L. Labrousse

Biventricular stimulation improves right and left ventricular function after tetralogy of Fallot repair: acute animal and clinical studies.

BACKGROUND Optimal treatment of right ventricular (RV) dysfunction observed in patients after tetralogy of Fallot (TOF) repair is unclear. Studies of biventricular (BiV) stimulation in patients with congenital heart disease have been retrospective or have included patients with heterogeneous disorders. OBJECTIVE The purpose of this study was to determine the effects on cardiac function of stimulating at various cardiac sites in an animal model of RV dysfunction and dyssynchrony and in eight symptomatic adults with repaired TOF. METHODS Pulmonary stenosis and regurgitation as well as RV scars were induced in 15 piglets to mimic repaired TOF. The hemodynamic effects of various configurations of RV and BiV stimulation were compared with sinus rhythm (SR) 4 months after surgery. In eight adults with repaired TOF, RV and left ventricular (LV) dP/dt(max) were measured invasively during SR, apical RV stimulation, and BiV stimulation. RESULTS At 4 months, RV dilation, dysfunction, and dyssynchrony were present in all piglets. RV stimulation caused a decrease in LV function but no change in RV function. In contrast, BiV stimulation significantly improved LV and RV function (P < .05). Echocardiography and epicardial electrical mapping showed activation consistent with right bundle branch block during SR and marked resynchronization during BiV stimulation. In patients with repaired TOF, BiV stimulation increased significantly RV and LV dP/dt(max) (P < .05). CONCLUSION In this swine model of RV dysfunction and in adults with repaired TOF, BiV stimulation significantly improved RV and LV function by alleviating electromechanical dyssynchrony.

Quantitative Analysis of Function and Perfusion during Dobutamine Stress in the Detection of Coronary Stenoses: Two-Dimensional Strain and Contrast Echocardiography Investigations

BACKGROUND The recent development of accurate methods to measure two-dimensional strain during dobutamine stress echocardiography has reactivated the debate as to the respective value of myocardial perfusion versus myocardial function assessment in detecting coronary stenoses. The aim of our study was to compare the effects of progressive coronary constrictions on two-dimensional strain and myocardial contrast echocardiography parameters during stress conditions. METHODS Nine open-chest pigs were studied in the setting of various degrees of coronary constrictions. Two-dimensional strain and myocardial contrast echocardiography with Flash refilling sequence acquisitions were obtained at rest and during dobutamine infusion. Values of longitudinal strain (LS), circumferential strain (CS), radial strain (RS), and wall thickening, as well as myocardial perfusion parameter (A.b), were then calculated. RESULTS At rest, accuracy for detecting coronary stenosis was higher for CS, LS, and A.b (74%, 67%, and 69%, respectively) than for RS or wall thickening (62% and 64%, respectively). Dobutamine stress echocardiography increased the accuracy of A.b and LS to 77% and to 73%, respectively. Sensitivity during stress was higher for CS (93%) and A.b (77%), whereas specificity was higher for LS (89%) than for other parameters. Combined evaluations (CS+A.b, CS+LS, and LS+A.b) during dobutamine stress echocardiography improved both sensitivity and accuracy for detecting coronary stenosis. CONCLUSION Quantitative evaluation of contraction by LS and CS analysis and perfusion (A.b) during stress echocardiography resulted in similar accuracy levels, whereas the radial component was less accurate. Maximal sensitivities and accuracies were obtained by combined evaluations during stress.

Haemodynamic impact of the left ventricular pacing site during graded ischaemia in an open-chest pig model

AIMS In post-operative setting after cardiac surgery, the choice of the optimal ventricular pacing site remains an issue, particularly in patients with ischaemic cardiomyopathy. We aimed to investigate the impact of the left ventricular (LV) pacing site in an animal model of incremental myocardial ischaemia. METHODS AND RESULTS Three epicardial LV pacing leads were implanted in 10 pigs [LV1 in the territory of the left anterior descending (LAD) artery, LV2 in the lateral border of this territory, LV3 in an anatomically opposed position]. A two-dimensional strain echocardiogram was performed at baseline and during two levels of incremental ischaemia, corresponding to 30 and 70% reduction of coronary flow in the LAD, during spontaneous sinus rhythm (SR) and during LV1, LV2, LV3, and multi-LV (LV1 + LV2 + LV3) pacing. At baseline (n = 10), LV + dP/dt(max) was decreased (P < 0.01) during LV1, LV2, LV3, and multi-LV pacing compared with SR. At first level of ischaemia (n = 7; 3 animals died from ventricular fibrillation), LV1 pacing (ischaemic area) induced a significant decrease in LV + dP/dt(max) compared with SR, LV2, LV3, and multi-LV pacing (P < 0.05). At second level of ischaemia (n = 6), LV1 pacing induced a significant decrease in LV + dP/dt(max) associated with an increase in the extent of myocardium with echocardiographic post-systolic shortening compared with SR, LV2, LV3, or multi-LV pacing (P < 0.05). In contrast, multi-LV pacing induced a significant haemodynamic improvement compared with SR, LV1, LV2, and LV3 (P < 0.05). CONCLUSIONS Pacing within an ischaemic area has detrimental impact on acute global and regional LV function. More studies are needed to assess the impact of multi-LV pacing in chronic ischaemic conditions.

