A survey of cardiac surgeons to evaluate the use of sutureless aortic valve replacement in Canada.

BACKGROUND: Sutureless aortic valve replacement (SuAVR) is gaining popularity for the treatment of aortic stenosis. We aimed to describe Canadian cardiac surgeons' practice patterns and perceptions regarding SuAVR. METHODS: Content experts (clinicians and methodologists) developed the survey. Domains in the questionnaire include: respondent characteristics, factors influencing the decision to implant a SuAVR, barriers to SuAVR use, and interest in participating in a trial. RESULTS: A total of 66 cardiac surgeons (median duration of practice: 15 years; range 8-20 years) from 18 hospitals across Canada responded to the survey for a response rate of 84%. Surgeons reported that the following patient characteristics increased the likelihood they would choose SuAVR: hostile root (73%), small annular size (55%), high Society of Thoracic Surgery risk score (42%), older age (40%), to support minimally invasive surgery (25%) and redo-operation (23%). The following patient characteristics made surgeons less likely to pursue SuAVR: young age (73%), low STS score (40%), and large annular size (30%). Reported barriers to SuAVR use included: cost (33%), permanent pacemaker risk (27%) and uncertain durability (12%). Of respondents, 73% were interested in participating in a randomized controlled trial comparing SuAVR with transcatheter aortic valve replacement. CONCLUSIONS: The primary reasons for surgeons selecting SuAVR were high surgical risk and anatomical challenges. Cost is a primary factor limiting SuAVR use.

Mechanical versus bioprosthetic valves in chronic dialysis: a systematic review and meta-analysis.

BACKGROUND: Many patients with end-stage kidney disease (ESKD) have valvular heart disease requiring surgery. The optimal prosthetic valve is not established in this population. We performed a systematic review and meta-analysis to assess outcomes of patients with dialysis-dependent ESKD who received mechanical or bioprosthetic valves. METHODS: We searched Cochrane Central, Medline and Embase from inception to January 2020. We performed screening, full-text assessment, risk of bias and data collection, independently and in duplicate. Data were pooled using a random-effects model. RESULTS: We identified 28 observational studies (n = 9857 patients, including 6680 with mechanical valves and 3717 with bioprosthetic valves) with a median follow-up of 3.45 years. Twenty-two studies were at high risk of bias and 1 was at critical risk of bias from confounding. Certainty in evidence was very low for all outcomes except bleeding. Mechanical valves were associated with reduced mortality at 30 days (relative risk [RR] 0.79, 95% confidence interval [CI] 0.65-0.97, I 2 = 0, absolute effect 27 fewer deaths per 1000) and at 6 or more years (mean 9.7 yr, RR 0.83, 95% CI 0.72-0.96, I 2 = 79%, absolute effect 145 fewer deaths per 1000), but increased bleeding (incidence rate ratio [IRR] 2.46, 95% CI 1.41-4.27, I 2 = 59%, absolute effect 91 more events per 1000) and stroke (IRR 1.63, 95% CI 1.21-2.20, I 2 = 0%, absolute effect 25 more events per 1000). CONCLUSION: Mechanical valves were associated with reduced mortality, but increased rate of bleeding and stroke. Given very low certainty for evidence of mortality and stroke outcomes, patients and clinicians may choose prosthetic valves based on factors such as bleeding risk and valve longevity. STUDY REGISTRATION: PROSPERO no. CRD42017081863.

Expertise-based design in surgical trials: a narrative review.

Randomized controlled trials (RCTs) are the most robust study design for evaluating the safety and efficacy of a therapeutic intervention. However, their internal validity are at risk when evaluating surgical interventions. This review summarizes existing expertise- based trials in surgery and related methodological concepts to guide surgeons performing this work. We provide caseloads required to reach the learning curve for various surgical interventions and report criteria for expertise from published and unpublished expertise-based trials. In addition, we review design and implementation concepts of expertise-based trials, including recruitment of surgeons, crossover, ethics, generalizability, sample size and definitions for learning curve. Several RCTs have used an expertise-based design. We found that the majority of definitions used for expertise were vague, heterogeneous, and inconsistent across trials evaluating the same surgical intervention. Statistical methods exist to adjust for the learning curve; however, there is limited guidance. We developed the following criteria for surgical expertise for future trials: 1) decide on the proxy to be used for the learning curve, and 2) assess eligible surgeons by comparing their performance to the previously defined expertise criteria.

