BACKGROUND: The long-term effectiveness of pulmonary arterial hypertension specific drug therapy (PAH-SDT) in Eisenmenger syndrome is controversial. We investigated short-term and long-term hemodynamic changes under PAH-SDT and their associations with outcomes in a bicentric cohort.METHODS: Over 20 years, we included 69 patients with congenital heart disease, an indexed pulmonary vascular resistance (PVRi) > 8 WU . m(2), and 292 standardized catheterizations at baseline and after PAH-SDT initiation or intensification. Oxygen consumption was measured and the Fick principle applied to calculate indexed pulmonary output (Qpi) and PVRi.RESULTS: After PAH-SDT initiation or intensification, median (interquartile range) PVRi decrease was 5.1 WU . m(2) (-1.4, 12.6) (p < 0.0001). Median Qpi and 6-minute walk test increases were +0.4 liter/min/m(2) (0.0, +0.9) (p < 0.0001) and +49 m (+15, +93) (p = 0.0003), respectively. Hemodynamic response combining increased Qpi with decreases in transpulmonary gradient and PVRi occurred in 68.0% of patients. After a median of 4.9 years, PVRi and Qpi changes were no longer significant. Over a median of 7.2 years, 23 (33.3%) patients met a composite criterion (death, n = 8; heart-lung transplantation or listing for transplantation, n = 15). The 15-year cumulative event rate was 49.2%. By multivariate analysis, independent predictors of events were superior vena cava oxygen saturation and hemodynamic response (p = 0.048 and p < 0.0001).CONCLUSIONS: In Eisenmenger syndrome, PAH-SDT induces early hemodynamic improvements, which decline over time. Hemodynamic changes under PAH-SDT vary across patients. Hemodynamic parameters at baseline and under PAH-SDT are associated with events. PAH-SDT may need to be individualized based on hemodynamic changes. (C) 2017 International Society for Heart and Lung Transplantation. All rights reserved.

Background: Early detection of right ventricular (RV) failure is required to improve the management of patients with congenital heart diseases. The aim of this study was to validate echocardiography for the early detection of overloaded RV dysfunction, compared with hemodynamic and myocyte contractility assessment. Methods: Using a porcine model reproducing repaired tetralogy of Fallot, RV function was evaluated over 4 months using standard echocardiography and speckle-tracking compared with hemodynamic parameters (conductance catheter). Sarcomere shortening and calcium transients were recorded in RV isolated myocytes. Contractile reserve (Delta E-max) was assessed by beta-adrenergic stimulation in vivo (dobutamine 5 mu g/kg) and ex vivo (isoproterenol 100 nM). Results: Six operated animals were compared with four age- and sex-matched controls. In the operated group, hemodynamic RV efficient ejection fraction was significantly decreased (29.7% [26.2%-34%] vs 42.9% [40.7%- 48.6%], P <.01), and inotropic responses to dobutamine were attenuated (Delta E-max was 51% vs 193%, P <.05). Echocardiographic measurements of fraction of area change, tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity (S') and RV free wall longitudinal systolic strain and strain rate were significantly decreased. Strain rate, S', and tricuspid annular plane systolic excursion were correlated with DEmax (r = 0.75, r = 0.78, and r = 0.65, respectively, P <.05). These alterations were associated in RV isolated myocytes with the decrease of sarcomere shortening in response to isoproterenol and perturbations of calcium homeostasis assessed by the increase of spontaneous calcium waves. Conclusions: In this porcine model, both standard and strain echocardiographic parameters detected early impairments of RV function and cardiac reserve, which were associated with cardiomyocyte excitation-contraction coupling alterations.

Background: The objective of this study was to examine early and long-term results of surgical aortic valvotomy in neonates and infants aged less than four months and to identify predictors of outcome.Methods: Between August 1994 and April 2012, 83 consecutive patients younger than 4 months of age underwent open heart valvotomy for critical aortic stenosis in our institution. Median age was 17 days (range 0-111 days). We examined clinical records to establish determinants of outcome and illustrate long-term results.Results: Fifty-six patients (67 %) were neonates. Associated cardiac malformations were found in 24 patients (29 %), including multilevel left heart obstruction in 5. The median follow-up was 4.2 years. The time-related survival rate was 87 and 85 % at 5 and 15 years, respectively. The time-related survival without reintervention was respectively 51, 35 and 18 % at 5, 10 and 15 years. The time-related survival without aortic valve replacement was respectively 67, 54 and 39 % at 5, 10 and 15 years. Ventricular dysfunction (p = 0.04), delayed sternal closure (p = 0.007), endocardial fibroelastosis (p = 0.02) and low z-score of the aortic annulus (p = 0.04) were found predictors of global mortality. Ventricular dysfunction (p = 0.01) and endocardial fibroelastosis (p = 0.04) were found predictors of reintervention.Conclusions: The experience, in our center, on the management of critical aortic stenosis, shows a low early and late mortality, but the aortic valvotomy is a palliative procedure and we see unfortunately a high rate of reintervention among which the aortic valve replacement. These results suggest to reconsider the use of aortic balloon valvotomy, and particularly for the neonates with a low cardiac output in order to avoid the myocardial stress and the neurological injury due to the cardiopulmonary bypass.

