Jean-Francois Légaré

Acute Kidney Injury After Cardiac Surgery Focus on Modifiable Risk Factors

Background— Acute kidney injury (AKI) after cardiac surgery is a major health issue. Lacking effective therapies, risk factor modification may offer a means of preventing this complication. The objective of the present study was to identify and determine the prognostic importance of such risk factors. Methods and Results— Data from a multicenter cohort of 3500 adult patients who underwent cardiac surgery at 7 hospitals during 2004 were analyzed (using multivariable logistic regression modeling) to determine the independent relationships between 3 thresholds of AKI (>25%, >50%, and >75% decrease in estimated glomerular filtration rate within 1 week of surgery or need for postoperative dialysis) with death rates, as well as to identify modifiable risk factors for AKI. The 3 thresholds of AKI occurred in 24% (n=829), 7% (n=228), and 3% (n=119) of the cohort, respectively. All 3 thresholds were independently associated with a >4-fold increase in the odds of death and could be predicted with several perioperative variables, including preoperative intra-aortic balloon pump use, urgent surgery, and prolonged cardiopulmonary bypass. In particular, 3 potentially modifiable variables were also independently and strongly associated with AKI. These were preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration. Conclusions— AKI after cardiac surgery is highly prevalent and prognostically important. Therapies aimed at mitigating preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration may offer protection against this complication.

Preoperative prediction of prolonged mechanical ventilation following coronary artery bypass grafting

OBJECTIVE Few studies have attempted to evaluate who would require prolonged mechanical ventilation following heart surgery. The objectives of this study were to identify predictors of prolonged ventilation in a large group of coronary artery bypass grafting (CABG) patients from a single institution. METHODS One thousand, eight hundred and twenty-nine consecutive patients undergoing CABG were reviewed retrospectively and evaluated for preoperative predictors of prolonged ventilation which included: age, gender, ejection fraction (EF), renal function, diabetes, angina status, New York Heart Association Class, number of diseased vessels, urgency of the procedure, re-operation, chronic lung disease (COPD) and intraoperative variables such as IABP, inotropes, stroke and myocardial infarction. Prolonged ventilation was defined as > or = 24 h. Stepwise logistic regression analysis was performed. RESULTS Patients were on average 65.4+/-10.6 years of age, 30% were diabetic, 80% had triple vessel disease and 93% were of functional class III/IV. The mean ejection fraction was 60+/-16 percent. Overall peri-operative mortality was 2.7%. There were 157 patients that required prolonged ventilation with a peri-operative mortality of 18.5% (P < 0.001). Preoperative independent predictors of prolonged ventilation were found to be: unstable angina (OR 5.6), EF < 50 (OR 2.3), COPD (OR 2.0), preop. renal failure (OR 1.9), female gender (OR 1.8) and age > 70 (OR 1.7). Based on these predictors, a model was created to estimate of the risk of prolonged ventilation in individual patients following CABG with results ranging from < or = 3% in patients without any risk factors to > or = 32% in patients with five or more independent risk factors. Certain intraoperative variables were strong predictors of prolonged ventilation and included: stroke (OR 12.3), re-operation for bleeding (OR 6.9) and perioperative MI (OR 5.8). CONCLUSION We were able to create a stable model where several preoperative and intra-operative variables were shown to be predictive of prolonged ventilation after CABG surgery. The ability to identify patients at increased risk for prolonged ventilation may allow the development of pre-emptive strategies and more effective resource allocation.

Is it safe to train residents to perform cardiac surgery

BACKGROUND The impact of surgical training on patient outcomes in cardiac surgery is unknown. METHODS All cases performed by residents from 1998 to 2001 were compared to staff surgeon cases using prospectively collected data. Operative mortality and a composite morbidity of: reoperation for bleeding perioperative myocardial infarction, infection, stroke, or ventilation more than 24 hours were compared using multivariate analysis. RESULTS Four residents performed 584 cases. The cases were as follows: coronary artery bypass grafting (CABG), 366 cases; aortic valve replacement (AVR) with or without CABG (AVR +/- CABG), 86 cases; mitral valve replacement, 31 cases; mitral valve repair, 25 cases; thoracic aneurysm/dissection, 22 cases; aortic root, 20 cases; transplantations, 14 cases; and adult congenital defect repairs, 20 cases. There were 2,638 CABGs and 363 AVR +/- CABG performed by the staff during the same period. Crude operative mortality in CABG patients was 2.5% (resident) and 2.9% (staff) (p = 0.62). In multivariate analysis, resident was not associated with operative mortality odds ratio (OR) of 0.59 (p = 0.19). Resident cases had a higher incidence of the composite morbidity outcome for CABG cases (19.4% vs 13.6% for staff; p = 0.003). However, in multivariate analysis, resident was not associated with increased morbidity (OR = 1.23, p = 0.16). The AVR +/- CABG crude mortality was 3.6% (resident) and 2.8% (staff) (p = 0.69). Because of the small number of cases (n = 447), operative mortality was combined with the composite morbidity outcome for the AVR +/- CABG model. In all, 16.7% of resident cases and 19.8% of staff cases had the composite outcome or died (p = 0.51). In multivariate analysis resident was not associated with this outcome (OR = 0.74, p = 0.35). CONCLUSIONS In this analysis of our experience with residency training, the operative morbidity and mortality in CABG and AVR patients was similar for residents and staff. Training residents to perform cardiac surgery appears to be safe.

