Nicolas Derval

Outcome After Implantation of a Cardioverter-Defibrillator in Patients With Brugada Syndrome A Multicenter Study

Background— Implantable cardioverter-defibrillator indications in Brugada syndrome remain controversial, especially in asymptomatic patients. Previous outcome data are limited by relatively small numbers of patients or short follow-up durations. We report the outcome of patients with Brugada syndrome implanted with an implantable cardioverter-defibrillator in a large multicenter registry. Methods and Results— A total of 378 patients (310 male; age, 46±13 years) with a type 1 Brugada ECG pattern implanted with an implantable cardioverter-defibrillator (31 for aborted sudden cardiac arrest, 181 for syncope, and 166 asymptomatic) were included. Fifteen patients (4%) were lost to follow-up. During a mean follow-up of 77±42 months, 7 patients (2%) died (1 as a result of an inappropriate shock), and 46 patients (12%) had appropriate device therapy (5±5 shocks per patient). Appropriate device therapy rates at 10 years were 48% for patients whose implantable cardioverter-defibrillator indication was aborted sudden cardiac arrest, 19% for those whose indication was syncope, and 12% for the patients who were asymptomatic at implantation. At 10 years, rates of inappropriate shock and lead failure were 37% and 29%, respectively. Inappropriate shock occurred in 91 patients (24%; 4±4 shocks per patient) because of lead failure (n=38), supraventricular tachycardia (n=20), T-wave oversensing (n=14), or sinus tachycardia (n=12). Importantly, introduction of remote monitoring, programming a high single ventricular fibrillation zone (>210–220 bpm), and a long detection time were associated with a reduced risk of inappropriate shock. Conclusions— Appropriate therapies are more prevalent in symptomatic Brugada syndrome patients but are not insignificant in asymptomatic patients (1%/y). Optimal implantable cardioverter-defibrillator programming and follow-up dramatically reduce inappropriate shock. However, lead failure remains a major problem in this population.

Prevalence, characteristics, and prognosis role of type 1 ST elevation in the peripheral ECG leads in patients with Brugada syndrome

BACKGROUNDnDespite isolated reports of Brugada syndrome (BrS) in the inferior or lateral leads, the prevalence and prognostic value of ST elevation in the peripheral electrocardiographic (ECG) leads in patients with BrS remain poorly known.nnnOBJECTIVEnTo study the prevalence, characteristics, and prognostic value of type 1 ST elevation and ST depression in the peripheral ECG leads in a large cohort of patients with BrS.nnnMETHODSnECGs from 323 patients with BrS (age 47 ± 13 years; 257 men) with spontaneous (n = 141) or drug-induced (n = 182) type 1 ECG were retrospectively reviewed. Two hundred twenty-five (70%) patients were asymptomatic, 72 (22%) patients presented with unexplained syncope, and 26 (8%) patients presented with sudden death (12 patients) or appropriated implantable cardioverter-defibrillator therapies (14 patients) at diagnosis or over a mean follow-up of 48 ± 34 months.nnnRESULTSnThirty (9%) patients presented with type 1 ST elevation in at least 1 peripheral lead (22 patients in the aVR leads, 2 in the inferior leads, 5 in both aVR and inferior leads, and 1 in the aVR and VL leads). Patients with type 1 ST elevation in the peripheral leads more often had mutations in the SCN5A gene, were more often inducible, had slower heart rate, and higher J-wave amplitude in the right precordial leads. Twenty-seven percent (8 of 30) of the patients with type 1 ST elevation in the peripheral leads experimented sudden death/appropriate implantable cardioverter-defibrillator therapy, whereas it occurred in only 6% (18 of 293) of other patients (P < .0001). In multivariate analysis, type 1 ECG in the peripheral leads was independently associated with malignant arrhythmic events (odds ratio 4.58; 95% confidence interval 1.7-12.32; P = .0025).nnnCONCLUSIONSnType 1 ST elevation in the peripheral ECG leads can be seen in 10% of the patients with BrS and is an independent predictor for a malignant arrhythmic event.