OBJECTIVES:Long-term outcomes after the arterial switch operation (ASO) for complex transposition of the great arteries (TGA) should be clarified.METHODS:A retrospective study was conducted in patients operated on between 1982 and 1998. Overall 220 postoperative survivors, 79.1% with a ventricular septal defect, 13.2% with multiple ventricular septal defects, and 29.1% with aortic arch obstruction, were followed for 17 years (0-28 years).RESULTS:The conditional survival rate was 96.7% [95% confidence interval (CI): 94.4-99.1] at 25 years. Late sudden death occurred in 2 asymptomatic patients. The cumulative incidence rate of death or reinterventions was 3.8% (95% CI: 2.9-4.8) at 25 years, with age at ASO <10 days and aortic regurgitation at discharge identified as independent risk factors. The cumulative incidence rate of neoaortic regurgitation was 41.6% (95% CI: 20.5-62.8) at 25 years with an aorto-pulmonary diameter mismatch at the time of the ASO, age at ASO <10 days and aortic regurgitation at discharge identified as independent risk factors. At the last follow-up, 53 patients (24.1%) had neoaortic root dilatation with an aortic sinus z-score ≥3 and 6 of them had a Bentall operation at a median delay of 14.1 years since the ASO. The only independent factors for neoaortic root dilatation were male sex and an aorto-pulmonary diameter mismatch at the time of the ASO.CONCLUSIONS:Despite a continual rate of reinterventions, long-term survival and cardiovascular outcome are excellent after ASO for complex TGA. Dilatation of the neoaortic root and neoaortic regurgitation may be observed with time and 2 late sudden deaths occurred, justifying a close follow-up in all patients.

Right ventricular (RV) dysfunction is a major determinant of long-term survival in congenital heart diseases. Early echo detection of RV failure is mandatory, but recent indices need to be validated. Objectives were to: (1) validate standard and strain echo indices for evaluation of RV systolic function, compared to hemodynamic parameters; (2) assess the accuracy of these indices for early detection of RV failure. Combined RV overload as observed in repaired tetralogy of Fallot was surgically reproduced in 2-month-old piglets (n=6). Age-matched piglets were used as controls (n=4). RV function was evaluated at baseline and 4 months of follow-up by standard and strain echo indices, compared to conductance catheter. Sarcomere shortening and calcium transients were recorded in RV isolated myocytes (IonOptix). Contractile reserve was assessed by in-vivo (dobutamine 5µg/kg) and ex-vivo (isoprenaline 100nM) β adrenergic stimulation. The integrity of T-tubules was controlled after Di-4-Anepps labeling. 4 months after surgery, hemodynamic RV ejection fraction (FEVD) was significantly decreased (29.7% [26.2-34] vs 42.9% [40.7-48.6], p<0.01), and inotropic responses to dobutamine were blunted (contractile reserve ΔEmax=51% vs 193%, p<0.05). On echocardiography FAC, TAPSE, S’ peak and RV free wall longitudinal strain rate were significantly reduced and correlated with FEVD. Peaks strain rate and S’ were correlated with ΔEmax (r=0.75 and 0.78, p<0.05). Isolated RV myocytes from operated animals showed hypertrophy, decreased sarcomere shortening peak in response to isporenaline (ΔL=7.8±2.8% vs 10.7±2.9%, p<0.05), and increased spontaneous calcium waves suggesting perturbations of calcium homeostasis. In this model, both standard and strain echo indices allowed the detection of early impairments of RV function and cardiac reserve, which are associated with cardiac excitation-contraction coupling alterations.

