Data fusion of left ventricle Electro-Anatomic Mapping and Multislice Computerized Tomography for Cardiac Resynchronisation Therapy optimization

International audienceCardiac Resynchronization Therapy is a treatment for bi-ventricular asynchronism. It can be optimized by the identification of the most effective pacing sites. The aim of this study is to provide a helpful tool to perform this identification by the fusion of electrical and anatomical information resulting from Electro-Anatomic Mapping (EAM) data and Multislice Computerized Tomography (MSCT) imaging. EAM data provide an approximation of the left ventricle (LV) 3D-surface (SEAM). Left cardiac chambers are segmented from MSCT imaging and surfaces are reconstructed (SCT). In order to represent this information in a unified framework, a three steps method is proposed: (1) the LV is separated from the left auricle on SCT providing S'CT; (2) a semi-automatic rigid registration method is applied to SEAM and S'CT; (3) activation time delays are estimated on S'CT from the EAM data. This method results in a graphical interface offering to clinicians means to identify abnormal electrical activity sites

0081: Prevalence and determinants or right ventricular dysfunction in severe aortic stenosis

Introductionsystolic pulmonary artery pressure (sPAP) is a well known predictor of outcome in patients with valvular heart disease. In spite of this fact, limited data are available regarding the assessment of RV function in patients with aortic stenosis (AS).Aimof this study is therefore to evaluate the prevalence and the determinants of RV dysfunction in severe AS patientsMethods201 patients (mean age:79.7±8.7, male sex 55.5%) with severe AS underwent 2D echocardiography and speckle tracking echocardiography (STE) for the evaluation of left ventricular and RV function, aortic valve gradients and sPAP. A tricuspid annular plane systolic excursion (TAPSE) ≤17mm was used to define reduced RV ventricular function.ResultsRV function was impaired in 48 patients (24%). Patients with reduced TAPSE had an impaired LV ejection fraction (LVEF) (49.2±15.4 vs 57.9±10.9%, p<0.0001), significantly altered STE parameters (GLS: –10.3 ±3.9 vs –13.2±3.5%, GCS: –7.0±3. vs –10.4±4.9%, GRS: 18.7±11.6 vs 28.4±15.6, all p<0.001) and a higher sPAP (48.4±15.8 vs 40.9±12.7mmHg, p=0.002) with respecto to patients with a normal RV function. Correlates of a reduced TAPSE were: LVEF (β=0.35, p<0.0001), LV global longitudinal, circumferential and radial strain (β=–0.40, β=–0.40, β=0.37 respectively, all p<0.0001), LV indexed stroke volume (β=0.44, s<0.0001), lnNT-proBNP (β=–0.51, p<0.0001) and sPAP (β=–0.27, p<0.0001). At Kaplan-Meier survival curve, a TAPSE ≤17mm was associated with a reduced survival in patients with AS (Log Rank test, p=0.034).ConclusionsIn patients with severe AS, RV function impairment is frequent and is associated with a poor prognosis. The correlations of TAPSE highlight the RV-LV interdependence in AS patients. Further studies will clarify the real and independent prognostic value of RV function in severe AS patients and test for the RV reverse remodelling after treatment of the AS

070: Heterogeneity in regional peaks of left ventricular deformation is correlated with exercise capacity in primitive hypertrophic cardiomyopathy

ObjectivePrevious studies have described a left ventricular (LV) heterogeneity in regional peaks of deformation in patients with primitive hypertrophic cardiomyopathy (HCM). We studied this heterogeneity in HCM patients with echocardiography both at rest and during exercise in order to evaluate its correlation with exercise capacity.MethodsThirty consecutive HCM patients were evaluated with echocardiography at rest and during exercise on a dedicated table. 2D speckle tracking echocardiography (STE) was used to assess LV deformation heterogeneity according to the standard deviation between systolic peaks of regional longitudinal strains.ResultsAge was 55.1±12.7 yrs, maximal wall thickness was 20.3±.4mm. Maximal load during exercise was 94±41 Watts. LV ejection fraction was preserved both at rest and during exercise (67±8% at rest and 69±8% during exercise). Global longitudinal strain (GLS) was altered (-15.5±4.1% at rest and -15.2±5.9% during exercise). Heterogeneity in regional peaks of deformation was 54.6±27.8ms at rest and 41.3±23.9ms during exercise. We noted correlations between maximal load achieved (r=-0.48, p=0.007), exercise GLS (r=0.47, p=0.009) and maximal LV thickness (r=0.48, p=0.007) with the level of LV deformation heterogeneity recorded during exercise. These correlations were lower if we considered LV deformation heterogeneity at rest. The population was then divided in 2 groups according to the level of exercise heterogeneity in regional peaks of deformation (cut-off value of 41ms, i.e. mean value of the global population). The group with the more marked heterogeneity of LV deformation showed the thicker wall, the lower GLS at exercise and the weaker exercise capacity. This result was independent of the age.ConclusionIn CMH patients exercise echocardiography add information. Indeed heterogeneity in regional peaks of deformation in longitudinal LV is correlated with exercise capacity and importance of myocardial hypertrophy

