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Background: In patients with stable coronary artery disease, it remains unclear whether an initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events.Methods: We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6).Results: There were 211 primary events in the PCI group and 202 events in the medical-therapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P=0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P=0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P=0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P=0.33).Conclusions: As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. (ClinicalTrials.gov number, NCT00007657 [ClinicalTrials.gov].). [ABSTRACT FROM AUTHOR]

Background: Thoracic epidural analgesia (TEA) and liposomal bupivacaine (LB) are two methods used for postoperative pain control after thoracic surgery. Some studies have compared LB to standard bupivacaine. However, data comparing the outcomes of LB to TEA after minimally invasive lung resection is limited. Therefore, the objective of our study was to compare postoperative pain, opioid usage, and outcomes between patients who received TEA vs . LB., Methods: We conducted a retrospective chart review of patients who underwent minimally invasive lung resections over an 8-month period. Intraoperatively, patients received either LB under direct vision or a TEA. Pain scores were obtained in the post-anesthesia care unit (PACU) and at 12, 24, and 48 hours postoperatively. Morphine milligram equivalents (MMEs) were calculated at 24 and 48 hours postoperatively. Postoperative outcomes were then compared between groups., Results: In total, 391 patients underwent minimally invasive lung resection: 236 (60%) wedge resections, 51 (13%) segmentectomies, and 104 (27%) lobectomies. Of these, 326 (83%) received LB intraoperatively. Fewer patients in the LB group experienced postoperative complications (18% vs . 34%, P=0.004). LB patients also had lower median pain scores at 24 (P=0.03) and 48 hours (P=0.001) postoperatively. There was no difference in MMEs at 24 hours (P=0.49). However, at 48 hours, patients who received LB required less narcotics (P=0.02). Median hospital length of stay (LOS) was significantly shorter in patients who received LB (2 vs . 4 days, P<0.001). On multivariable analysis, increasing age, postoperative complications, and use of TEA were independently associated with a longer hospital LOS., Conclusions: Compared to TEA, LB intercostal block placed under direct vision reduced morphine use 48 hours after thoracic surgery. It was also associated with fewer postoperative complications and shorter median hospital LOS. LB is a good alternative to TEA for pain management after minimally invasive lung resection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1405/coif). A.S. is personally funded by the John D. Mitchell Fellowship. R.B. has research grants and clinical trials support from MedGenome, Roche, Verastem, Genentech, Merck, Bicycles therapeutics, Serum, Intuitive, Siemens, NIH and DOD. Additionally, he has four patents through BWH (no royalties to date) and equity in a new start-up company, Navigation Sciences. These disclosures or conflicts of interest are not relevant to this manuscript. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Introduction: Hyperthermic intraoperative cisplatin (HIOC) is associated with acute kidney injury (AKI). Administration of high-dose magnesium attenuates cisplatin-induced AKI (CP-AKI) in animal models but has not been rigorously examined in humans., Methods: We tested the feasibility and safety of different doses of magnesium in mesothelioma patients receiving HIOC. In Pilot Study 1, we administered a 36-h continuous infusion of magnesium at 0.5 g/h, targeting serum magnesium levels between 3 and 4.8 mg/dL. In Pilot Study 2A, we administered a 6 g bolus followed by an infusion starting at 2 g/h, titrated to achieve levels between 4 and 6 mg/dL. We eliminated the bolus in Pilot Study 2B., Results: In Pilot Study 1, all five patients enrolled completed the study; however, median postoperative Mg levels were only 2.4 mg/dL. In Pilot Study 2A, two of four patients (50%) were withdrawn due to bradycardia during the bolus. In Pilot Study 2B, two patients completed the study whereas two developed postoperative bradycardia attributed to the magnesium., Conclusions: A 0.5 g/h infusion for 36 h did not achieve therapeutic magnesium levels, while an infusion at 2 g/h was associated with bradycardia. These studies informed the design of a randomized clinical trial testing whether intravenously Mg attenuates HIOC-associated AKI., (© 2023 Wiley Periodicals LLC.)

Randomized clinical trials have not demonstrated a survival benefit with percutaneous coronary intervention in stable ischemic heart disease (SIHD). We evaluated the generalizability of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial findings to the broader population of veterans with SIHD. Veterans who underwent coronary angiography between 2005 and 2013 for SIHD were identified from the Veterans Affairs Clinical Assessment, Reporting and Tracking Program (VA CART). Patient-level comparisons were made between patients from VA CART who met the eligibility criteria for COURAGE and veterans enrolled in COURAGE between 1999 and 2004. All-cause mortality over long-term follow-up was assessed using Cox proportional hazards models. COURAGE-eligible patients from VA CART (n = 59,758) were older, had a higher body mass index, a greater prevalence of co-morbidities, but fewer diseased vessels on index coronary angiography, and were less likely to be on optimal medical therapy at baseline and on 1-year follow-up compared with VA COURAGE participants (n = 968). Patients from VA CART (median follow-up 6.5 years) had higher all-cause mortality (adjusted hazard ratio [aHR] 1.98 [1.61 to 2.43]) than participants from VA COURAGE (median follow-up: 4.6 years). Risks of mortality were greater in the 56.4% patients from CART who were medically managed (aHR 1.94 [1.49 to 2.53]) and in the 43.6% who underwent percutaneous coronary intervention (aHR 1.99 [1.45 to 2.74]), compared with their respective VA COURAGE arms. In conclusion, in this noncontemporaneous patient-level analysis, veterans in the randomized COURAGE trial had more favorable outcomes than the population of veterans with SIHD at large., Competing Interests: Disclosures Dr. Smilowitz serves on an advisory board for Abbott Vascular. Dr. Shah serves on an advisory board for Philips Volcano and Terumo Medical. The remaining authors have no conflicts of interest to declare., (Published by Elsevier Inc.)