Pulmonary vein isolation using a circular, open irrigated mapping and ablation catheter (nMARQ): a report on feasibility and efficacy

AIMSnPulmonary vein isolation (PVI) is the mainstay of interventional treatment of paroxysmal atrial fibrillation (PAF). We report on the feasibility and efficacy of a novel, open-irrigated mapping and radiofrequency (RF) ablation catheter.nnnMETHODS AND RESULTSnThirty-nine consecutive patients (pts; age 60 ± 10 years, 8 females) suffering from drug-refractory PAF referred for PVI were included in this prospective study. Pulmonary vein isolation was performed with the use of a novel 10-pole circular, open-irrigated mapping and ablation catheter (nMARQ, Biosense Webster). Outcome parameters were the acute success rate in establishing complete PVI and the rate of sustained sinus rhythm (SR) during follow-up (FU). Ten patients underwent a repeat procedure for recurrent AF. Ninety-eight percent of the PVs could be acutely isolated using solely the nMARQ catheter by applying a mean total of 10.0 ± 4.6 min of RF energy. The mean total procedure duration was 86 ± 29 min, and the mean fluoroscopy time was 22.2 ± 6.5 min, respectively. Transient reconnection provoked by adenosine was observed in 10 of 24 patients, most frequently in the right superior PV. Cardiac tamponade related to transseptal puncture occurred in one patient. Reconnected PVs could be identified as a source of recurrent AF in 9 of 10 patients undergoing a repeat procedure. Single and multiple procedure success rates during a mean FU of 140 ± 75 days were 66 and 77%, respectively.nnnCONCLUSIONnIrrigated multi-electrode RF ablation is fast and effective, providing a high rate of isolated PVs without the need of touch-up lesions. Success rates were comparable with other techniques with a low complication rate. Recurrences of AF were mainly due to recovered pulmonary vein/left atrium conduction.

Epicardial deposition of endothelial progenitor and mesenchymal stem cells in a coated muscle patch after myocardial infarction in a murine model

OBJECTIVESnTo assess, using an in vivo engraftment strategy combining bone marrow cell (BMC) transplantation and tissue cardiomyoplasty, the functional outcome of distinct vascular progenitor cell therapy (endothelial progenitor (EPC) and mesenchymal stem (MSC) cells) at distance of myocardium infarction (MI). The study was also designed to test whether scaffold mixing progenitors with unfractionated BMC could improve progenitor recruitment in the damaged myocardium.nnnMETHODSnTo track engrafted progenitor cells in vivo, cultured murine MSC and EPC were transduced with eGFP lentiviruses. Thirty days after cryogenical induction of MI, C57BL/6J mice were randomized to receive muscle patch placement coated or not (control group), labeled EPC or MSC mixed to the ration of 1:10, or not with unfractionated BMC. Two weeks after transplantation, cardiac function was recorded and heart sections were examined to detect GFP-labeled progenitor cells and analyze cell differentiation.nnnRESULTSnThis study showed that either type of mono cell therapy improved angiogenesis and cell survival in the scar but only MSC exhibited the capacity to invade the scar. We found no evidence of myocardial or vascular regeneration from progenitor cells. Engraftment of the progenitors/unfractionated BMC mix increased repopulation and thickness of the scar.nnnCONCLUSIONnCombined therapy with unfractionated BMC and expanded MSC appeared thus promising for scar repopulation.

Complexity and Distribution of Drivers in Relation to Duration of Persistent Atrial Fibrillation

BACKGROUNDnThe underlying mechanisms sustaining human persistent atrial fibrillation (PsAF) is poorly understood.nnnOBJECTIVESnThis study sought to investigate the complexity and distribution of AF drivers in PsAF of varying durations.nnnMETHODSnOf 135 consecutive patients with PsAF, 105 patients referred for de novo ablation of PsAF were prospectively recruited. Patients were divided into 3 groups according to AF duration: PsAF presenting in sinus rhythm (AF induced), PsAFxa0<12 months, and PsAF >12 months. Patients wore a 252-electrode vest for body surface mapping. Localized drivers (re-entrant or focal) were identified using phase-mapping algorithms.nnnRESULTSnIn this patient cohort, the most prominent re-entrant driver regions included the pulmonary vein (PV) regions and inferoposterior left atrial wall. Focal drivers were observed in 1 or both PV regions in 75% of patients. Comparing between the 3 groups, with longer AF duration AF complexity increased, reflected by increased number of re-entrant rotations (pxa0< 0.05), number of re-entrant rotations and focal events (pxa0< 0.05), and number of regions harboring re-entrant (pxa0< 0.01) and focal (pxa0< 0.05) drivers. With increased AF duration, a higher proportion of patients had multiple extra-PV driver regions, specifically in the inferoposterior left atrium (pxa0< 0.01), superior right atrium (pxa0<xa00.05), and inferior right atrium (pxa0< 0.05). Procedural AF termination was achieved in 70% of patients, but decreased with longer AF duration.nnnCONCLUSIONSnThe complexity of AF drivers increases with prolonged AF duration. Re-entrant and focal drivers are predominantly located in the PV antral and adjacent regions. However, with longer AF duration, multiple drivers are distributed at extra-PV sites. AF termination rate declines as patients progress to longstanding PsAF, underscoring the importance of early intervention.