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.

The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is not appropriate for withholding surgery in high-risk patients with aortic stenosis: a retrospective cohort study

BackgroundThe European System for Cardiac Operative Risk Evaluation (EuroSCORE) is a widely used risk assessment tool in patients with severe aortic stenosis to determine operability and to select patients for alternative therapies such as transcatheter aortic valve implantation. The objective of this study was to determine the accuracy of the EuroSCORE in predicting mortality following aortic valve replacement (AVR).MethodsThe logistic EuroSCORE was determined for all consecutive patients that underwent conventional AVR between 1995 and 2005 at our institution. Provincial Vital Statistics were used to determine all-cause mortality. The accuracy of the prognostic risk prediction provided by logistic EuroSCORE was assessed by comparing observed and expected operative mortality.ResultsDuring the study period, a total of 1,421 patients underwent AVR including 237 patients (16.7%) that had a logistic EuroSCORE > 20. Among these patients, the mean predicted operative mortality was 38.7% (SD = 18.1). The actual mortality of these patients was significantly lower than that predicted by EuroSCORE (11.4% vs. 38.7%, observed/expected ratio 0.29, 95% CI 0.15–0.52, P < 0.05). The EuroSCORE overestimated mortality within all strata of predicted risk. Although medium-term mortality is significantly higher among patients with EuroSCORE > 20 (log rank P = 0.0001), approximately 60% are alive at five years.ConclusionActual operative mortality in patients undergoing AVR is significantly lower than that predicted by the logistic EuroSCORE. Additionally, medium-term survival following AVR is acceptable in high-risk patients with EuroSCORE > 20. More accurate risk prediction models are needed for risk-stratifying patients with severe aortic stenosis.

Myocardial fibrosis in response to Angiotensin II is preceded by the recruitment of mesenchymal progenitor cells

Myocardial fibrosis is characterized by significant extracellular matrix (ECM) deposition. The specific cellular mediators that contribute to the development of fibrosis are not well understood. Using a model of fibrosis with Angiotensin II (AngII) infusion, our aim was to characterize the cellular elements involved in the development of myocardial fibrosis. Male C57Bl/6 and Tie2-GFP mice were given AngII (2.0 mg/kg/min) or saline (control) via mini osmotic pumps for up to 7 days. Hearts were harvested, weighed and processed for analysis. Cellular infiltration and collagen deposition were quantified. Immunostaining was performed for specific markers of leukocytes (CD45, CD11b), myofibroblasts (SMA), endothelial cells (vWF) and hematopoietic progenitor cells (CD133). Bone marrow (BM) origin of infiltrating cells was assessed using GFP+ chimeric animals. Relative qRT–PCR was performed for pro-fibrotic cytokines (transforming growth factor (TGF)-β1, CTGF) as well as the chemokine stromal-derived factor (SDF)-1α. Myocardial-infiltrating cells were grown in vitro. AngII exposure resulted in multifocal myocardial cellular infiltration, which preceded extensive ECM deposition. A limited number of myocardial-infiltrating cells were positive for leukocyte markers but were significantly positive for myofibroblast (SMA) and endothelial cell (vWF) markers. However, using Tie2-GFP mice, where endothelial cells are GFP+, myocardial-infiltrating cells were not GFP+. Transcript levels for SDF-1α were significantly elevated at 1 day of AngII exposure suggesting that hematopoietic progenitor cells may be recruited. This was confirmed by positive CD133 staining of infiltrating cells and evident GFP+ cellular infiltration when exposing GFP+ BM chimeras to AngII. Furthermore, a significant number of CD133+/SMA+ cells were grown in vitro from the myocardium of AngII-exposed animals (P<0.01). Myocardial ECM deposition is preceded by the infiltration of the myocardium with hematopoietic cells that express mesenchymal markers. These data suggest that mesenchymal progenitor cells are recruited, and may have a primary role, in the initiation of myocardial fibrosis.

New Onset Postoperative Atrial Fibrillation is Associated with a Long-Term Risk for Stroke and Death Following Cardiac Surgery†

We sought to evaluate the long‐term impact of post‐cardiac surgery atrial fibrillation on the risk of stroke and survival.

Results of Collis gastroplasty and selective fundoplication, using a left thoracoabdominal approach, for failed antireflux surgery.

