Differences in Postoperative Atrial Fibrillation Incidence and Outcomes After Cardiac Surgery According to Assessment Method and Definition: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most frequent complication of cardiac surgery. Despite clinical and economic implications, ample variability in POAF assessment method and definition exist across studies. We performed a study-level meta-analysis to evaluate the influence of POAF assessment method and definition on its incidence and association with clinical outcomes. METHODS AND RESULTS: A systematic literature search was conducted to identify studies comparing the outcomes of patients with and without POAF after cardiac surgery that also reported POAF assessment method. The primary outcome was POAF incidence. The secondary outcomes were in-hospital mortality, stroke, intensive care unit length of stay, and postoperative length of stay. Fifty-nine studies totaling 197 774 patients were included. POAF cumulative incidence was 26% (range: 7.3%-53.1%). There were no differences in POAF incidence among assessment methods (27%, [range: 7.3%-53.1%] for continuous telemetry, 27% [range: 7.9%-50%] for telemetry plus daily ECG, and 19% [range: 7.8%-42.4%] for daily ECG only; P>0.05 for all comparisons). No differences in in-hospital mortality, stroke, intensive care unit length of stay, and postoperative length of stay were found between assessment methods. No differences in POAF incidence or any other outcomes were found between POAF definitions. Continuous telemetry and telemetry plus daily ECG were associated with higher POAF incidence compared with daily ECG in studies including only patients undergoing isolated coronary artery bypass grafting. CONCLUSIONS: POAF incidence after cardiac surgery remains high, and detection rates are variable among studies. POAF incidence and its association with adverse outcomes are not influenced by the assessment method and definition used, except in patients undergoing isolated coronary artery bypass grafting.

Vein Graft Use and Long-Term Survival Following Coronary Bypass Grafting.

BACKGROUND: Although placement of at least 1 arterial graft during coronary artery bypass grafting (CABG) has a proven survival benefit, it is unknown what degree of revascularization with saphenous vein grafting (SVG) is associated with improved survival. OBJECTIVES: The authors sought to determine whether undergoing surgery performed by a surgeon who is liberal with vein graft utilization is associated with improved survival in patients undergoing single arterial graft CABG (SAG-CABG). METHODS: This was a retrospective, observational study of SAG-CABG performed in Medicare beneficiaries from 2001 to 2015. Surgeons were stratified by number of SVG utilized per SAG-CABG into conservative (≥1 SD below mean), average (within 1 SD of mean), and liberal (≥1 SD above mean). Long-term survival was estimated using Kaplan-Meier analysis and compared among surgeon groups before and after augmented inverse-probability weighting. RESULTS: There were 1,028,264 Medicare beneficiaries undergoing SAG-CABG from 2001 to 2015 (mean age 72.0 ± 7.9 years, 68.3% male). Over time, 1-vein and 2-vein SAG-CABG utilization increased, whereas 3-vein and ≥4-vein SAG-CABG utilization decreased (P < 0.001). Surgeons who were conservative vein graft users performed a mean 1.7 ± 0.2 vein grafts per SAG-CABG, whereas those who were liberal vein graft users performed a mean 2.9 ± 0.2 vein grafts per SAG-CABG. Weighted analysis demonstrated no difference in median survival among patients undergoing SAG-CABG by liberal vs conservative vein graft users (adjusted median survival difference 27 days). CONCLUSIONS: Among Medicare beneficiaries undergoing SAG-CABG, there is no association between surgeon proclivity for vein graft utilization and long-term survival, suggesting that a conservative approach to vein graft utilization is reasonable.

Gender Disparities in Cardiac Surgery Trials: Leadership, Authorship, and Patient Enrollment.

