analyses were conducted with a random effects model RESULTS: Twelve studies describing a total of 8 369 patients were eligible. The prevalence at population based settings was 3.2% (95% confidence interval [CI] 2.4 - 4.0); annual growth rate was 0.82 mm/year (95% CI 0.20 - 1.45). The estimated risks of aortic diameters exceeding 30 mm and 55 mm in five years were 45.0% (95% CI 28.5 - 61.5) and 0.3% (95% CI 0 - 0.6) respectively, while those beyond five years were 70.2% (95% CI 46.9 - 93.6) and 5.2% (95% CI 2.2 - 8.2). The rates of rupture and aneurysm related death were minimal until five years (0.1% and 0.1%, respectively) and beyond (0.4% and 0.2%, respectively). Overall mortality was 7.5% (95% CI 3.9 - 11.0) and 17.3% (95% CI 9.5 - 25.1) up to and beyond five years. Overall mortality from three studies showed no statistical difference between AAE and aneurysms (hazard ratio 0.62, 95% CI 0.32 - 1.21; p = .16). Cancer (35.0%) and cardiovascular diseases (31.9%) were major causes of death. CONCLUSION: AAE carries minimal risk of aneurysm related lethal events during the first five years, but a similar overall mortality risk as abdominal aortic aneurysm. Cancer and cardiovascular diseases are leading causes of death in patients with AAE.

Impact of previous coronary artery bypass grafting on patients undergoing transcatheter aortic valve implantation for aortic stenosis.

Re-operation after coronary artery bypass grafting (CABG) is associated with increased risk for morbidity and mortality. Transcatheter aortic valve implantation (TAVI) is an alternative for patients with aortic stenosis, but the outcomes of patients with a history of CABG are unknown. The aim of this study was to explore the association between previous CABG and the outcome of patients undergoing TAVI. Out of 372 consecutive patients who underwent TAVI from 2007 to 2013, 122 (32.8%) had previous CABG, whereas 250 (67.2%) did not. A comparison was made between groups. Subgroup analysis compared patients with and without previous CABG in 3 patient subsets: inoperable, operable, and those who underwent transapical TAVI. Patients with previous CABG were younger (81.99±6.78 vs 84.81±7.06 years, respectively, p<0.001). These patients also had more high-risk features (e.g., peripheral vascular disease, previous myocardial infarction, past cerebrovascular disease, and lower average left ventricular ejection fraction (p<0.05 for all). Procedural aspects were mostly similar between groups. No disparities in mortality rates at 1 year were noted (22.1% vs 21.6%, respectively, p=0.91). Subgroup analyses yielded similar outcomes for all 3 groups. In conclusion, although patients with previous CABG present with more high-risk features, they share similar short- and long-term outcomes with patients without previous CABG, irrespective of their surgical risk. This includes patients who underwent transapical access. TAVI in patients with previous CABG is safe and does not confer a significant risk for adverse outcome.

The general surgery job market: analysis of current demand for general surgeons and their specialized skills.

BACKGROUND: The majority of general surgery residents pursue fellowships. However, the relative demand for general surgical skills vs more specialization is not understood. Our objective was to describe the current job market for general surgeons and compare the skills required by the market with those of graduating trainees. STUDY DESIGN: Positions for board eligible/certified general surgeons in Oregon and Wisconsin from 2011 to 2012 were identified by review of job postings and telephone calls to hospitals, private practice groups, and physician recruiters. Data were gathered on each job to determine if fellowship training or specialized skills were required, preferred, or not requested. Information on resident pursuit of fellowship training was obtained from all residency programs within the represented states. RESULTS: Of 71 general surgery positions available, 34% of positions required fellowship training. Rural positions made up 46% of available jobs. Thirty-five percent of positions were in nonacademic metropolitan settings and 17% were in academic metropolitan settings. Fellowship training was required or preferred for 18%, 28%, and 92% of rural, nonacademic, and academic metropolitan positions, respectively. From 2008 to 2012, 67% of general surgery residents pursued fellowship training. CONCLUSIONS: Most general surgery residents pursue fellowship despite the fact that the majority of available jobs do not require fellowship training. The motivation for fellowship training is unclear, but residency programs should tailor training to the skills needed by the market with the goal of improving access to general surgical services.