Characteristics of Ventricular Tachycardia Ablation in Patients With Continuous Flow Left Ventricular Assist Devices

Background—Left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation or as destination therapy. Patients with LVADs are at high risk for ventricular arrhythmias. This study describes ventricular arrhythmia characteristics and ablation in patients implanted with a Heart Mate II device. Methods and Results—All patients with a Heart Mate II device who underwent ventricular arrhythmia catheter ablation at 9 tertiary centers were included. Thirty-four patients (30 male, age 58±10 years) underwent 39 ablation procedures. The underlying cardiomyopathy pathogenesis was ischemic in 21 and nonischemic in 13 patients with a mean left ventricular ejection fraction of 17%±5% before LVAD implantation. One hundred and ten ventricular tachycardias (VTs; cycle lengths, 230–740 ms, arrhythmic storm n=28) and 2 ventricular fibrillation triggers were targeted (25 transseptal, 14 retrograde aortic approaches). Nine patients required VT ablation <1 month after LVAD implantation because of intractable VT. Only 10/110 (9%) of the targeted VTs were related to the Heart Mate II cannula. During follow-up, 7 patients were transplanted and 10 died. Of the remaining 17 patients, 13 were arrhythmia-free at 25±15 months. In 1 patient with VT recurrence, change of turbine speed from 9400 to 9000 rpm extinguished VT. Conclusions—Catheter ablation of VT among LVAD recipients is feasible and reasonably safe even soon after LVAD implantation. Intrinsic myocardial scar, rather than the apical cannula, seems to be the dominant substrate.

Characterization of contact force during endocardial and epicardial ventricular mapping.

Background—The optimal contact force (CF) for ventricular mapping and ablation remains unvalidated. We assessed CF in different endocardial and epicardial regions during ventricular tachycardia substrate mapping using a CF-sensing catheter (Smartouch; Biosense-Webster) and compared the transseptal versus retroaortic approach. Methods and Results—In total, 8979 mapping points with CF, and force vector orientation (VO) were recorded in 21 patients, comprising 13 epicardial, 12 left ventricular (6 transseptal and 6 retroaortic approach), and 12 right ventricular endocardial maps. VO was defined as adequate when the vector was directed toward the myocardium. During epicardial mapping, 46% of the points showed an adequate VO and a median CF of 8 (4–13) g, however, with significant differences among the 8 regions. When VO was inadequate, median CF was higher at 16 (10–24) g (P<0.0001). During left ventricular and right ventricular endocardial mapping, 94% of VO were adequate. Median CF of adequate VO was higher in the left ventricular and right ventricular endocardium than in the epicardium (15 [8–25] and 13 [7–22] g versus 8 [4–13] g, respectively; both P<0.001). Global median left ventricular CF with transseptal approach was not statistically different from retroaortic approach, but CF in the apicoinferior and apicoseptal regions was higher with transseptal approach (P<0.001). Conclusions—Ventricular mapping demonstrates important regional variations in CF, but in general, CF is higher endocardially than epicardially where poor catheter orientation is associated with higher CF. A transseptal approach may lead to improved contact particularly in the apicoseptal and inferior regions.

Persistent Atrial Fibrillation From the Onset: A Specific Subgroup of Patients With Biatrial Substrate Involvement and Poorer Clinical Outcome

OBJECTIVESnThis study sought to characterize the clinical characteristics, atrial substrate, and prognosis in a subgroup of patients with persistent atrial fibrillation (AF) from the onset (PsAFonset).nnnBACKGROUNDnPatients with AF frequently progress from trigger-driven paroxysmal arrhythmias to substrate-dependent persistent arrhythmias.nnnMETHODSnPatients referred for persistent AF (PsAF) ablation were enrolled from 3 centers. Consecutive patients with PsAFonset (nxa0= 129) were compared with patients with PsAF that progressed from paroxysmal AF (nxa0= 231). In addition, 90 patients (30 patients with PsAFonset and 60 control subjects) were studied with noninvasive mapping to characterize the AF drivers. The degree of fractionation and endocardial voltages were assessed invasively.nnnRESULTSnPatients with PsAFonset were younger (pxa0= 0.047) and more obese (pxa0< 0.001); there were more men (pxa0=xa00.034), more patients with hypertension (pxa0= 0.044), and these patients had larger left (pxa0< 0.05) and right atria (pxa0< 0.05). Baseline AF cycle length was shorter in the PsAFonset group (pxa0< 0.01); the degree of fractionation was higher (pxa0< 0.001 for both atria), and the endocardial voltage was lower (pxa0< 0.05 for both atria). Patients with PsAFonsetxa0had higher a number of re-entrant driver regions (pxa0< 0.001) and extrapulmonary vein regions that had re-entrant drivers (pxa0< 0.05), whereas control subjects displayed more focal driver regions (pxa0= 0.029). The acute AF termination rate was lower in the PsAFonset group (42% vs. 81%; pxa0< 0.001). During a mean follow-up of 17 ± 11 months fromxa0thexa0last procedure, patients with PsAFonset had significantly higher AF, atrial tachycardia (AT), and AF/AT recurrence rates (pxa0< 0.01).nnnCONCLUSIONSnPatients with PsAFonset represent a distinct subgroup defined by specific demographics, underlying diffuse biatrial substrate disease, and worse clinical outcome. The findings highlight the importance of defining criteria for early detection of atrial substrate disease.