Multivariate ensemble classification for the prediction of symptoms in patients with Brugada syndrome

Identification of asymptomatic patients at higher risk for suffering cardiac events remains controversial and challenging in Brugada syndrome (BS). In this work, we proposed an ECG-based classifier to predict BS-related symptoms, by merging the most predictive electrophysiological features derived from the ventricular depolarization and repolarization periods, along with autonomic-related markers. The initial feature space included local and dynamic ECG markers, assessed during a physical exercise test performed in 110 BS patients (25 symptomatic). Morphological, temporal and spatial properties quantifying the ECG dynamic response to exercise and recovery were considered. Our model was obtained by proposing a two-stage feature selection process that combined a resampled-based regularization approach with a wrapper model assessment for balancing, simplicity and performance. For the classification step, an ensemble was constructed by several logistic regression base classifiers, whose outputs were fused using a performance-based weighted average. The most relevant predictors corresponded to the repolarization interval, followed by two autonomic markers and two other makers of depolarization dynamics. Our classifier allowed for the identification of novel symptom-related markers from autonomic and dynamic ECG responses during exercise testing, suggesting the need for multifactorial risk stratification approaches in order to predict future cardiac events in asymptomatic BS patients. Graphical abstract Pipeline for feature selection and predictive modeling of symptoms in Brugada syndrome.Peer ReviewedPostprint (author's final draft

073: Very long-term effects of pacing therapy in Hypertrophic Obstructive Cardiomyopathy (HOCM)

The clinical value of DDD pacing as primary treatment of HOCM remains controversial. Very long-term data are lacking.Aimssingle-centre observational study aimed at describing the very long term effects on symptoms, clinical and echocardiographic outcomesPatients54 patients (59±14 years) with symptomatic (NYHA Class >2) drug-refractory HOCM implanted with a DDD pacemaker with or without defibrillator between 1991 and 2007 and followed up to 20 years (mean 11.5; range 0,4-21,8).Main resultsare summarised in table. No patient had myomectomy or septal ablation during follow-up (f/u). NYHA functional class and other symptoms were significantly improved at 1-2 years and at the end of f/u. Left ventricular outflow tract (LVOT) gradient decreased by a mean of 78% at 1-2 years and 89% at end f/u consistent with SAM resolution. LV ejection fraction decreased over time with a mean value of 56% at end f/u without evidence of cavity dilatation. The actuarial survival rate was 90% at 5-yrs and 65% at 10-yrs. 24 patients died, 19 from non cardiac cause and 5 cardiovascular. 2 patients had heart transplant after 8 and 13yrs.ConclusionThe clinical and echocardiographic outcome of HOCM patients treated by DDD pacing seems favourable, inviting to re-evaluate the exact value of the therapy in further controlled studiesTable – Main results.Baseline3 months1-2 yearsEnd f/uP valueNYHA functional class, (%)<0,0001Grade 10313536Grade 243535957Grade 3521667Grade 45000Syncope/nearsyncope (%)76/482/22/22/2<0,0001Angina (%)57444<0,0001LVOT gradient (mmHg)79±3620±2411±158±21<0,0001SAM (%)96383016<0,0001LVEF (%)63,5±7,561±759±756±90,05LVEDD (%)47±5NANA43±120,3

Electrocardiographic correlates of mechanical dyssynchrony in recipients of cardiac resynchronization therapy devices