Background: Central airway occlusion is a feared complication of general anesthesia in patients with mediastinal masses. Maintenance of spontaneous ventilation and avoiding neuromuscular blockade are recommended to reduce this risk. Physiologic arguments supporting these recommendations are controversial and direct evidence is lacking. The authors hypothesized that, in adult patients with moderate to severe mediastinal mass-mediated tracheobronchial compression, anesthetic interventions including positive pressure ventilation and neuromuscular blockade could be instituted without compromising central airway patency., Methods: Seventeen adult patients with large mediastinal masses requiring general anesthesia underwent awake intubation followed by continuous video bronchoscopy recordings of the compromised portion of the airway during staged induction. Assessments of changes in anterior-posterior airway diameter relative to baseline (awake, spontaneous ventilation) were performed using the following patency scores: unchanged = 0; 25 to 50% larger = +1; more than 50% larger = +2; 25 to 50% smaller = -1; more than 50% smaller = -2. Assessments were made by seven experienced bronchoscopists in side-by-side blinded and scrambled comparisons between (1) baseline awake, spontaneous breathing; (2) anesthetized with spontaneous ventilation; (3) anesthetized with positive pressure ventilation; and (4) anesthetized with positive pressure ventilation and neuromuscular blockade. Tidal volumes, respiratory rate, and inspiratory/expiratory ratio were similar between phases., Results: No significant change from baseline was observed in the mean airway patency scores after the induction of general anesthesia (0 [95% CI, 0 to 0]; P = 0.953). The mean airway patency score increased with the addition of positive pressure ventilation (0 [95% CI, 0 to 1]; P = 0.024) and neuromuscular blockade (1 [95% CI, 0 to 1]; P < 0.001). No patient suffered airway collapse or difficult ventilation during any anesthetic phase., Conclusions: These observations suggest a need to reassess prevailing assumptions regarding positive pressure ventilation and/or paralysis and mediastinal mass-mediated airway collapse, but do not prove that conventional (nonstaged) inductions are safe for such patients., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Morvan syndrome (MvS) is a rare acquired paraneoplastic autoimmune neuromyotonia with central and autonomic nervous system involvement that has been incompletely described in the literature. We describe the successful administration of general anesthesia for robotic thymectomy to an MvS patient with severe encephalopathy, cardiac dysautonomia, and peripheral nerve hyperexcitation. Importantly, thymus removal provided effective source control with eventual resolution of MvS symptoms. MvS is briefly reviewed and novel observations are described of related interactions between nondepolarizing neuromuscular blockade (NDNMB) and bispectral index (BIS)., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Background: Elevated low-density lipoprotein cholesterol (LDL-C) is associated with increased cardiovascular events, especially in high-risk populations., Objectives: This study sought to evaluate the influence of LDL-C on the incidence of cardiovascular events either following a coronary revascularization procedure (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or optimal medical therapy alone in patients with established coronary heart disease and type 2 diabetes (T2DM)., Methods: Patient-level pooled analysis of 3 randomized clinical trials was undertaken. Patients with T2DM were categorized according to the levels of LDL-C at 1 year following randomization. The primary endpoint was major adverse cardiac or cerebrovascular events ([MACCE] the composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke)., Results: A total of 4,050 patients were followed for a median of 3.9 years after the index 1-year assessment. Patients whose 1-year LDL-C remained ≥100 mg/dl experienced higher 4-year cumulative risk of MACCE (17.2% vs. 13.3% vs. 13.1% for LDL-C between 70 and <100 mg/dl and LDL-C <70 mg/dl, respectively; p = 0.016). When compared with optimal medical therapy alone, patients with PCI experienced a MACCE reduction only if 1-year LDL-C was <70 mg/dl (hazard ratio: 0.61; 95% confidence interval: 0.40 to 0.91; p = 0.016), whereas CABG was associated with improved outcomes across all 1-year LDL-C strata. In patients with 1-year LDL-C ≥70 mg/dl, patients undergoing CABG had significantly lower MACCE rates as compared with PCI., Conclusions: In patients with coronary heart disease with T2DM, lower LDL-C at 1 year is associated with improved long-term MACCE outcome in those eligible for either PCI or CABG. When compared with optimal medical therapy alone, PCI was associated with MACCE reductions only in those who achieved an LDL-C <70 mg/dl., Competing Interests: Author Relationship With Industry Funded by a research grant from Gilead Science, the National Heart, Lung, and Blood Institute, U.S. Department of Veterans Affairs, and the Canadian Institutes of Health Research. Dr. Farkouh has received research grants from Amgen, Novo Nordisk, and Novartis. Dr. Mancini has received grants, honoraria, Advisory Board, and speaking fees from Sanofi, Amgen, Boehringer Ingelheim, and Novo Nordisk; and has served on the Advisory Board for Esperion. Dr. Bittner has contracts between University of Alabama at Birmingham and the following sponsors: Amgen as an investigator on pharmacoepidemiologic analyses, AstraZeneca as National Coordinator for the STRENGTH trial, Bayer as site principal investigator for the COMPASS trial, DalCor as National Coordinator for the DalGene Trial, Esperion as National Coordinator for the CLEAR Outcomes Trial, Sanofi as steering committee member for ODYSSEY OUTCOMES trial, The Medicines Company as site principal investigator for the ORION IV Trial, and Sanofi for attending Advisory Boards to present ODYSSEY OUTCOMES data. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020. Published by Elsevier Inc.)

Several risk scores in acute coronary syndromes are available, but few models exist for stable coronary artery disease to guide decision-making and prognosis. A multivariate model was developed using 23 baseline candidate variables from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Therapy EvaluationTrial (n = 2,287 patients). Discrimination of the model was evaluated by the concordance c-index. The procedure was validated using 100 random half samples. We identified 9 independent predictors of death or myocardial infarction (MI) during a 5-year follow-up. The following predictors and points contributing to the risk score were: heart failure (3), number of diseased coronary arteries (1 for each vessel), diabetes (1), age (1 for each 15 years ≥ age 45), previous revascularization (1), current smoking (1), female (1), previous MI (1), and high-density lipoprotein cholesterol (1: 31 to 40 mg/dL; 2: <30 mg/dL). The risk tool had a potential range from 0 to 15, corresponding to 5-year event rates of 5.8% to 56%. C-indices ranged from 0.67 for the full data set to 0.62 for the validating subsamples. Respective observed versus predicted 5-year event rates for 3 predefined risk strata revealed: 30% had a low-risk score of 0 to 3 (9.3% vs 9.3%, or 1.9%/year); 59% had an intermediate-risk score of 4-6 (18.0% vs 18.1%, or 3.6%/year); and 11% had a high-risk score of 7-11 (36% vs 36.5%, or 7.2%/year). This stable coronary artery disease risk score permitted a prognostic assessment of 5-year probability of death or MI with an approximate 4-fold range in event rates from the lowest (9.3%) to the highest (36%) terciles, thus enabling better clinical practice decisions that allow physicians to tailor the intensity of treatment to the level of risk., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: We developed a novel approach for localization and resection of lung nodules, using image-guided video-assisted thoracoscopic surgery (iVATS). We report our experience of translating iVATS into clinical care., Methods: Methodology and workflow for iVATS developed as part of the Phase I/II trial were used to train surgeons, radiologists, anesthesiologists, and radiology technologists. Radiation dose, time from induction to incision, placement of T-bar to incision and incision to closure, hospital stay, and complication rates were recorded., Results: Fifty patients underwent iVATS for resection of 54 nodules in a clinical hybrid operating room (OR) by six surgeons. Fifty-two (97%) nodules were successfully resected. Forty-two (84%) patients underwent wedge resection, four (7%) lobectomies, and two (4%) segmentectomy all with lymph node dissection. Median time from induction to incision was 89 minutes (range: 13-256 minutes); T-bar placement was 14 minutes (10-29 minutes); and incision to closure, 107 minutes (41-302 minutes). Average and total procedure radiation dose were: median = 6 mSieverts (range: 2.9-35 mSieverts). No deaths were reported and median length of stay was 3 days (range: 1-12 days)., Conclusions: Translation of iVATS into clinical practice has been initiated using a safe step-wise process, combining intraoperative C-arm computed tomography scanning and thoracoscopic surgery in a hybrid OR., (© 2020 The Authors. Journal of Surgical Oncology published by Wiley Periodicals, Inc.)