Safety and efficacy outcomes of overlapping second-generation everolimus-eluting stents versus first-generation drug-eluting stents.

The safety and efficacy outcomes of stent overlap with second-generation drug-eluting stents (DES) have not been well established. This study aimed to compare the 1-year clinical outcomes of overlapping everolimus-eluting stents (EES) with those of overlapping first-generation DES. This retrospective analysis included 350 patients treated with overlapping EES (169 patients with 237 lesions), sirolimus-eluting stents (SES, 102 patients with 252 lesions), or paclitaxel-eluting stents (PES, 79 patients with 182 lesions). End points were major adverse cardiovascular events (MACE: defined as the composite of death, myocardial infarction, or target lesion revascularization), target vessel revascularization, and definite stent thrombosis at 1 year. During a follow-up of 1 year, overall MACE occurred in 6.5% of EES-, 16.8% of SES-, and 10.1% of PES-treated patients (p = 0.026). Myocardial infarction was lowest in the EES group versus SES and PES groups (0 vs 1.0% vs 2.5%, respectively; p = 0.080), and mortality was similar (3.6% vs 9.0% vs 5.1%, p = 0.162). The EES patients showed a trend toward lower rates of 1-year target lesion revascularization (3.1% vs 8.2% vs 6.5%, p = 0.181) and target vessel revascularization (3.7% vs 9.1% vs 11.7%, p = 0.051) compared with the SES- and PES-treated patients. The cumulative incidence of definite stent thrombosis was lowest in the EES group (0 for EES vs 3.9% for SES vs 2.5% for PES, p = 0.014). In conclusion, stent overlap with EES versus first-generation DES was associated with lower rates of MACE and stent thrombosis. Our results suggest that the use of EES when deploying overlapping stents is effective and safe.

Nuisance and alarming bleeding do not correlate with on-treatment platelet reactivity.

AIMS: We hypothesized that patients with a history of either alarming or nuisance bleeding events, compared to those with no history of bleeding, would have lower levels of on-treatment platelet reactivity (aspirin and a thienopyridine). METHODS AND RESULTS: In total, 42 patients with no bleeding, 34 with nuisance bleeding, and 14 with alarming bleeding underwent platelet reactivity testing 1 month to 1 year after PCI with light transmission aggregometry (LTA 5 and 20 µM adenosine disphosphate [ADP]), vasodilator stimulated phosphoprotein phosphorylation (VASP) and VerifyNow P2Y12. Clinical and demographic characteristics of the 3 groups were generally similar, except that patients with alarming bleeding were less likely to be Caucasian; only 6 patients (6.7%) were taking prasugrel. There was considerable overlap between no bleeding, nuisance bleeding and alarming bleeding groups with respect to on-treatment platelet reactivity. Furthermore, there was no difference in the median platelet reactivity values for all assays. Prevalence of high on-treatment platelet reactivity did not differ among the 3 groups; 32.6% of patients had high on-treatment platelet reactivity as measured by LTA with 5 µM ADP (P=.91); 40.0% as measured by VASP (P=.35); and 35.6% as measured by VerifyNow P2Y12 (P=.61). CONCLUSION: The use of platelet reactivity assays to identify patients on thienopyridine therapy at higher risk of bleeding is an unfounded strategy.