Usefulness of cardiac catheterization in Eisenmenger syndrome is controversial. We investigated the prognostic value of invasive hemodynamic parameters. 69 consecutive patients with congenital heart disease and pulmonary vascular resistance (PVR)>8UW.m2 (Eisenmenger syndrome, n=63; non-correctable left-to-right shunt, n=6), with at least 1 catheterization after 1994, were included. Pulmonary artery pressures (PAP) and oxygen (O2) consumption were measured using the same standardized method. PVR were calculated using the Fick principle. Outcome was assessed in 2015 and survival analysis was performed. Mean age at first catheterization with this protocol was 38.4±13.3 y.o. Pre-tricuspid, post-tricuspid and combined shunts were observed in 44 (63.8%), 23 (33.3%) and 2 (2.9%) cases. Patients were free of any pulmonary anti-hypertensive drugs in 54 (78.3%) cases. A Who status 3 or 4 was observed in 37 patients (53.6%). Median PVR and diastolic PAP were 24.6 [19.2-37.6] UW.m2 and 40.0mmHg [34.5-50]. There was no complication. During a median follow-up of 7.2 y. [5.2-11.6], 23 (33.3%) patients reached a composite outcome criteria (death n=12; heart-lung transplantation n=8; transplantation list registration n=7). Outcome was associated with pulmonary O2 sat. <70% (p=0.01), aortic O2 sat. ≤88% (p=0.02), mixed venous blood O2 sat. ≤65% (p=0.01), PVR ≥30UW.m2 (p=0.02), diastolic PAP ≥45mmHg (p=0.01) and who 3-4 (p=0.01). After adjustment for the position of the shunt and the number of anti-hypertensive drugs, diastolic PAP≥45mmHg and Who 3-4 remained associated with outcome in Cox regression analysis (HR 5.6, p=0.006; HR=5.3, p=0.008). There were trends that did not reach significance for the other hemodynamic parameters. In addition to functional status, first catheterization provides prognostic information in patients with Eisenmenger syndrome. If these information could improve the therapeutic algorithm remains to be demonstrated (figure next page).Download : Download high-res image (175KB)Download : Download full-size imageAbstract 0425 – Figure: Kaplan Meier survival curves Abstract 0425 – Figure: Kaplan Meier survival curves

We read with great interest the paper of Clavel et al. [(1)][1] in this issue of iJACC . The authors focused on the elliptic shape of the left ventricular outflow tract (LVOT) that was first shown by Baumgartner on transthoracic echocardiography in 1990 [(2)][2]. Clavel et al. compared the

PURPOSE:To assess the feasibility of exercise perfusion computed tomography (CT) in patients suspected of having hemodynamically significant coronary stenosis.MATERIALS AND METHODS:This study had institutional review board approval, and all patients gave informed consent. Thirty-two consecutive patients (26 men [mean age, 63 years] and six women [mean age, 71 years]) with 55 coronary stenoses of at least 50% underwent coronary CT angiography (one stenosis in 13 patients, two stenoses in 15 patients, and three stenoses in four patients). CT myocardial perfusion imaging was performed within 1 minute after patients performed supine exercise on an ergometer secured to the CT table. The pressure-rate product was computed to assess level of exercise. The myocardial enhancement ratio between stenotic and normally perfused territories was determined for each stenosis. Fractional flow reserve less than 0.8, as measured during invasive coronary angiography, was the reference for defining significant stenoses. Receiver operating characteristic curves were constructed to determine the myocardial enhancement ratio cutoff value.RESULTS:In the per-patient analysis, a myocardial enhancement ratio cutoff of 0.8 performed best for identifying functionally significant stenosis: Sensitivity was 95% (21 of 22 patients), specificity was 90% (nine of 10 patients), positive predictive value was 95% (21 of 22 patients), negative predictive value was 90% (nine of 10 patients), and accuracy was 94% (30 of 32 patients). Corresponding values in the per-stenosis analysis were 97% (29 of 30 stenoses), 96% (23 of 24 stenoses), 97% (29 of 30 stenoses), 96% (23 of 24 stenoses), and 96% (52 of 54 stenoses), respectively.CONCLUSION:Exercise CT myocardial perfusion imaging is feasible and accurate for assessment of the functional significance of coronary stenosis.

Background: Morphology of the left ventricular outflow tract (LVOT) in atrioventricular septal defects (AVSDs) has been reported to be at risk for development of obstruction. The purpose of the present study was to identify the incidence, the risk factors, and the surgical outcomes of subaortic stenosis in repaired AVSDs. Methods: Records of 427 consecutive patients who underwent anatomical repair for all types of AVSDs from January 2000 to December 2012 were reviewed. Outcomes, independent risk factors, reoperation, and death were analyzed. Results: In a median follow-up of five years (range: 17 months11.8 years), eight patients required nine reoperations for subaortic stenosis. Study group (n = 11) included three additional patients for whom repair was performed in a different institution. Median delay for reoperation was 11.9 years (range: 1.319.4 years). Surgical relief of subaortic stenosis was obtained by means of the enlargement of the LVOT: resection of fibrous structures in all reoperated patients and associated with septal myectomy in four. Two patients required a modified Konno procedure. Five reoperations were associated with left atrioventricular valve repair or replacement. Statistical analysis didn't reveal any morphologic or demographic risk factors. No early or late death occurred. Conclusion: The development of subaortic stenosis after repair of AVSD remains a rare complication in midterm follow-up (incidence: 1.9%). The performance of preventive gesture during repair seemed to be unjustified. The surgical management of this reoperation consists of a simple and safe procedure.

