François Dagenais

Mitral-Valve Repair versus Replacement for Severe Ischemic Mitral Regurgitation

BACKGROUND Ischemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited. METHODS We randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank. RESULTS At 12 months, the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group (mean change from baseline, -6.6 and -6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio with repair, 0.79; 95% confidence interval, 0.42 to 1.47; P=0.45 by the log-rank test). There was no significant between-group difference in LVESVI after adjustment for death (z score, 1.33; P=0.18). The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group (32.6% vs. 2.3%, P<0.001). There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events, in functional status, or in quality of life at 12 months. CONCLUSIONS We observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes. (Funded by the National Institutes of Health and the Canadian Institutes of Health; ClinicalTrials.gov number, NCT00807040.).

Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation

BACKGROUND In a trial comparing coronary-artery bypass grafting (CABG) alone with CABG plus mitral-valve repair in patients with moderate ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI) or survival after 1 year. Concomitant mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation, but patients had more adverse events. We now report 2-year outcomes. METHODS We randomly assigned 301 patients to undergo either CABG alone or the combined procedure. Patients were followed for 2 years for clinical and echocardiographic outcomes. RESULTS At 2 years, the mean (±SD) LVESVI was 41.2±20.0 ml per square meter of body-surface area in the CABG-alone group and 43.2±20.6 ml per square meter in the combined-procedure group (mean improvement over baseline, -14.1 ml per square meter and -14.6 ml per square meter, respectively). The rate of death was 10.6% in the CABG-alone group and 10.0% in the combined-procedure group (hazard ratio in the combined-procedure group, 0.90; 95% confidence interval, 0.45 to 1.83; P=0.78). There was no significant between-group difference in the rank-based assessment of the LVESVI (including death) at 2 years (z score, 0.38; P=0.71). The 2-year rate of moderate or severe residual mitral regurgitation was higher in the CABG-alone group than in the combined-procedure group (32.3% vs. 11.2%, P<0.001). Overall rates of hospital readmission and serious adverse events were similar in the two groups, but neurologic events and supraventricular arrhythmias remained more frequent in the combined-procedure group. CONCLUSIONS In patients with moderate ischemic mitral regurgitation undergoing CABG, the addition of mitral-valve repair did not lead to significant differences in left ventricular reverse remodeling at 2 years. Mitral-valve repair provided a more durable correction of mitral regurgitation but did not significantly improve survival or reduce overall adverse events or readmissions and was associated with an early hazard of increased neurologic events and supraventricular arrhythmias. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

Surgical treatment of moderate ischemic mitral regurgitation.

BACKGROUND Ischemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitral-valve repair to coronary-artery bypass grafting (CABG) are uncertain. METHODS We randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair (combined procedure). The primary end point was the left ventricular end-systolic volume index (LVESVI), a measure of left ventricular remodeling, at 1 year. This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank. RESULTS At 1 year, the mean LVESVI among surviving patients was 46.1±22.4 ml per square meter of body-surface area in the CABG-alone group and 49.6±31.5 ml per square meter in the combined-procedure group (mean change from baseline, -9.4 and -9.3 ml per square meter, respectively). The rate of death was 6.7% in the combined-procedure group and 7.3% in the CABG-alone group (hazard ratio with mitral-valve repair, 0.90; 95% confidence interval, 0.38 to 2.12; P=0.81). The rank-based assessment of LVESVI at 1 year (incorporating deaths) showed no significant between-group difference (z score, 0.50; P=0.61). The addition of mitral-valve repair was associated with a longer bypass time (P<0.001), a longer hospital stay after surgery (P=0.002), and more neurologic events (P=0.03). Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group (11.2% vs. 31.0%, P<0.001). There were no significant between-group differences in major adverse cardiac or cerebrovascular events, deaths, readmissions, functional status, or quality of life at 1 year. CONCLUSIONS In patients with moderate ischemic mitral regurgitation, the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling. Mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation but an increased number of untoward events. Thus, at 1 year, this trial did not show a clinically meaningful advantage of adding mitral-valve repair to CABG. Longer-term follow-up may determine whether the lower prevalence of mitral regurgitation translates into a net clinical benefit. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