Safety of reloading prasugrel in addition to clopidogrel loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI) commonly receive a loading dose of either clopidogrel or prasugrel, in addition to aspirin. The present study aimed to assess the safety of reloading prasugrel in patients who had initially received a loading dose of clopidogrel compared to prasugrel loading alone. The study included a cohort of 606 consecutive patients with acute coronary syndrome who had received a 60-mg loading dose of prasugrel before PCI. These patients were then categorized into clopidogrel preloading (300 or 600 mg) followed by prasugrel reloading (CP-load group, n = 90) and prasugrel loading only (P-load group, n = 516). Both groups received a 10-mg maintenance dose of prasugrel after PCI. The primary end point was in-hospital Thrombolysis In Myocardial Infarction-defined major bleeding. The secondary end points were other in-hospital bleeding complications and major cardiovascular events. Patients in the CP-load group compared to the P-load group were younger, with lower rates of cardiovascular risk factors. Significantly more patients in the CP-load group presented with biomarker-positive myocardial infarction (80.0% vs 30.6%, p ≤0.001) and cardiogenic shock (5.6% vs 1.4%, p = 0.022). No significant differences (p = NS) were seen in Thrombolysis In Myocardial Infarction major bleeding (2.6% vs 2.8%), Thrombolysis In Myocardial Infarction major or minor bleeding (12.2% vs 7.0%), the need for blood transfusion (2.6% vs 2.1%), and vascular complications (1.3% vs 2.0%) between groups. The CP-load group experienced more in-hospital major adverse cardiac events (5.6% vs 1.6%, p = 0.031), urgent coronary artery bypass grafting (3.3% vs 0.2%, p = 0.011), and longer hospital and intensive care unit stays. In conclusion, preloading with clopidogrel should not be prohibitive to reloading with prasugrel in patients presenting with acute coronary syndrome and undergoing PCI with respect to bleeding and vascular complications.

Safety and efficacy of prasugrel use in patients undergoing percutaneous coronary intervention and anticoagulated with bivalirudin.

The randomized TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38 trial compared prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). Patients treated with prasugrel had fewer ischemic events but more procedure-related bleeding. In the present study, we aimed to determine the effect of bivalirudin on bleeding in patients treated with prasugrel. A total of 692 patients with consecutive acute coronary syndrome underwent PCI with stent implantation and were anticoagulated with bivalirudin. The patients were divided into 2 groups according to the antiplatelet regimen (clopidogrel or prasugrel) chosen during or just after PCI. The bleeding complications during hospitalization were tabulated. Ischemic events were analyzed during hospitalization and at 30 days. Prasugrel was used in 96 patients (13.9%) and clopidogrel in 596 (86.1%). The clinical and procedural characteristics were similar, although the clopidogrel patients more often reported systemic hypertension (p = 0.01), previous PCI (p <0.001), and chronic renal insufficiency (p = 0.05). During hospitalization, the bleeding and ischemic complication rates were similar and low in both groups (major in-hospital complications 4.2% for clopidogrel vs 2.1% for prasugrel, p = 0.6; Thrombolysis In Myocardial Infarction major bleeding 2.5% vs 2.1%, p = 1.00; Thrombolysis In Myocardial Infarction minor bleeding 4.2% vs 5.2%, p = 0.6). At 30 days, no differences were found in ischemic events between both groups (target vessel revascularization/major adverse cardiac events 5.4% vs 2.1%, p = 0.2). In conclusion, prasugrel, when given after bivalirudin as the intraprocedural antithrombin agent for patients with acute coronary syndrome undergoing PCI, is as safe and effective as clopidogrel.

Safety and efficacy of the XIENCE V everolimus-eluting stent compared to first-generation drug-eluting stents in contemporary clinical practice.

Data from randomized clinical trials have shown the safety and efficacy of the XIENCE V in selected populations. However, limited data are available comparing the XIENCE V to the first-generation CYPHER sirolimus-eluting stent. This study aimed to assess the long-term safety and clinical efficacy of the XIENCE V everolimus-eluting stent compared to first-generation stents in an unselected patient population. This retrospective analysis included 6,069 patients treated with CYPHER, TAXUS, and XIENCE stents from 2003 to 2009 at our institution. The patients were followed up for ≥1 year after the index procedure. The baseline characteristics were generally comparable among the 3 groups, with the exception of a significantly greater prevalence of diabetes mellitus, systemic hypertension, and a history of angioplasty and coronary bypass surgery among the XIENCE patients. The XIENCE patients also had a twofold greater rate of type C lesions. One-year follow-up data were available for 82% of the patients. The 1-year major adverse cardiovascular events rate was 9.3% for the XIENCE stent versus 9.8% for the CYPHER stent and 11.5% for the TAXUS stent (p = 0.11). Mortality was lower in the XIENCE group than in the CYPHER and TAXUS groups (3.6% vs 4.9% vs 7.2%, respectively, p <0.001), and target lesion revascularization was similar (5.9% vs 5.2% vs 5.6%, respectively; p = 0.34). Stent thrombosis was lower in the XIENCE patients (0.2% vs 1.2% vs 0.7%, p = 0.007). In conclusion, in a contemporary United States clinical practice with an unselected patient population, use of the XIENCE V stent was associated with an improved safety profile and reduction of all-cause mortality and stent thrombosis compared to first-generation drug-eluting stents. The XIENCE V failed to demonstrate superiority for overall major adverse cardiovascular events, Q-wave myocardial infarction, and revascularization rates.