Outcomes of sutureless aortic valve replacement versus conventional aortic valve replacement and transcatheter aortic valve replacement, updated systematic review, and meta-analysis.

BACKGROUND: Sutureless aortic valve replacement (SuAVR) is an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study compares the effectiveness of SuAVR to SAVR and TAVR. METHODS: We searched MEDLINE and EMBASE from inception to July 2021 for studies evaluating SuAVR, SAVR, and TAVR in adults with aortic stenosis. We performed screening, full-text assessment, data collection, and risk of bias evaluation independently and in duplicate. We evaluated risk of bias using by Cochrane and CLARITY's tools, and certainty in evidence using the GRADE framework. Data were pooled using a random-effects model. RESULTS: We identified one randomized and 78 observational studies (n = 60,689; SuAVR vs. SAVR = 39,171, vs. TAVR = 21,518). All studies were at high or unclear risk of bias, with very-low certainty in effect estimates. Compared to TAVR, SuAVR demonstrates no significant difference in mortality at 30-days (odds ratio [OR]: 0.52, 95% confidence interval [CI: 0.85, 1.16], I2 = 0%), but decreased odds at 2-years (OR: 0.39, 95% CI [0.17, 0.88], I2 = 0%). SuAVR also reduced odds of mild paravalvular regurgitation (OR: 0.11, 95% CI [0.06, 0.21], I2 = 50%). Compared to SAVR, SuAVR was associated with a similar mortality at 30-days (OR: 0.99, 95% CI [0.85, 1.16], I2 = 0%) and 2-years (OR: 0.99, 95% CI [0.43-2.30], I2 = 7%). SuAVR significantly increased odds of permanent pacemaker implantation (OR: 2.5, 95% CI [2.25, 2.77], I2 = 0%). Pooled effect estimates were consistent with results from the randomized trial comparing SuAVR and SAVR. CONCLUSION: Based on very-low quality evidence, SuAVR is associated with similar short- and midterm outcomes compared to TAVR and SAVR. Comparative randomized data with long-term follow-up are required to clarify the role of SuAVR.

Balloon versus self-expandable transcatheter aortic valve implantation for bicuspid aortic valve stenosis: A meta-analysis of observational studies.

BACKGROUND: There is a rising trend for transcatheter aortic valve implantation (TAVI) in bicuspid aortic stenosis patients. Data on the use of self-expandable (SEV) vs. balloon-expandable (BEV) valves in these patients are scarce. Therefore, we systematically compared clinical outcomes in bicuspid aortic stenosis patients treated with SEV and BEV. METHODS: Data were extracted from PubMed/MEDLINE, EMBASE, CENTRAL/CCTR, ClinicalTrials.gov, SciELO, LILACS, Google Scholar and reference lists of relevant articles. Eight studies published from 2013 to 2020 including a total of 1,080 patients (BEV: n = 620; SEV: n = 460) were selected. Primary endpoints were procedural, 30-day and 1-year mortality. Secondary endpoints were new pacemaker implantation, annular rupture, coronary obstruction, moderate-to-severe paravalvular leak, need of second valve, stroke and acute kidney injury. RESULTS: We found no statistically significant difference in mortality between patients treated with BEV vs. SEV during index procedure, at 30 days and at 1 year. BEVs showed a statistically significant higher risk of annulus rupture (2.5%) in comparison with SEV (0%) (OR 5.81 [95% CI, 3.78-8.92], p < .001). New generation BEVs were also associated with significantly less paravalvular leak when compared to new generation SEVs (OR 0.08 [95% CI, 0.02-0.35], p = .001). CONCLUSIONS: This meta-analysis of observational studies of TAVI for bicuspid valves, showed no difference in short- and mid-term TAVI mortality with BEVs and SEVs. BEVs presented a higher risk of annular rupture in comparison with SEV.