BACKGROUND: Studies have highlighted the paucity of women-led randomized controlled trials (RCTs) in cardiovascular medicine. Whether this finding also applies to cardiac surgery has not been evaluated. In this study, we evaluate women authorship, leadership, and women enrollment in cardiac surgery RCTs. METHODS: A systematic literature search was conducted to identify RCTs comparing 2 or more adult cardiac surgical procedures published from 2000 to 2022. Women-led RCTs were defined as those with a woman as either a first or last author. Linear regression and correlation analyses were used. RESULTS: Of 58 RCTs, 8 (13.8%) were women-led; 17 (29.3%) RCTs had no women authors. Overall, 17.9% of all authors were women, but only 1.2% of all authors were women cardiac surgeons and only 19% of the RCTs had a women cardiac surgeon among the authors. The median proportion of women authors was 14.3% by RCT, which was significantly higher in women-led compared with men-led RCTs (28.6% vs 11.8%; P = .01). No significant change in the proportion of women authors was observed during the study period. North American RCTs had a higher proportion of women authors compared with other geographic regions (28.6% vs 12.5%; P = .01). No correlation was found between the proportion of women authors and the proportion of women participants enrolled in individual RCTs. CONCLUSIONS: During the last 2 decades, only a minority of cardiac surgery RCTs were women-led, and no significant increase in women authorship occurred. There are important geographic differences in women authorship.

Public reporting for coronary artery bypass graft surgery: The quest for the optimal scorecard.

OBJECTIVE: A number of publicly available rating algorithms are used to assess hospital performance in coronary artery bypass grafting (CABG). However, concerns remain that these algorithms fail to correlate with each other and inadequately capture the case complexity of individual center practices. METHODS: Composite star ratings for isolated CABG from the Society of Thoracic Surgeons public reporting database were extracted for 2018-2019. U.S. News & World Report Best Hospitals was used to extract CABG ratings as well as overall cardiology and heart surgery ranking, and the Centers for Medicare & Medicaid Services Hospital Compare was used to extract CABG volume and 30-day mortality. Spearman correlation coefficients were used to assess possible relationships. Expert opinion on risk adjustment and program evaluation was incorporated. RESULTS: Correlations between Society of Thoracic Surgeons star rating and U.S. News & World Report overall ranking in cardiology and heart surgery (r = 0.15) and Centers for Medicare & Medicaid Services 30-day mortality (r = -0.27) were poor. Society of Thoracic Surgeons star rating correlated weakly with U.S. News & World Report CABG ratings (r = 0.33) and with Centers for Medicare & Medicaid Services CABG volume (r = 0.32), whereas the latter 2 correlated moderately (r = 0.52) with each other. Of the 75 centers with accredited cardiac surgery training programs, 13 (17%) did not participate in Society of Thoracic Surgeons public reporting. Important gaps were identified in risk assessment, and potential solutions are proposed. CONCLUSIONS: Correlations between current CABG public reporting systems are weak. Further work is needed to refine and standardize CABG rating systems to more adequately capture the scope and complexity of an individual center's clinical practice and to better inform patients.

Perioperative Anemia and Transfusions and Late Mortality in Coronary Artery Bypass Patients.

BACKGROUND: Perioperative anemia and transfusions are associated with adverse operative outcomes after coronary artery bypass graft surgery (CABG). Their individual association with long-term outcomes is unclear. METHODS: Patients aged 65 years and older who had undergone CABG and were in The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (n = 504,596) from 2011 to 2018 were linked to Centers for Medicare and Medicaid Service data to assess long-term survival. The association of intraoperative anemia defined by intraoperative nadir hematocrit (nHct) and red blood cell (RBC) transfusions, and their interactions, on long-term mortality were assessed with Kaplan-Meier estimates and multivariable Cox regression. Restricted cubic splines were used to explore the association between nHct as a continuous variable and long-term mortality. RESULTS: 258,398 on-pump CABG STS Adult Cardiac Surgery Database patients surviving the perioperative period were linked to Centers for Medicare and Medicaid Service claims files. Per World Health Organization criteria, 41% had preoperative anemia. Mean intraoperative nHct was 24%; RBC transfusion rate was 43.7%. Univariable analysis associated both RBC transfusion and lower nHct with worse survival. Lower nHct was only marginally associated with risk-adjusted mortality: adjusted hazard ratio (AHR) 1.04 (95% CI, 1.01-1.06) and 1.07 (95% CI, 1.00-1.14) at nHct 20% and at nHct 14%, respectively. RBC transfusion was associated with significantly higher adjusted mortality irrespective of timing of transfusion: AHR intraoperative 1.21 (95% CI, 1.18-1.27); AHR postoperative 1.26 (95% CI, 1.22-1.30); AHR both 1.46 (95% CI, 1.40-1.52) and across all levels of nHct. RBC transfusion was not associated with improved survival at any level of nHct. CONCLUSIONS: Among Medicare CABG patients, RBC transfusions were associated with increased risk-adjusted late mortality across all levels of nHct whereas intraoperative anemia was only marginally so. Tolerance of lower intraoperative nHct than currently accepted may be preferable to transfusions.

