The Association of Anemia with Cardiopulmonary Exercise Capacity and Adverse Patient Outcomes in Noncardiac Surgery

Cardiorespiratory impairment and preoperative anemia are associated with postoperative adverse events. Since hemoglobin concentration contributes to oxygen delivery, the association of anemia with outcomes may be due to patient inability to meet postoperative metabolic demands. This thesis examined the association of hemoglobin concentration with two measures of cardiorespiratory reserve, VO2 peak and AT. In patients undergoing major elective surgery, hemoglobin concentration explained 4.9% of the variation in VO2 peak and AT. Each 10 g/L increase in hemoglobin was associated with decreased postoperative complications in a multivariable model adjusted for VO2 peak [aOR 0.86 (95% CI, 0.77-0.96), p=0.007] and AT [aOR 0.86 (95% CI, 0.77-0.97), p=0.01], but not a composite endpoint reflecting end-organ impairment due to decreased systemic oxygen delivery. The magnitude of increased risk for postoperative adverse events associated with anemia is likely small. Interventions mitigating modifiable risk factors, of which anemia is just one, could lead to outcome improvements.M.Sc

Improved Re-estimation of Perioperative Cardiac Risk Using the Surgical Apgar Score: A Retrospective Cohort Study

Objective: To assess whether the Surgical Apgar Score (SAS) improves re-estimation of perioperative cardiac risk. Background: The SAS is a novel risk index that integrates three relevant and easily measurable intraoperative parameters (blood loss, heart rate, mean arterial pressure) to predict outcomes. The incremental prognostic value of the SAS when used in combination with standard preoperative risk indices is unclear. Methods: We conducted a retrospective cohort study of adults (18 years and older) who underwent elective noncardiac surgery at a quaternary care hospital in Canada (2009-2014). The primary outcome was postoperative acute myocardial injury. The SAS (range 0-10) was calculated based on intraoperative estimated blood loss, lowest mean arterial pressure, and lowest heart rate documented in electronic medical records. Incremental prognostic value of the SAS when combined with the Revised Cardiac Risk Index was assessed based on discrimination (c-statistic), reclassification (integrated discrimination improvement, net reclassification index), and clinical utility (decision curve analysis). Results: The cohort included 16,835 patients, of whom 607 (3.6%) patients had acute postoperative myocardial injury. Addition of the SAS to the Revised Cardiac Risk Index improved risk estimation based on the integrated discrimination improvement [2.0%; 95% confidence interval (CI): 1.5%-2.4%], continuous net reclassification index (54%; 95% CI: 46%-62%), and c-index, which increased from 0.68 (95% CI: 0.65-0.70) to 0.75 (95% CI: 0.73-0.77). On decision curve analysis, addition of the SAS to the Revised Cardiac Risk Index resulted in a higher net benefit at all decision thresholds. Conclusions: When combined with a validated preoperative risk index, the SAS improved the accuracy of cardiac risk assessment for noncardiac surgery. Further research is needed to delineate how intraoperative data can better guide postoperative decision-making

Effect of a national guideline on postoperative troponin surveillance: a retrospective cohort study

Purpose: We aimed to evaluate the effect of the 2017 Canadian Cardiovascular Society (CCS) guidelines on troponin surveillance after noncardiac surgery. Methods: This was a single-centre, retrospective, observational study. Patients aged 40 yr or older undergoing intermediate- to high-risk elective noncardiac surgery between 2016 and 2021 were included. We compared the number and percentage of troponin tests ordered before and after the guidelines were published and compared patient characteristics, specifically cardiovascular comorbidity, using odds ratio’s (OR) with 95% confidence intervals (CIs). Outcomes were myocardial injury, myocardial infarction (MI), and in-hospital mortality. Results: The cohort included 36,386 patients and the median age was 63 yr. Between 2016 and 2018, troponin surveillance was done in 2,461 (13%) of the 19,046 patients, compared with 2,398 (14%) of the 17,340 patients who had surgery between 2019 and 2021 (OR, 1.08; 95% CI, 1.02 to 1.15). Patients who had surgery in the second period had less cardiovascular comorbidity; the adjusted OR for troponin surveillance was 1.14 (95% CI, 1.07 to 1.21). In the two periods, troponin was elevated in 561 (2.9%) and 470 (2.7%) patients, an MI was documented in 54 (0.3%) and 36 (0.2%) patients, and 95 (0.5%) and 73 (0.4%) patients died, respectively. After adjustment for baseline differences in the two periods, the ORs for MI and mortality were 0.83 (95% CI, 0.54 to 1.27) and 0.88 (95% CI, 0.64 to 1.19), respectively. Conclusion: Although the odds of troponin ordering were slightly but significantly higher after publication of the CCS guidelines, the odds for detecting an MI and for mortality did not change

Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy

In myelofibrosis (MF), driver mutations in JAK2, MPL, or CALR impact survival and progression to blast phase, with the greatest risk conferred by triple-negative status. Subclonal mutations, including mutations in high-molecular risk (HMR) genes, such as ASXL1, EZH2, IDH1/2, and SRSF2 have also been associated with inferior prognosis. However, data evaluating the impact of next-generation sequencing in MF patients treated with JAK1/2 inhibitors are lacking. Using a 54-gene myeloid panel, we performed targeted sequencing on 100 MF patients treated with ruxolitinib (n = 77) or momelotinib (n = 23) and correlated mutational profiles with treatment outcomes. Ninety-nine patients had at least 1 mutation identified, 46 (46%) had 2 mutations, and 34 (34%) patients had >= 3 mutations. Seventy-nine patients carried a mutation in JAK2V617F, 14 patients had mutations in CALR, 6 patients had an MPL mutation, and 2 patients were triple negative. No mutation was significantly associated with spleen or anemia response. A high Dynamic International Prognostic Scoring System score and pretreatment transfusion dependence were associated with a shorter time to treatment failure (TTF), and this association retained significance on multivariable analysis. Patients with ASXL1 (hazard ratio [HR], 1.86; P = .03) and EZH2 mutations (HR, 2.94; P = .009) and an HMR profile (HR, 2.06; P = .01) had shorter TTF. On multivariate analysis, ASXL1 or EZH2 mutations were independently associated with shorter TTF and overall survival. These findings help identify patients unlikely to have a durable response with current JAK1/2 inhibitors and provide a framework for future studies