Correlation between computer tomography‐derived scar topography and critical ablation sites in postinfarction ventricular tachycardia

BackgroundMyocardial wall thickness (WT) in patients with a prior myocardial infarction has been used to indicate scarring. However, the correlation of WT with sites critical to ventricular tachycardia (VT) has not been previously investigated. The purpose of this study was to correlate electroanatomic mapping data obtained during VT ablation with WT determined by cardiac computed tomography (CT).Methods and resultsCardiac CTs were performed in 15 consecutive patients (mean age 63 ± 10 years, 86% male, left ventricular ejection fraction 27 ± 12%) with a prior infarct referred for VT ablation. The CTs were registered to the electroanatomic maps obtained during the mapping procedure. Pacing was performed throughout the scar at sites with fractionated electrograms and isolated potentials. Ablation sites were identified by pace‐mapping or entrainment‐mapping and these sites were correlated with WT. Bipolar and unipolar voltage amplitude and bipolar electrogram width correlated with WT (correlation coefficient: 0.63, 0.65, and 0.41, respectively, P < 0.001). Ablation target sites were identified for 58 of 113 inducible VTs. The ablation target sites were located on CT‐defined ridges (WT: 4.2 ± 1.2 mm) bordered by areas of thinning (WT: 2.6 ± 1.1 mm, P < 0.0001) in 14 of 15 patients. Ablation targets were found on ridges in 49 of 58 VTs (84%) for which target sites were identified. A total of 70 ridges were localized in the 15 patients. VT became noninducible postablation in 11 of 15 patients (73%).ConclusionWT measured by CT identifies ridges of myocardial tissue that often are critical for postinfarction VT and that can be appropriate target sites for ablation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142923/1/jce13441_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142923/2/jce13441.pd

Additional value of three-dimensional echocardiography in patients with cardiac resynchronization therapy

SummaryBackgroundThere is no gold standard technique for quantification of ventricular dyssynchrony.AimTo investigate whether additional real-time three-dimensional morphologic assessment of ventricular dyssynchrony affects response after biventricular pacing.MethodsForty-one patients with severe heart failure were implanted with a biventricular pacing device and underwent two-dimensional (time dispersion of 12 left ventricular electromechanical delays) and three-dimensional echocardiographic assessment of ventricular dyssynchrony (dispersion of time to minimum regional volume for 16 left ventricular segments), before implantation, 2 days postimplantation with optimization of the pacing interventricular delay and 6 months postimplantation.ResultsIndividual optimization of sequential biventricular pacing based on three-dimensional ventricular dyssynchrony provided more improvement (p<0.05) in left ventricular ejection fraction and cardiac output than simultaneous biventricular pacing. During the different configurations of sequential biventricular pacing, the changes in three-dimensional ventricular dyssynchrony were highly correlated with those of cardiac output (r=−0.67, p<0.001) and ejection fraction (r=−0.68, p<0.001). The correlations between two-dimensional ventricular dyssynchrony and cardiac output or ejection fraction were significant but less (r=−0.60, p<0.01 and r=−0.56, p<0.05, respectively). After 6 months, 76% of patients were considered responders (10% decrease in end-systolic volume). Before implantation, we observed a significant difference between responders and non-responders in terms of three-dimensional (p<0.05) – but not two-dimensional – ventricular dyssynchrony.ConclusionThis prospective study demonstrated the additional value of three-dimensional assessment of ventricular dyssynchrony in predicting response after biventricular pacing and optimizing the pacing configuration

Atrial Tachycardias Arising from Ablation of Atrial Fibrillation: A Proarrhythmic Bump or an Antiarrhythmic Turn?

The occurrence of atrial tachycardias (AT) is a direct function of the volume of atrial tissue ablated in the patients with atrial fibrillation (AF). Thus, the incidence of AT is highest in persistent AF patients undergoing stepwise ablation using the strategic combination of pulmonary vein isolation, electrogram based ablation and left atrial linear ablation. Using deductive mapping strategy, AT can be divided into three clinical categories viz. the macroreentry, the focal and the newly described localized reentry all of which are amenable to catheter ablation with success rate of 95%. Perimitral, roof dependent and cavotricuspid isthmus dependent AT involve large reentrant circuits which can be successfully ablated at the left mitral isthmus, left atrial roof and tricuspid isthmus respectively. Complete bidirectional block across the sites of linear ablation is a necessary endpoint. Focal and localized reentrant AT commonly originate from but are not limited to the septum, posteroinferior left atrium, venous ostia, base of the left atrial appendage and left mitral isthmus and they respond quickly to focal ablation. AT not only represents ablation-induced proarrhythmia but also forms a bridge between AF and sinus rhythm in longstanding AF patients treated successfully with catheter ablation

