Prognostic capabilities of coronary computed tomographic angiography before non-cardiac surgery: Prospective cohort study

Objectives To determine if coronary computed tomographic angiography enhances prediction of perioperative risk in patients before non-cardiac surgery and to assess the preoperative coronary anatomy in patients who experience a myocardial infarction after non-cardiac surgery. Design Prospective cohort study. Setting 12 centers in eight countries. Participants 955 patients with, or at risk of, atherosclerotic disease who underwent non-cardiac surgery. Interventions Coronary computed tomographic angiography was performed preoperatively; clinicians were blinded to the results unless left main disease was suspected. Results were classified as normal, non-obstructive (<50% stenosis), obstructive (one or two vessels with ≥50% stenosis), or extensive obstructive (≥50% stenosis in two vessels including the proximal left anterior descending artery, three vessels, or left main). Main outcome measure Composite of cardiovascular death and non-fatal myocardial infarction within 30 days after surgery (primary outcome). This was the dependent variable in Cox regression. The independent variables were scores on the revised cardiac risk index and findings on coronary computed tomographic angiography. Results The primary outcome occurred in 74 patients (8%). The model that included both scores on the revised cardiac risk index and findings on coronary computed tomographic angiography showed that coronary computed tomographic angiography provided independent prognostic information (P=0.014; C index=0.66). The adjusted hazard ratios were 1.51 (95% confidence interval 0.45 to 5.10) for non-obstructive disease; 2.05 (0.62 to 6.74) for obstructive disease; and 3.76 (1.12 to 12.62) for extensive obstructive disease. For the model with coronary computed tomographic angiography compared with the model based on the revised cardiac risk index alone, with 30 day risk categories of <5%, 5-15%, and >15% for the primary outcome, the results of risk reclassification indicate that in a sample of 1000 patients that coronary computed tomographic angiography would have resulted appropriately in 17 net patients receiving a higher risk estimation among the 77 patients who would have experienced the primary outcome (P<0.001). Coronary computed tomographic angiography, however, would have resulted inappropriately in 98 net patients receiving a higher risk estimation, among the 923 patients who would not have experienced the primary outcome (P<0.001). Among patients who had a perioperative myocardial infarction, preoperative coronary anatomy showed extensive obstructive disease in 31% (22/71), obstructive disease in 41% (29/71), non-obstructive disease in 24% (17/71), and normal findings in 4% (3/71). Conclusions Though findings on coronary computed tomographic angiography can improve estimation of risk for patients who will experience perioperative cardiovascular death or myocardial infarction, findings are more than five times as likely to lead to an inappropriate overestimation of risk among patients who will not experience these outcomes. Perioperative myocardial infarction occurs across the spectrum of coronary artery disease, suggesting that there could be several pathophysiologic mechanisms

Association of DMD Gene Variant Classes With Motor Outcomes in a Drug Registration Clinical Trial Setting

Background and Objectives: Duchenne muscular dystrophy (DMD) is caused by pathogenic variants of the DMD gene, leading to the loss of dystrophin. Clinical variability in DMD can complicate interpretation of interventional data in clinical trials. One source of clinical variability is allelic heterogeneity (different pathogenic variants with different effects on dystrophin protein expression). We sought to determine whether gene variant classes in clinical trial participants potentially affect clinical trial data interpretation. Methods: We analyzed 186 vamorolone trial participants with DMD (VBP15-002/003; VBP15-004) who were 4 to steroid-naïve at baseline. We stratified participants into gene variant classes by either variant location in the gene affecting different gene promoters (5′ [Dp427-only] vs 3′ [Dp427+other isoforms]) or residual dystrophin levels (null vs possible non-null [5′ gene variants, exon 44 skippable, splice site]). We evaluated associations with baseline motor outcomes and treatment response (prednisone and vamorolone). Results: Participants with variants in ex63 and downstream (null for Dp427+Dp140+Dp71 protein isoforms) showed poorer baseline motor outcomes for time to stand from supine velocity than those with variants in ex1-44 (Dp427 only). No significant baseline differences were found between likely null and possible non-null variants. Participants with only Dp427 involvement showed significantly better treatment response for the 6-minute walk distance. Most of the comparisons of baseline motor function and treatment response were similar between variant classes. Discussion:The large variation in baseline motor function in young, steroid-naïve patients with DMD is only minimally explained by different gene variant classes. While there is strong literature support for 3′ variants leading to a more severe motor and cognitive DMD phenotype, we found this variant class under-represented in our clinical trials. This suggests that they may fail inclusion criteria (failure to follow commands; poor motor function). Subgroup analyses in DMD clinical trials at a young age range based on gene variant class may not reveal significant differences and would be relatively noninformative