Nonrandomized Comparison of Coronary Artery Bypass Surgery and Percutaneous Coronary Intervention for the Treatment of Unprotected Left Main Coronary Artery Disease in Octogenarians

Background— The objective of the present study was to compare the midterm follow-up results of percutaneous coronary intervention (PCI) and coronary bypass graft surgery (CABG) for the treatment of unprotected left main coronary artery disease in octogenarians. Methods and Results— A total of 249 consecutive patients ≥80 years of age diagnosed with left main coronary artery disease underwent coronary revascularization in our center between January 2002 and January 2008; 145 patients underwent CABG, and 104 patients had PCI. Major adverse cardiac and cerebrovascular events (MACCE [cardiac death, myocardial infarction, cerebrovascular event, revascularization]) were evaluated at a mean follow-up of 23±16 months. Patients who underwent PCI were older; had higher creatinine levels, lower ejection fraction, and higher EuroSCORE; and presented more frequently with an acute coronary syndrome. Drug-eluting stents were used in 48% of PCI patients. A propensity score analysis was performed to adjust for baseline differences between the 2 groups. Survival free of cardiac death or myocardial infarction (PCI, 65.4%; CABG, 69.7%) and MACCE-free survival (PCI, 56.7%; CABG, 64.8%) at follow-up were similar between the groups (adjusted hazard ratio for survival free of cardiac death or myocardial infarction, 1.28; 95% CI, 0.64 to 2.56; P=0.47; adjusted hazard ratio for MACCE-free survival, 1.11; 95% CI, 0.59 to 2.0; P=0.73). The EuroSCORE value was an independent predictor of MACCE regardless of the type of revascularization (hazard ratio, 1.17 for each EuroSCORE increase of 1 point; 95% CI, 1.09 to 1.25; P<0.0001). Conclusions— In this single-center, nonrandomized study, there were no significant differences in cardiac death or myocardial infarction and MACCE between CABG and PCI for the treatment of left main coronary artery disease in octogenarians after a mean follow-up of 2 years. Baseline EuroSCORE was the most important predictor of MACCE regardless of the type of revascularization. Randomized studies comparing both revascularization strategies in this high-risk coronary population are warranted.

Impact of Prosthesis-Patient Mismatch on Long-Term Survival After Aortic Valve Replacement Influence of Age, Obesity, and Left Ventricular Dysfunction

OBJECTIVES This study was designed to evaluate the effect of valve prosthesis-patient mismatch (PPM) on late survival after aortic valve replacement (AVR) and to determine if this effect is modulated by patient age, body mass index (BMI), and pre-operative left ventricular (LV) function. BACKGROUND We recently reported that PPM is an independent predictor of operative mortality after AVR, particularly when associated with LV dysfunction. METHODS The indexed valve effective orifice area (EOA) was estimated in 2,576 patients having survived AVR and was used to define PPM as not clinically significant if it was >0.85 cm(2)/m(2), as moderate if >0.65 and < or =0.85 cm(2)/m(2), and severe if < or =0.65 cm(2)/m(2). RESULTS After adjustment for other risk factors, severe PPM was associated with increased late overall mortality (hazard ratio [HR]: 1.38; p = 0.03) and cardiovascular mortality (HR: 1.63; p = 0.0006) in the whole cohort. Severe PPM was also associated with increased overall mortality in patients <70 years old (HR: 1.77; p = 0.002) and in patients with a BMI <30 kg/m(2) (HR: 2.1; p = 0.006), but had no impact in older patients or in obese patients. Moderate PPM was a predictor of mortality in patients with LV ejection fraction <50% (HR: 1.21; p = 0.01), but not in patients with preserved LV function. CONCLUSIONS Moderate PPM is associated with increased late mortality in patients with LV dysfunction, but with normal prognosis in those with preserved LV function. Notwithstanding the previously demonstrated deleterious effect of severe PPM on early mortality, this factor appears to increase late mortality only in patients <70 years old and/or with a BMI <30 kg/m(2) or an LV ejection fraction <50%.

Restrictive annuloplasty for ischemic mitral regurgitation may induce functional mitral stenosis.

