Tim Boussy

Inferior and Lateral Electrocardiographic Repolarization Abnormalities in Brugada Syndrome

Background—Repolarization abnormalities in the inferior-lateral leads in Brugada syndrome (BS) have not been systematically investigated. Methods and Results—280 patients (age, 41±18 years; 168 males) with BS were screened for inferior-lateral repolarization abnormalities. The repolarization abnormalities were classified either as early repolarization pattern or coved ≥2-mm Brugada pattern and as spontaneous or class I antiarrhythmic drug (AAD) induced. Thirty-two patients (11%) had inferior-lateral spontaneous early repolarization pattern. These patients were less likely to be asymptomatic at first presentation (13 of 32 versus 156 of 248 patients, P=0.02), and spontaneous type I ECG was more frequent among them (38% versus 21%, P=0.05). The spontaneous early repolarization pattern occurred more frequently among patients with BS than in 283 family members not having BS (11% versus 6%, P=0.03). Class I AAD administration provoked inferior-lateral coved Brugada pattern in 13 patients with BS. These patients had longer baseline PR intervals (206±48 versus 172±31 ms, P<0.001) and class I AAD–induced QRS interval prolongation (108 to 178 versus 102 ms to 131 ms, P<0.001). In 3 patients, the class I AAD–provoked coved Brugada pattern was only present in the inferior leads. Conclusions—Inferior-lateral early repolarization pattern occurs spontaneously relatively frequently in BS. These patients have a more severe phenotype. Class I AAD administration provokes inferior-lateral coved Brugada pattern in 4.6% of patients. We report for the first time 3 patients in whom the class I AAD–provoked coved Brugada pattern was only observed in the inferior leads.

Combined Endocardial and Epicardial Catheter Ablation in Arrhythmogenic Right Ventricular Dysplasia Incorporating Scar Dechanneling Technique

Background— Ventricular tachycardia (VT) ablation in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) has a low success rate. A more extensive epicardial (Epi) arrhythmogenic substrate could explain the low efficacy. We report the results of combined endocardial (Endo) and Epi VT ablation and conducting channel (CC) elimination. Methods and Results— Eleven consecutive patients with ARVD/C were included in the study. A high-density 3D Endo (321±93 sites mapped) and Epi (302±158 sites mapped) electroanatomical voltage map was obtained during sinus rhythm to define scar areas (<1.5 mV) and CCs inside the scars, between scars, or between the tricuspid annulus and a scar. The end point of the ablation procedure was the elimination of all identified CCs (scar dechanneling) and the abolition of all inducible VTs. The mean procedure and fluoroscopy time were 177±63 minutes and 20±8 minutes, respectively. Epi scar area was larger in all cases (26±18 versus 94±45 cm2, P<0.01). The combined Endo and Epi VT ablation eliminated all clinical and induced VTs, and the addition of scar dechanneling resulted in noninducibility in all cases. Seven patients continued on sotalol. During a median follow-up of 11 months (6–24 months), only 1 (9%) patient had a VT recurrence. There was a single major bleeding event that did not preclude a successful procedure. Conclusions— Combined Endo and Epi mapping reveals a wider Epi VT substrate in patients with ARVD/C with clinical VTs. As a first-line therapy, combined Endo and Epi VT ablation incorporating scar dechanneling achieves a very good short- and midterm success rate.

Usefulness of contrast-enhanced cardiac magnetic resonance in identifying the ventricular arrhythmia substrate and the approach needed for ablation

AIMS The endocardial vs. epicardial origin of ventricular arrhythmia (VA) can be inferred from detailed electrocardiogram (ECG) analysis. However, despite its clinical usefulness, ECG has limitations. Alternatively, scarred tissue sustaining VAs can be identified by contrast-enhanced cardiac magnetic resonance (ce-CMR). The objective of this study was to determine the clinical value of analysing the presence and distribution pattern of scarred tissue in the ventricles to identify the VA site of origin and the ablation approach required. METHODS AND RESULTS A ce-CMR study was carried out before the index ablation procedure in a cohort of 80 patients with non-idiopathic VA. Hyper-enhancement (HE) in each ventricular segment was coded as absent, subendocardial, transmural, mid-myocardial, or epicardial. The endocardial or epicardial VA site of origin was also assigned according to the approach needed for ablation. The clinical VA was successfully ablated in 77 (96.3%) patients, all of them showing HE on ce-CMR. In segments with successful ablation of the clinical ventricular tachycardia, HE was absent in 3 (3.9%) patients, subendocardial in 19 (24.7%), transmural in 36 (46.7%), mid-myocardial in 8 (10.4%), and subepicardial in 11 (14.3%) patients. Epicardial ablation of the index VA was necessary in 3 (6.1%) ischaemic and 12 (42.9%) non-ischaemic patients. The presence of subepicardial HE in the successful ablation segment had 84.6% sensitivity and 100% specificity in predicting an epicardial origin of the VA. CONCLUSION Contrast-enhanced cardiac magnetic resonance is helpful to localize the target ablation substrate of non-idiopathic VA and also to plan the approach needed, especially in non-ischaemic patients.