Performance And Limitations Of Non-Invasive Cardiac Activation Mapping

BACKGROUNDnActivation mapping using noninvasive electrocardiographic imaging (ECGi) has recently been used to describe the physiology of different cardiac abnormalities. These descriptions differ from prior invasive studies, and both methods have not been thoroughly confronted in a clinical setting.nnnOBJECTIVEnThe goal of the present study was to provide validation of noninvasive activation mapping in a clinical setting through direct confrontation with invasive epicardial contact measures.nnnMETHODSnFifty-nine maps were obtained in 55 patients and aligned on a common geometry. Nearest-neighbor interpolation was used to avoid map smoothing. Quantitative comparison was performed by computing between-map correlation coefficients and absolute activation time errors.nnnRESULTSnThe mean activation time error was 20.4 ± 8.6 ms, and the between-map correlation was poor (0.03 ± 0.43). The results suggested high interpatient variability (correlation -0.68 to 0.82), wide QRS patterns, and paced rhythms demonstrating significantly better mean correlation (0.68 ± 0.17). Errors were greater in scarred regions (21.9 ± 10.8 ms vs 17.5 ± 6.7 ms; P < .01). Fewer epicardial breakthroughs were imaged using noninvasive mapping (1.3 ± 0.5 vs 2.3 ± 0.7; P < .01). Primary breakthrough locations were imaged 75.7 ± 38.1 mm apart. Lines of conduction block (jumps of ≥50 ms between contiguous points) due to structural anomalies were recorded in 27 of 59 contact maps and were not visualized at these same sites noninvasively. Instead, artificial lines appeared in 33 of 59 noninvasive maps in regions of reduced bipolar voltage amplitudes (P = .03). An in silico model confirms these artificial constructs.nnnCONCLUSIONnOverall, agreement of ECGi activation mapping and contact mapping is poor and heterogeneous. The between-map correlation is good for wide QRS patterns. Lines of block and epicardial breakthrough sites imaged using ECGi are inaccurate. Further work is required to improve the accuracy of the technique.

Prevalence and long-term prognosis of patients with ‘narrower than normal’ QRS complexes

AimsnVery narrow QRS have been reported in sudden death survivors but prevalence and prognosis role of narrow QRS is unknown.nnnMethods and resultsn546 healthy men between 50 and 60 years (group 1) and 373 similar patients with coronary artery disease (368 men, group 2) underwent signal averaged ECG (SA-ECG) allowing precise measurement of QRS duration. All cause-mortality was determined after 18u2009±u20093 years follow-up. Mean QRS duration was 97u2009±u200913u2009ms in group 1 and 103u2009±u200916u2009ms in group 2. Tenth percentile was 84u2009ms in group 1 and 85u2009ms in group 2. All cause-mortality in group 1 was 10.4% (57/546): 6/85 in case of QRSu2009<85u2009ms (7%) and 2/23 (9%) in case of QRSu2009>120u2009ms (ns). HR for all-cause mortality was 0.75 (95% CI 0.32-1.76, Pu2009=u20090.52) for QRSu2009<85u2009ms and 0.86 (95% CI 0.21-3.53, Pu2009=u20090.84) for QRSu2009>120u2009ms. All cause mortality in group 2 was 29% (109/373): 7/44 in case of QRSu2009<85u2009ms (16%) and 22/44 (50%) in case of QRSu2009>120u2009ms (Pu2009=u20090.002). HR for all-cause mortality was 0.65 (95% CI 0.29-1.45, Pu2009=u20090.29) for QRSu2009<85u2009ms and 1.73 (95% CI 1.02-2.94, Pu2009=u20090.05) for QRSu2009>120u2009ms.nnnConclusionnQRS durationu2009<80-85u2009ms can be observed in a significant proportion of middle-aged healthy males and in similar patients with ischemic heart disease. Narrow QRS were not linked to prognosis in any group.