Prematurity is a recognized risk factor for morbidity and mortality following cardiac surgery. Postoperative and long-term outcomes after cardiac surgery performed in the preterm period are poorly described. The aim of this study was to analyze a population of preterm neonates operated on for critical congenital heart disease (CHD) before 37 weeks of gestational age (wGA) with special attention given to early and late mortality and morbidity. Between 2000 and 2013, 28 preterm neonates (median gestational age (GA) 34.3 weeks) underwent cardiopulmonary bypass (CPB) surgery for critical CHD before 37 wGA; records were retrospectively reviewed. All patients except three with single ventricle physiology had a single-stage anatomic repair. Overall mortality was 43 % (95 % CI 25–62). Risk factors for death were birth weight (p = 0.032) and weight at surgery (p = 0.037), independently of GA, preoperative status, CPB and aortic clamp time. Seven patients, including those with univentricular hearts, died during the postoperative period, and five in the first year after surgery. Median follow-up was 5.9 years (range 1 month–12.8 years). Kaplan–Meier survival rate was 75 % (95 % CI 59–91) at 1 month, and 57 % (95 % CI 39–75) at 1 and 5 years. Eight patients required reoperations after a delay of 2.8 ± 1.3 months; eight had bronchopulmonary dysplasia. At the end of follow-up, nine patients were asymptomatic. One-stage biventricular repair for critical CHD on preterm neonates was feasible. Mortality remained high but acceptable, mainly confined to the first postoperative year and related to small weight. Despite reoperations, long-term clinical status was good in most survivors. Further long-term prospective investigations are necessary to evaluate neurodevelopmental outcomes.

Right ventricular (RV) dysfunction is a major determinant of long-term survival in congenital heart diseases. Early echocardiographic detection of RV failure is mandatory, but recent parameters need to be validated. Objectives were to: (1) validate standard and strain echocardiographic parameters for evaluation of RV systolic function, compared to hemodynamic parameters; (2) assess the accuracy of these parameters for early detection of RV failure. Combined RV overload as observed in repaired tetralogy of Fallot was surgically reproduced in 2-month-old piglets (n=6). Age-matched piglets were used as controls (n=4). RV function was evaluated at baseline and 4 months of follow-up by standard and strain echocardiographic parameters, compared to hemodynamic (conductance catheter). Sarcomere shortening and calcium transients were recorded in RV isolated myocytes (IonOptix). Contractile reserve was assessed by in-vivo (dobutamine 5奯kg) and ex-vivo (isoprenaline 100nM) ?-adrenergic stimulation. 4 months after surgery, hemodynamic RV ejection fraction (FEVD) was significantly decreased (29.7% [26.2-34] vs 42.9% [40.7-48.6], p<0.01), and inotropic responses to dobutamine were attenuated (contractile reserve ΔEmax = 51% vs 193% for controls). On echocardiography FAC, TAPSE, S’ peak and RV free wall longitudinal strain rate were significantly decreased and correlated with FEVD. Strain rate and S’ peak were correlated with ?Emax (r=0.75 and 0.78, p<0.05). Isolated RV myocytes from operated animals exhibited hypertrophy, decreased sarcomere shortening peak in response to isporenaline (ΔL= 7.8 ± 2.8% vs 10.7 ± 2.9%, p<0.05), and increased spontaneous calcium waves suggesting perturbations of calcium homeostasis. In this model, both standard and strain echocardiographic parameters allowed the detection of early impairments of RV function and cardiac reserve, which are associated with cardiac excitation-contraction coupling alterations.

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.

