Emmanuel Le Bret

Right ventricular failure secondary to chronic overload in congenital heart disease: An experimental model for therapeutic innovation

OBJECTIVE Mortality and morbidity related to right ventricular failure remain a problem for the long-term outcome of congenital heart diseases. Therapeutic innovation requires establishing an animal model reproducing right ventricular dysfunction secondary to chronic pressure-volume overload. METHODS Right ventricular tract enlargement by transvalvular patch and pulmonary artery banding were created in 2-month-old piglets (n = 6) to mimic repaired tetralogy of Fallot. Age-matched piglets were used as controls (n = 5). Right ventricular function was evaluated at baseline and 3 and 4 months of follow-up by hemodynamic parameters and electrocardiography. Right ventricular tissue remodeling was characterized using cellular electrophysiologic and histologic analyses. RESULTS Four months after surgery, right ventricular peak pressure increased to 75% of systemic pressure and pulmonary regurgitation significantly progressed, end-systolic and end-diastolic volumes significantly increased, and efficient ejection fraction significantly decreased compared with controls. At 3 months, the slope of the end-systolic pressure-volume relationship was significantly elevated compared with baseline and controls; a significant rightward shift of the slope, returning to the baseline value, was observed at 4 months, whereas stroke work progressed at each step and was significantly higher than in controls. Four months after surgery, QRS duration was significantly prolonged as action potential duration. Significant fibrosis and myocyte hypertrophy without myolysis and inflammation were observed in the operated group at 4 months. CONCLUSION Various aspects of early right ventricular remodeling were analyzed in this model. This model reproduced evolving right ventricular alterations secondary to chronic volumetric and barometric overload, as observed in repaired tetralogy of Fallot with usual sequelae, and can be used for therapeutic innovation.

Diagnostic accuracy of dual-source multislice computed tomographic analysis for the preoperative detection of coronary artery anomalies in 100 patients with tetralogy of Fallot

OBJECTIVES A detailed preoperative evaluation of coronary anatomy is mandatory before surgical intervention for tetralogy of Fallot. In pediatric patients, the preoperative evaluation of coronary anatomy has relied classically on conventional angiographic analysis and, more recently, on echocardiographic analysis, which have well-known limitations and complications. Recent technological improvements allow the use of multislice computed tomographic analysis to evaluate coronary artery anatomy in very young children, even those with high heart rates. The purpose of this prospective study was to assess the accuracy of preoperative dual-source computed tomographic analysis in detecting coronary artery abnormalities by using surgical findings as the reference standard. METHODS We prospectively evaluated 100 patients with tetralogy of Fallot before surgical intervention between November 2006 and September 2009 by using dual-source computed tomographic analysis with either retrospective, electrocardiographically gated, helical computed tomographic analysis or prospective, electrocardiographically triggered, sequential computed tomographic acquisition. The patients had a median age of 6.8 months (range, 1.2 months-6.8 years) and a median weight of 7.9 kg (range, 3-30 kg). RESULTS Compared with surgical findings, dual-source computed tomographic analysis had 100% sensitivity and 100% specificity for detecting coronary artery abnormalities. Major coronary artery abnormalities were found in 7 (7%) patients. The radiation dose was low. CONCLUSIONS Dual-source computed tomographic analysis is an accurate and noninvasive tool for delineating coronary artery anatomy before surgical intervention in children with tetralogy of Fallot. Dual-source computed tomographic analysis might deserve to be used routinely instead of angiographic analysis and in combination with echocardiographic analysis for the preoperative assessment of patients with tetralogy of Fallot.

Right ventricular failure secondary to chronic overload in congenital heart diseases: benefits of cell therapy using human embryonic stem cell-derived cardiac progenitors.

OBJECTIVE Despite the increasing incidence of right ventricular (RV) failure in adult patients with congenital heart disease, current therapeutic options are still limited. By contrast to left-heart diseases, cell-based myocardial regeneration applied to the right ventricle is poorly studied, even though it may be a therapeutic solution. As human embryonic stem cell-derived cardiac progenitors seem to be good candidates owing to their proliferation capacity, our aim was to assess, in a large animal model of overloaded RV dysfunction, the feasibility and effects of such a cell therapy. METHODS Human MesP1(+)/SSEA-1(+) cardiogenic mesodermal cells were administered using multiple intramyocardial injections 4 months after a surgical procedure mimicking the repaired tetralogy of Fallot, and their effects were observed 3 months later on hemodynamic, rhythmic, and histologic parameters. RESULTS All pigs (sham n = 6, treated n = 6) survived without complication, and cell therapy was clinically well tolerated. Although functional, contractility, and energetics parameters evolved similarly in both groups, benefits regarding arrhythmic susceptibility were observed in the treated group, associated with a significant decrease of peri-myocyte fibrosis (5.71% ± 2.49% vs 12.12% ± 1.85%; P < .01) without interstitial fibrosis change (5.18% ± 0.81% vs 5.49% ± 1.01%). Such a decrease could be related to paracrine effects, as no human cells could be detected within the myocardium. CONCLUSIONS Cell therapy using intramyocardial injections of human MesP1(+)/SSEA-1(+) cardiogenic mesodermal cells seems to have benefits regarding overloaded RV tissue remodeling and arrhythmic susceptibility, but this mode of administration is not sufficient to obtain a significant improvement in RV function.