SummaryBackgroundThe relationship between electrical and mechanical indices of cardiac dyssynchronization in systolic heart failure (HF) remains poorly understood.ObjectivesWe examined retrospectively this relationship by using the daily practice tools in cardiology in recipients of cardiac resynchronization therapy (CRT) systems.MethodsWe studied 119 consecutive patients in sinus rhythm and QRS≥120ms (mean: 160±17ms) undergoing CRT device implantation. P wave duration, PR, ePR (end of P wave to QRS onset), QT, RR–QT, JT and QRS axis and morphology were putative predictors of atrioventricular (diastolic filling time [DFT]/RR), interventricular mechanical dyssynchrony (IVMD) and left intraventricular mechanical dyssynchrony (left ventricular pre-ejection interval [PEI] and other measures) assessed by transthoracic echocardiography (TTE). Correlations between TTE and electrocardiographic measurements were examined by linear regression.ResultsStatistically significant but relatively weak correlations were found between heart rate (r=−0.5), JT (r=0.3), QT (r=0.3), RR–QT intervals (r=0.5) and DFT/RR, though not with PR and QRS intervals. Weak correlations were found between: (a) QRS (r=0.3) and QT interval (r=0.3) and (b) IVMD>40ms; and between (a) ePR (r=−0.2), QRS (r=0.4), QT interval (r=0.3) and (b) LVPEI, though not with other indices of intraventricular dyssynchrony.ConclusionsThe correlations between electrical and the evaluated mechanical indices of cardiac dyssynchrony were generally weak in heart failure candidates for CRT. These data may help to explain the discordance between electrocardiographic and echocardiographic criteria of ventricular dyssynchrony in predicting the effect of CRT

Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease so far related to mutations in the cardiac ryanodine receptor (RYR2) or the cardiac calsequestrin (CASQ2) genes. Because mutations in RYR2 or in CASQ2 are not retrieved in all CPVT cases, we searched for mutations in the physiological protein partners of RyR2 and CSQ2 in a large cohort of CPVT patients with no detected mutation in these two genes. Based on a candidate gene approach, we focused our investigations on triadin and junctin, two proteins that link RyR2 and CSQ2. Mutations in the triadin (TRDN) and in the junctin (ASPH) genes were searched in a cohort of 97 CPVT patients. We identified three mutations in triadin which cosegregated with the disease on a recessive mode of transmission in two families, but no mutation was found in junctin. Two TRDN mutations, a 4 bp deletion and a nonsense mutation, resulted in premature stop codons; the third mutation, a p.T59R missense mutation, was further studied. Expression of the p.T59R mutant in COS-7 cells resulted in intracellular retention and degradation of the mutant protein. This was confirmed after in vivo expression of the mutant triadin in triadin knock-out mice by viral transduction. In this work, we identified TRDN as a new gene responsible for an autosomal recessive form of CPVT. The mutations identified in the two families lead to the absence of the protein, thereby demonstrating the importance of triadin for the normal function of the cardiac calcium release complex in humans

Vagus nerve stimulation: State of the art of stimulation and recording strategies to address autonomic function neuromodulation

International audienceObjective. Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. Approach. This review examines the state of the art of VNS applied to two emerging modulations of autonomic function: heart failure and obesity, especially morbid obesity. Main results. We report that VNS may benefit from improved stimulation delivery using very advanced technologies. However, most of the results from fundamental animal studies still need to be demonstrated in humans

SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome.

International audienceBACKGROUND: Mutations in SCN5A are identified in approximately 20% to 30% of probands affected by Brugada syndrome (BrS). However, in familial studies, the relationship between SCN5A mutations and BrS remains poorly understood. The aim of this study was to investigate the association of SCN5A mutations and BrS in a group of large genotyped families. METHODS AND RESULTS: Families were included if at least 5 family members were carriers of the SCN5A mutation, which was identified in the proband. Thirteen large families composed of 115 mutation carriers were studied. The signature type I ECG was present in 54 mutation carriers (BrS-ECG+; 47%). In 5 families, we found 8 individuals affected by BrS but with a negative genotype (mutation-negative BrS-ECG+). Among these 8 mutation-negative BrS-ECG+ individuals, 3, belonging to 3 different families, had a spontaneous type I ECG, whereas 5 had a type I ECG only after the administration of sodium channel blockers. One of these 8 individuals had also experienced syncope. Mutation carriers had, on average, longer PR and QRS intervals than noncarriers, demonstrating that these mutations exerted functional effects. CONCLUSIONS: Our results suggest that SCN5A mutations are not directly causal to the occurrence of a BrS-ECG+ and that genetic background may play a powerful role in the pathophysiology of BrS. These findings add further complexity to concepts regarding the causes of BrS, and are consistent with the emerging notion that the pathophysiology of BrS includes various elements beyond mutant sodium channels