Duct stenting versus modified Blalock-Taussig shunt in neonates and infants with duct-dependent pulmonary blood flow: A systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis is to evaluate whether duct stenting is associated with better survival and other clinical outcomes compared with the modified Blalock-Taussig shunt in infants with duct-dependent pulmonary flow. METHODS: A systematic search of the Medline, Embase, and Cochrane databases was performed by 4 independent reviewers from inception to March 2019. Meta-analysis was performed using the DerSimonian and Laird method with inverse-variance weighting. The quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation framework. RESULTS: Six comparative observational studies were included, of which 3 were rated low risk of bias. There was no difference in 30-day mortality between the Blalock-Taussig shunt and duct stenting groups (risk ratio, 1.02; 95% confidence interval, 0.46-2.27; P = .96; I2 = 0%). However, there was benefit in favor of duct stenting for medium-term mortality (risk ratio, 0.63; 95% confidence interval, 0.40-0.99; P = .05; I2 = 0%). Duct stenting demonstrated a reduced risk for procedural complications compared with the Blalock-Taussig shunt (risk ratio, 0.50; 95% confidence interval, 0.31-0.81; P = .005; I2 = 0%). However, there was an increased risk for unplanned reintervention for duct stenting (risk ratio, 1.77; 95% confidence interval, 1.39-2.26; P < .00001; I2 = 10%). Duct stenting demonstrated shorter mean intensive care unit length of stay (mean difference, -4.69 days; 95% confidence interval, -7.30 to -2.07; P = .0004; I2 = 80%), as well as shorter hospital length of stay (mean difference, -5.78 days; 95% confidence interval, -9.27 to -2.28; P = .0009, I2 = 75%). The overall quality of evidence was rated low using the Grading of Recommendations, Assessment, Development, and Evaluation framework. CONCLUSIONS: Duct stenting demonstrated comparable early mortality, lower medium-term mortality, lower risk of procedural complications, and higher risk of reintervention compared with the Blalock-Taussig shunt.

Left Atrial Appendage Occlusion: A Narrative Review.

Left atrial appendage occlusion (LAAO) is a proposed alternative to oral anticoagulation in reducing stroke in patients with atrial fibrillation. It is suggested that LAAO is most suitable in patients at increased risk of stroke or bleeding or with contraindication to pharmacologic intervention. Despite the increase in evidence evaluating LAAO, the relative safety and efficacy of the procedure remains uncertain. Presently, several ongoing randomized trials are comparing various devices to each other and to pharmacologic anticoagulation. The objectives of this narrative review were to present the evidence on percutaneous and surgical LAAO devices, review current guidelines, and summarize landmark trials.

Outcomes after Ross procedure in adult patients: A meta-analysis and microsimulation.

OBJECTIVE: We conducted a meta-analysis to estimate the risk of adverse events, life expectancy, and event-free life expectancy after the Ross procedure in adults. METHODS: We searched databases for reports evaluating the Ross procedure in patients aged more than or equal to 16 years of age. A microsimulation model was used to evaluate age- and gender-specific life expectancy for patients undergoing the Ross procedure. RESULTS: Data were pooled from 63 articles totaling 19 155 patients from 20 countries. Perioperative mortality was 2.5% (95% confidence interval [CI]: 1.9-3.1; N = 9978). We found a mortality risk of 5.9% (95% CI: 4.8-7.2) at a mean follow-up of 7.2 years (N = 7573). The rate of perioperative clinically significant bleeding was 1.0% (95% CI: 0.1-3.0); re-exploration for bleeding 4.6% (95% CI: 3.1-6.3); postoperative clinically significant bleeding from 30 days until a mean of 7.1 years was 0.5% (95% CI: 0.2-1.0). At a mean of 6.9 years of follow-up, reintervention rate of any operated valve was 7.9% (95% CI: 5.7-10.3). The risk of valve thrombosis was 0.3% (95% CI: 0.2-0.5) at 7.6 years; peripheral embolism 0.3% (95% CI: 0.2-0.4) at 6.4 years; stroke 0.9% (95% CI: 0.7-1.2) at 6.5 years; and endocarditis 2.1% (95% CI: 1.6-2.6) at 8.0 years. Microsimulation reported a 40-year-old undergoing the Ross procedure to have a life expectancy of 35.4 years and event-free life expectancy of 26.6 years. CONCLUSIONS: Ross procedure in nonelderly adults is associated with low mortality and low risk of adverse events both at short- and long-term follow-up. The surgical community must prioritize a large, expertize-based randomized controlled trial to definitively address the risks and benefits of the Ross procedure compared to conventional aortic valve replacement.

The Ross procedure versus prosthetic and homograft aortic valve replacement: a systematic review and meta-analysis.