Background: Current quality guidelines recommend the removal of urinary catheters on or before postoperative day two, to prevent catheter-associated urinary tract infections (CAUTI). The goal of this study was to evaluate the impact urinary catheter removal on the need for urinary recatheterization (UR) of patients with epidural anesthesia undergoing thoracic surgery., Materials and Methods: All patients undergoing thoracic surgery between November 4 th , 2017 and January 9 th , 2018 who had a urinary catheter placed at the time of intervention were prospectively evaluated. Patient characteristics including: history of benign prostatic hyperplasia (BPH), catheter related variables and rates of UR were collected through chart review and daily visits to the wards. BPH was defined as history of transurethral resection of the prostate or treatment with selective α 1 -adrenergic receptor antagonists., Results: Over a two-month period 267 patients were included, 124 (46%) were male. Epidural catheters were placed in 88 (33%) patients. Median duration of urinary catheters for the cohort was 1 day (0 days - 18 days), and it was significantly higher in patients with epidural anesthesia (Table 1). Overall 20 (7%) patients required UR. On initial analysis, there was no statistical difference in the rate of UR among patients with and without epidural catheters [9/88 (10%) vs 11/179 (6%), p=0.23). The rate of UR was higher in males than in females (14/124 (11%) vs 6/143 (4%), p=0.03). Fifteen (12%) patients had a diagnosis of BPH. The rate of UR was three-times higher in this group than in those without BPH [4/15 (27%) vs 10/109 (9%) p=0.05]. Four (1%) patients developed a CAUTI during follow-up, and the rate of CAUTI was not different between those with and without epidural catheters., Conclusion: Urinary catheters in patients with thoracic epidural anesthesia can be safely removed, as evidenced by low reinsertion and infection rates. Removal of urinary catheters in patients with a history of BPH should be carefully evaluated, as over 1/4 will require urinary recatheterization in this subgroup. Further study of this group is needed to avoid unnecessary patient discomfort associated with recatheterization.

Background: The importance of glycosylated hemoglobin A1c (A1c) control as part of comprehensive risk factor management in patients with stable ischemic heart disease (SIHD) and diabetes mellitus (DM) is controversial., Objectives: The purpose of this study was to determine whether a greater number of controlled risk factors at 1 year, including A1c, affects survival in patients with DM and SIHD., Methods: Of 690 patients with DM followed in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 592 (86%) had complete ascertainment of 7 pre-specified risk factors at baseline and after 1 year: systolic blood pressure, low-density lipoprotein cholesterol, nonsmoking, physical activity, diet adherence, body mass index, and A1c. The primary outcome measure was mortality beyond 1 year after randomization., Results: During a mean follow-up of 7.0 ± 4.2 years beyond 1 year after randomization, 186 subjects died (31.4% overall, 4.5%/year). The greater the number of risk factors controlled at 1 year, the higher the probability of survival (unadjusted log rank p = 0.002). Compared with 0 to 1 controlled risk factors, attaining 3 to 7 goals predicted progressively lower mortality (hazard ratio for control of 6 or 7 risk factors was 0.13; 95% confidence interval: 0.05 to 0.40). Importantly, only 10.3% of subjects achieved control of 6 or 7 risk factors. In multivariate analysis, the strongest predictors of improved survival were no smoking, regular physical activity, dietary adherence, and A1c <7%., Conclusions: In this high-risk subset of SIHD patients with DM, the number of controlled risk factors, particularly lifestyle behaviors and A1c, were associated with improved survival. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657)., (Copyright © 2019 American College of Cardiology Foundation. All rights reserved.)

Background The severity of coronary artery disease (CAD) and of ischemia are evaluated to guide therapy, but their relative prognostic importance remains uncertain. Accordingly, we sought to clarify their association with long-term survival in the COURAGE trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation). Methods and Results Survival data from after the original trial period ended was obtained at 15 Veterans Affairs sites and 13 of 18 United States non-Veterans Affairs sites. Date of death was obtained from the Veterans Affairs system-wide Corporate Data Warehouse and the National Death Index. Of the original 2287 patients in COURAGE, 1370 (60%) had both stress perfusion imaging and quantitative coronary angiography available, with extended survival evaluated in 767 subjects. Survival was calculated by the Kaplan-Meier method, and a Cox proportional-hazards model adjusted for baseline differences. There were 369 all-cause deaths during a median follow-up of 7.9 years (range, 0-15 years). The number of coronary arteries diseased predicted survival (HR, 1.25; 95% CI, 1.09-1.43), whereas severity of ischemia did not (HR, 0.99; 95% CI, 0.80-1.22). Percutaneous coronary intervention did not offer a survival advantage over optimal medical therapy (HR, 0.95; 95% CI, 0.77-1.16) and there was no interaction between therapeutic strategy and number of coronary arteries diseased or severity of ischemia. In fully adjusted models, the number of coronary arteries diseased was not associated with increased mortality. Conclusions In univariate analysis, the number of coronary arteries diseased predicted long-term mortality, but severity of ischemia did not. Adjusted for baseline variables, neither assessment approach predicted mortality. Overall, there was no survival benefit from percutaneous coronary intervention in any subset defined by either angiographic or ischemic severity. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00007657.