Validation of an animal model of right ventricular dysfunction and right bundle branch block to create close physiology to postoperative tetralogy of Fallot

BACKGROUND In the past 5 years a few number of studies and case reports have come out focusing on biventricular (BiV) stimulation for treatment of congenital heart disease related ventricular dysfunction. The few available studies include a diverse group of pathophysiological entities ranging from a previously repaired tetralogy of Fallot (TOF) to a functional single ventricle anatomy. Patients status is too heterogeneous to build important prospective study. To well understand the implication of prolonged electromechanical dyssynchrony we performed a chronic animal model that mimics essential parameters of postoperative TOF. METHODS Significant pulmonary regurgitation, mild stenosis, as well as right ventricular outflow tract (RVOT) scars were induced in 15 piglets to mimic repaired TOF. 4 months after hemodynamics and dyssynchrony parameters were compared with a control group and with a population of symptomatic adult with repaired TOF. RESULTS Comparing the animal model with the animal control group on echocardiography, RV dilatation, RV and LV dysfunction, broad QRS complex and dyssynchrony were observed on the animal model piglets. Moreover, epicardial electrical mapping showed activation consistent with a right bundle branch block. The animal models displayed the same pathophysiological parameters as the post TOF repair patients in terms of QRS duration, pulmonary regurgitation biventricular dysfunction and dyssynchrony. CONCLUSION This chronic swine model mimics electromechanical ventricular activation delay, RV and LV dysfunction, as in adult population of repair TOF. It does appear to be a very useful and interesting model to study the implication of dyssynchrony and the interest of resynchronization therapy in TOF failing ventricle.

0514 : Isolation of cardiac myocytes from human heart

Background The investigation of single cardiac myocytes from healthy and diseased hearts of various species is a valuable tool to explore cardiac physio/ pathophysiology. The application of cell isolation to human donor tissue has been proofed to be difficult due to the limited amount of human tissue (mainly human right atrial appendages during cardiac surgery). Another limitation is the low viability of cardiomyocytes after isolation. In this study, we present a method to obtain single cardiac myocytes from different regions of human heart. Methods and results Human hearts rejected for transplantation were obtained from Bordeaux hospital. This protocol was approved by the Agence de la Biomedecine. Left atrial (LA) and ventricular (LV) myocytes were obtained by enzymatic dissociation. The ventricles and right atrium were removed and used for other studies (e.g. high resolution optical mapping). LA was cannulated by the circumflex artery and mounted into a Langendorff perfusion system after suture of the leaky atrial branches. LA was perfused with a Ca2+-free solution (~10 min), then collagenase and protease solution (0.08 mM Ca2+) and recirculated for ~25 min. Enzymes were washed out with a 0.2 mM Ca2+ solution. LA was separated into 4 regions: Endocardium, Epicardium, roof and pulmonary vein; LV myocytes were also obtained. Cells were re-suspended into a 1.8 mM Ca2+ solution by steps. Ca2+ transients were recorded (Fura-2, field stimulation) using an IonOptix system and cell membrane was stained with di-8 ANEPPS and visualized under confocal microscopy. Ca2+ tolerant myocytes were obtained from the 4 LA regions and LV. Human cardiac myocytes respond to electrical stimulation and Ca2+ transient can be recorded. Analysis of functional and structural data will be presented. Conclusion Isolation of single cardiac myocytes from human samples is a tedious task, but we present data showing reliable method to obtain functional and structural insights. The author hereby declares no conflict of interest

Stimulation cardiaque en pédiatrie : indications, stratégies d’implantation, évolution, techniques d’avenir

Resume Bien que les indications d’implantation de pacemaker presentent de nombreuses similitudes entre enfants et adultes, il existe plusieurs particularites dans la population pediatrique justifiant une approche specifique. Le bloc auriculo-ventriculaire congenital, le bloc auriculo-ventriculaire postoperatoire, la dysfonction sinusale, le syndrome bradycardietachycardie, le syndrome du QT long congenital et la resynchronisation biventriculaire constituent les principales indications d’implantation en pediatrie. La caracteristique propre des jeunes patients est qu’ils seront stimules sur une duree prolongee, impliquant : 1) une reflexion parfois difficile concernant la decision d’implanter un dispositif definitif de stimulation, d’autant qu’en l’absence d’etudes cliniques randomisees menees en pediatrie, les recommandations emanant des societes savantes sont pour la plupart basees sur des consensus ; 2) une fois la decision prise d’implanter un stimulateur cardiaque, la question de la voie d’abord est egalement essentielle. L’implantation d’un pacemaker peut etre realisee chez l’enfant par voie endocardique ou epicardique avec un faible taux de complication a court et moyen terme. Cependant, les complications a plus long terme, moins etudiees, pourraient s’averer plus problematiques. L’effet d’une stimulation prolongee durant toute une vie sur un site ventriculaire suboptimal ou meme deletere pourrait avoir ete sous-evalue. De meme, les enfants sont exposes a un risque plus important de complications tardives en rapport avec leur materiel de stimulation. Dans cette revue, nous proposons la description des principales indications de stimulation cardiaque en pediatrie, discutons de l’interet et des limites des differentes voies d’abord et essayons d’envisager les futurs progres qui pourraient permettre une veritable revolution dans la discipline.