Reoperations for left atrioventricular valve dysfunction after repair of atrioventricular septal defect

OBJECTIVES Postoperative left atrioventricular valve (LAVV) dysfunction is known to be the principal risk factor influencing outcome after repair of all types of atrioventricular septal defect (AVSD). The purpose of the present study was to identify the risk factors for reoperation and to assess the outcomes after reoperation for LAVV dysfunction. METHODS Records of 412 patients who underwent anatomical repair for different types of AVSD from January 2000 to July 2012 were reviewed. The study group (n = 60) included 13 additional patients for whom repair ± LAVV reoperation was performed in a primary institution. Outcomes, independent risk factors, reoperation and death were analysed. RESULTS There were 7 early, (1.7%) and 1 late death. Forty-seven (11.4%) required 64 reoperations for LAVV dysfunction. The median delay for the first LAVV reoperation was 3.5 months (range: 5 days to 10.0 years). Unbalanced ventricles with small left ventricle [odds ratio (OR) = 4.06, 95% confidence interval (CI): 1.58-10.44, P = 0.004], double-orifice LAVV (OR = 5.04, 95% CI: 1.39-18.27, P = 0.014), prior palliative surgery (OR = 3.5, 95% CI: 1.14-10.8, P = 0.029) and discharge echocardiography documenting LAVV regurgitation grade >2 (OR = 21.96, 95% CI: 8.91-54.09, P < 0.001) were found to be independent risk factors for LAVV reoperation. Twelve-year survival and freedom from LAVV reoperation rates were, respectively, 96.1% (95% CI: 94.1-98.1) and 85.8% (95% CI: 81.3-90.3). Survival was significantly worse in patients who underwent LAVV reoperation (P < 0.001) and in those who underwent valve replacement vs valve repair (P = 0.020). CONCLUSION After AVSD repair, LAVV dysfunction appears to be the principal factor that influences outcome. It can usually be managed by repair. Need for multiple reoperations is not uncommon. Long-term outcome in patients with repaired LAVV is favourable.

Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery Associated With Severe Left Ventricular Dysfunction: Results in Normothermia

BACKGROUND Repair of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) carries a high risk of operation, particularly in those with poor left ventricular function. In this study, we assessed the outcomes of patients who presented with severe preoperative left ventricular dysfunction (shortening fraction <15%) who underwent the repair under normothermic bypass. METHODS Since September 2002, 21 infants with severe left ventricular dysfunction underwent surgical repair using a direct coronary reimplantation technique. Mean age of patients was 5.3 +/- 3.8 months. Moderate or severe mitral regurgitation present in 5 patients was not addressed at the operation. Repair was performed under normothermic cardiopulmonary bypass and myocardial protection was achieved by intermittent antegrade normothermic blood cardioplegia. RESULTS Mean cardiopulmonary bypass and cross-clamp times were 153.5 +/- 51 and 50 +/- 14.5 minutes, respectively. There was one (4.7%) early death because of sudden cardiac arrest 48 hours after successful weaning from mechanical ventilation. One patient required urgent left coronary artery stenting on the 34th postoperative day because of early reimplantation failure. There was no late death. Echocardiographic evaluation revealed a significant improvement in terms of shortening fraction (preoperative, 10.3 +/- 3.2% vs follow-up, 33 +/- 7.7%, p < 0.0001). CONCLUSIONS Our results suggest that the repair of anomalous origin of the left coronary artery from the pulmonary artery can be accomplished with acceptable mortality and morbidity rates even in patients having severely depressed left ventricular function. Normothermic cardiopulmonary bypass is safe and effective in children who have a limited tolerance to further ischemic insult.

Video-assisted thoracoscopic clipping of patent ductus arteriosus: close to the gold standard and minimally invasive competitor of percutaneous techniques.

Objective To review our 12-year experience in video-assisted thoracoscopic surgery (VATS) for patent ductus arteriosus. Methods VATS was performed in 743 patients. Three groups were compared: 24 low-birth-weight infants (LBWIs), 676 children between 2.5–25 kg and 43 boys > 25 kg. A diameter of > 8 mm was the main contraindication. For 85 consecutive patients, hospital stay underwent cost analysis. Results Median age was 1.6 years (range 5 days–33 years) and median weight 9.0 kg (range 1.2–65 kg). Mortality was nil. Median operative time was 20 min and hospital stay 2 days. Residual patency at discharge was 0% in LBWIs, 0.7% in children, and 4.7% in boys (P = NS) and 0, 0.3, and 4.7% at follow-up (P = 0.001). Persistent recurrent laryngeal nerve dysfunction was recorded in 4.2% of LBWIs, 0.3% of children and 0% of boys (P = 0.012). Total mean cost was 5954 ± 2110. Conclusions The success rate of VATS clipping compares favorably with the thoracotomic approach but without chest wall trauma and it may have a very favorable cost-effective therapeutic balance compared to transcatheter techniques.