OBJECTIVE To study patterns of failure following primary antireflux surgery and to evaluate efficacy of reoperation using a left thoracoabdominal Collis gastroplasty and selective fundoplication. METHODS Thirty-one patients who underwent reoperative antireflux surgery between 1991 and 2000 were studied. Transabdominal fundoplication had been performed in 21 patients, and ten patients had a partial fundoplication by left thoracotomy, 1-33 years (mean, 15 years) previously. All patients presented with clinically disabling symptoms. Objective studies documented for all patients, a disrupted fundoplication, a short esophagus, and an associated hiatus hernia (Type I: 21 patients, 68%; Type III: ten patients, 32%), esophagitis (nine patients, 29%), and Barretts mucosa (five patients, 16%). Abnormal esophageal motility was found in nine of 26 (36%) patients studied. All patients were reoperated using a left thoracoabdominal approach, with epidural analgesia. A Collis gastroplasty was used to lengthen the esophagus, incorporating a complete (24 patients, 77%) or partial (seven patients, 23%) fundoplication based of preoperative esophageal function studies. RESULTS There was no perioperative mortality. Median length of hospitalization was 8 days, and was uncomplicated for 18 (58%) patients. Postoperative morbidity was considered minimal, and comprised left lower lobe infiltrates (six patients, 19%), atrial fibrillation (three patients, 10%), urinary tract infection (one patient, 3%), superficial wound infection (one patient, 3%), aspiration (one patient, 3%), and nausea (one patient, 3%). Median follow-up was 42 months (6-105 months), and was complete for 29 patients. Six patients (21%) had moderate-severe post-thoracotomy pain, for up to 18 months postoperatively, and five patients (17%) required esophageal dilation, ranging from two to six dilations within the first 6 months after surgery. Overall, 93% (27/29) of patients were satisfied with the results of surgery, in terms of quality of swallowing and control of preoperative symptoms. CONCLUSIONS In this series, failure of primary antireflux surgery was related to short esophagus. Intermediate-term subjective results of reoperative antireflux surgery were good for selected patients who undergo esophageal lengthening and fundoplication. The left thoracoabdominal approach was safe, generally well tolerated, and provided excellent exposure of the esophagogastric junction for complex reoperative antireflux surgery.

Protocol for the PREHAB study—Pre-operative Rehabilitation for reduction of Hospitalization After coronary Bypass and valvular surgery: a randomised controlled trial

Introduction Frailty is a geriatric syndrome characterised by reductions in muscle mass, strength, endurance and activity level. The frailty syndrome, prevalent in 25–50% of patients undergoing cardiac surgery, is associated with increased rates of mortality and major morbidity as well as function decline postoperatively. This trial will compare a preoperative, interdisciplinary exercise and health promotion intervention to current standard of care (StanC) for elective coronary artery bypass and valvular surgery patients for the purpose of determining if the intervention improves 3-month and 12-month clinical outcomes among a population of frail patients waiting for elective cardiac surgery. Methods and analysis This is a multicentre, randomised, open end point, controlled trial using assessor blinding and intent-to-treat analysis. Two-hundred and forty-four elective cardiac surgical patients will be recruited and randomised to receive either StanC or StanC plus an 8-week exercise and education intervention at a certified medical fitness facility. Patients will attend two weekly sessions and aerobic exercise will be prescribed at 40–60% of heart rate reserve. Data collection will occur at baseline, 1–2 weeks preoperatively, and at 3 and 12 months postoperatively. The primary outcome of the trial will be the proportion of patients requiring a hospital length of stay greater than 7 days. Potential impact of study The healthcare team is faced with an increasingly complex older adult patient population. As such, this trial aims to provide novel evidence supporting a health intervention to ensure that frail, older adult patients thrive after undergoing cardiac surgery. Ethics and dissemination Trial results will be published in peer-reviewed journals, and presented at national and international scientific meetings. The University of Manitoba Health Research Ethics Board has approved the study protocol V.1.3, dated 11 August 2014 (H2014:208). Trial registration number The trial has been registered on ClinicalTrials.gov, a registry and results database of privately and publicly funded clinical studies (NCT02219815).

Fibroblast progenitor cells are recruited into the myocardium prior to the development of myocardial fibrosis

Using an established model of myocardial hypertrophy and fibrosis after angiotensin II (AngII) infusion, our aim was to characterize the early cellular element involved in the development of myocardial fibrosis in detail. Male Lewis rats were infused with saline or AngII (0.7 mg/kg per day) for up to seven days. Collagen deposition and cellular infiltration were identified by histology stains. Infiltrating cells were grown in vitro and examined by flow cytometry and immunostaining. Chemokine expression was measured using qRT‐PCR. AngII infusion resulted in multifocal myocardial cellular infiltration (peak at three days) that preceded collagen deposition. Monocyte chemotactic protein (MCP)‐1 transcripts peaked after one day of AngII exposure. Using a triple‐labelling technique, the infiltrating cells were found to express markers of leucocyte (ED1+), mesenchymal [α‐smooth muscle actin (SMA)+] and haematopeotic progenitor cells (CD133+) suggesting a fibroblast progenitor phenotype. In vitro, ED1+/SMA+/CD133+ cells were isolated and grown from AngII‐exposed animals. Comparatively few cells were cultured from untreated control hearts, and they were found to be ED1−/SMA+/CD133−. We provide evidence that myocardial ECM deposition is preceded by infiltration into the myocardium by cells that express a combination of haematopoietic (ED1, CD133) and mesenchymal (SMA) cell markers, which is a characteristic of the phenotype of fibroblast precursor cells, termed fibrocytes. This suggests that fibrocytes rather than (as is often presumed) leucocytes may have effector functions in the initiation of myocardial fibrosis.