Decision analysis in cardiac surgery: a scoping review and methodological primer.

OBJECTIVES: Randomized controlled trials are the gold standard for evidence generation in medicine but are limited by their real-world generalizability, resource needs, shorter follow-up durations and inability to be conducted for all clinical questions. Decision analysis (DA) models may simulate trials and observational studies by using existing data and evidence- and expert-informed assumptions and extend analyses over longer time horizons, different study populations and specific scenarios, helping to translate population outcomes to patient-specific clinical and economic outcomes. Here, we present a scoping review and methodological primer on DA for cardiac surgery research. METHODS: A scoping review was performed using the PubMed/MEDLINE, EMBASE and Web of Science databases for cardiac surgery DA studies published until December 2021. Articles were summarized descriptively to quantify trends and ascertain methodological consistency. RESULTS: A total of 184 articles were identified, among which Markov models (N = 92, 50.0%) were the most commonly used models. The most common outcomes were costs (N = 107, 58.2%), quality-adjusted life-years (N = 96, 52.2%) and incremental cost-effectiveness ratios (N = 89, 48.4%). Most (N = 165, 89.7%) articles applied sensitivity analyses, most frequently in the form of deterministic sensitivity analyses (N = 128, 69.6%). Reporting of guidelines to inform the model development and/or reporting was present in 22.3% of articles. CONCLUSION: DA methods are increasing but remain limited and highly variable in cardiac surgery. A methodological primer is presented and may provide researchers with the foundation to start with or improve DA, as well as provide readers and reviewers with the fundamental concepts to review DA studies.

One-time screening for abdominal aortic aneurysm in Ontario, Canada: a model-based cost-utility analysis.

BACKGROUND: Screening programs for abdominal aortic aneurysm (AAA) are not available in Canada. We sought to determine the effectiveness and costutility of AAA screening in Ontario. METHODS: We compared one-time ultrasonography-based AAA screening for people aged 65 years to no screening using a fully probabilistic Markov model with a lifetime horizon. We estimated life-years, quality-adjusted life-years (QALYs), AAA-related deaths, number needed to screen to prevent 1 AAA-related death and costs (in Canadian dollars) from the perspective of the Ontario Ministry of Health. We retrieved model inputs from literature, Statistics Canada, and the Ontario Case Costing Initiative. RESULTS: Screening reduced AAA-related deaths by 84.9% among males and 81.0% among females. Compared with no screening, screening resulted in 0.04 (18.96 v. 18.92) additional life-years and 0.04 (14.95 v. 14.91) additional QALYs at an incremental cost of $80 per person among males. Among females, screening resulted in 0.02 (21.25 v. 21.23) additional life-years and 0.01 (16.20 v. 16.19) additional QALYs at an incremental cost of $11 per person. At a willingness-to-pay of $50 000 per year, screening was cost-effective in 84% (males) and 90% (females) of model iterations. Screening was increasingly cost-effective with higher AAA prevalence. INTERPRETATION: Screening for AAA among people aged 65 years in Ontario was associated with fewer AAA-related deaths and favourable cost-effectiveness. To maximize QALY gains per dollar spent and AAA-related deaths prevented, AAA screening programs should be designed to ensure that populations with high prevalence of AAA participate.

Bicuspid aortic stenosis: National three-year outcomes of transcatheter versus surgical aortic valve replacement among Medicare beneficiaries.