The value of a family history of sudden death in patients with diagnostic type I Brugada ECG pattern

AIMS We sought to investigate the value of a family history of sudden death (SD) in Brugada syndrome (BS). METHODS AND RESULTS Two hundred and eighty consecutive patients (mean age: 41 ± 18 years, 168 males) with diagnostic type I Brugada ECG pattern were included. Sudden death occurred in 69 (43%) of 157 families. One hundred and ten SDs were analysed. During follow-up VF (ventricular fibrillation) or SD-free survival rate was not different between patients with or without a family history of SD of a first-degree relative, between patients with or without a family history of multiple SD of a first-degree relative at any age and between patients with or without a family history of SD in first-degree relatives ≤35 years. One patient had family history of SD of two first-degree relative ≤35 years with arrhythmic event during follow-up. In univariate analysis male gender (P = 0.01), aborted SD (P < 0.001), syncope (P = 0.04), spontaneous type I ECG (P < 0.001), and inducibility during electrophysiological (EP) study (P < 0.001) were associated with worse prognosis. The absence of syncope, aborted SD, spontaneous type I ECG, and inducibility during EP study was associated with a significantly better prognosis (P < 0.001). CONCLUSION Family history of SD is not predictive for future arrhythmic events even if considering only SD in first-degree relatives or SD in first-degree relatives at a young age. The absence of syncope, aborted SD, spontaneous type I ECG, and inducibility during EP study is associated with a good five-year prognosis.

Improving Safety of Epicardial Ventricular Tachycardia Ablation Using the Scar Dechanneling Technique and the Integration of Anatomy, Scar Components, and Coronary Arteries Into the Navigation System

A 54-year-old patient with a nonischemic cardiomyopathy, mild left ventricular dysfunction, and a nonsyncopal ventricular tachycardia was admitted for an ablation procedure. Preprocedural contrast-enhanced cardiac magnetic resonance (ce-CMR) was performed with a 3T clinical scanner (Magnetom Trio, Siemens Healthcare, Erlangen, Germany). A free-breathing 3-dimensional navigator and electrocardiographically gated inversion-recovery gradient-echo sequence was applied in the axial orientation, starting 5 minutes after an intravenous injection of 0.2 mmol/kg gadodiamide. Image acquisition parameters were set to allow a true isotropic 1.2×1.2×1.2-mm spatial resolution, and the acquisition time was targeted below 9 minutes to permit simultaneous evaluation of the coronary tree and myocardial enhancement. To minimize motion artifacts, the acquisition window was selected with a high-temporal-resolution 4-chamber cine view. The patient was instructed to maintain shallow and steady breathing during the acquisition. The full volume was reconstructed in the left ventricular short-axis orientation, and the resulting images were processed with self-customized software (TCTK [Tissue Characterization Tool Kit], Barcelona, Spain). An algorithm based on the pixel signal intensity was applied to characterize the hyperenhanced area as scar core or border zone. The processed images were imported into the CARTO system (Biosense Webster, Diamond Bar, CA). The study showed …

The usefulness of the consensus clinical diagnostic criteria in Brugada syndrome

BACKGROUND Consensus statements were proposed for the diagnosis of Brugada syndrome (BS). The clinical diagnostic criteria were defined as documented ventricular fibrillation or ventricular tachycardia (VT), family history of sudden cardiac death at <45 years, diagnostic ECGs of family members, inducibility of VT during electrophysiological study, syncope or nocturnal agonal respiration. The clinical validation of these criteria is still missing. Methods and results 280 patients (41 ± 18 years, male: 168 pts) with diagnostic coved type I ECG were included. Consensus clinical diagnostic criteria were present in 244 (87%) patients (40 ± 18 y, 142 males). In 36 pts (13% of the 280 pts, 51 ± 12 years, 27 males) consensus clinical diagnostic criteria were not met. Nine patients (25%) presented with spontaneous type I ECG. Ten of the 36 patients (28%) had a history of atrial fibrillation and 13 (36%) had conduction disease on the baseline ECG. In 23 patients (64%) family screening was not performed. Two of the 36 patients had undocumented syncope during follow-up. Univariate analysis showed no significant difference in event free survival between patients with or without consensus clinical diagnostic criteria. CONCLUSIONS In a significant number of patients with diagnostic ECG pattern the current diagnostic criteria for BS are not met. These patients have frequently spontaneous type I ECG and clinical signs of Brugada syndrome as paroxysmal atrial fibrillation or conduction disturbances. Our results suggest that in patients with a diagnostic type I ECG pattern the current clinical consensus diagnostic criteria have limited added diagnostic value.

Genetic basis of ventricular arrhythmias.