Background: Individual risk factor control improves survival in patients with stable ischemic heart disease (SIHD). It is uncertain if multiple risk factor control further extends survival., Objectives: This study determined whether a greater number of risk factors at goal predicted improved survival in SIHD patients., Methods: Of 2,287 participants in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 2,102 (92%) had complete ascertainment of 6 pre-specified risk factors: systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, diet, and body mass index. Participants received interventions to control these risk factors. The outcome measure was mortality., Results: During a mean follow-up of 6.8 years, 473 (22.5%) subjects died. In univariate analysis, the greater the number of risk factors controlled, the higher the probability of survival (unadjusted log rank: p < 0.001). In multivariate analysis, the strongest predictors at 1 year of improved survival were being a nonsmoker, regular physical activity, having a systolic blood pressure <130 mm Hg, and following the American Heart Association Step 2 diet. Baseline risk factor values and evidence-based medications did not independently predict survival once risk factor control at 1 year was included in the model. Having 4 to 6 risk factors compared with 0 to 1 risk factor at goal predicted lower mortality (hazard ratios for 4 and 6 controlled risk factors: 0.64; 95% confidence interval: 0.41 to 0.98, and 0.27; 95% confidence interval: 0.09 to 0.79, respectively)., Conclusions: The greater the number of risk factors in control, the higher the probability of survival in patients with SIHD. More effective strategies are needed to achieve comprehensive risk factor control, including healthy behaviors. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The impact of treatment strategies on outcomes in patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) according to presenting angina has not been rigorously assessed., Methods: We performed a patient-level pooled-analysis (n = 5027) of patients with stable CAD and T2DM randomized to optimal medical therapy [OMT], percutaneous coronary intervention [PCI] + OMT, or coronary artery bypass grafting [CABG] + OMT. Endpoints were death/myocardial infarction (MI)/stroke, post-randomization revascularization (both over 5 years), and angina control at 1 year., Results: Increasing severity of baseline angina was associated with higher rates of death/MI/stroke (p = 0.009) and increased need for post-randomization revascularization (p = 0.001); after multivariable adjustment, only association with post-randomization revascularization remained significant. Baseline angina severity did not influence the superiority of CABG + OMT to reduce the rate of death/MI/stroke and post-randomization revascularization compared to other strategies. CABG + OMT was superior for angina control at 1 year compared to both PCI + OMT and OMT alone but only in patients with ≥ Class II severity at baseline. Comparisons between PCI + OMT and OMT were neutral except that PCI + OMT was superior to OMT for reducing the rate of post-randomization revascularization irrespective of presenting angina severity., Conclusions: Presenting angina severity did not influence the superiority of CABG + OMT with respect to 5-year rates of death/MI/stroke and need for post-randomization revascularization. Presenting angina severity minimally influenced relative benefits for angina control at 1 year., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There are scant outcomes data in patients with type 2 diabetes and stable coronary artery disease (CAD) stratified by detailed angiographic burden of CAD or left ventricular ejection fraction (LVEF)., Objectives: This study determined the effect of optimal medical therapy (OMT), with or without percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), on long-term outcomes with respect to LVEF and number of diseased vessels, including proximal left anterior descending artery involvement., Methods: A patient-level pooled analysis was undertaken in 3 federally-funded trials. The primary endpoint was the composite of death, myocardial infarction (MI), or stroke, adjusted for trial and randomization strategy., Results: Among 5,034 subjects, 15% had LVEF <50%, 77% had multivessel CAD, and 28% had proximal left anterior descending artery involvement. During a median 4.5-year follow-up, CABG + OMT was superior to PCI + OMT for the primary endpoint (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.59 to 0.85; p = 0.0002), death (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.024), and MI (HR: 0.50; 95% CI: 0.38 to 0.67; p = 0.0001), but not stroke (HR: 1.54; 95% CI: 0.96 to 2.48; p = 0.074). CABG + OMT was also superior to OMT alone for prevention of the primary endpoint (HR: 0.79; 95% CI: 0.64 to 0.97; p = 0.022) and MI (HR: 0.55; 95% CI: 0.41 to 0.74; p = 0.0001), and was superior to PCI + OMT for the primary endpoint in patients with 3-vessel CAD (HR: 0.72; 95% CI: 0.58 to 0.89; p = 0.002) and normal LVEF (HR: 0.71; 95% CI: 0.58 to 0.87; p = 0.0012). There were no significant differences in OMT versus PCI + OMT., Conclusions: CABG + OMT reduced the primary endpoint during long-term follow-up in patients with type 2 diabetes and stable CAD, supporting this as the preferred management strategy., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine whether sex-based differences exist in clinical effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) in patients with stable coronary artery disease., Background: A prior pre-specified unadjusted analysis from COURAGE showed that women randomized to PCI had a lower rate of death or myocardial infarction during a median 4.6-year follow-up with a trend for interaction with respect to sex., Methods: We analyzed outcomes in 338 women (15%) and 1949 men (85%) randomized to PCI plus OMT versus OMT alone after adjustment for relevant baseline characteristics., Results: There was no difference in treatment effect by sex for the primary end point (death or myocardial infarction; HR, 0.89; 95% CI, 0.77-1.03 for women and HR, 1.02, 95% CI 0.96-1.10 for men; P for interaction = .07). Although the event rate was low, a trend for interaction by sex was nonetheless noted for hospitalization for heart failure, with only women, but not men, assigned to PCI experiencing significantly fewer events as compared to their counterparts receiving OMT alone (HR, 0.59; 95% CI, 0.40-0.84, P < .001 for women and HR, 0.86; 95% CI, 0.74-1.01, P = .47 for men; P for interaction = .02). Both sexes randomized to PCI experienced significantly reduced need for subsequent revascularization (HR, 0.72; 95% CI, 0.62-0.83, P < .001 for women; HR, 0.84; 95% CI, 0.79-0.89, P < .001 for men; P for interaction = .02) with evidence of a sex-based differential treatment effect., Conclusion: In this adjusted analysis of the COURAGE trial, there were no significant differences in treatment effect on major outcomes between men and women. However, women assigned to PCI demonstrated a greater benefit as compared to men, with a reduction in heart failure hospitalization and need for future revascularization. These exploratory observations require further prospective study., (Copyright © 2015. Published by Elsevier Inc.)

The impact of baseline exercise capacity on clinical outcomes in patients with stable ischemic heart disease randomized to an initial strategy of optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI) in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial has not been studied. A post hoc analysis was performed in 1,052 patients of COURAGE (PCI + OMT: n = 527, OMT: n = 525) who underwent exercise treadmill testing at baseline. Patients were categorized into 2 exercise capacity groups based on metabolic equivalents (METs) achieved during baseline exercise treadmill testing (<7 METs: n = 464, ≥7 METs: n = 588) and were followed for a median of 4.6 years. The primary composite end point of death or myocardial infarction was similar in the PCI + OMT group and the OMT group for patients with exercise capacity <7 METs (19.1% vs 16.1%, p = 0.31) and ≥7 METs (13.3% vs 10.3%, p = 0.27). After adjusting for baseline covariates, the hazard ratio (99% confidence interval) for the primary end point for the PCI + OMT group versus the OMT group was 1.42 (0.90 to 2.23, p = 0.05) and for the exercise capacity subgroups of ≥7 METs and <7 METs was 0.75 (0.46 to 1.22, p = 0.13). There was no statistically significant interaction between the original treatment arm allocation (PCI + OMT vs OMT) and baseline exercise capacity. In conclusion, there was no difference in the long-term clinical outcomes in patients with exercise capacity <7 METs compared with ≥7 METs, irrespective of whether they were assigned to initial PCI. Patients with exercise capacity <7 METs did not derive a proportionately greater clinical benefit from PCI + OMT compared with those patients who received OMT alone., (Published by Elsevier Inc.)

Background: Percutaneous coronary intervention (PCI) relieves angina in patients with stable ischemic heart disease, but clinical trials have not shown that it improves survival. Between June 1999 and January 2004, we randomly assigned 2287 patients with stable ischemic heart disease to an initial management strategy of optimal medical therapy alone (medical-therapy group) or optimal medical therapy plus PCI (PCI group) and did not find a significant difference in the rate of survival during a median follow-up of 4.6 years. We now report the rate of survival among the patients who were followed for up to 15 years., Methods: We obtained permission from the patients at the Department of Veterans Affairs (VA) sites and some non-VA sites in the United States to use their Social Security numbers to track their survival after the original trial period ended. We searched the VA national Corporate Data Warehouse and the National Death Index for survival information and the dates of death from any cause. We calculated survival according to the Kaplan-Meier method and used a Cox proportional-hazards model to adjust for significant between-group differences in baseline characteristics., Results: Extended survival information was available for 1211 patients (53% of the original population). The median duration of follow-up for all patients was 6.2 years (range, 0 to 15); the median duration of follow-up for patients at the sites that permitted survival tracking was 11.9 years (range, 0 to 15). A total of 561 deaths (180 during the follow-up period in the original trial and 381 during the extended follow-up period) occurred: 284 deaths (25%) in the PCI group and 277 (24%) in the medical-therapy group (adjusted hazard ratio, 1.03; 95% confidence interval, 0.83 to 1.21; P=0.76)., Conclusions: During an extended-follow-up of up to 15 years, we did not find a difference in survival between an initial strategy of PCI plus medical therapy and medical therapy alone in patients with stable ischemic heart disease. (Funded by the VA Cooperative Studies Program and others; COURAGE ClinicalTrials.gov number, NCT00007657.).