OBJECTIVE: Randomized trials of transcatheter versus surgical aortic valve replacements have excluded bicuspid anatomy. We compared 3-year outcomes of transcatheter aortic valve replacement versus surgical aortic valve replacement in patients aged more than 65 years with bicuspid aortic stenosis. METHODS: The Centers for Medicare and Medicaid data were used to identify 6450 patients undergoing isolated surgical aortic valve replacement (n = 3771) or transcatheter aortic valve replacement (n = 2679) for bicuspid aortic stenosis (2012-2019). Propensity score matching with 21 baseline characteristics including frailty created 797 pairs. RESULTS: Unmatched patients undergoing transcatheter aortic valve replacement were older than patients undergoing surgical aortic valve replacement (78 vs 70 years), with more comorbidities and frailty (all P < .001). After matching, transcatheter aortic valve replacement was associated with a similar mortality risk compared with surgical aortic valve replacement within the first 6 months (hazard ratio [HR], 1.08, 95% CI, 0.67-1.69) but a higher mortality risk between 6 months and 3 years (HR, 2.16, 95% CI, 1.22-3.83). Additionally, transcatheter aortic valve replacement was associated with a lower risk of heart failure readmissions before 6 months (HR, 0.51, 95% CI, 0.31-0.87) but a higher risk between 6 months and 3 years (HR, 4.78, 95% CI, 2.21-10.36). The 3-year risks of aortic valve reintervention (HR, 1.03, 95% CI, 0.30-3.56) and stroke (HR, 1.21, 95% CI, 0.75-1.96) were similar. CONCLUSIONS: Among matched Medicare beneficiaries undergoing transcatheter aortic valve replacement or surgical aortic valve replacement for bicuspid aortic stenosis, 3-year mortality was higher after transcatheter aortic valve replacement. However, transcatheter aortic valve replacement was associated with a similar risk of mortality and a lower risk of heart failure readmissions during the first 6 months after the intervention. Randomized comparative data are needed to best inform treatment choice.

Intravenous iron administration before cardiac surgery reduces red blood cell transfusion in patients without anaemia.

BACKGROUND: Reducing the need for blood transfusion among patients undergoing cardiac surgery FLA reduce postoperative complications and mortality. Our study aimed to assess the effects of administering preoperative i.v. ferric carboxymaltose on postoperative red cell transfusion requirements in patients without anaemia undergoing on-pump cardiac surgery. METHODS: This double-blind, randomised, placebo-controlled trial was conducted between October 2016 and November 2019, with a follow-up period of up to 6 weeks after surgery. Patients without anaemia who underwent on-pump cardiac surgery were included as participants and administered i.v. iron in the form of ferric carboxymaltose or placebo once, 24-72 h before surgery. The primary outcome was the number of red cell units transfused during the first four postoperative days, and the secondary outcome measures were blood haemoglobin concentrations at 4 days and 6 weeks after surgery. RESULTS: The 200 patients included were randomly assigned to the ferric carboxymaltose (n=102) and placebo (n=98) groups. By postoperative Day 4, a significantly lower mean number of red cell units were transfused in the ferric carboxymaltose than in the placebo group, 0.3 (0.8) vs 1.6 (4.4), respectively; P=0.007. The mean haemoglobin concentrations on postoperative Day 4 were 9.7 (1) g dl-1 and 9.3 (1) g dl-1, respectively (P=0.03). Corresponding values at 6 weeks after surgery were 12.6 (1.4) g dl-1 and 11.8 (1.5) g dl-1, respectively (P=0.012). CONCLUSIONS: In patients without anaemia undergoing on-pump cardiac surgery, treatment with a single dose of 1000 mg ferric carboxymaltose i.v. 1-3 days before surgery significantly reduced the need for red cell transfusions and increased the postoperative haemoglobin concentration. CLINICAL TRIAL REGISTRATION: NCT02939794.

Impact of Neighborhood Social Deprivation on Health Care Costs Associated With TAVR.

BACKGROUND: Cumulative costs of transcatheter aortic valve replacement (TAVR) differ in the referral, procedural and postprocedural phases depending on patient comorbidities, type of procedure, and procedural complications. Our goal was to determine the association between neighborhood measures of social deprivation and TAVR costs in each of the 3 phases. METHODS: Demographics, patient comorbidities, procedural details, in-hospital complications, and costs for adults undergoing TAVR between 2017 and 2020 in Ontario, Canada were obtained from administrative databases and linked to social deprivation data using the Ontario Marginalization Index. The 3 dimensions of social deprivation assessed were (1) material deprivation, (2) residential instability, and (3) ethnic concentration. Hierarchical generalized linear models were used to determine the association between neighborhood social deprivation and cumulative TAVR costs, reported in 2018 Canadian dollars. RESULTS: We identified a total of 7617 TAVR referrals with 3784 patients undergoing TAVR within our study period. Cumulative mean costs in the referral, procedural and postprocedural phases were $8116±$11 374, $32 790±$17 766, and $18 901±$32 490, respectively. After adjustment for clinical and demographic variables, higher factor scores in residential instability were associated with greater cumulative costs in the postprocedural phase, whereas higher factor scores in the other 2 dimensions of marginalization were not significantly associated with higher costs in any of the 3 phases. CONCLUSIONS: This analysis shows that residential instability is associated with higher cumulative costs in the postprocedural phase of TAVR. This lays the foundation for future studies to understand the mechanism of this finding and identify potential mitigation policies.