OBJECTIVES: Young adults undergoing aortic valve replacement (AVR) have decreased life expectancy compared to matched controls. The Ross procedure aims to improve valve lifespan while avoiding anticoagulation. We prepared a systematic review and meta-analysis to assess the Ross procedure compared to conventional AVR. METHODS: We searched MEDLINE, EMBASE and Cochrane CENTRAL for studies evaluating the Ross procedure versus any conventional AVR in adult patients. We performed screening, full-text assessment, risk of bias evaluation and data collection independently and in duplicate. We evaluated the risk of bias with the ROBINS-I and Cochrane tools and quality of evidence with the GRADE framework. We pooled data using the random- and fixed-effects models. RESULTS: Thirteen observational studies and 2 randomized controlled trials (RCTs) were identified (n = 5346). No observational study was rated as having low risk of bias. The Ross procedure was associated with decreased late mortality in observational and RCT data [mean length of follow-up 2.6 years, relative risk (RR) 0.56, 95% confidence interval (CI) 0.38-0.84, I2 = 58%, very low quality]. The RCT estimate of effect was similar (mean length of follow-up 8.8 years, RR 0.33, 95% CI 0.11-0.96, I2 = 66%, very low quality). No difference was observed in mortality <30 days after surgery. All-site reintervention was similar between groups in cohorts and significantly reduced by the Ross procedure in RCTs (RR 1.41, 95% CI 0.89-2.24, I2 = 55%, very low quality and RR 0.41, 95% CI 0.22-0.78, I2 = 68%, high quality, respectively). CONCLUSIONS: Observational data, with residual confounding, and RCT data suggest a late survival benefit with the Ross procedure with no increased risk of reintervention when compared to conventional AVR. Considering the quality of available evidence and limited follow-up, additional high-quality randomized studies are required to strengthen these findings. Systematic review PROSPERO registration: CRD42016052512.

Hemodynamic outcomes of the Ross procedure versus other aortic valve replacement: a systematic review and meta-analysis.

INTRODUCTION: Life expectancy in young adults undergoing mechanical or bioprosthetic aortic valve replacement (AVR) may be reduced by up to 20 years compared to age matched controls. The Ross procedure is a durable, anticoagulation-sparing alternative. We performed a systematic review and meta-analysis to compare the valve hemodynamics of the Ross procedure versus other AVR. EVIDENCE ACQUISITION: We searched Cochrane CENTRAL, MEDLINE and EMBASE from inception to February 2017 for randomized controlled trials (RCTs) and observational studies (n≥10 Ross). Independently and in duplicate, we performed title and abstract screening, full-text eligibility assessment, and data collection. We evaluated the risk of bias with the Cochrane and CLARITY tools, and the quality of evidence with the GRADE framework. EVIDENCE SYNTHESIS: We identified 2 RCTs and 13 observational studies that met eligibility criteria (N.=1412). In observational studies, the Ross procedure was associated with a lower mean aortic gradient at discharge (MD -9 mmHg, 95% CI: -13 to -5, P<0.0001, I2=97%) and latest follow-up (MD -5 mmHg, 95% CI: -7 to -3, P<0.0001, I2=92%). There was no significant difference in the incidence of severe aortic regurgitation at latest follow-up (RR 1.3, 95% CI: 0.3 to 5.8, P=0.70, I2=30%). In RCTs, the Ross procedure was associated with a lower mean gradient at latest follow-up (MD -15 mmHg, 95% CI: -32 to 2, P=0.08, I2=99%). The mean pulmonic gradient for the Ross procedure was 18.0 mmHg (95% CI: 16 to 20, P<0.0001) at latest follow-up. The evidence for all outcomes from observational studies was deemed to be of very low quality, while the evidence from RCTs was downgraded for imprecision and moderately serious risk of bias. CONCLUSIONS: Compared to conventional AVR, the Ross procedure was associated with better aortic valve hemodynamics. Future studies should evaluate the impact of the Ross procedure on exercise capacity and quality of life.

Mini-thoracotomy vs. conventional sternotomy mitral valve surgery: a systematic review and meta-analysis.

