Louis-Mathieu Stevens

Long-term outcomes after autograft versus homograft aortic root replacement in adults with aortic valve disease: a randomised controlled trial.

BACKGROUND The ideal substitute for aortic valve replacement in patients with aortic valve disease is not known. Our hypothesis was that the regulatory and adaptive properties of a living valve substitute could improve the long-term outcomes in patients. We therefore compared these outcomes after autograft aortic root replacement (Ross procedure) versus homograft aortic root replacement in adults. METHODS Male and female patients (<69 years) requiring aortic valve surgery were randomly assigned in a one-to-one ratio to receive an autograft or a homograft aortic root replacement in one centre in the UK. The random allocation sequence was computer generated. Treatment was not masked. The primary endpoint was survival of patients at 10 years after surgery. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN03530985. FINDINGS 228 patients were randomly assigned to receive an autograft or a homograft aortic root replacement. 12 patients were excluded because they were younger than 18 years; 108 in each group received the surgery they were assigned to and were analysed. There was one (<1%) perioperative death in the autograft group versus three (3%) in the homograft group (p=0.621). At 10 years, four patients died in the autograft group versus 15 in the homograft group. Actuarial survival at 10 years was 97% (SD 2) in the autograft group versus 83% (4) in the homograft group. Hazard ratio for death in the homograft group was 4.61 (95% CI 1.71-16.03; p=0.0060). Survival of patients in the autograft group was similar to that in an age-matched and sex-matched British population (96%). INTERPRETATION Our findings support the hypothesis that a living valve implanted in the aortic position can significantly improve the long-term outcomes in patients. FUNDING Funding Magdi Yacoub Institute.

Long-term outcomes after elective isolated mechanical aortic valve replacement in young adults

OBJECTIVES The aim of this study was to determine long-term survival and clinical outcomes after elective isolated mechanical aortic valve replacement in young adults. METHODS A clinical observational study was conducted in a cohort of 450 consecutive adults less than 65 years of age who had undergone elective isolated mechanical aortic valve replacement (AVR) between 1997 and 2006. Patients who had undergone previous cardiac surgery, and those undergoing concomitant procedures or urgent surgery were excluded. Follow-up was 93.3% complete with a mean follow-up of 9.1±3.5 years. The primary end point was survival. Life table analyses were used to determine age- and gender-matched general population survival. Secondary end points were reoperation and valve-related complications. RESULTS Overall actuarial survival at 1, 5, and 10 years was 98%±1%, 95%±1%, and 87%±1%, respectively, which was lower than expected in the age- and gender-matched general population in Quebec. Actuarial freedom from prosthetic valve dysfunction was 99%±0.4%, 95%±1%, and 91%±1% at 1, 5, and 10 years, respectively. Actuarial freedom from valve reintervention was 98%±1%, 96%±1%, and 94%±1% at 1, 5 and 10 years, respectively. Actuarial survival free from reoperation at 10 years was 82%±2%. Actuarial freedom from major hemorrhage was 98%±1%, 96%±1%, and 90%±2% at 1, 5, and 10 years, respectively. CONCLUSIONS In young adults undergoing elective isolated mechanical AVR, survival remains suboptimal compared with an age- and gender-matched general population. Furthermore, there is a low but constant hazard of prosthetic valve reintervention after mechanical AVR.

Impact of Timing and Surgical Approach on Outcomes After Mitral Valve Regurgitation Operations