Transcatheter Closure of Large Atrial Septal Defects Feasibility and Safety in a Large Adult and Pediatric Population

Background—Data are needed on the safety and efficacy of device closure of large atrial septal defects. Methods and Results—Between 1998 and 2013, 336 patients (161 children <15 years) with large, isolated, secundum atrial septal defects (balloon-stretched diameter ≥34 mm in adults or echocardiographic diameter >15 mm/m2 in children) were managed using the Amplatzer device, at the Marie Lannelongue Hospital. Transthoracic echocardiographic guidance was used starting in 2005 (n=219; 65.2%). Balloon-stretched diameter was >40 mm in 36 adults; mean values were 37.6±3.3 mm in other adults and 26.3±6.3 mm/m2 in children. Amplatzer closure was successful in 311 (92.6%; 95% confidence interval, 89%–95%) patients. Superior and posterior rim deficiencies were more common in failed than in successful procedures (superior, 24.0% versus 4.8%; P=0.002; and posterior, 32.0% versus 4.2%; P<0.001). Device migration occurred in 4 adults (2 cases each of surgical and transcatheter retrieval); in the 21 remaining failures, the device was unreleased and withdrawn. After a median follow-up of 10.0 years (2.5–17 years), all patients were alive with no history of late complications. Conclusions—Closure of large atrial septal defects using the Amplatzer device is safe and effective in both adults and children. Superior and posterior rim deficiencies are associated with procedural failure. Closure can be performed under transthoracic echocardiographic guidance in experienced centers. Early device migration is rare and can be safely managed by device extraction. Long-term follow-up showed no deaths or major late complications in our population of 311 patients.

Intra-diaphragmatic pacemaker implantation in very low weight premature neonate.

Implantation of a pacemaker (PM) in very low weight premature neonates can be a challenging procedure because of the actual dimension of generators. Ideal placement of the PM is still controversial. We describe a technique of intra-diaphragmatic PM implantation in a 1.3 kg neonate.

Tissue Doppler echocardiographic and color M-mode estimation of left atrial pressure in infants*

Objectives: Using recorded flow and tissue Doppler, we evaluated the relation of peak velocity of early transmitral Doppler filling (E)/early diastolic velocity of the lateral mitral annulus (Ea) ratio and of E/flow propagation velocity (Vp) ratio to mean left atrial pressure in infants after surgery for congenital heart disease. Design: Experimental design. Setting: Pediatric intensive care unit. Patients: Thirty-seven infants aged 4 (3–8) months. Interventions: Patients underwent postoperative invasive hemodynamic monitoring with simultaneously obtained Doppler measurements. Measurements and Main Results: Values are expressed as median (25th–75th percentiles). Heart rate was 145 (135–157) beats/min. Left atrial pressure was 10 (8–12) mm Hg with E/Ea 16 (12–19) and E/Vp 1.9 (1.3–2.4). E/Ea and E/Vp ratios were higher in patients with left atrial pressure >10 mm Hg (n = 18), than in patients with left atrial pressure ≤10 mm Hg (n = 19) (E/Ea, 16 [15–25] vs. 12 [9–17], p = .01; E/Vp, 2.3 [1.9–2.8] vs. 1.4 [1–1.9]. respectively, p = .001). At a cutoff point of 15, E/Ea sensitivity for left atrial pressure >10 mm Hg was 17 of 18 (94%) with specificity 13 of 18 (72%). At a cutoff point of 2, E/Vp sensitivity for left atrial pressure >10 mm Hg was 15 of 18 (83%) with specificity 16 of 18 (89%). Areas under the receiver operating characteristic curves were 0.76 (E/Ea) and 0.83 (E/Vp). Conclusions: Doppler ratios might be considered as promising noninvasive tools for left atrial pressure evaluation in infants after cardiac surgery.

Slide tracheoplasty in infant with congenital tracheal stenosis and tracheomalacia after esophageal atresia with tracheoesophageal fistula repair.

Slide tracheoplasty can be applied successfully to all types of long segment congenital tracheal stenosis. In case of short segment tracheal stenosis, direct resection and anastomosis is often preferred. We report a case illustrating a new side benefit of the slide tracheoplasty in a patient presenting a relatively short hypoplastic tracheal segment coexisting with tracheomalacia after EA with TEF repair.