Cost-effectiveness of bilateral vs. single internal thoracic artery grafts at 10 years.

AIMS: Using bilateral internal thoracic arteries (BITAs) for coronary artery bypass grafting (CABG) has been suggested to improve survival compared to CABG using single internal thoracic arteries (SITAs) for patients with advanced coronary artery disease. We used data from the Arterial Revascularization Trial (ART) to assess long-term cost-effectiveness of BITA grafting compared to SITA grafting from an English health system perspective. METHODS AND RESULTS: Resource use, healthcare costs, and quality-adjusted life years (QALYs) were assessed across 10 years of follow-up from an intention-to-treat perspective. Missing data were addressed using multiple imputation. Incremental cost-effectiveness ratios were calculated with uncertainty characterized using non-parametric bootstrapping. Results were extrapolated beyond 10 years using Gompertz functions for survival and linear models for total cost and utility. Total mean costs at 10 years of follow-up were £17 594 in the BITA arm and £16 462 in the SITA arm [mean difference £1133 95% confidence interval (CI) £239 to £2026, P = 0.015]. Total mean QALYs at 10 years were 6.54 in the BITA arm and 6.57 in the SITA arm (adjusted mean difference -0.01 95% CI -0.2 to 0.1, P = 0.883). At 10 years, BITA grafting had a 33% probability of being cost-effective compared to SITA, assuming a cost-effectiveness threshold of £20 000. Lifetime extrapolation increased the probability of BITA being cost-effective to 51%. CONCLUSIONS: BITA grafting has significantly higher costs but similar quality-adjusted survival at 10 years compared to SITA grafting. Extrapolation suggests this could change over lifetime.

The value of perioperative biomarker release for the assessment of myocardial injury or infarction in cardiac surgery.

OBJECTIVES: Cardiac biomarkers are indicators of irreversible cell damage. Current myocardial infarction (MI) definitions require concomitant clinical characteristics. For perioperative MI, a correlation of biomarker elevations and mortality has been suggested. Definitions emerged relying on cardiac biomarker release only. This approach is questionable as several clinical and experimental scenarios exist where relevant biomarker release can occur apart from MI. METHODS: We reviewed the clinical and basic science literature and revealed important aspects regarding the use and interpretation of cardiac biomarker release with special focus on their interpretation in the perioperative setting. RESULTS: Ischaemic biomarkers may be released without cell death in multiple conditions, such as after endurance runs in athletes, temporary inotropic stimulation in animal models and flow variations in in vitro cell models. In addition, access through atrial tissue during cannulation or concomitant valve procedures adds sources of enzyme release that may not be related to ventricular ischaemia (i.e. MI). Such non-cell death-related mechanisms may explain the lack of poor correlations of enzyme release and long-term outcomes in recent trials. In addition, the 3 main biomarkers, troponin T, I and creatine kinase myocardial band, differ in their release kinetics, which may differentially trigger MI events in trial patients. CONCLUSIONS: The identification of irreversible myocardial injury in cardiac surgery based only on biomarker release is unreliable. Cell death- and non-cell death-related mechanisms create a mix in the perioperative setting that requires additional markers for proper identification of MI. In addition, the 3 most common ischaemic biomarkers display different release kinetics adding to the confusion. We review the topic.

Representation of Women in Randomized Trials in Cardiac Surgery: A Meta-Analysis.