Establishing the validity of appropriate use criteria (AUC) for percutaneous coronary intervention (PCI) in the setting of stable ischemic heart disease can support their adoption for quality improvement. We conducted a post hoc analysis of 2,287 Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial patients with stable ischemic heart disease randomized to PCI with optimal medical therapy (OMT) or OMT alone. Within appropriateness categories, we compared rates of death, myocardial infarction, revascularization subsequent to initial therapy, and angina-specific health status as determined by the Seattle Angina Questionnaire in patients randomized to PCI + OMT to those randomized to OMT alone. A total of 1,987 patients (87.9%) were mapped to the 2012 publication of the AUC, with 1,334 (67.1%) classified as appropriate, 551 (27.7%) uncertain, and 102 (5.1%) as inappropriate. There were no significant differences between PCI and OMT alone in the rate of mortality and myocardial infarction by appropriateness classification. Rates of revascularization were significantly lower in patients initially receiving PCI + OMT who were classified as appropriate (hazard ratio 0.65; 95% confidence interval 0.53 to 0.80; p <0.001) or uncertain (hazard ratio 0.49; 95% confidence interval 0.32 to 0.76; p = 0.001). Furthermore, among patients classified as appropriate by the AUC, Seattle Angina Questionnaire scores at 1 month were better in the PCI-treated group compared with the medical therapy group (80 ± 23 vs 75 ± 24 for angina frequency, 73 ± 24 vs 68 ± 24 for physical limitations, and 68 ± 23 vs 60 ± 24 for quality of life; all p <0.01), with differences generally persisting through 12 months. In contrast, health status scores were similar throughout the first year of follow-up in PCI + OMT patients compared with OMT alone in patients classified as uncertain or inappropriate. In conclusion, these findings support the validity of the AUC in efforts to improve health care quality through optimal use of PCI., (Published by Elsevier Inc.)

Purpose: To facilitate localization and resection of small lung nodules, we developed a prospective clinical trial (ClinicalTrials.gov number NCT01847209) for a novel surgical approach which combines placement of fiducials using intra-operative C-arm computed tomography (CT) guidance with standard thoracoscopic resection technique using image-guided video-assisted thoracoscopic surgery (iVATS)., Methods: Pretrial training was performed in a porcine model using C-arm CT and needle guidance software. Methodology and workflow for iVATS was developed, and a multi-modality team was trained. A prospective phase I-II clinical trial was initiated with the goal of recruiting eligible patients with small peripheral pulmonary nodules. Intra-operative C-arm CT scan was utilized for guidance of percutaneous marking with two T-bars (Kimberly-Clark, Roswell, GA) followed by VATS resection of the tumor., Results: Twenty-five patients were enrolled; 23 underwent iVATS, one withdrew, and one lesion resolved. Size of lesions were: 0.6-1.8 cm, mean = 1.3 ± 0.38 cm.. All 23 patients underwent complete resection of their lesions. CT imaging of the resected specimens confirmed the removal of the T-bars and the nodule. Average and total procedure radiation dose was in the acceptable low range (median = 1501 μGy*m(2), range 665-16,326). There were no deaths, and all patients were discharged from the hospital (median length of stay = 4 days, range 2-12). Three patients had postoperative complications: one prolonged air-leak, one pneumonia, and one ileus., Conclusions: A successful and safe step-wise process has been established for iVATS, combining intra-operative C-arm CT scanning and thoracoscopic surgery in a hybrid operating room., (© 2015 Wiley Periodicals, Inc.)

A patient with an endobronchial tumor and critical airway obstruction developed hypoxia and hypercarbia and, subsequently, cardiac arrest during a palliative laser core-out excision. The differential diagnosis included tension pneumothorax, as well as airway obstruction due to swelling of residual tumor or to blood clots. In this case, empiric needle decompression could have had deleterious consequences. Immediate bedside lung ultrasonography provided real-time information leading to the stabilization of the patient. This case provides compelling motivation for anesthesiologists to acquire this easily learned skill.

Objectives: The aim of this study was to determine the relative utility of anatomic and ischemic burden of coronary artery disease for predicting outcomes., Background: Both anatomic burden and ischemic burden of coronary artery disease determine patient prognosis and influence myocardial revascularization decisions. When both measures are available, their relative utility for prognostication and management choice is controversial., Methods: A total of 621 patients enrolled in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial with baseline quantitative nuclear single-photon emission computed tomography (SPECT) and quantitative coronary angiography were studied. Several multiple regression models were constructed to determine independent predictors of the endpoint of death, myocardial infarction (MI) (excluding periprocedural MI) and non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Ischemic burden during stress SPECT, anatomic burden derived from angiography, left ventricular ejection fraction, and assignment to either optimal medical therapy (OMT) + percutaneous coronary intervention (PCI) or OMT alone were analyzed., Results: In nonadjusted and adjusted regression models, anatomic burden and left ventricular ejection fraction were consistent predictors of death, MI, and NSTE-ACS, whereas ischemic burden and treatment assignment were not. There was a marginal (p = 0.03) effect of the interaction term of anatomic and ischemic burden for the prediction of clinical outcome, but separately or in combination, neither anatomy nor ischemia interacted with therapeutic strategy to predict outcome., Conclusions: In a cohort of patients treated with OMT, anatomic burden was a consistent predictor of death, MI, and NSTE-ACS, whereas ischemic burden was not. Importantly, neither determination, even in combination, identified a patient profile benefiting preferentially from an invasive therapeutic strategy. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) is an important clinical co-morbidity that increases the risk of death and myocardial infarction in patients with coronary artery disease (CAD) even when treated with guideline-directed therapies. It is unknown, however, whether CKD influences the effects of CAD treatments on patients' health status, their symptoms, function, and quality of life. We performed a post hoc analysis of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) study to compare health status in patients with stable CAD with and without CKD defined as a glomerular filtration rate of <60 ml/min/1.73 m(2) randomized to either percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) or OMT alone. Health status was measured at baseline, 1, 3, 6, 12, 24, and 36 months of follow-up with the Seattle Angina Questionnaire in 310 patients with CKD and 1,719 patients without CKD. Linear mixed-effects models were used to analyze Seattle Angina Questionnaire scores longitudinally. Mean scores for angina-related quality of life, angina frequency, and physical limitation domains improved from baseline values in both patients with and without CKD and plateaued. Early improvement (1 to 6 months) was more common in patients treated with PCI plus OMT than with OMT alone in both patients with and without CKD. Treatment satisfaction scores were high at baseline in all groups and did not change significantly over time. In conclusion, although CKD is an important determinant of event-free survival in patients with stable CAD, it neither precludes satisfactory treatment of angina with PCI plus OMT or OMT alone nor is it associated with an unsatisfactory quality of life., (Published by Elsevier Inc.)

