Steven R. Meyer

Rationale and design of the Left Atrial Appendage Occlusion Study (LAAOS) III

BACKGROUND Occlusion of the left atrial appendage (LAA) is a promising approach to stroke prevention in atrial fibrillation (AF). However, evidence of its efficacy and safety to date is lacking. We herein describe the rationale and design of a definitive LAA occlusion trial in cardiac surgical patients with AF. METHODS We plan to randomize 4,700 patients with AF in whom on-pump cardiac surgical procedure is planned to undergo LAA occlusion or no LAA occlusion. The primary outcome is the first occurrence of stroke or systemic arterial embolism over a mean follow-up of four years. Other outcomes include total mortality, operative safety outcomes (chest tube output in the first post-operative 24 hours, rate of post-operative re-exploration for bleeding in the first 48 hours post-surgery and 30-day mortality), re-hospitalization for heart failure, major bleed, and myocardial infarction. RESULTS Left Atrial Appendage Occlusion Study (LAAOS) III is funded in a vanguard phase by the Canadian Institutes for Health Research (CIHR), the Canadian Network and Centre for Trials Internationally, and the McMaster University Surgical Associates. As of September 9, 2013, 162 patients have been recruited into the study. CONCLUSIONS LAAOS III will be the largest trial to explore the efficacy of LAA occlusion for stroke prevention. Its results will lead to a better understanding of stroke in AF and the safety and efficacy of surgical LAA occlusion.

Absence of Donor-Specific Anti-HLA Antibodies after ABO-Incompatible Heart Transplantation in Infancy – Altered Immunity or Age?

Specific B‐cell tolerance toward donor blood group antigens develops in infants after ABO‐incompatible heart transplantation, whereas their immune response toward protein antigens such as HLA has not been investigated. We assessed de novo HLA‐antibodies in 122 patients after pediatric thoracic transplantation (28 ABO‐incompatible) and 36 controls. Median age at transplantation was 1.7 years (1 day to 17.8 year) and samples were collected at median 3.48 years after transplantation. Antibodies were detected against HLA‐class I in 21 patients (17.2%), class II in 18 (14.8%) and against both classes in 10 (8.2%). Using single‐antigen beads, donor‐specific antibodies (DSAs) were identified in six patients (all class II, one additional class I). Patients with DSAs were significantly older at time of transplantation. In patients who had undergone pretransplant cardiac surgeries, class II antibodies were more frequent, although use of homografts or mechanical heart support had no influence. DSAs were absent in ABO‐incompatible recipients and class II antibodies were significantly less frequent than in children with ABO‐compatible transplants. This difference was present also when comparing only children transplanted below 2 years of age. Therefore, tolerance toward the donor blood group appears to be associated with an altered response to HLA beyond age‐related effects.

Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology/Canadian Society of Cardiac Surgery Position Statement on Revascularization—Multivessel Coronary Artery Disease

This position statement addresses issues in revascularization for multivessel coronary artery disease (CAD) from the perspective of both cardiologists and cardiac surgeons. Recommendations are made based on evidence from clinical trials and observational studies, with an emphasis on the increasing number of individuals with significant comorbid disease burden and functional debilitation who are being referred for definitive management of their multivessel CAD in the context of routine clinical practice. These types of individuals have traditionally not been included in the many clinical trials that have been the basis for guidelines and recommendations, and the objective of the proposed medical intervention or revascularization (or both) would not necessarily be to improve prognosis but to improve quality of life. One purpose of this document is to propose practical multidisciplinary approaches to the management of these patients. Recommendations are made for revascularization in acute coronary syndromes and stable CAD, with specific considerations for individuals with left ventricular dysfunction and heart failure, chronic renal failure, and chronic obstructive pulmonary disease. We also consider the use of various risk scores, including the Society of Thoracic Surgeons score, the EuroSCORE, and the SYNTAX II score. The importance of a heart team approach is also emphasized. The complementary role of coronary bypass surgery and percutaneous coronary intervention is highlighted, along with the importance of optimal medical therapy.

Pretransplant diabetes, not donor age, predicts long-term outcomes in cardiac transplantation.