Background Women have traditionally been underrepresented in randomized clinical trials (RCTs). We performed a systematic evaluation of the inclusion of women in cardiac surgery RCTs published in the past 2 decades. Methods and Results MEDLINE, EMBASE, and the Cochrane Library were searched (2000 to July 2020) for RCTs written in English, comparing ≥2 adult cardiac surgical procedures. The percentage of women enrolled and its association with year of publication, sample size, mean age, funding source, geographic location, number of sites involved, and interventions tested were analyzed using a meta-analytic approach. Fifty-one trials were included. Of 25 425 total patients, 5029 were women (20.8%; 95% CI, 17.6-24.4; range, 0.5%-57.9%). The proportion of women dropped significantly during the study period (29.6% in 2000 versus 13.1% in 2019, P<0.001). Women were significantly more represented in European trials (26.2%; 95% CI, 21.2-31.9), and less represented in trials of coronary bypass surgery versus other interventions (16.8%; 95% CI, 12.3-22.7 versus 33.6%; 95% CI, 27.4-40.5; P=0.0002) and in trials enrolling younger patients (P=0.009); the percentage of women was higher in industry-sponsored versus non-industry sponsored trials (31.7%; 95% CI, 27.2-36.6 versus 15.5%; 95% CI, 10.0-23.2; P=0.0004) and was not associated with trial sample size (P=0.52) or study design (multicenter versus monocenter: P=0.22). After exclusion of trials conducted at Veteran Affairs centers, women representation was 24.4% (95% CI, 21.1-28.0; range, 10.4%-57.9%), with no significant changes during the study period. Conclusions The proportion of women in cardiac surgery trials is low and likely inadequate to provide meaningful estimates of the treatment effect.

Aortic hemodynamics assessment prior and after valve sparing reconstruction: A patient-specific 4D flow-based FSI model.

INTRODUCTION: Valve-sparing root replacement (VSRR) of the ascending aorta is a life-saving procedure for the treatment of aortic aneurysms, but patients remain at risk for post-operative events involving the downstream native aorta, the mechanism for which is uncertain. It is possible that proximal graft replacement of the ascending aorta induces hemodynamics alterations in the descending aorta, which could trigger adverse events. Herein, we present a fluid-structure interaction (FSI) protocol, based on patient-specific geometry and boundary conditions, to assess impact of proximal aortic grafts on downstream aortic hemodynamics and distensibility. METHODS: Cardiac magnetic resonance (CMR), including MRA, cine-CMR and 4D flow sequences, was performed prior and after VSRR on one subject. Central blood pressure was non-invasively acquired at the time of the CMR: data were used to reconstruct the pre- and post-VSRR model and derive patient-specific boundary conditions for the FSI and a computational fluid dynamic (CFD) analysis with the same settings. Results were validated comparing the predicted velocity field against 4D flow dataset, over four landmarks along the aorta, and the predicted distensibility against the cine-CMR derived value. RESULTS: Instantaneous velocity magnitudes extracted from 4D flow and FSI were similar (p > 0.05), while CFD-predicted velocity was significantly higher (p < 0.001), especially in the descending aorta of the pre-VSRR model (vmax was 73 cm/s, 76 cm/s and 99 cm/s, respectively). As measured in cine-CMR, FSI predicted an increase in descending aorta distensibility after grafting (i.e., 4.02 to 5.79 10-3 mmHg-1). In the descending aorta, the post-VSRR model showed increased velocity, aortic distensibility, stress and strain and wall shear stress. CONCLUSIONS: Our Results indicate that i) the distensibility of the wall cannot be neglected, and hence the FSI method is necessary to obtain reliable results; ii) graft implantation induces alterations in the hemodynamics and biomechanics along the thoracic aorta, that may trigger adverse vessel remodeling.

Decision analysis and personalized clinical tool for cerebrospinal fluid drains in thoracoabdominal aortic aneurysms repair.