Clinical outcomes and treatment after drug-eluting stent failure: the absence of traditional risk factors for in-stent restenosis.

BACKGROUND: The optimal percutaneous treatment of drug-eluting stent (DES) in-stent restenosis (ISR) and the correlates for recurrent DES ISR remain unclear. METHODS AND RESULTS: From 2003 to 2008, 563 patients presenting with recurrent symptoms of ischemia and angiographic ISR after DES implantation were included. Of these, 327 were treated with re-DES (58.1%), 132 underwent vascular brachytherapy (23.4%), and 104 were treated with conventional balloon angioplasty (18.5%). Variables associated with target lesion revascularization at 1 year were explored by individual proportional hazard models. This population presents a high prevalence of comorbidities, including diabetes (43.7%), previous myocardial infarction (MI) (45.8%), coronary bypass graft surgery (39.2%), chronic renal failure (18.8%), and heart failure (17.3%). Baseline clinical characteristics were balanced among the 3 groups; however, patients undergoing vascular brachytherapy presented with more complex lesions and a higher prevalence of prior stent/vascular brachytherapy failure than did the rest of the population. The overall incidence of recurrent DES failure at 1-year follow-up was 12.2%, which was similar among the 3 groups (P=0.41). The rate of the composite end point (death, Q-wave-MI and target lesion revascularization) at 1-year follow-up was 14.1% for re-DES, 17.5% for vascular brachytherapy, and 18.0% for conventional balloon angioplasty (P=0.57). After univariable analysis tested the traditional known covariates related to ISR, none of them were associated with repeat target lesion revascularization. CONCLUSIONS: Recurrence of ISR after DES treatment failure is neither infrequent nor benign, and optimal therapy remains unclear and challenging. Given the absence of traditional risk factors for ISR in this population, further research is required to elucidate both the correlates involved in DES ISR and the optimal treatment for this condition.

Correlation between light transmission aggregometry, VerifyNow P2Y12, and VASP-P platelet reactivity assays following percutaneous coronary intervention.

BACKGROUND: High on-treatment platelet reactivity is an established risk factor for adverse cardiac events in patients taking clopidogrel following percutaneous coronary intervention (PCI). METHODS: Two hundred patients underwent platelet reactivity testing with VerifyNow P2Y12, vasodilator-stimulated phosphoprotein phosphorylation (VASP), and light transmission aggregometry (LTA) with both 5 and 20 µM of adenosine diphosphate (ADP) following PCI. High on-treatment platelet reactivity was defined as a maximum platelet aggregation ≥46% for LTA ADP 5 µM or ≥60% for 20 µM; platelet reactivity index (PRI) ≥50% for VASP; and platelet reactivity units ≥235 for VerifyNow. Correlation between assays was tested using Spearman coefficients (ρ); agreement among tests in regards to high on-treatment platelet reactivity was evaluated with Kappa statistics (κ). RESULTS: All Spearman correlations had P values <0.001, although ρ ranged from 0.60-0.86. The incidence of high on-treatment platelet reactivity was 39.3% with VASP, 27.3% with VerifyNow, 23.1% with LTA ADP 5 µM, and 16.2% with LTA ADP 20 µM. The strongest correlation was between LTA ADP 5 µM and LTA ADP 20 µM (κ= 0.53, 95% CI 0.37-0.68); the weakest was between VASP and LTA ADP 5 µM (κ= 0.33, 95% CI 0.19-0.47). Overall, the level of agreement between assays was in the moderate to poor range. CONCLUSION: Despite evidence that the most commonly used tests are correlated, agreement among tests is modest at best and demonstrates they are not interchangeable.