BACKGROUND This study investigated whether the timing of mitral valve (MV) repair or surgical approach affects outcomes in patients with MV regurgitation. METHODS Between 1992 and 2009, 2,255 patients underwent MV operations, including 1,305 with isolated MV regurgitation operations (1,054 repairs, 251 replacements). Surgical approaches were sternotomy in 377, video-assisted right minithoracotomy in 481, or robot-assisted in 447. Mean follow-up was 6.4±4.5 years (maximum, 19 years). RESULTS Sternotomy MV repairs decreased during the study while minimally invasive MV repairs increased. Robotic MV repair patients were younger, with fewer women, had better left ventricular ejection fractions, and were more likely to have myxomatous degeneration (all p<0.001). The robotic approach led to a higher MV repair rate and increased use of leaflet/chordal procedures but had longer cardiopulmonary bypass and aortic cross-clamp times (all p<0.001). The 30-day mortality for isolated MV repair was similar for all approaches (p=0.409). Fewer neurological events were observed in the videoscopic and robotic groups (p=0.013). Adjusted survival was similar for all approaches (p=0.357). Survival in patients in New York Heart Association class I to II with myxomatous degeneration or annular dilatation was similar to a matched population but was worse for patients in class III to IV or undergoing MV replacement. CONCLUSIONS MV repair in patients with severe MV regurgitation should be performed before New York Heart Association class III to IV symptoms develop. Minimally invasive MV repair techniques render similar outcomes as the sternotomy approach.

Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer

PURPOSE Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients who underwent radical prostatectomy. EXPERIMENTAL DESIGN A set of 1826 fully annotated prostate cancers treated by radical prostatectomy were analysed in a tissue microarray (TMA) format for NF-κB p65 immunohistochemistry-based protein expression. We performed standard Cox proportional hazard regression models for follow-up data, bootstrap procedure for model internal validation, Harrells concordance index for model discrimination and graphical assessment of predicted versus actual outcomes for model calibration. RESULTS We observed a significant association between an increase in the nuclear frequency of NF-κB p65 and Gleason score (P<0.001), overall BCR (P<0.001) and development of metastases (P=0.001). NF-κB was found to be an independent predictor of BCR (P<0.001, Cox regression). However its contribution to the predictive accuracy of a multivariate model, which included preoperative PSA, Gleason score, extraprostatic extension, lymph node invasion, seminal vesicle involvement and surgical margin status, was modest. CONCLUSIONS Our study offers validating results linking NF-κB p65 with disease progression using a large cohort of European men. However, the contribution of NF-κB to a post-surgical predictive model appears modest. Further validating work should focus on evaluating the contribution of NF-κB p65 in pre-treatment models.

Early results of extra-aortic annuloplasty ring implantation on aortic annular dimensions.

OBJECTIVES Dilatation of the aortic annulus is a cause of recurrent aortic regurgitation following the Ross or Yacoub procedures. Use of an extra-aortic annuloplasty ring is a potentially useful adjunct procedure. The aim of this study was to analyze the early effectiveness and mid-term stability of this surgical approach. METHODS From 2011 to 2015, 50 patients (mean age, 43 ± 14 years) underwent adjunct extra-aortic annuloplasty ring implantation (n = 39 Dacron rings and n = 11 ExAo rings [CORONEO Inc, Montreal, Canada]). Median ring size was 28 mm (range, 27-32 mm). All patients had aortic regurgitation or a dilated aortic annulus. Concomitant surgical procedure was a valve-sparing remodeling procedure (n = 32) or a Ross procedure (n = 18). Baseline and follow-up echocardiographic systolic and diastolic aortic annular dimensions were prospectively collected. Longitudinal analyses were performed using mixed-effect models. Median follow-up was 12 months (98% complete). RESULTS Use of an extra-aortic annuloplasty ring resulted in a significant decrease in both systolic (27.9 ± 0.5 mm preoperatively vs 23.6 ± 0.3 mm at discharge, P < .001) and diastolic (24.8 ± 0.4 mm preoperatively vs 20.3 ± 0.3 mm at discharge, P < .001) dimensions. Mean systolic and diastolic dimensions remained statistically unchanged up to 2 years postoperatively, compared with their predischarge values. Systolic expansion of the annulus was conserved early after surgery (16% systolic expansion) and preserved up to 2 years after ring implantation. CONCLUSIONS Use of an extra-aortic annuloplasty ring is effective at reducing annular diameters. This remains stable at mid-term follow-up, with preservation of aortic annular dynamics. Longer-term studies are required to determine the continued stability and impact on long-term clinical outcomes.