Predictors of premature termination and completion of randomized controlled trials.

Randomized clinical trials (RCTs) have a key role in progressing biomedical research and guiding clinical decision making, but premature termination remains high (up to 30%), raising concerns regarding funding expenditure and resource allocation. This brief report sought to identify variables associated with RCTs' premature termination and completion.

The Impact of Heparin on Mortality Following Open Ruptured Abdominal Aortic Aneurysm Repair.

BACKGROUND: Systemic administration of heparin is widely used in patients undergoing open elective abdominal aortic aneurysm (AAA) repair. However, no clear consensus exists in the use of intraoperative heparin during open ruptured AAA (rAAA) repair. In this study, we assessed the safety of intravenous heparin administration in patients undergoing open rAAA repair. METHODS: A retrospective cohort study comparing patients who received and did not receive heparin during open rAAA repair in the Vascular Quality Initiative database between 2003 and 2020 was conducted. The primary outcomes were 30-day and 10-year mortality. The secondary outcomes included estimated blood loss, number of packed red blood cells transfused, early postoperative transfusions, and postsurgical complications. Propensity score matching was used to adjust for potentially confounding variables. The outcomes were compared between the 2 groups using relative risk for binary outcomes and paired t-test and the Wilcoxon rank-sum test for normally and non-normally distributed continuous variables, respectively. Survival was examined using Kaplan-Meier curves and compared using a Cox proportional hazards model. RESULTS: A total of 2,410 patients who underwent open rAAA repair between 2003 and 2020 were studied. Of the 2,410 patients, 1,853 patients received intraoperative heparin and 557 did not. Propensity score matching on 25 variables yielded 519 pairs for the heparin to no heparin comparison. Thirty-day mortality was lower in the heparin group (risk ratio: 0.74; 95% confidence interval [CI]: 0.66-0.84) and in-hospital was also lower in the heparin group (risk ratio: 0.68; 95% CI: 0.60-0.77). Furthermore, estimated blood loss was 910 mL (95% CI: 230 mL to 1,590 mL) lower in the heparin group and the mean number of packed red blood cells transfused intraoperatively and postoperatively were 17 units lower in the heparin group (95% CI: 8-42). Ten-year survival was higher for patients who received heparin, and their rate of survival was approximately 40% higher than those who did not receive heparin (hazard ratio: 0.62; 95% CI, 0.53-0.72; P < 0.0001). CONCLUSIONS: In patients who received systemic heparin administration at the time of open rAAA repair, there were significant short-term and long-term survival benefits within 30 days and at 10 years. Heparin administration may have afforded a mortality benefit or been a surrogate for healthier and less moribund patients at the time of the procedure.