Early Repolarization Syndrome: Diagnostic and Therapeutic Approach

An early repolarization pattern can be observed in 1% up to 13% of the overall population. Whereas, this pattern was associated with a benign outcome for many years, several more recent studies demonstrated an association between early repolarization and sudden cardiac death, so-called early repolarization syndrome. In early repolarization syndrome patients, current imbalances between epi- and endo-cardial layers result in dispersion of de- and repolarization. As a consequence, J waves or ST segment elevations can be observed on these patients' surface ECGs as manifestations of those current imbalances. Whereas, an early repolarization pattern is relatively frequently found on surface ECGs in the overall population, the majority of individuals presenting with an early repolarization pattern will remain asymptomatic and the isolated presence of an early repolarization pattern does not require further intervention. The mismatch between frequently found early repolarization patterns in the overall population, low incidences of sudden cardiac deaths related to early repolarization syndrome, but fatal, grave consequences in affected patients remains a clinical challenge. More precise tools for risk stratification and identification of this minority of patients, who will experience events, remain a clinical need. This review summarizes the epidemiologic, pathophysiologic and diagnostic background and presents therapeutic options of early repolarization syndrome

Confidence-based Training for Clinical Data Uncertainty in Image-based Prediction of Cardiac Ablation Targets

International audienceVentricular radio-frequency ablation (RFA) can have a critical impact on preventing sudden cardiac arrest but is challenging due to a highly complex arrhythmogenic substrate. This work aims to identify local image characteristics capable of predicting the presence of local abnormal ventricular activities (LAVA). This can allow, pre-operatively and non-invasively, to improve and accelerate the procedure. To achieve this, intensity and texture-based local image features are computed and random forests are used for classification. However using machine-learning approaches on such complex multimodal data can prove difficult due to the inherent errors in the training set. In this manuscript we present a detailed analysis of these error sources due in particular to catheter motion and the data fusion process. We derived a principled analysis of confidence impact on classification. Moreover, we demonstrate how formal integration of these uncertainties in the training process improves the algorithm's performance, opening up possibilities for non-invasive image-based prediction of RFA targets

A gene-expression profiling score for prediction of outcome in patients with follicular lymphoma: a retrospective training and validation analysis in three international cohorts

Patients with follicular lymphoma (FL) have heterogeneous outcomes. Predictor models able to distinguish, at diagnosis, patients at high versus low risk of progression are still needed. A training set of fresh-frozen tumour biopsies was prospectively obtained from 160 untreated patients with high-tumour-burden follicular lymphoma enrolled in the phase 3 randomised PRIMA trial, in which rituximab maintenance was evaluated after rituximab plus chemotherapy induction (median follow-up 6·6 years [IQR 6·0-7·0]). RNA of sufficient quality was obtained for 149 of 160 cases, and Affymetrix U133 Plus 2.0 microarrays were used for gene-expression profiling. We did a multivariate Cox regression analysis to identify genes with expression levels associated with progression-free survival independently of maintenance treatment in a subgroup of 134 randomised patients. Expression levels from 95 curated genes were then determined by digital expression profiling (NanoString technology) in 53 formalin-fixed paraffin-embedded samples of the training set to compare the technical reproducibility of expression levels for each gene between technologies. Genes with high correlation (>0·75) were included in an L2-penalised Cox model adjusted on rituximab maintenance to build a predictive score for progression-free survival. The model was validated using NanoString technology to digitally quantify gene expression in 488 formalin-fixed, paraffin-embedded samples from three independent international patient cohorts from the PRIMA trial (n=178; distinct from the training cohort), the University of Iowa/Mayo Clinic Lymphoma SPORE project (n=201), and the Barcelona Hospital Clinic (n=109). All tissue samples consisted of pretreatment diagnostic biopsies and were confirmed as follicular lymphoma grade 1-3a. The patients were all treated with regimens containing rituximab and chemotherapy, possibly followed by either rituximab maintenance or ibritumomab-tiuxetan consolidation. We determined an optimum threshold on the score to predict patients at low risk and high risk of progression. The model, including the multigene score and the threshold, was initially evaluated in the three validation cohorts separately. The sensitivity and specificity of the score for the prediction of the risk of lymphoma progression at 2 years were assessed on the combined validation cohorts. FINDINGS: In the training cohort, the expression levels of 395 genes were associated with a risk of progression. 23 genes reflecting both B-cell biology and tumour microenvironment with correlation coefficients greater than 0·75 between the two technologies and sample types were retained to build a predictive model that identified a population at an increased risk of progression (p<0·0001). In a multivariate Cox model for progression-free survival adjusted on rituximab maintenance treatment and Follicular Lymphoma International Prognostic Index 1 (FLIPI-1) score, this predictor independently predicted progression (adjusted hazard ratio [aHR] of the high-risk group compared with the low-risk group 3·68, 95% CI 2·19-6·17 [p<0·0001]). The 5-year progression-free survival was 26% (95% CI 16-43) in the high-risk group and 73% (64-83) in the low-risk group. The predictor performances were confirmed in each of the individual validation cohorts (aHR comparing high-risk to low-risk groups 2·57 [95% CI 1·65-4·01] in cohort 1; 2·12 [1·32-3·39] in cohort 2; and 2·11 [1·01-4·41] in cohort 3). In the combined validation cohort, the median progression-free survival was 3·1 years (95% CI 2·4-4·8) in the high-risk group and 10·8 years (10·1-not reached) in the low-risk group (p<0·0001). The risk of lymphoma progression at 2 years was 38% (95% CI 29-46) in the high-risk group and 19% (15-24) in the low-risk group. In a multivariate analysis, the score predicted progression-free survival independently of anti-CD20 maintenance treatment and of the FLIPI score (aHR for the combined cohort 2·30, 95% CI 1·72-3·07). INTERPRETATION: We developed and validated a robust 23-gene expression-based predictor of progression-free survival that is applicable to routinely available formalin-fixed, paraffin-embedded tumour biopsies from patients with follicular lymphoma at time of diagnosis. Applying this score could allow individualised therapy for patients according to their risk category