OBJECTIVES The purpose of this study was to evaluate mitral valve hemodynamic performance and functional capacity in patients with ischemic mitral regurgitation (MR) who underwent restrictive mitral valve annuloplasty (MVA). BACKGROUND Restrictive MVA combined with coronary artery bypass graft is the conventional approach for the surgical management of patients with ischemic MR. We hypothesized that the restriction of the mitral annulus could cause an obstruction to antegrade mitral flow that may affect the patients functional capacity. METHODS A dobutamine stress echocardiography (DSE) and a 6-min walk test (6MWT) were performed in 24 patients with ischemic MR 13 +/- 3 months after restrictive MVA and coronary artery bypass graft and in 20 control patients with coronary artery disease matched for age, gender, and left ventricular ejection fraction. RESULTS None of the 24 MVA patients had significant MR after operation. Compared with control patients, MVA patients had significantly (p < 0.001) higher resting and stress peak gradients (rest: 13 +/- 4 mm Hg vs. 4 +/- 1 mm Hg; DSE: 19 +/- 6 mm Hg vs. 6 +/- 3 mm Hg) and systolic pulmonary arterial pressures (PAP) (rest: 42 +/- 13 mm Hg vs. 27 +/- 8 mm Hg; DSE: 58 +/- 12 mm Hg vs. 38 +/- 11 mm Hg) and lower (p = 0.01) 6MWT distance (358 +/- 95 m vs. 433 +/- 61 m). The resting peak mitral gradient correlated with systolic PAP (r = -0.67; p = 0.001) and 6MWT distance (r = -0.78; p < 0.0001) in the MVA group. CONCLUSIONS The results suggest that performing a restrictive MVA in patients with ischemic MR may create a functional mitral stenosis. This hemodynamic sequel is associated with higher PAP and a worse functional capacity.

High Tidal Volumes in Mechanically Ventilated Patients Increase Organ Dysfunction after Cardiac Surgery

Background: High tidal volumes in patients with acute respiratory distress syndrome and acute lung injury lead to ventilator-induced lung injury and increased mortality. We evaluated the impact of tidal volumes on cardiac surgery outcomes. Methods: We examined prospectively recorded data from 3,434 consecutive adult patients who underwent cardiac surgery. Three groups of patients were defined based on the tidal volume delivered on arrival at the intensive care unit: (1) low: below 10, (2) traditional: 10–12, and (3) high: more than 12 ml/kg of predicted body weight. We assessed risk factors for three types of organ failure (prolonged mechanical ventilation, hemodynamic instability, and renal failure) and a prolonged stay in the intensive care unit. Results: The mean tidal volume/actual weight was 9.2 ml/kg, and the tidal volume/predicted body weight was 11.5 ml/kg. Low, traditional, and high tidal volumes were used in 724 (21.1%), 1567 (45.6%), and 1,143 patients (33.3%), respectively. Independent risks factors for high tidal volumes were body mass index of 30 or more (odds ratio [OR] 6.25; CI: 5.26–7.42; P < 0.001) and female sex (OR 4.33; CI: 3.64–5.15; P < 0.001). In the multivariate analysis, high and traditional tidal volumes were independent risk factors for organ failure, multiple organ failure, and prolonged stay in the intensive care unit. Organ failures were associated with increased intensive care unit stay, hospital mortality, and long-term mortality. Conclusion: Tidal volumes of more than 10 ml/kg are risk factors for organ failure and prolonged intensive care unit stay after cardiac surgery. Women and obese patients are particularly at risk of being ventilated with injurious tidal volumes.

High-Dose Tranexamic Acid Is an Independent Predictor of Early Seizure After Cardiopulmonary Bypass