Comparison between Society of Thoracic Surgeons score and logistic EuroSCORE for predicting mortality in patients referred for transcatheter aortic valve implantation.

BACKGROUND: The primary inclusion criteria from both the Society of Thoracic Surgeons (STS) score and the logistic EuroSCORE are currently used to identify high-risk and inoperable patients eligible for transcatheter aortic valve implantation (TAVI). We aimed to examine the correlation between STS and logistic EuroSCOREs and their performance characteristics in patients referred for TAVI. METHODS: The study cohort consisted of 718 high-risk patients with severe aortic stenosis who were considered for participation in a TAVI clinical trial. The performance of the STS and logistic EuroSCOREs was evaluated in three groups: (a) medical management or balloon aortic valvuloplasty (BAV), 474 (66%); (b) 133 patients (18.5%) with surgical aortic valve replacement (AVR); (c) 111 (15.4%) with TAVI. The mean age was 81.8 ± 8.1 years, and 394 (54.8%) were female. RESULTS: The mean STS score was 11.5 ± 6.1, and the mean logistic EuroSCORE was 39.7 ± 23.0. Pearson correlation coefficient showed moderate correlation between the STS and logistic EuroSCOREs (r = 0.61, P < .001). At a median follow-up of 190 days (range, 67-476), 282 patients (39.2%) died. The STS and logistic EuroSCOREs were both higher in patients who died as compared to those in survivors (13.1 ± 6.2 vs.10.0 ± 5.8 and 43.4 ± 23.1 vs. 37.5 ± 22, respectively; P < .001). The observed and predicted 30-day mortality rates in the medical/BAV group were 10.1% observed, 12.3% by STS and 43.1% by logistic EuroSCORE. In the surgical AVR group, the rates were 12.8% observed, 8.4% by STS and 25.6% by logistic EuroSCORE. In the TAVI group, the rates were 11.7% observed, 11.8% by STS and 41.2% by logistic EuroSCORE. The odds ratio (OR) for 30-day mortality in the medical/BAV group was 1.05 (P = .01) with STS and 1.003 (P = .7) with logistic EuroSCORE. In the surgical AVR group, the OR was 1.09 (P = .07) with STS and 1.007 (P = .6) with logistic EuroSCORE. In the TAVI group, the OR was 1.14 (P = .03) with STS and 1.03 (P = .04) with logistic EuroSCORE. CONCLUSION: In high-risk patients with severe aortic stenosis, STS score is superior to the logistic EuroSCORE in predicting mortality. Clinical judgment should play a major role in the selection of patients with severe aortic stenosis for the different therapeutic options.

Relation of body mass index to on-treatment (clopidogrel + aspirin) platelet reactivity.

Previous research has suggested that obesity is associated with increased high on-treatment platelet reactivity. We therefore tested platelet reactivity in 251 patients with VerifyNow P2Y12, vasodilator-stimulated phosphoprotein phosphorylation, and light transmission aggregometry with adenosine diphosphate 5 and 20 µM 6 to 24 hours after percutaneous coronary intervention. High on-treatment platelet reactivity was defined as a maximum platelet aggregation ≥46% for light transmission aggregometry with adenosine diphosphate 5 µM or ≥60% for 20 µM, platelet reactivity index ≥50% for vasodilator-stimulated phosphoprotein phosphorylation, and P2Y12 reaction units ≥235 for VerifyNow. The relation between body mass index (BMI) and platelet reactivity values was examined with Spearman coefficients; BMI and high on-treatment platelet reactivity were assessed with Student's t test. Multivariable logistic regression for high on-treatment platelet reactivity was also performed. Average BMI was 30.3 ± 5.9 kg/m² and 44% of patients had a BMI ≥30 kg/m². Overall there was very poor correlation between BMI and on-treatment platelet reactivity, with Spearman coefficients ranging from 0.08 to 0.10. BMI was also not associated with the various definitions of high on-treatment platelet reactivity. Multivariable logistic regressions showed no association between BMI and high on-treatment platelet reactivity. In conclusion, and contrary to previous reports, we found no association whatsoever between BMI and on-treatment platelet reactivity as quantified by a variety of platelet function tests.