Microaxial Devices for Ventricular Failure: A Multicentre, Population-Based Experience

BACKGROUND Impella microaxial devices provide circulatory assistance for patients with acute decompensated heart failure. This study reviews the population-based provincial experience in British Columbia. METHODS We performed a retrospective review of the prospectively maintained database. Impella devices were inserted for acute cardiogenic shock refractory to maximal therapy, as a bridge to decision or to long-term mechanical support. RESULTS Between August 2007 and September 2009, 35 patients received 37 Impella devices (Impella LP 2,5, n=2; Impella LP 5,0, n=29; and Impella RD 5.0, n=6) (Abiomed Inc, Danvers, MA). Devices were inserted in the setting of dilated cardiomyopathy (n=13), acute myocardial infarction (n=6), postcardiotomy shock (n=6), and other etiologies (n=12). Mean age was 53.0±13.7 years. Mean left ventricular ejection fraction was 19±9% at the time of insertion. Nineteen patients required aggressive resuscitation, all patients were on inotropic support, 97% of patients were intubated, and 46% of patients received mechanical circulatory support prior to insertion of the Impella devices. Mean duration of support was 3.7±3.0 days. In all, 49% were successfully weaned, and 22% were transferred to long-term mechanical support. Four patients have subsequently undergone successful cardiac transplantation. The 30-day mortality was 40%, and 6-month mortality was 49%. Complications included gastrointestinal bleeding (n=1), hemoptysis (n=1), and thrombocytopenia (n=4). There were no cardiovascular or cerebrovascular events. CONCLUSION Temporary support with Impella microaxial ventricular assist devices adds a valuable therapeutic option in selected patients with acute decompensated heart failure.

Twenty-year experience with the CarboMedics mechanical valve prosthesis.

BACKGROUND The CarboMedics mechanical prosthesis (CarboMedics Inc, Austin, TX) has been used for mitral and aortic valve replacement for more than 20 years in our institution. This study describes the long-term survival of patients with this prosthesis as well as the valve-related events. METHODS Between June 1988 and May 2010, 3,297 patients underwent either single aortic valve replacement (AVR) (2,242 patients) or mitral valve replacement (MVR) (1,055 patients) with the CarboMedics mechanical valve prosthesis. They were followed annually for valve-related complications at the Montreal Heart Institute valve clinic. RESULTS Operative mortality was 4% with AVR and 7% with MVR. Total follow-up was 23,671 patient-years (range, 1 month to 21 years; average, 7.5 ± 5.3 years). At 20 years, patient freedom from late mortality was 43.2% in the AVR group and 40.9% in the MVR group. Freedom from valve-related mortality was 78.3% for AVR and 74.6% for MVR. Freedom from thromboembolic event was 91.6% for AVR and 88.5% for MVR. Freedom from reoperation was 89.2% for AVR and 80.3% for MVR. Freedom from bleeding event was 89.5% for AVR and 88% for MVR. Freedom from endocarditis was 97.3% for both AVR and MVR. Freedom from valve thrombosis was 98.9% for AVR and 91.4% for MVR. There was no structural valve failure in our cohort. CONCLUSIONS The CarboMedics valve is an effective and durable mechanical valve prosthesis with a low event rate and no structural failure at 20 years.

Stem Cell Therapy for the Treatment of Nonischemic Cardiomyopathy: A Systematic Review of the Literature and Meta-analysis of Randomized Controlled Trials