Objectives: This study sought to assess the independent effect of high-density lipoprotein-cholesterol (HDL-C) level on cardiovascular risk in patients with stable ischemic heart disease (SIHD) who were receiving optimal medical therapy (OMT)., Background: Although low HDL-C level is a powerful and independent predictor of cardiovascular risk, recent data suggest that this may not apply when low-density lipoprotein-cholesterol (LDL-C) is reduced to optimal levels using intensive statin therapy., Methods: We performed a post-hoc analysis in 2,193 men and women with SIHD from the COURAGE trial. The primary outcome measure was the composite of death from any cause or nonfatal myocardial infarction (MI). The independent association between HDL-C levels measured after 6 months on OMT and the rate of cardiovascular events after 4 years was assessed. Similar analyses were performed separately in subjects with LDL-C levels below 70 mg/dl (1.8 mmol/l)., Results: In the overall population, the rate of death/MI was 33% lower in the highest HDL-C quartile as compared with the lowest quartile, with quartile of HDL-C being a significant, independent predictor of death/MI (p = 0.05), but with no interaction for LDL-C category (p = 0.40). Among subjects with LDL-C levels <70 mg/dl, those in the highest quintile of HDL-C had a 65% relative risk reduction in death or MI as compared with the lowest quintile, with HDL-C quintile demonstrating a significant, inverse predictive effect (p = 0.02)., Conclusions: In this post-hoc analysis, patients with SIHD continued to experience incremental cardiovascular risk associated with low HDL-C levels despite OMT during long-term follow-up. This relationship persisted and appeared more prominent even when LDL-C was reduced to optimal levels with intensive dyslipidemic therapy. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: It is unknown if baseline angiographic findings can be used to estimate residual risk of patients with chronic stable angina treated with both optimal medical therapy (OMT) and protocol-assigned or symptom-driven percutaneous coronary intervention (PCI)., Methods: Death, myocardial infarction (MI), and hospitalization for non-ST-segment elevation acute coronary syndrome were adjudicated in 2,275 COURAGE patients. The number of vessels diseased (VD) was defined as the number of major coronary arteries with ≥50% diameter stenosis. Proximal left anterior descending, either isolated or in combination with other disease, was also evaluated. Depressed left ventricular ejection fraction (LVEF) was defined as ≤50%. Cox regression analyses included these anatomical factors as well as interaction terms for initial treatment assignment (OMT or OMT + PCI)., Results: Percutaneous coronary intervention and proximal left anterior descending did not influence any outcome. Death was predicted by low LVEF (hazard ratio [HR] 1.86, CI 1.34-2.59, P < .001) and VD (HR 1.45, CI 1.20-1.75, P < .001). Myocardial infarction and non-ST-segment elevation acute coronary syndrome were predicted only by VD (HR 1.53, CI 1.30-1.81 and HR 1.24, CI 1.06-1.44, P = .007, respectively)., Conclusions: In spite of OMT and irrespective of protocol-assigned or clinically driven PCI, LVEF and angiographic burden of disease at baseline retain prognostic power and reflect residual risk for secondary ischemic events., (© 2013.)

In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) study, a revascularization strategy trial with optimal medical therapy in both arms, the low-density lipoprotein (LDL) cholesterol goal was 60 to 85 mg/dl; this was revised to <70 mg/dl in 2004. COURAGE patients (n = 2,287) were titrated with increasing statin doses to achieve the initial LDL cholesterol goal using a prespecified protocol. Ezetimibe was not available when study enrollment began in 1999 but became available after approval in 2003. After maximizing statin dose, ezetimibe was added to reach the LDL cholesterol goal in 34% of patients (n = 734). Median baseline LDL cholesterol was higher in patients who received ezetimibe than in those who did not (109 vs 96 mg/dl). At baseline, 18% of patients who would later receive ezetimibe had LDL cholesterol <85 mg/dl, and 8% had LDL cholesterol <70 mg/dl. On maximum tolerated statin (with or without other lipid-lowering drugs), 40% had LDL cholesterol <85 mg/dl and 23% had LDL cholesterol <70 mg/dl before starting ezetimibe. At the final study visit, 68% of ezetimibe patients achieved LDL cholesterol <85 mg/dl, and 46% achieved LDL cholesterol <70 mg/dl. Using Cox regression analysis, the most significant factors associated with achieving LDL cholesterol goals were lower baseline LDL cholesterol, average statin dose, and ezetimibe use. In conclusion, after maximizing statin dose, the addition of ezetimibe results in a substantial increase in the percentage of patients who reach LDL cholesterol goal, a key component of optimal medical therapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The COURAGE trial reported similar clinical outcomes for patients with stable ischemic heart disease (SIHD) receiving optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). The current post hoc substudy analysis examined the relationship between baseline stress myocardial ischemia and clinical outcomes based on randomized treatment assignment., Methods: A total of 1,381 randomized patients (OMT n = 699, PCI + OMT n = 682) underwent baseline stress myocardial perfusion single-photon emission computed tomographic imaging. Site investigators interpreted the extent of ischemia by the number of ischemic segments using a 6-segment myocardial model. Patients were divided into those with no to mild (<3 ischemic segments) and moderate to severe ischemia (≥ 3 ischemic segments). Cox proportional hazards models were calculated to assess time to the primary end point of death or myocardial infarction., Results: At baseline, moderate to severe ischemia occurred in more than one-quarter of patients (n = 468), and the incidence was comparable in both treatment groups (P = .36). The primary end point, death or myocardial infarction, was similar in the OMT and PCI + OMT treatment groups for no to mild (18% and 19%, P = .92) and moderate to severe ischemia (19% and 22%, P = .53, interaction P value = .65). There was no gradient increase in events for the overall cohort with the extent of ischemia., Conclusions: From the COURAGE trial post hoc substudy, the extent of site-defined ischemia did not predict adverse events and did not alter treatment effectiveness. Currently, evidence supports equipoise as to whether the extent and severity of ischemia impact on therapeutic effectiveness., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: The extent to which recurrent events in patients with stable coronary artery disease is attributable to progression of an index lesion originally ≥50% diameter stenosis (DS) but not revascularized or originally <50% DS is unknown during optimal medical therapy (OMT)., Methods and Results: In the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 205 patients assigned to OMT plus percutaneous coronary intervention (PCI) and 284 patients assigned to OMT only had symptom-driven angiograms suitable for analysis. Percentages of patients in the OMT+PCI and OMT-only cohorts with index lesions originally <50% DS were 30% and 32%, respectively; 20% and 68% had index lesions originally ≥50% DS. In both groups, index lesions originally <50% or ≥50% DS represented <4% and <25% of all such lesions, respectively. The only angiographic predictor of myocardial infarction or acute coronary syndrome was the number of lesions originally ≥50% DS that had not been revascularized (odds ratio, 1.15; confidence limits, 1.01-1.31; P<0.04)., Conclusions: Lesions originally <50% DS were index lesions in one third of patients referred for symptom-driven repeat angiography, but represented <4% of all such lesions. Nonrevascularized lesions originally ≥50% DS were more often index lesions in OMT-only patients, but still represented a minority (<25%) of all such lesions. These findings underscore the need for improved therapies to arrest plaque progression and reliable strategies for selecting stenoses warranting PCI.