BACKGROUND AND AIM: The routine use of cerebrospinal fluid (CSF) drainage in patients undergoing operative repair of thoracoabdominal aneurysms (TAAA) has been associated with decreased rates of spinal cord ischemia. The use of CSF drains is not without consequence, however with complications including subarachnoid hemorrhage, epidural hematoma, meningitis, and, in 1% of cases, death. To date, a decision analysis tool to help clinicians decide when to use and not to use a CSF drain does not exist. In this analysis, we set out to develop a decision analysis tool for CSF drain placement in patients undergoing operative repair of TAAA. METHODS: A Markov state-transition cohort model that compared TAAA repair with adjunctive CSF drain insertion to TAAA repair without drain insertion for the outcome of life expectancy was developed in TreeAge 2020. The cycle length was 1 month and the time horizon was 60 months. RESULTS: The use of a CSF drain was associated with improved 5-year life expectancy (3.21 ± 0.10 vs. 3.09 ± 0.11 life-years gained). In the sensitivity analysis that varied the effectiveness of a CSF drain (odds ratio closer to 1 = less effective), the use of a CSF drain resulted in higher life expectancy in almost all scenarios. CONCLUSIONS: The routine use of a CSF drain in patients undergoing TAAA repair is safe and effective, with few exceptions. This decision analysis tool can be used by clinicians to develop a personalized approach.

The cost-effectiveness of transcatheter aortic valve replacement in low surgical risk patients with severe aortic stenosis.

AIMS: The economic value of transcatheter aortic valve replacement (TAVR) in low surgical risk patients with severe, symptomatic aortic stenosis is not known. Our objective was to determine the cost-effectiveness of balloon-expandable TAVR and self-expandable TAVR relative to surgical aortic valve replacement (SAVR) in low-risk patients. METHODS AND RESULTS: A fully probabilistic Markov cohort model was constructed to estimate differences in costs and effectiveness [quality-adjusted life years (QALYs)] over the patient's life-time time from the third-party payer's perspective. Clinical outcomes modelled were alive/well (no complications), permanent stroke, ≥moderate paravalvular leak, new pacemaker, rehospitalization, and death. A network meta-analysis of the PARTNER 3 and Evolut Low Risk trial was performed to compare balloon-expandable TAVR, self-expandable TAVR, and SAVR for the efficacy inputs. Incremental-cost effectiveness ratios (ICER) were calculated. The total life-time costs in the balloon-expandable TAVR, self-expandable-TAVR, and SAVR arms were $37 330 ± 4724, $39 660 ± 4862, and $34 583 ± 6731, respectively, and total life-time QALYs gained were 9.15 ± 3.23, 9.13 ± 3.23, and 9.05 ± 3.20, respectively. The ICERs for balloon-expandable TAVR and self-expandable TAVR against SAVR were $27 196/QALY and $59 641/QALY, respectively. Balloon-expandable TAVR was less costly and more effective than self-expandable TAVR. There was substantial uncertainty, with 53% and 58% of model iterations showing balloon-expandable TAVR to be the preferred option at willingness-to-pay thresholds of $50 000/QALY and $100 000/QALY, respectively. CONCLUSION: Compared with SAVR, TAVR, particularly with balloon-expandable prostheses may be a cost-effective option for patients with severe aortic stenosis at low surgical risk.

The Cost of Innovation and Evidence in Cardiac Surgery.

This review summarizes a systematic analysis of 216 randomized trials of cardiovascular interventions performed during 2008-2019, according to the source of trial funding. The systematic analysis showed that on average the results of each trial would change significance if only 5 patients experienced different outcomes. Industry-sponsored trials were more likely to use composite endpoints, noninferiority designs, and twice as likely as nonindustry trials to report results favoring the device arm. Over 80% of industry trials used reporting strategies or "spin" suggesting the device arm was advantageous versus fewer than half of non-industry trials. The review discusses the implications of these findings.

Characteristics of Contemporary Randomized Clinical Trials and Their Association With the Trial Funding Source in Invasive Cardiovascular Interventions.