Outcomes of coronary arterial perforations during percutaneous coronary intervention with bivalirudin anticoagulation.

Coronary perforation (CP) is a rare but catastrophic event that may be influenced by the procedural anticoagulation regimen. This study compared the consequences of CP in patients who underwent anticoagulation with bivalirudin (BIV; a nonreversible direct thrombin inhibitor with a shorter 1/2-life than heparin) to those in patients who underwent anticoagulation with heparin (HEP) at time of CP. Patients with CP were identified from 33,613 procedures available in our institutional angioplasty registry. The outcome of this group was compared based on anticoagulation regimen (BIV vs HEP). The primary end point for this analysis was the composite of in-hospital death, cardiac tamponade, or emergency cardiac surgery. Overall a cohort of 69 patients (0.2%) with CP was identified. BIV was the intraprocedural anticoagulant in 41 patients, whereas HEP was used in 28. Baseline characteristics were comparable between groups except for a higher frequency of systemic hypertension and hypercholesterolemia in the BIV group. Procedural characteristics were also similar including lesion complexity and perforation severity. Nearly 1/2 of CPs in each group was managed with prolonged balloon inflation alone. Protamine was used in 46% of HEP-treated patients. Covered stents tended to be used more frequently in the BIV group (p = 0.061). The primary composite end point was similar between groups (odds ratio 1.42, 95% confidence interval 0.47 to 4.29, p = 0.53). However, there was a lower rate of cardiac surgery requirement in BIV-treated patients (p = 0.037). In conclusion, our study suggests that choice of procedural anticoagulant agent does not influence outcome when CP occurs. Therefore, use of BIV should not be discouraged in patients undergoing high-risk intervention for perforations.

Integrilin in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: The adjunctive use of eptifibatide in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) remains controversial. We therefore set out to determine the safety and efficacy of eptifibatide in this population. METHODS: The study comprised 857 consecutive patients who underwent primary PCI for STEMI at the Washington Hospital Center. Three hundred eighteen patients also received adjunctive therapy with eptifibatide. Patients who had received thrombolysis prior to undergoing cardiac catheterization were excluded. The primary end-point was all-cause mortality and the composite of all-cause mortality or Q-wave MI. The primary safety end-point was the rate of thrombolysis in myocardial infarction (TIMI) major bleeding. RESULTS: The eptifibatide group was younger, had a higher body mass index, and a lower proportion of patients with systemic hypertension, diabetes mellitus, previous history of ischemic heart disease, coronary revascularization, and congestive heart failure. This cohort also used bivalirudin less often (23.3% vs. 72%; P < 0.001). Following multivariable analysis, the eptifibatide group had a significantly lower rate of all-cause mortality (hazard ratio 0.55; 95% confidence interval 0.34-0.89; P = 0.01) and the composite of all-cause mortality or Q-wave MI (hazard ratio 0.59; 95% confidence interval 0.37-0.95; P = 0.03) at 6 months. The rate of TIMI major bleeding was similar in both groups (hazard ratio 0.54; 95% confidence interval 0.25-1.17; P = 0.12). CONCLUSION: The adjunctive use of eptifibatide in patients presenting with STEMI may be associated with improved clinical outcomes. (J Interven Cardiol 2011;24:351-356).

Effects of optimal medical treatment with or without coronary revascularization on angina and subsequent revascularizations in patients with type 2 diabetes mellitus and stable ischemic heart disease.