Abstract  Background and Aim: Accepting donors of advanced age may increase the number of hearts available for transplantation. Objectives were to review the outcomes of using cardiac donors 50 years of age and older and to identify predictors of outcome at a single institution. Methods: A retrospective analysis of all adult cardiac transplants (n = 338) performed at our institution between 1988 and 2002 was conducted. Results: Of these, 284 patients received hearts from donors <50 years old and 54 received hearts from donors ≥50 years old. Recipients of hearts from older donors had a greater frequency of pretransplant diabetes (19% vs 33%), renal failure (16% vs 30%), and dialysis (3% vs 9%). There were no differences in ICU or postoperative length of stay, days ventilated, or early rejection episodes. Recipients of older donor hearts, however, had increased perioperative mortality (7% vs 17%; p = 0.03). Multivariate analysis identified older donors (OR 2.599; p = 0.03) and donor ischemia time (OR 1.006; p = 0.002) as significant predictors of perioperative mortality. Actuarial survival at 1 (87% vs 74%), 5 (76% vs 69%), and 10 (59% vs 58%) years was similar (p = 0.08) for the two groups. Separate multivariate analyses identified pretransplant diabetes as the sole predictor of long‐term survival (HR 1.659; p = 0.02) and transplant coronary disease (HR 2.486; p = 0.003). Conclusions: Despite increased perioperative mortality, donors ≥50 years old may be used with long‐term outcomes similar to those of younger donor hearts. This has potential to expand the donor pool. Pretransplant diabetes has a significant impact on long‐term outcomes in cardiac transplantation and requires further investigation.

Glutaraldehyde treatment of allograft tissue decreases allosensitization after the Norwood procedure

OBJECTIVE Cryopreserved allograft tissue used in the Norwood procedure for infants with hypoplastic left heart syndrome causes a marked immunologic sensitization that may complicate future heart transplantation. Treatment of the allograft tissue before implantation may prevent this sensitization. The purpose of this study was to assess the anti-human leukocyte antigen antibody response to glutaraldehyde-treated allograft tissue used in the repair of hypoplastic left heart syndrome. METHODS Since June 2005, the University of Alberta has subjected allograft vascular tissue used in the Norwood procedure to glutaraldehyde treatment. An observational study was designed to assess whether glutaraldehyde treatment of the allograft tissue affected subsequent panel reactive antibody after patch implantation. Panel reactive antibodies for class I (human leukocyte antigen-A, B, C) and class II (human leukocyte antigen-DR, DQ) antibodies were measured 4 months postoperatively using flow cytometry. RESULTS Fourteen patients underwent a Norwood procedure using glutaraldehyde-treated allograft tissue. Historical controls consisted of 12 patients who underwent a Norwood procedure using untreated allograft tissue. At 4 months, infants who had received glutaraldehyde-treated allograft tissue had lower class I panel reactive antibody (7.3% +/- 17.4% [median, 0%] vs 61.9% [median, 73%] +/- 39.9%; P = .0005) and class II panel reactive antibody (6.1% [median, 0%] +/- 22.7% vs 49.3% [median, 63%] +/- 41.9%, P = .001) compared with the historical controls. CONCLUSION Intraoperative glutaraldehyde treatment of allograft tissue used in hypoplastic left heart syndrome repair prevents the profound immunologic sensitization that occurs in the majority of infants undergoing surgical palliation. In patients requiring subsequent heart transplantation, this decreases the risk of antibody-mediated rejection and increases the likelihood of finding a suitable donor, thus improving access to transplantation.

Incidence and outcomes of acute kidney injury following orthotopic lung transplantation: a population-based cohort study