Regional Differences in Outcomes for Patients Undergoing Transcatheter Aortic Valve Replacement in New York State and Ontario.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become the standard of care for a wide spectrum of patients with severe aortic stenosis. However, there are wide variations in access to TAVR among jurisdictions. It is unknown if such variation is associated with differences in postprocedural outcomes. Our objective was to determine whether differences in health care delivery in jurisdictions with high vs low access of care to TAVR translate to differences in postprocedural outcomes. METHODS: In this observational, retrospective cohort study, we identified all Ontario and New York State residents greater than 18 years of age who received TAVR from January 1, 2012, to December 31, 2018. Our primary outcomes were post-TAVR 30 day in-hospital mortality and all-cause readmissions. Using indirect standardization, we calculated the observed vs expected outcomes for New York patients, had they been treated in Ontario. RESULTS: Our cohort consisted of 16,814 TAVR patients at 36 hospitals in New York State and 5007 TAVR patients at 11 hospitals in Ontario. In Ontario, TAVR access rates increased from ∼18.2 TAVR per million in 2012 to 87.4 TAVR per million in 2018, whereas for New York State, the rates increased from 31.9 to 220.4 TAVR per million. For 30-day mortality, 3.1% of Ontario TAVR patients had an in-hospital death, compared with 2.5% of New York patients. With adjustment, this translated to an observed-expected ratio of 0.70 (95% confidence interval [CI], 0.54-0.92) for New York patients. CONCLUSIONS: Having greater access to TAVR may be associated with improved outcomes, potentially because of intervention earlier in the trajectory of the disease.

ESC/EACTS vs. ACC/AHA guidelines for the management of severe aortic stenosis.

Aortic stenosis (AS) is a serious and complex condition, for which optimal management continues to evolve rapidly. An understanding of current clinical practice guidelines is critical to effective patient care and shared decision-making. This state of the art review of the 2021 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines and 2020 American College of Cardiology/American Heart Association Guidelines compares their recommendations for AS based on the evidence to date. The European and American guidelines were generally congruent with the exception of three key distinctions. First, the European guidelines recommend intervening at a left ventricular ejection fraction of 55%, compared with 60% over serial imaging by the American guidelines for asymptomatic patients. Second, the European guidelines recommend a threshold of ≥65 years for surgical bioprosthesis, whereas the American guidelines employ multiple age categories, providing latitude for patient factors and preferences. Third, the guidelines endorse different age cut-offs for transcatheter vs. surgical aortic valve replacement, despite limited evidence. This review also discusses trends indicating a decreasing proportion of mechanical valve replacements. Finally, the review identifies gaps in the literature for areas including transcatheter aortic valve implantation in asymptomatic patients, the appropriateness of Ross procedures, concomitant coronary revascularization with aortic valve replacement, and bicuspid AS. To summarize, this state of the art review compares the latest European and American guidelines on the management of AS to highlight three areas of divergence: timing of intervention, valve selection, and surgical vs. transcatheter aortic valve replacement criteria.

Real-World Examination of Revascularization Strategies for Left Main Coronary Disease in Ontario, Canada.

BACKGROUND: Randomized trials have compared percutaneous coronary intervention and coronary artery bypass grafting (CABG) in patients with left main coronary artery disease undergoing nonemergent revascularization. However, there is a paucity of real-world contemporary observational studies comparing percutaneous coronary intervention (PCI) and CABG. OBJECTIVES: The purpose of this study was to compare the long-term clinical outcomes of CABG versus PCI in patients with left main coronary disease. METHODS: Clinical and administrative databases for Ontario, Canada, were linked to obtain records of all patients with angiographic evidence of left main coronary artery disease (≥50% stenosis) treated with either isolated CABG or PCI from 2008 to 2020. Emergent, cardiogenic shock, and ST-segment elevation myocardial infarction patients were excluded. Baseline characteristics of patients were compared and 1:1 propensity score matching was performed. Late mortality and major adverse cardiac and cerebrovascular events were compared between the matched groups using a Cox proportional hazard model. RESULTS: After exclusions, 1,299 and 21,287 patients underwent PCI and CABG, respectively. Prior to matching, PCI patients were older (age 75.2 vs 68.0 years) and more likely to be women (34.6% vs 20.1%), although they had less CAD burden. Propensity score matching on 25 baseline covariates yielded 1,128 well-matched pairs. There was no difference in early mortality between PCI and CABG (5.5% vs 3.9%; P = 0.075). Over 7-year follow-up, all-cause mortality (53.6% vs 35.2%; HR: 1.63; 95% CI: 1.42-1.87; P < 0.001) and major adverse cardiac and cerebrovascular events (66.8% vs 48.6%; HR: 1.77; 95% CI: 1.57-2.00) were significantly higher with PCI than CABG. CONCLUSIONS: CABG was the most common revascularization strategy in this real-world registry. Patients undergoing PCI were much older and of higher risk at baseline. After matching, there was no difference in early mortality but improved late survival and freedom from major adverse cardiac and cerebrovascular events with CABG.