INTRODUCTION: Minimal access mitral valve surgery (mini-MVS) approaches are becoming increasingly common. They are thought to be associated with less perioperative bleeding and postoperative pain, resulting in shorter hospital length-of-stay (LOS) and faster return to daily activities. However, there are concerns that this approach may have inferior surgical results - with resultant increases in morbidity and mortality - when compared to conventional mitral valve surgery. To address this gap in the literature, we undertook a systematic review and meta-analysis, comparing right thoracotomy mini-MVS (MT-MVS) to conventional mitral valve surgery using a median sternotomy (sternotomy-MVS) approach. EVIDENCE ACQUISITION: We searched the Cochrane Library, MEDLINE, PubMed, EMBASE and Clinicaltrials.gov for randomized trials comparing MT-MVS to sternotomy-MVS in adults. Outcomes of interest were mortality, stroke, hospital length of stay, bleeding, cardiopulmonary bypass (CPB) and cross-clamp times. Studies reporting reoperation data were excluded. References were screened independently and in duplicate, and studies deemed to be potentially relevant were evaluated for inclusion by full-text review. Risk of bias was assessed using the Cochrane tool. Extracted outcome data were pooled for meta-analysis using RevMAN 5.3. The overall quality of evidence for each outcome was evaluated using the GRADE framework. EVIDENCE SYNTHESIS: Three trials including 280 patients met eligibility criteria. Studies were considered to be at high risk of bias due to lack of blinding and small number of patients. Pooled results showed no significant difference in mortality (RR 0.50, 95% CI [0.05 to 5.39], low quality) or stroke (RR 0.50, 95% CI [0.05 to 5.39], low quality). Technique-related outcomes were also similar: cardiopulmonary bypass (CPB) time (MD 17.72 minutes, 95% CI [-7.22 to 42.67), very low quality), cross-clamp time (MD 5.31 minutes, 95% CI [-14.35 to 24.96), very low quality), and bleeding (MD -148.95 mL, 95% CI [-491.02 to 193.12), low quality). Length of stay was significantly shorter in the mini-MVS group (MD -1.89 days, 95% CI [-3.57 to -0.22], P=0.03, low quality). CONCLUSIONS: MT-MVS does not result in increased morbidity and mortality or procedural duration, and may decrease hospital LOS. Our preliminary results suggest that MT-MVS is a safe and potentially beneficial approach to the surgical management of mitral valve disease. However, current evidence is of low quality and larger, more methodologically rigorous randomized trials are required.

Hepatitis C Virus-Induced Degradation of Cell Death-Inducing DFFA-Like Effector B Leads to Hepatic Lipid Dysregulation.

UNLABELLED: Individuals chronically infected with hepatitis C virus (HCV) commonly exhibit hepatic intracellular lipid accumulation, termed steatosis. HCV infection perturbs host lipid metabolism through both cellular and virus-induced mechanisms, with the viral core protein playing an important role in steatosis development. We have recently identified a liver protein, the cell death-inducing DFFA-like effector B (CIDEB), as an HCV entry host dependence factor that is downregulated by HCV infection in a cell culture model. In this study, we investigated the biological significance and molecular mechanism of this downregulation. HCV infection in a mouse model downregulated CIDEB in the liver tissue, and knockout of the CIDEB gene in a hepatoma cell line results in multiple aspects of lipid dysregulation that can contribute to hepatic steatosis, including reduced triglyceride secretion, lower lipidation of very-low-density lipoproteins, and increased lipid droplet (LD) stability. The potential link between CIDEB downregulation and steatosis is further supported by the requirement of the HCV core and its LD localization for CIDEB downregulation, which utilize a proteolytic cleavage event that is independent of the cellular proteasomal degradation of CIDEB. IMPORTANCE: Our data demonstrate that HCV infection of human hepatocytesin vitroandin vivoresults in CIDEB downregulation via a proteolytic cleavage event. Reduction of CIDEB protein levels by HCV or gene editing, in turn, leads to multiple aspects of lipid dysregulation, including LD stabilization. Consequently, CIDEB downregulation may contribute to HCV-induced hepatic steatosis.

Routine Surveillance Versus Independent Assessment by an Outcome Adjudication Committee in Assessing Patients for Sternal Surgical Site Infections After Cardiac Surgery.

Based on a cohort of 966 patients, routine surveillance data were not sufficiently accurate for use in clinical trials investigating surgical site infections. Surveillance data can only be used if adequate 90-day follow-up is provided and if cases identified by surveillance are independently reviewed by a blinded outcome adjudication committee.