BACKGROUND Acute kidney injury (AKI) is a serious complication following lung transplantation (LTx). We aimed to describe the incidence and outcomes associated with AKI following LTx. METHODS A retrospective population-based cohort study of all adult recipients of LTx at the University of Alberta between 1990 and 2011. The primary outcome was AKI, defined and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, in the first 7 post-operative days. Secondary outcomes included risk factors, utilization of renal replacement therapy (RRT), occurrence of post-operative complications, mortality and kidney recovery. RESULTS Of 445 LTx recipients included, AKI occurred in 306 (68.8%), with severity classified as Stage I in 38.9% (n = 173), Stage II in 17.5% (n = 78) and Stage III in 12.4% (n = 55). RRT was received by 36 (8.1%). Factors associated with AKI included longer duration of cardiopulmonary bypass [per minute, odds ratio (OR) 1.003; 95% confidence interval (CI), 1.001-1.006; P = 0.02], and mechanical ventilation [per hour (log-transformed), OR 5.30; 95% CI, 3.04-9.24; P < 0.001], and use of cyclosporine (OR 2.03; 95% CI, 1.13-3.64; P = 0.02). In-hospital and 1-year mortality were significantly higher in those with AKI compared with no AKI (7.2 versus 0%; adjusted P = 0.001; 14.4 versus 5.0%; adjusted P = 0.02, respectively). At 3 months, those with AKI had greater sustained loss of kidney function compared with no AKI [estimated glomerular filtration rate, mean (SD): 68.9 (25.7) versus 75.3 (22.1) mL/min/1.73 m(2), P = 0.01]. CONCLUSIONS By the KDIGO definition, AKI occurred in two-thirds of patients following LTx. AKI portended greater risk of death and loss of kidney function.

Association between transient acute kidney injury and morbidity and mortality after lung transplantation: a retrospective cohort study.

PURPOSE Acute kidney injury (AKI) is a common occurrence after lung transplantation (LTx). Whether transient AKI or early recovery is associated with improved outcome is uncertain. Our aim was to describe the incidence, factors, and outcomes associated with transient AKI after LTx. MATERIALS AND METHODS We performed a retrospective cohort study of all adult recipients of LTx at the University of Alberta between 1990 and 2011. Our primary outcome transient AKI was defined as return of serum creatinine below Kidney Disease-Improving Global Outcome AKI stage I within 7days after LTx. Secondary outcomes included occurrence of postoperative complications, mortality, and long-term kidney function. RESULTS Of 445 LTx patients enrolled, AKI occurred in 306 (68.8%) within the first week after LTx. Of these, transient AKI (or early recovery) occurred in 157 (51.3%). Transient AKI was associated with fewer complications including tracheostomy (17.2% vs 38.3%; P<.001), reintubation (16.4% vs 41.9%; P<.001), decreased duration of mechanical ventilation (median [interquartile range], 69 [41-142] vs 189 [63-403] hours; P<.001), and lower rates of chronic kidney disease at 3 months (28.5% vs 51.1%, P<.001) and 1 year (49.6% vs 66.7%, P=.01) compared with persistent AKI. Factors independently associated with persistent AKI were higher body mass index (per unit; odds ratio [OR], 0.91; 95% confidence interval, 0.85-0.98; P=.01), cyclosporine use (OR, 0.29; 0.12-0.67; P=.01), longer duration of mechanical ventilation (per hour [log transformed]; OR, 0.42; 0.21-0.81; P=.01), and AKI stages II to III (OR, 0.16; 0.08-0.29; P<.001). Persistent AKI was associated with higher adjusted hazard of death (hazard ratio, 1.77 [1.08-2.93]; P=.02) when compared with transient AKI (1.44 [0.93-2.19], P=.09) and no AKI (reference category), respectively. CONCLUSIONS Transient AKI after LTx is associated with fewer complications and improved survival. Among survivors, persistent AKI portends an increased risk for long-term chronic kidney disease.

A new model to predict acute kidney injury requiring renal replacement therapy after cardiac surgery