Sudden cardiac death caused by malignant ventricular arrhythmias is the most important cause of death in the industrialized world. Most of these lethal arrhythmias occur in the setting of ischemic heart disease. A significant number of sudden deaths, especially in young individuals, are caused by inherited ventricular arrhythmic disorders, however. Genetically induced ventricular arrhythmias can be divided in two subgroups: the primary electrical disorders or channelopathies, and the secondary arrhythmogenic cardiomyopathies. This article focuses on the genetic background of these electrical disorders and the current knowledge of genotype-phenotype interactions.

The Brugada syndrome: facts and controversies.

The diagnosis of Brugada syndrome (BS) is based on a combination of clinical (malignant arrhythmias presenting as syncopal or sudden death episodes) and electrocardiographic (pathognomonic ST segment elevation morphology) features. Over the last 15 years, since its introduction as a distinct clinical entity, the BS has been extensively investigated worldwide. In this article an overview of recent developments concerning the genetic background, the diagnostic tools and the therapeutic alternatives will be presented. In the last years, the results of the first medium-term follow-up studies have also been published. Some of these studies present contradictory results, especially concerning the identification of useful sudden death predictors in asymptomatic patients. The review presented here will discuss this prognostic controversy and will offer possible explanations for the different results.ZusammenfassungDie Diagnose des Brugada-Syndroms (BS) ergibt sich aufgrund der Klinik (maligne Arrhythmien mit Synkopen oder plötzlicher Herztod) sowie aufgrund von EKG-Veränderungen (pathognomonische ST-Hebungen). Vor 15 Jahren wurde das BS als eigenständiges Syndrom entdeckt. Seither wird es weltweit intensiv erforscht. Dieser Artikel gibt einen Überblick über die Entdeckungen der letzten Jahre bezüglich des genetischen Hintergrunds sowie der diagnostischen und therapeutischen Möglichkeiten. In den letzten Jahren wurden die Ergebnisse der ersten mittelfristigen Nachsorgestudien veröffentlicht. Einige dieser Studien erbrachten widersprüchliche Ergebnisse, vor allem bezüglich der Identifikation von Risikofaktoren für den plötzlichen Herztod bei asymptomatischen Patienten. Diese Übersicht geht auf die prognostischen Widersprüche ein und gibt mögliche Erklärungen für die unterschiedlichen Ergebnisse.

Noninvasive Evaluation of Radiofrequency Lesions in the Human Ventricular Myocardium by Contrast-Enhanced Cardiac Magnetic Resonance

The usefulness of contrast-enhanced cardiac magnetic resonance (ce-CMR) to guide the ventricular tachycardia (VT) ablation procedure has not been yet studied. Applied to tissue characterization, ce-CMR has demonstrated its ability to differentiate between normal and scarred tissue, providing details that also permit us to identify dysfunctional but viable myocardium. It has been suggested that the zones characterized as viable myocardium are probably the substrate for the VT reentry circuits.1 On the other hand, it has been described that the lesions produced by radiofrequency (RF) application in the myocardium may be detected by ce-CMR in animal experiments.2,3 However, there is no evidence showing that RF lesions can be observed in vivo in humans. We report the case of a 79-year-old patient with normal coronary arteries and 48% left ventricular (LV) ejection fraction, who presented with repetitive episodes of well tolerated VT (Figure 1). A 1.5-T ce-CMR study was performed the day before the ablation and repeated 24 hours after the procedure. Ten minutes after intravenous administration of gadolinium (gadodiamide, GE Healthcare) at a dose of 0.2 mmol/kg, sequential short axis …

Leaving out control groups: an internal contrast analysis of gene expression profiles in atrial fibrillation patients--a systems biology approach to clinical categorization.

Atrial fibrillation (AF) is a frequent chronic dysrythmia with an incidence that increases with age (>40). Because of its medical and socio-economic impacts it is expected to become an increasing burden on most health care systems. AF is a multi-factorial disease for which the identification of subtypes is warranted. Novel approaches based on the broad concepts of systems biology may overcome the blurred notion of normal and pathological phenotype, which is inherent to high throughput molecular arrays analysis. Here we apply an internal contrast algorithm on AF patient data with an analytical focus on potential entry pathways into the disease. We used a RMA (Robust Multichip Average) normalized Affymetrix micro-array data set from 10 AF patients (geo_accession #GSE2240). Four series of probes were selected based on physiopathogenic links with AF entryways: apoptosis (remodeling), MAP kinase (cell remodeling), OXPHOS (ability to sustain hemodynamic workload) and glycolysis (ischemia). Annotated probe lists were polled with Bioconductor packages in R (version 2.7.1). Genetic profile contrasts were analysed with hierarchical clustering and principal component analysis. The analysis revealed distinct patient groups for all probe sets. A substantial part (54% till 67%) of the variance is explained in the first 2 principal components. Genes in PC1/2 with high discriminatory value were selected and analyzed in detail. We aim for reliable molecular stratification of AF. We show that stratification is possible based on physiologically relevant gene sets. Genes with high contrast value are likely to give pathophysiological insight into permanent AF subtypes.