Objectives: Our purpose was to clarify the clinical utility of identifying metabolic syndrome (MetS) in patients with coronary artery disease (CAD)., Background: It is uncertain whether MetS influences prognosis in patients with CAD and whether the risk associated with MetS exceeds the risk associated with the sum of its individual components., Methods: In a post hoc analysis, we compared the incidence of death or myocardial infarction (MI) in stable CAD patients in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial according to the presence (+) or absence (-) of MetS and diabetes: Group A, -MetS/-diabetes; Group B, +MetS/-diabetes; Group C, -MetS/+diabetes; and Group D, +MetS/+diabetes. We explored which MetS components best predicted adverse outcomes and whether MetS had independent prognostic significance beyond its individual components., Results: Of 2,248 patients, 61% had MetS and 34% diabetes. Risk for death or MI increased from Group A (14%) to Group D (25%, p < 0.001). Hypertension (hazard ratio [HR]: 1.30; 95% confidence interval [CI]: 0.98 to 1.71; p = 0.07), low high-density lipoprotein cholesterol (HR: 1.26; 95% CI: 1.03 to 1.55; p = 0.03), and elevated glucose (HR: 1.17; 95% CI: 0.96 to 1.47; p = 0.11) most strongly predicted death or MI. MetS was associated with an increased risk of death or MI (unadjusted HR: 1.41; 95% CI: 1.15 to 1.73; p = 0.001). However, after adjusting for its individual components, MetS was no longer significantly associated with outcome (HR: 1.15; 95% CI: 0.79 to 1.68; p = 0.46). Allocation to initial percutaneous coronary intervention did not affect the incidence of death or MI within any group., Conclusions: Among stable CAD patients in the COURAGE trial, the presence of MetS identified increased risk for death or MI, but MetS did not have independent prognostic significance after adjusting for its constituent components. The addition of early percutaneous coronary intervention to optimal medical therapy did not significantly reduce the risk of death or MI regardless of MetS or diabetes status. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial compared percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) to OMT alone in reducing the risk of cardiovascular events in 2287 patients with stable coronary disease. We examined the cost-effectiveness of PCI as a function of angina severity at the time of randomization., Methods and Results: Angina severity was assessed with the Seattle Angina Questionnaire (SAQ). Patients were grouped into tertiles based on the distribution of baseline scores such that higher tertiles represented better health status. Clinically significant improvement from baseline within individual patients was defined as score increases of >8 for physical limitation, >20 for angina frequency, and >16 for quality-of-life domains. The incremental cost-effectiveness ratio for PCI was calculated as the difference in costs divided by the difference in proportion of patients with clinically significant improvement. Improvement in angina severity was significantly greater for PCI patients in the lowest and middle tertiles. The number of patients needed to treat was much larger for the highest tertile. The added in-trial cost of PCI ranged from $7300 to $13 000. Incremental cost-effectiveness ratios ranged from $80 000 to $330 000 for the lowest and middle tertiles and from $520 000 to >$3 million for the highest tertile for 1 additional patient to achieve significant clinical improvement in health status., Conclusions: The incremental cost of PCI to provide meaningful clinical benefit above that achieved by OMT alone was lower for patients with severe angina than for those with mild or no angina. However, it is uncertain that at any level of angina severity that PCI as an initial strategy would achieve a socially acceptable cost threshold. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00007657.

Aberrant tracheobronchial anatomy is reported at an incidence of approximately 10% and most frequently involves the segmental and subsegmental bronchi. The most relevant abnormality to the practice of anesthesiology is the presence of a tracheal bronchus. Although typically an asymptomatic finding during bronchoscopy, a tracheal bronchus has important implications for airway management and lung isolation. Coexisting abnormalities may further complicate lung isolation. We describe a patient with a tracheal bronchus, coexisting with a left-shifted carina and apically retracted left mainstem bronchus, presenting for right extrapleural pneumonectomy. Attempts to place a left-sided double-lumen endotracheal tube were unsuccessful. We discuss our solution, review the literature, and present potential solutions for lung isolation in patients with a tracheal bronchus.

Background: The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial enrolled patients from 3 distinct healthcare systems (HCSs) in North America. The primary aim of this study was to determine whether there is a treatment difference in cardiovascular outcomes by HCS., Methods and Results: The study population included 968 patients from the US Department of Veterans Affairs (VA), 386 from the US non-VA, and 931 from Canada with different comorbidities and prognoses. The primary outcome was all-cause mortality or nonfatal myocardial infarction (MI) during the median 4.6-year follow-up. Baseline demographics were similar between percutaneous coronary intervention and optimal medical therapy treatment groups within each HCS. After follow-up, the primary end point of total mortality and nonfatal MI was not statistically significant between percutaneous coronary intervention and optimal medical therapy, regardless of HCS: VA, 22.3% versus 21.9% (hazard ratio, 1.05; 95% CI, 0.80-1.38; P=0.95); US non-VA, 15.8% versus 21.8% (hazard ratio, 0.70; 95% CI, 0.43-1.12; P=0.24); Canadian HCS, 17.3% versus 13.5% (hazard ratio, 1.30; 95% CI, 0.93-1.83; P=0.17). The interaction between HCSs and treatment was not statistically significant. Long-term mortality was significantly higher in the VA system as a result of significantly greater comorbidity and worse left ventricular function., Conclusions: In the COURAGE trial, addition of percutaneous coronary intervention to optimal medical therapy did not improve 5-year survival or reduce MI or other major adverse cardiovascular events regardless of whether patients were Canadian or American or US veterans or non-veterans. Outcome differences were largely explained by differences in baseline characteristics known to affect long-term prognosis.

Chronic kidney disease (CKD) is a risk factor for poor outcomes in patients with coronary artery disease (CAD), but it is unknown whether CKD influences the efficacy of alternative CAD treatment strategies. Thus, we compared outcomes in stable CAD patients with and without CKD randomized to percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) or OMT alone in a post hoc analysis of the 2,287 patient COURAGE study. At baseline, 320 patients (14%) had CKD defined as a glomerular filtration rate of <60 mL/min/1.73 m(2), as estimated by the abbreviated 4-variable Modification of Diet in Renal Disease equation. The patients with CKD were older (68 +/- 9 vs 61 +/- 10 years; p <0.001) and more often had diabetes mellitus (42% vs 33%; p = 0.002), hypertension (81% vs 65%; p <0.03), heart failure (13% vs 3.4%; p <001), and three-vessel CAD (37% vs 29%, p = 0.01). After adjustment for these differences, CKD remained an independent predictor of death or nonfatal myocardial infarction (hazard ratio 1.48, 95% confidence interval 1.15 to 1.90). PCI had no effect on these outcomes. Furthermore, at 36 months, a similar percentage of patients with CKD treated with OMT (70%) and PCI plus OMT (76%) were angina free compared to patients without CKD. In conclusion, CKD is an important determinant of clinical outcomes in patients with stable CAD, regardless of the treatment strategy. Although PCI did not reduce the risk of death or myocardial infarction when added to OMT for patients with CKD, it also was not associated with worse outcomes in this high-risk group.