Social Deprivation and Post-TAVR Outcomes in Ontario, Canada: A Population-Based Study.

Background Transcatheter aortic valve replacement (TAVR)/intervention has become the standard of care for treatment of severe aortic stenosis across the spectrum of risk. There are socioeconomic disparities in access to TAVR. The impact of these disparities on postprocedural outcomes remains unknown. Our objective was to examine the association between neighborhood-level social deprivation and post-TAVR mortality and hospital readmission. Methods and Results We conducted a population-based retrospective cohort study of all 4145 patients in Ontario, Canada, who received TAVR from April 1, 2017, to March 31, 2020. Our co-primary outcomes were 1-year postprocedure mortality and 1-year postprocedure readmission. Using Cox proportional hazards models for mortality and cause-specific competing risk hazard models for readmission, we evaluated the relationship between neighborhood-level measures of residential instability, material deprivation, and concentration of racial and ethnic groups with post-TAVR outcomes. After multivariable adjustment, we found a statistically significant relationship between residential instability and postprocedural 1-year mortality, ranging from a hazard ratio of 1.64 to a hazard ratio of 2.05. There was a significant association between the highest degree of residential instability and 1-year readmission (hazard ratio, 1.23 [95% CI, 1.01-1.49]). There was no association between material deprivation and concentration of racial and ethnic groups with post-TAVR outcomes. Conclusions Residential instability was associated with increased risk for post-TAVR mortality, and the highest quintile of residential instability was associated with increased post-TAVR readmission. To reduce health disparities and promote an equitable health care system, further research and policy interventions will be required to identify and support economically and socially minoritized patients undergoing TAVR.

Assessing the robustness of negative vascular surgery randomized controlled trials using their reverse fragility index.

OBJECTIVE: The reverse fragility index (RFI) describes the number of event conversions needed to convert a statistically nonsignificant dichotomous outcome to a significant one. The objective of the present study was to assess the RFI of vascular surgery randomized controlled trials (RCTs) comparing endovascular vs open surgery for the treatment of abdominal aortic aneurysms (AAAs), carotid artery stenosis (CAS), and peripheral artery disease (PAD). METHODS: MEDLINE and Embase were searched for RCTs that had investigated AAAs, CAS, or PAD with statistically nonsignificant binary primary outcomes. The primary outcome for the present study was the median RFI. Calculation of the RFI was performed by creating two-by-two contingency tables and subtracting events from the group with fewer events and adding nonevents to the same group until a two-tailed Fisher exact test had produced a statistically significant result (P ≤ .05). RESULTS: Of 4187 reports, 49 studies reporting 103 different primary end points were included. The overall median RFI was 7 (interquartile range [IQR], 5-13). The specific RFIs for AAA, CAS, and PAD were 10 (IQR, 6-15.5), 6 (IQR, 5-9.5), and 7 (IQR, 5.5-10), respectively. Of the 103 end points, 42 (47%) had had a loss to follow-up greater than the RFI, of which 10 were AAA trials (24%), 23 were CAS trials (55%), and 9 were PAD trials (21%). The Pearson correlation demonstrated a significant positive relationship between a study's RFI and the impact factor of its publishing journal (r = 0.38; 95% confidence interval [CI], 0.20-0.54; P < .01), length of follow-up (r = 0.43; 95% CI, 0.26-0.58; P < .01), and sample size (r = 0.28; 95% CI, 0.09-0.45; P < .01). CONCLUSIONS: A small number of events (median, 7) was required to change the outcome of negative RCTs from statistically nonsignificant to significant, with 47% of the studies having missing data that could have reversed the finding of its primary outcome. Reporting of the RFI relative to the loss to follow-up could be of benefit in future trials and provide confidence regarding the robustness of the P value.