BACKGROUND: In the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, an initial strategy of coronary revascularization and optimal medical treatment (REV) compared with an initial optimal medical treatment with the option of subsequent revascularization (MED) did not reduce all-cause mortality or the composite of cardiovascular death, myocardial infarction, and stroke in patients with type 2 diabetes mellitus and stable ischemic heart disease. In the same population, we tested whether the REV strategy was superior to the MED strategy in preventing worsening and new angina and subsequent coronary revascularizations. METHODS AND RESULTS: Among the 2364 men and women (mean age, 62.4 years) with type 2 diabetes mellitus, documented coronary artery disease, and myocardial ischemia, 1191 were randomized to the MED and 1173 to the REV strategy preselected in the percutaneous coronary intervention (796) and coronary artery bypass graft (377) strata. Compared with the MED strategy, the REV strategy at the 3-year follow-up had a lower rate of worsening angina (8% versus 13%; P<0.001), new angina (37% versus 51%; P=0.001), and subsequent coronary revascularizations (18% versus 33%; P<0.001) and a higher rate of angina-free status (66% versus 58%; P=0.003). The coronary artery bypass graft stratum patients were at higher risk than those in the percutaneous coronary intervention stratum, and had the greatest benefits from REV. CONCLUSIONS: In these patients, the REV strategy reduced the occurrence of worsening angina, new angina, and subsequent coronary revascularizations more than the MED strategy. The symptomatic benefits were observed particularly for high-risk patients. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00006305.

Impact of smoking on acute phase outcomes of myocardial infarction.

OBJECTIVES: Previous studies have found an apparent paradox in smokers: acute phase outcomes after an acute myocardial infarction are superior to those of nonsmokers. Furthermore, it is reported that smoking has an impact on the metabolism of clopidogrel. This study aimed to examine whether this paradoxical finding exists in patients who undergo drug-eluting stent implantation and are treated with clopidogrel. METHODS: From April 2003 to June 2010, 1424 consecutive patients with acute myocardial infarction who underwent primary or rescue percutaneous coronary intervention with drug-eluting stent and clopidogrel were enrolled. They were divided into three groups: current smokers (n = 486); previous smokers (n = 349); and nonsmokers (n = 589). The primary end point was a composite of 30-day, all-cause death, nonfatal myocardial infarction, or definite stent thrombosis. RESULTS: Compared with nonsmokers, current smokers were younger (P < 0.001) and more often men (P < 0.001). They had larger myocardial infarctions than did nonsmokers [maximum troponin I, 8.9 (2.4, 38.4) vs. 6.8 (1.4, 30.1) ng/ml, P = 0.01]. Current smokers less frequently met the primary end point than did nonsmokers (2.9 vs. 6.1%, P = 0.01). However, after adjustment for baseline and angiographic characteristics, the beneficial effect of smoking was no longer seen (odds ratio 1.35, confidence interval: 0.53-3.44, P = 0.5). CONCLUSION: A beneficial effect of smoking ('smoker's paradox') in the unadjusted primary end point continues to be present; however, after adjustment for differences in baseline characteristics, no benefit was detectable.

Outcomes of patients with acute myocardial infarction from a saphenous vein graft culprit undergoing percutaneous coronary intervention.

OBJECTIVES: We sought to describe characteristics of patients presenting with an acute MI from a SVG culprit, compared with a native culprit. BACKGROUND: Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) results in worse outcomes than native vessel PCI, but outcomes of such patients with acute myocardial infarction (MI) setting are not well-described. METHODS: Patients presenting with ST-elevation or non-ST-elevation MI undergoing PCI from 2000 to 2010 were retrospectively analyzed to identify the culprit as a SVG vs. native vessel. Multiple linear regression was used to identify predictors of peak troponin-I level. Cox proportional hazards regression was used to identify predictors of 30-day mortality and 1-year major adverse cardiac events (MACE). RESULTS: 192 patients underwent PCI for a SVG culprit, compared with 4,001 with a native culprit. After multivariable adjustment, SVG culprit remained significantly associated with lower levels of the logarithm of the peak troponin (ß = -0.17, SE = 0.07, P = 0.02). The likelihood of MACE was higher in SVG vs. native culprits in patients with small to modest troponin elevations. Patients with a SVG culprit also suffered higher unadjusted rates of mortality at 30 days (14.3% vs. 8.4%, P = 0.03) and MACE at 1 year (36.8% vs. 24.5%, P = 0.005); a modest effect upon mortality and MACE remained after multivariable adjustment. CONCLUSION: Even minimal elevations of troponin in patients with a SVG culprit may portend a poorer prognosis than in patients with a native culprit. The risk of PCI in this setting is driven by mortality and arises from both substantial comorbidities and the SVG itself.