Rethinking cardiac risk reduction after noncardiac surgery: The postoperative Carpe diem

Patients undergoing noncardiac surgery frequently experience major adverse cardiac events. As a significant proportion of these patients develop cardiac complications despite optimal use of preoperative clinical risk‐prediction algorithms, physicians have long searched for better methods of forecasting and ameliorating cardiac risk in this population. Recently, postoperative troponin levels have been found to be powerful and independent predictors of cardiovascular mortality in patients undergoing noncardiac surgery. Importantly, the predictive properties of these markers outperform preoperative clinical risk‐prediction algorithms. We thus posit that the assessment of postoperative troponin represents an as yet untapped “golden opportunity” for cardiac risk reduction. As cardiac troponin isolates an unusually high‐risk subgroup, we outline a strategy that utilizes this marker to improve cardiac outcomes. Where pertinent, strengths and limitations of this approach are discussed and areas of uncertainty identified. As with all hypotheses, this proposition fuels many questions and calls for a research agenda dedicated to quantifying risk or benefit, and defining best practices. Journal of Hospital Medicine 2012. © 2012 Society of Hospital MedicinePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94474/1/1975_ftp.pd

An international prospective cohort study evaluating major vascular complications among patients undergoing noncardiac surgery : the VISION Pilot Study

Objectives: Among patients undergoing noncardiac surgery, our objectives were to: (1) determine the feasibility of undertaking a large international cohort study; (2) estimate the current incidence of major perioperative vascular events; (3) compare the observed event rates to the expected event rates according to the Revised Cardiac Risk Index (RCRI); and (4) provide an estimate of the proportion of myocardial infarctions without ischemic symptoms that may go undetected without perioperative troponin monitoring. Design: An international prospective cohort pilot study. Participants: Patients undergoing noncardiac surgery who were >45 years of age, receiving a general or regional anesthetic, and requiring hospital admission. Measurements: Patients had a Roche fourth-generation Elecsys troponin T measurement collected 6 to 12 hours postoperatively and on the first, second, and third days after surgery. Our primary outcome was major vascular events (a composite of vascular death [i.e., death from vascular causes], nonfatal myocardial infarction, nonfatal cardiac arrest, and nonfatal stroke) at 30 days after surgery. Our definition for perioperative myocardial infarction included: (1) an elevated troponin T measurement with at least one of the following defining features: ischemic symptoms, development of pathologic Q waves, ischemic electrocardiogram changes, coronary artery intervention, or cardiac imaging evidence of myocardial infarction; or (2) autopsy findings of acute or healing myocardial infarction. Results: We recruited 432 patients across 5 hospitals in Canada, China, Italy, Colombia, and Brazil. During the first 30 days after surgery, 6.3% (99% confidence interval 3.9–10.0) of the patients suffered a major vascular event (10 vascular deaths, 16 nonfatal myocardial infarctions, and 1 nonfatal stroke). The observed event rate was increased 6-fold compared with the event rate expected from the RCRI. Of the 18 patients who suffered a myocardial infarction, 12 (66.7%) had no ischemic symptoms to suggest myocardial infarction. Conclusions: This study suggests that major perioperative vascular events are common, that the RCRI underestimates risk, and that monitoring troponins after surgery can assist physicians to avoid missing myocardial infarction. These results underscore the need for a large international prospective cohort study

International Fragility Fracture Network Delphi consensus statement on the principles of anaesthesia for patients with hip fracture

Globally, the number of hip fractures is expected to double between 2017 and 2050, from ~2.2 million to ~4.5 million. For the purposes of analgesia and remobilisation, ~ 99% of hip fractures should be fixed surgically, requiring anaesthesia. Surgery for hip fracture has become increasingly standardised, but peri‐operative medical and anaesthetic care varies considerably. Peri‐operative morbidity and mortality remain high. Guidelines exist for the anaesthetic management of patients with hip fracture, but are specific to the healthcare systems of Western nations. This consensus statement (advises basic standards of anaesthetic care that hip fracture patients should expect to receive in any country, regardless of resources. On behalf of the Fragility Fracture Network (FFN), the Anaesthesia Working Group (SW) invited internationally recognised experts in hip fracture anaesthesia and national professional leaders to contribute to a Consensus Com-mittee