BACKGROUND Risk factors associated with early seizure after cardiopulmonary bypass (CPB) were examined. The role of tranexamic acid in seizure development was evaluated. METHODS Early seizure was defined as a seizure occurring within 24 hours of CPB, without neurologic deficit or new lesion on brain imaging. Independent determinants of early seizure were examined by multivariate logistic regression modelling. RESULTS Between 2004 and 2009, early seizure occurred in 119 of 8,929 patients (1.3%). A significant increase in the yearly rate of early seizure was observed in 2004 (0.73%) vs 2009 (1.97%; p<0.0001). Multivariate analysis showed the following variables were independent predictors of early seizure: age older than 75 years (adjusted odds ratio [OR], 2.1; p=0.0001), open heart procedure (OR, 12.0; p<0.0001), preoperative renal failure (OR, 3.2; p<0.0001), peripheral vascular disease (OR, 1.8; p=0.02), and total tranexamic acid dose of 100 mg/kg or more (OR, 2.6; p<0.0001). Risk of seizure was related to tranexamic acid in a dose-dependent fashion, with higher doses associated with increased risk of seizure. The use of CO2 in a subset of patients undergoing open heart procedures did not decrease the incidence of early seizure (4.8% vs 2.5% for no CO2; p=0.27). Postoperative chest tube drainage and blood product use were similar between patients receiving low-dose and high-dose tranexamic acid. CONCLUSIONS High-dose tranexamic acid (≥100 mg/kg) is independently associated with an increased risk of early seizure. Future tranexamic acid trials should assess the blood-conserving effect of tranexamic acid at a lower dosage and specifically monitor for seizure occurrence.

Metabolic Syndrome Is Associated With Faster Degeneration of Bioprosthetic Valves

Background— Several studies have reported similarities between calcification of the native aortic valve and atherosclerosis. Recent studies also suggested that hypercholesterolemia may be a risk factor for calcific degeneration of bioprosthetic valves. The metabolic syndrome (MS) is associated with a higher risk of vascular atherosclerosis. We thus hypothesized that the atherogenic features of MS could accelerate bioprosthetic valve degeneration. Methods and Results— We included 217 patients who underwent aortic valve replacement with a bioprosthetic valve in the study. Of these patients, 71 patients (33%) had MS defined according to the modified criteria proposed by the National Cholesterol Education Program Adult Treatment Panel III. The annualized increase in mean transprosthetic gradient and the worsening of transprosthetic regurgitation measured by Doppler echocardiography were used to assess the deterioration of valve hemodynamic function. Patients with MS had higher progression of gradient (+4±5 mm Hg/year versus +2±2 mm Hg/year, P<0.001), higher proportion of ≥1/3 degree worsening of regurgitation (25% versus 12%, P=0.02), and higher proportion of valve function deterioration defined as regurgitation worsening and/or ≥3 mm Hg/year increase in gradient (41% versus 25%, P=0.02) when compared with patients without MS. On multivariate analysis, MS was an independent predictor of gradient progression (P=0.01), regurgitation worsening (P=0.02), and valve function deterioration (P=0.02). The other independent predictors were diabetes, renal insufficiency, and higher mean gradient at baseline. Conclusions— This is the first study to report that the MS is independently associated with faster bioprosthetic valve degeneration. This study could pave the way for the development of a new medical therapy able to significantly reduce the structural valve deterioration of bioprostheses.

Distribution of SPARC during neovascularisation of degenerative aortic stenosis

Objective: To examine the hypothesis that degenerative aortic stenosis (AS) is associated with the development of blood vessels and the expression of the secreted protein, acidic and rich in cysteine/osteonectin (SPARC), a matricellular protein that is involved in ossification, the modulation of angiogenesis and the production of metalloproteinases. Methods: 30 surgically excised AS valves and 20 normal aortic valves were studied. Results: Blood vessels were detected in the aortic valves from patients with degenerative AS, whereas normal valves were avascular structures. Blood vessels in AS valves expressed endothelial nitric oxide synthase, CD34 and von Willebrand factor (vWF). Blood vessels were located in three distinct regions: near calcified nodules, under the leaflet border and in rich cellular areas forming cell islands. Blood vessels were predominantly present in early and intermediate grades of calcification. Cell islands were densely populated by CD45-positive cells where endothelial cells (CD34+, vWF+) forming cord-like structures were present. Immunoblotting detected SPARC only in AS valves and immunohistological analysis located SPARC in mature blood vessels. The proportion of blood vessels positive for SPARC was higher in valves with a lower grade of calcification. In cell islands, SPARC was distributed to mature blood vessels and to macrophages, where it co-located with matrix metalloproteinase-9, whereas no expression was detected in endothelial cells forming cord-like structures. Conclusion: The localisation of SPARC to mature blood vessels and its predominant expression in AS valves with a lower calcification grade suggest that the spatial and temporal distribution of this matricellular protein is tightly controlled to participate in the neovascularisation of AS valves.