We explored the safety and quality-of-life consequences of treating patients with stable coronary disease and high-risk features initially with optimal medical therapy (OMT) alone compared to OMT plus percutaneous coronary intervention. This was a post hoc analysis of Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial patients. We defined high risk as the onset of Canadian Cardiovascular Society class III angina within 2 months or stabilized acute coronary syndrome within 2 weeks of enrollment. The primary end point was death or myocardial infarction after 4.6 years. Of the 2,287 patients enrolled in the COURAGE trial, 264 (12%) were high risk and had a relative risk of 1.56 for death or myocardial infarction (p = 0.0008) compared to those with non-high-risk features. A total of 35 primary events occurred in the OMT group and 32 in the percutaneous coronary intervention plus OMT group (hazard ratio 1.11, 95% confidence interval 0.69 to 1.79; p = 0.68). No significant difference was found in the prevalence of angina between the 2 groups at 1 year. During the first year of follow-up, 30% of the OMT patients crossed over to the revascularization group. In conclusion, an initial strategy of OMT alone for high-risk patients in the COURAGE trial did not result in increased death or myocardial infarction at 4.6 years or worse angina at 1 year, but it was associated with a high rate of crossover to revascularization.

Objectives: Our aim was to access clinical effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) in older patients with stable coronary artery disease (CAD)., Background: While older patients with CAD are at increased risk for cardiac events compared with younger patients, it is unclear whether PCI may mitigate this risk more effectively than OMT alone or, alternatively, may be associated with more complications., Methods: We conducted a pre-specified analysis of outcomes in stable CAD patients stratified by age and randomized to PCI+OMT or OMT alone in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) trial., Results: A total of 1,381 patients (60%) were <65 years of age (mean 56+/-6 years) and 904 patients (40%) were >or=65 years of age (mean 72+/-5 years). Achieved treatment targets for blood pressure, low-density lipoprotein cholesterol, adherence to diet and exercise, and angina-free status did not differ by age or treatment assignment. Among older patients, there was a 2- to 3-fold higher death rate, but similar rates of myocardial infarction, stroke, and major cardiac events compared with younger patients. The addition of PCI to OMT did not improve or worsen clinical outcomes in patients>or=65 years of age during a median 4.6 year follow-up., Conclusions: These data support adherence to American College of Cardiology/American Heart Association clinical practice guidelines that advocate OMT as an appropriate initial management strategy, regardless of age. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657).

Purpose of Review: Extrapleural pneumonectomy is a radical and aggressive surgery that presents a great challenge to the thoracic anesthesiologist. This surgery is performed routinely by only a few centers in the world and this review represents our institution's experience in anesthetic care., Recent Findings: Prominent among the developing multimodal treatment options is the combination of extrapleural pneumonectomy with intraoperative intracavitary hyperthermic chemotherapy. Outcome survival benefits have recently been demonstrated for the less completely cytoreductive pleurectomy procedure when combined with intraoperative intracavitary hyperthermic chemotherapy and trials are well under way for extrapleural pneumonectomy plus intraoperative intracavitary hyperthermic chemotherapy. Anesthetic management of extrapleural pneumonectomy is further impacted by these developments., Summary: Anesthetic management importantly contributes to containment of the perioperative complications of extrapleural pneumonectomy. An appreciation of the technical aspects and physiologic disruptions associated with extrapleural pneumonectomy is critical to effective management. While data on this relatively uncommon surgical procedure are scarce, some referral centers have accumulated extensive experience. This review summarizes relevant surgical aspects and anesthetic insights from the Brigham and Women's Hospital experience. Included are the anesthetic implications of intraoperative intracavitary hyperthermic chemotherapy in combination with extrapleural pneumonectomy - an emerging therapeutic option in the treatment of malignant pleural mesothelioma.

Major improvements in medical therapy and percutaneous coronary intervention for coronary artery disease (CAD) have emerged during the previous 2 decades, but no randomized trial in patients with stable CAD has been powered to compare these 2 strategies for the hard clinical end points of death or myocardial infarction (MI), and previous studies have not evaluated the effect of coronary stents and intensive medical therapy on cardiac events during long-term follow-up. Between 1999 and 2004, 2,287 patients with documented myocardial ischemia and angiographically confirmed CAD were randomized to the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial, with a principal hypothesis that a strategy of percutaneous coronary intervention plus intensive, guideline-driven medical therapy would be superior to a strategy of intensive medical therapy alone. The primary end point was a composite of all-cause mortality or acute MI (time to first event) during a 2.5- to 7-year (median 5) follow-up. Baseline characteristics were a mean age of 62 +/- 5 years, 85% men, and 86% Caucasian. Mean duration of angina before randomization was 26 months (average 10 episodes/week), and 29% of patients were smokers, 67% had hypertension, 38% had previous MI, 71% had dyslipidemia, 34% had diabetes, 27% had previous revascularization, and 69% had multivessel CAD. Approximately 55% of patients met established criteria for the metabolic syndrome. In conclusion, baseline characteristics of the COURAGE trial study population indicate a highly symptomatic group of patients with CAD who have a significant duration and frequency of antecedent angina pectoris and a high prevalence of cardiac risk factors.

Background: Major improvements in medical therapy and percutaneous coronary intervention (PCI) for coronary heart disease have occurred during the past decade, but no randomized trial has compared these 2 strategies for the "hard" clinical end points of death or myocardial infarction nor have earlier studies incorporated the use of coronary stents and aggressive multifaceted medical therapy during long-term follow-up., Methods: The COURAGE trial is a multicenter study of patients with documented myocardial ischemia and angiographically confirmed single or multivessel coronary artery disease who are randomized to a strategy of PCI plus intensive medical therapy or intensive medical therapy alone. Medical therapy in both groups is guideline-driven and includes: aspirin, clopidogrel, simvastatin (low-density lipoprotein cholesterol target 60-85 mg/dL), long-acting metoprolol and/or amlodipine, lisinopril or losartan, and long-acting nitrates, as well as lifestyle interventions. The primary end point is a composite of all-cause mortality or acute myocardial infarction, and there will be 85% power to detect an absolute 4.6% (relative 22%) difference between strategies. The principal hypothesis is that PCI plus aggressive medical therapy (projected event rate 16.4%) will be superior to aggressive medical therapy alone (projected event rate 21%) during a 2.5- to 7-year (median of 5 years) follow-up., Conclusions: COURAGE is the largest prospective randomized trial of PCI versus intensive medical therapy to date and will define the incremental benefits of PCI in the setting of contemporary optimal medical therapy for chronic coronary heart disease. A total of 2287 patients have been enrolled, and follow-up will conclude in June 2006.