Importance: Changes in evidence-based practice and guideline recommendations depend on high-quality randomized clinical trials (RCTs). Commercial device and pharmaceutical manufacturers are frequently involved in the funding, design, conduct, and reporting of trials, the implications of which have not been recently analyzed. Objective: To evaluate the design, outcomes, and reporting of contemporary randomized clinical trials of invasive cardiovascular interventions and their association with the funding source. Design, Setting, and Participants: This cross-sectional study analyzed published RCTs between January 1, 2008, to May 31, 2019. The trials included those involving coronary, vascular and structural interventional cardiology, and vascular and cardiac surgical procedures. Main Outcomes and Measures: We assessed (1) trial characteristics, (2) finding of a statistically significant difference in the primary end point favoring the experimental intervention, (3) reporting of implied treatment advantage in trials without significant differences in primary end point, (4) existence of major discrepancies between registered and published primary outcomes, (5) number of patients whose outcomes would need to switch from a nonevent to an event to convert a significant difference in primary end point to nonsignificant, and (6) association with funding source. Results: Of the 216 RCTs analyzed, 115 (53.2%) reported having commercial sponsorship. Most trials had 80% power to detect an estimated treatment effect of 30%, and 128 trials (59.3%) used composite primary end points. The median (interquartile range [IQR]) sample size was 502 (204-1702) patients, and the median (IQR) follow-up duration was 12 (1.0-14.4) months. Overall, 123 trials (57.0%) reported a statistically significant difference in the primary outcome favoring the experimental intervention; reporting strategies that implied an advantage were identified in 55 (65.5%) of 84 trials that reported nonsignificant differences. Commercial sponsorship was associated with a statistically significantly greater likelihood of favorable outcomes reporting (exponent of regression coefficient ß, 2.80; 95% CI, 1.09-7.18; P = .03) and with the reporting of findings that are inconsistent with the trial results. Discrepancies between the registered and published primary outcomes were found in 82 trials (38.0%), without differences in trial sponsorship. A median (IQR) number of 5 (2.8-12.5) patients experiencing a different outcome would have change statistically significant results to nonsignificant. Commercial sponsorship was associated with a greater number of patients (exponent of regression coefficient ß, 1.29; 95% CI, 1.00-1.66; P = .04). Conclusions and Relevance: These results suggest that contemporary RCTs of invasive cardiovascular interventions are relatively small and fragile, have short follow-up, and have limited power to detect large treatment effects. Commercial support appeared to be associated with differences in trial design, results, and reporting.

An assessment of the quality of current clinical meta-analyses.

BACKGROUND: The objective of this study was to assess the overall quality of study-level meta-analyses in high-ranking journals using commonly employed guidelines and standards for systematic reviews and meta-analyses. METHODS: 100 randomly selected study-level meta-analyses published in ten highest-ranking clinical journals in 2016-2017 were evaluated by medical librarians against 4 assessments using a scale of 0-100: the Peer Review of Electronic Search Strategies (PRESS), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Institute of Medicine's (IOM) Standards for Systematic Reviews, and quality items from the Cochrane Handbook. Multiple regression was performed to assess meta-analyses characteristics' associated with quality scores. RESULTS: The overall median (interquartile range) scores were: PRESS 62.5(45.8-75.0), PRISMA 92.6(88.9-96.3), IOM 81.3(76.6-85.9), and Cochrane 66.7(50.0-83.3). Involvement of librarians was associated with higher PRESS and IOM scores on multiple regression. Compliance with journal guidelines was associated with higher PRISMA and IOM scores. CONCLUSION: This study raises concerns regarding the reporting and methodological quality of published MAs in high impact journals Early involvement of information specialists, stipulation of detailed author guidelines, and strict adherence to them may improve quality of published meta-analyses.

Randomized Trials in Cardiac Surgery: JACC Review Topic of the Week.

Compared with randomized controlled trials (RCTs) in medical specialties, RCTs in cardiac surgery face specific issues. Individual and collective equipoise, rapid evolution of the surgical techniques, as well as difficulties in obtaining funding, and limited education in clinical epidemiology in the surgical community are among the most important challenges in the design phase of the trial. Use of complex interventions and learning curve effect, differences in individual operators' expertise, difficulties in blinding, and slow recruitment make the successful completion of cardiac surgery RCTs particularly challenging. In fact, over the course of the last 20 years, the number of cardiac surgery RCTs has declined significantly. In this review, a team of surgeons, trialists, and epidemiologists discusses the most important challenges faced by RCTs in cardiac surgery and provides a list of suggestions for the successful design and completion of cardiac surgery RCTs.