BACKGROUND Stem cell (SC) therapy improves left ventricular function and dimensions in ischemic heart disease. Few small-scale trials have studied the effects of SC therapy on nonischemic cardiomyopathy (CMP), the leading cause of heart transplantation in the adults. The objectives were to gain a better insight into the effects of SC therapy for nonischemic CMP by conducting a systematic review of the literature and meta-analysis of randomized controlled trials. METHODS Medline, EBM Reviews-Cochrane Central Register of Controlled Trials, Embase, and the ClinicalTrials.gov databases were screened for randomized controlled trials involving SC for treatment of nonischemic CMP. Weighted mean differences of improvement of left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) were calculated using a random effect analysis model. RESULTS Four trials were included in this meta-analysis (244 patients). The weighted mean LVEF improvement was 4.87% (95% confidence interval, 1.32-8.43%) in the treatment group compared with the control group (P = 0.01). The weighted mean decrease of LVEDD in the treatment group was of -2.19 mm (95% confidence interval, -5.69 to 1.30) compared with the control group (P = 0.22). On subgroup analysis, results were similar in studies involving peripheral CD34-positive or bone marrow-derived mononuclear cells (P = 0.33 for subgroup differences). CONCLUSIONS This is the first meta-analysis to show that for the treatment of nonischemic CMP, SC therapy might improve LVEF, but not LVEDD. Further trials should aim to circumscribe the optimal SC regimen in this setting, and to assess long-term clinical outcomes as primary end points.

Is the Ross procedure a riskier operation? Perioperative outcome comparison with mechanical aortic valve replacement in a propensity-matched cohort.

OBJECTIVES The aim of this study was to compare perioperative outcomes in young adults following isolated Ross procedure versus mechanical aortic valve replacement (AVR) in a high-volume centre. METHODS From 2007 to 2015, 337 elective isolated mechanical AVRs and 137 Ross procedures were performed in young adults (<65 years) at our centre. Using a 1:1 propensity score match analysis, 140 patients were included in the study (n = 70 in each group). Perioperative outcomes were defined using STS guidelines. The primary outcome was operative mortality. RESULTS Median age was 52 [14] years and EuroSCORE II was 1.0 [0.4]%. There were no mortalities in the two groups. There were no differences in the incidence of myocardial injury (0% overall) and neurological complications (0.7% overall). Three (4%) reinterventions for bleeding were required in the Ross cohort versus six (9%) in the mechanical AVR cohort (P = 0.49). A significant increase in serum creatinine (>2-fold increase) was more commonly observed after the Ross procedure (11 vs 1%; P = 0.03), but there was no significant difference in the rate of temporary dialysis. Twenty-seven patients (39%) required ≥1 blood product transfusion in the Ross group, whereas 21 patients (31%) did so in the mechanical AVR group (P = 0.47). Median hospital length of stay was similar in both the groups (6 days). CONCLUSIONS There are no differences in mortality or major perioperative outcomes in adults undergoing an isolated Ross procedure or mechanical AVR.

256-Slice CT Angiographic Evaluation of Coronary Artery Bypass Grafts: Effect of Heart Rate, Heart Rate Variability and Z-Axis Location on Image Quality

Purpose The objective of this study is to assess the effect of heart rate, heart rate variability and z-axis location on coronary artery bypass graft (CABG) image quality using a 256-slice computed tomography (CT) scanner. Methods A total of 78 patients with 254 CABG (762 graft segments) were recruited to undergo CABG assessment with 256-slice CT and prospective ECG-gating. Two observers rated graft segments for image quality on a 5-point scale. Quantitative measurements were also made. Logistic and cumulative link mixed models were used to assess the predictors of graft image quality. Results Graft image quality was judged as diagnostic (scores 5 (excellent), 4 (good) and 3 (moderate)) in 96.6% of the 762 segments. Interobserver agreement was excellent (kappa ≥0.90). Graft image quality was not affected by heart rate level. However, high heart rate variability was associated with an important and significant image quality deterioration (odds ratio 4.31; p  =  0.036). Distal graft segments had significantly lower image quality scores than proximal segments (p ≤ 0.02). Significantly higher noise was noted at the origin of the mammary grafts (p  =  0.001), owing to streak artifacts from the shoulders. Conclusion CABG imaging with 270-msec rotation 256-slice CT and prospective ECG-gating showed an adequate image quality in 96.6% of graft segments, and an excellent interobserver agreement. Graft image quality was not influenced by heart rate level. Image quality scores were however significantly decreased in patients with high heart rate variability, as well as in distal graft segments, which are closer to the heart.