Vascular responses to the multiple overlapped paclitaxel-eluting stents for the treatment of bare-metal in-stent restenotic lesions: angiographic and intravascular ultrasound analysis from the TAXUS-V ISR trial.

BACKGROUND: Although effective coverage of coronary diffuse in-stent restenosis (ISR) lesions has warranted the use of multiple drug-eluting stents, the vessel response to paclitaxel-eluting stent (PES) overlap is not fully understood. METHODS AND MATERIALS: In the TAXUS-V ISR, i.e., comparing PES versus brachytherapy for the treatment of bare-metal ISR, angiographic analyses at 9-month follow-up were available in 184 ISR lesions treated with PES. RESULTS: In-stent late loss in entire stented segment of multiple PES (n=50) was 0.45+/-0.48 mm, whereas that of single PES (n=134) was 0.3+/-0.47 mm, P=.06. No aneurysm was observed at overlapping PES segments at 9 months. Stent thrombosis up to 9 months was observed in one in each group (single PES, 0.7% vs. multiple PES, 1.8%; P=.47). In a subset of 30 patients, volumetric intravascular ultrasound analysis demonstrated that in-stent net volume obstruction was 12.3+/-12.4 in single PES (n=20) and 14.9+/-9.8 in multiple PES (n=10), P=.60. The changes of vessel and lumen at the overlapping PES segment were similar to those of the adjacent 5-mm segments (Deltaminimum lumen area, mm(2): -1.2+/-1.0, -1.1+/-1.1, -0.8+/-0.9, P=.48; Deltavessel volume, mm(3)/mm: -0.2+/-1.4, 0.1+/-1.7, 0.3+/-1.3, P=.37; proximal, overlap, distal segment, respectively). There was no late incomplete stent apposition at overlapping PES segments. CONCLUSIONS: No in vivo evidence of adverse local vessel response at the site of overlapping PES for the treatment of bare-metal ISR has been demonstrated.

Utility of radiologic review for noncardiac findings on multislice computed tomography in patients with severe aortic stenosis evaluated for transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) without replacement requires precise knowledge of the anatomic dimensions and physical characteristics of the peripheral vasculature and aortic valve annulus at the insertion of the aortic valve leaflet and root at the level of the sinus of Valsalva. Multislice computed tomography (CT) allows detailed and precise assessment of the anatomic variables. Noncardiovascular structures are also amenable to assessment by CT. Of the 394 patients screened for TAVI, 259 (65.7%) had non-contrast CT to evaluate chest anatomy and contrast CT to evaluate ilio-femoral anatomy. Significant noncardiac findings were defined as those requiring immediate evaluation or intervention or additional clinical or radiologic follow-up. Noncardiovascular findings known before CT were not included. Of the 259 patients, 105 (40.5%) were men. The mean age was 82.3 +/- 8.1 years. New, significant noncardiovascular findings were found in 89 (34.3%) and malignancy in 11 (4.2%) patients. Insignificant noncardiovascular findings were identified in 222 patients (85.7%). Signs of fluid retention were noted on CT in 105 patients (40.5%), with pleural effusion in 100 (38.6%), ascites in 17 (6.5%), and pericardial effusion in 14 (5.4%). Important peripheral vascular disease was found in 98 patients (37.8%), resulting in exclusion of 49 (19.1%) from TAVI using the transfemoral approach. An aortic aneurysm was found in 10 patients (3.8%) and a "porcelain" aorta (heavily calcified ascending aorta) in 19 (7.3%). In conclusion, malignancy and other noncardiovascular abnormalities are often found in patients who undergo CT for evaluation for TAVI. Populations must be meticulously examined to ensure that important findings are not missed.

Meta-analysis and imputation refines the association of 15q25 with smoking quantity.

Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.