Background: Acute kidney injury after cardiac surgery is associated with adverse in-hospital and long-term outcomes. Novel risk factors for acute kidney injury have been identified, but it is unknown whether their incorporation into risk models substantially improves prediction of postoperative acute kidney injury requiring renal replacement therapy. Methods: We developed and validated a risk prediction model for acute kidney injury requiring renal replacement therapy within 14 days after cardiac surgery. We used demographic, and preoperative clinical and laboratory data from 2 independent cohorts of adults who underwent cardiac surgery (excluding transplantation) between Jan. 1, 2004, and Mar. 31, 2009. We developed the risk prediction model using multivariable logistic regression and compared it with existing models based on the C statistic, Hosmer–Lemeshow goodness-of-fit test and Net Reclassification Improvement index. Results: We identified 8 independent predictors of acute kidney injury requiring renal replacement therapy in the derivation model (adjusted odds ratio, 95% confidence interval [CI]): congestive heart failure (3.03, 2.00–4.58), Canadian Cardiovascular Society angina class III or higher (1.66, 1.15–2.40), diabetes mellitus (1.61, 1.12–2.31), baseline estimated glomerular filtration rate (0.96, 0.95–0.97), increasing hemoglobin concentration (0.85, 0.77–0.93), proteinuria (1.65, 1.07–2.54), coronary artery bypass graft (CABG) plus valve surgery (v. CABG only, 1.25, 0.64–2.43), other cardiac procedure (v. CABG only, 3.11, 2.12–4.58) and emergent status for surgery booking (4.63, 2.61–8.21). The 8-variable risk prediction model had excellent performance characteristics in the validation cohort (C statistic 0.83, 95% CI 0.79–0.86). The net reclassification improvement with the prediction model was 13.9% (p < 0.001) compared with the best existing risk prediction model (Cleveland Clinic Score). Interpretation: We have developed and validated a practical and accurate risk prediction model for acute kidney injury requiring renal replacement therapy after cardiac surgery based on routinely available preoperative clinical and laboratory data. The prediction model can be easily applied at the bedside and provides a simple and interpretable estimation of risk.

Role of preoperative intravenous iron therapy to correct anemia before major surgery: study protocol for systematic review and meta-analysis

BackgroundPreoperative anemia is a common and potentially serious hematological problem in elective surgery and increases the risk for perioperative red blood cell (RBC) transfusion. Transfusion is associated with postoperative morbidity and mortality. Preoperative intravenous (IV) iron therapy has been proposed as an intervention to reduce perioperative transfusion; however, studies are generally small, limited, and inconclusive.Methods/DesignWe propose performing a systematic review and meta-analysis. We will search MEDLINE, EMBASE, EBM Reviews, Cochrane-controlled trial registry, Scopus, registries of health technology assessment and clinical trials, Web of Science, ProQuest Dissertations and Theses, and conference proceedings in transfusion, hematology, and surgery. We will contact our study drug manufacturer for unpublished trials. Titles and abstracts will be identified and assessed by two reviewers for potential relevance. Eligible studies are: randomized or quasi-randomized clinical trials comparing preoperative administration of IV iron with placebo or standard of care to reduce perioperative blood transfusion in anemic patients undergoing major surgery. Screening, data extraction, and quality appraisal will be conducted independently by two authors. Data will be presented in evidence tables and in meta-analytic forest plots.Primary efficacy outcomes are change in hemoglobin concentration and proportion of patients requiring RBC transfusion. Secondary outcomes include number of units of blood or blood products transfused perioperatively, transfusion-related acute lung injury, neurologic complications, adverse events, postoperative infections, cardiopulmonary complications, intensive care unit (ICU) admission/readmission, length of hospital stay, acute kidney injury, and mortality.Dichotomous outcomes will be reported as pooled relative risks and 95% confidence intervals. Continuous outcomes will be reported using calculated weighted mean differences. Meta-regression will be performed to evaluate the impact of potential confounding variables on study effect estimates.DiscussionReducing unnecessary RBC transfusions in perioperative medicine is a clinical priority. This involves the identification of patients at risk of receiving transfusions along with blood conservation strategies. Of potential pharmacological blood conservation strategies, IV iron is a compelling intervention to treat preoperative anemia; however, existing data are uncertain. We propose performing a systematic review and meta-analysis evaluating the efficacy and safety of IV iron administration to anemic patients undergoing major surgery to reduce transfusion and perioperative morbidity and mortality.Systematic review registrationPROSPERO CRD42015016771

Pre-dismissal surveillance echocardiography second day after TAVR.

Transcatheter aortic valve implantation (TAVI) has been recognized as an alternative treatment for high-risk surgical patients with symptomatic severe aortic stenosis (AS). Valve migration is a potentially life-threatening complication of TAVI that usually occurs during implantation. Late (>24 h) ([