Integrated hybrid Raman/fiber Bragg grating interrogation scheme for distributed temperature and point dynamic strain measurements

We propose and experimentally demonstrate the feasibility of an integrated hybrid optical fiber sensing interrogation technique that efficiently combines distributed Raman-based temperature sensing with fiber Bragg grating (FBG)-based dynamic strain measurements. The proposed sensing system is highly integrated, making use of a common optical source/receiver block and exploiting the advantages of both (distributed and point) sensing technologies simultaneously. A multimode fiber is used for distributed temperature sensing, and a pair of FBGs in each discrete sensing point, partially overlapped in the spectral domain, allows for temperature-independent discrete strain measurements. Experimental results report a dynamic strain resolution of 7.8  nε/√Hz within a full range of 1700 με and a distributed temperature resolution of 1°C at 20 km distance with 2.7 m spatial resolution

Atrial Fibrillation Mechanisms and Implications for Catheter Ablation

AF is a heterogeneous rhythm disorder that is related to a wide spectrum of etiologies and has broad clinical presentations. Mechanisms underlying AF are complex and remain incompletely understood despite extensive research. They associate interactions between triggers, substrate and modulators including ionic and anatomic remodeling, genetic predisposition and neuro-humoral contributors. The pulmonary veins play a key role in the pathogenesis of AF and their isolation is associated to high rates of AF freedom in patients with paroxysmal AF. However, ablation of persistent AF remains less effective, mainly limited by the difficulty to identify the sources sustaining AF. Many theories were advanced to explain the perpetuation of this form of AF, ranging from a single localized focal and reentrant source to diffuse bi-atrial multiple wavelets. Translating these mechanisms to the clinical practice remains challenging and limited by the spatio-temporal resolution of the mapping techniques. AF is driven by focal or reentrant activities that are initially clustered in a relatively limited atrial surface then disseminate everywhere in both atria. Evidence for structural remodeling, mainly represented by atrial fibrosis suggests that reentrant activities using anatomical substrate are the key mechanism sustaining AF. These reentries can be endocardial, epicardial, and intramural which makes them less accessible for mapping and for ablation. Subsequently, early interventions before irreversible remodeling are of major importance. Circumferential pulmonary vein isolation remains the cornerstone of the treatment of AF, regardless of the AF form and of the AF duration. No ablation strategy consistently demonstrated superiority to pulmonary vein isolation in preventing long term recurrences of atrial arrhythmias. Further research that allows accurate identification of the mechanisms underlying AF and efficient ablation should improve the results of PsAF ablation