L'évaluation du débit cardiaque en néonatologie est complexe et les procédures classiques sont risquées. La velocimetrie électrique (VE) est un système non invasif mais peu de données existent chez le nouveau-né. Ce travail compare les valeurs du volume d'éjection (SV) mesuré par VE et echographie cardiaque chez les enfants hospitalisées en réanimation néonatale par des mesures répétées de VE avant et après echographie par le même opérateur. 32 enfants sont inclus permettant 53 mesures avec un âge gestationnel (AG) et un poids moyens de 29 SA et 1265g. Les corrélations de Pearson et analyses de Bland Altman sur la cohorte retrouvent r= 0,499 (p<0.001) et une erreur moyenne de −1.29 ml (95%CI: −4 ml-+1.5 ml). Cette corrélation disparait en cas de canal artériel persistant (r= 0.292; p= 0.131). Elle n'est pas influencée par l'AG (coefficient corrélation partielle r=0.499; p<0.001). Le coefficient de variation est de 50% pour la VE et de 35% pour l'échographie. Il n'y a pas de différence entre les mesures de SV avant et après echographie à 10 minutes d'intervalles (3.43±SD vs 3.36±SD;p=0.13, Wilcoxon). La VEest facile, rapide et reproductible. Elle peut être une aide précieuse à l'évaluation hémodynamique néonatale notamment chez le prématuré, surtout en absence de canal artériel.

Background Evaluation of cardiac output in neonates might be difficult because of the complexity and risks of invasive classical procedures. New systems like electrical cardiometry (EC: Osypka Medical, Berlin, Germany and La Jolla, California, USA) have been proposed but few data are available in neonates. We investigated stroke volume (SV) using EC in term and preterm infants. Methods Eligible patients were neonates admitted to the NICU and undergoing echocardiography for any clinical reasons, without congenital heart disease. We measured SV with EC and echocardiography, within 10 min. Measurements were repeated 6 times by the same operator to calculate repeatability before and after echocardiography. Data have been compared with correlation and Bland-Altman analysis. Results 59 neonates were enrolled, allowing 150 paired measurements. Mean gestational age and birth weight were 33.9 ± 3.4 wks and 1988 ± 823 g, respectively. Results of Pearson correlation and Bland-Altman analysis for the whole population were (r = 0.611; p < 0.001) and (mean error [echo-EC] -1.35 mL [95% CI: -6.55 mL ± 3.85 ml]), respectively. Correlation is maintained even with PDA (r = 0.627; p < 0.001). Gestational age seems to do not influence the correlation between EC and echo (Partial correlation coefficient r = 0.36; p < 0.0001). Repeatability (coefficient of variation) was 46% for EC and 52% for echocardiography. There was no difference in SV measured by EC after 10 min (3.76 ± SD vs 3.78 ± SD; p = 0.56, Wilcoxon test). Conclusions EC is feasible, reproducible and quick. It could be an useful tool for continuous monitoring and haemodynamic evaluation in neonates. EC is particularly interesting for the clinical management of preterm neonates.

Background: Several noninvasive CT-derived methods for evaluating the functional significance of coronary artery stenosis seen by computed tomography coronary angiography (CCTA) have been reported to correlate with fractional flow reserve (FFR) measured during invasive coronary angiography (ICA). Computed tomography myocardial perfusion imaging (CTMPI) following supine exercise has never been previously evaluated. Methods and Results: We studied 32 consecutive patients with 55 coronary stenoses ≥50% by CCTA. CTMPI was performed after supine exercise (X-CTMPI) on an ergometer secured to the CT table, and the myocardial enhancement ratio (MER) between stenotic and normally perfused territories was determined for each stenosis. FFR <0.8, as measured during ICA was the reference for defining a significant coronary stenosis. In the per-patient analysis, a MER cutoff of 0.8 was best for identifying functionally significant stenosis: sensitivity was 95%, specificity 90%, positive predictive value 95%, negative p...

La vélocimétrie électrique (VE) est une nouvelle technique non invasive de monitorage hémodynamique. Il n'existe pas de données pour le moment chez les nouveau-nés au décours de procédures respiratoires comme l'extubation ou la kinésithérapie respiratoire. Le but de ce travail est de savoir si elles entrainent des modifications hémodynamiques. Pour cela dans notre population des nouveau-nés prématurés on recueille le volume d'éjection (SV), débit cardiaque (DC), l'index de contractilité (ICON) et la fréquence cardiaque (FC) avec la VE avant, après et à 5, 10, 15, 30 et 60 minutes de l'extubation ou de manœuvres d'accélération du flux expiratoire (AFE). 11 (AFE) et 13 (extubation) enfants sont inclus avec un âge gestationnel et un poids moyen de 29 SA et 1313g. Aucune différence entre les valeurs mesurées n'a été relevée au décours des procédures d'AFE et d'extubation quel que soit le paramètre (p=0.318 pour SV; p=0.559 DC; p=0.23 ICON; p=0.78 FC, tests de Friedman). Aucune différence n'est relevée en analysant séparément les 2 groupes. Aucune modification hémodynamique n'est relevée dans notre cohorte de prématurés. Ces résultats préliminaires méritent d'être approfondis notamment par mesure spécifique du débit cérébral par NIRS.