A. Messali

Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia

Background— The pathophysiological background of catecholaminergic polymorphic ventricular tachycardia is well understood, but the clinical features of this stress-induced arrhythmic disorder, especially the incidence and risk factors of arrhythmic events, have not been fully ascertained. Methods and Results— The outcome in 101 catecholaminergic polymorphic ventricular tachycardia patients, including 50 probands, was analyzed. During a mean follow-up of 7.9 years, cardiac events defined as syncope, aborted cardiac arrest, including appropriate discharges from implantable defibrillators, or sudden cardiac death occurred in 27 patients, including 2 mutation carriers with normal exercise tests. The estimated 8-year event rate was 32% in the total population and 27% and 58% in the patients with and without &bgr;-blockers, respectively. Absence of &bgr;-blockers (hazard ratio [HR], 5.48; 95% CI, 1.80 to 16.68) and younger age at diagnosis (HR, 0.54 per decade; 95% CI, 0.33 to 0.89) were independent predictors. Fatal or near-fatal events defined as aborted cardiac arrest or sudden cardiac death occurred in 13 patients, resulting in an estimated 8-year event rate of 13%. Absence of &bgr;-blockers (HR, 5.54; 95% CI, 1.17 to 26.15) and history of aborted cardiac arrest (HR, 13.01; 95% CI, 2.48 to 68.21) were independent predictors. No difference was observed in cardiac and fatal or near-fatal event rates between probands and family members. Conclusions— Cardiac and fatal or near-fatal events were not rare in both catecholaminergic polymorphic ventricular tachycardia probands and affected family members during the long-term follow-up, even while taking &bgr;-blockers, which was associated with a lower event rate. Further studies evaluating concomitant therapies are necessary to improve outcome in these patients.

Death Due to an Implantable Cardioverter Defibrillator

Inappropriate therapy due to noise oversensing caused a true ventricular fibrillation (VF) and death of a patient. A 49‐year‐old patient with a history of dilated cardiomyopathy received a double‐chamber implantable cardioverter defibrillator (ICD) in 1991 for a sustained inducible ventricular tachycardia (VT). One appropriate shock delivered in 1994 terminated an episode of VT. The generator was replaced in 1995 and in 2000, and was connected to the initial leads. Three months after the second replacement, the patient received six consecutive shocks related to detection of noise interpreted as VF. Unfortunately, the sixth shock triggered a true VF, which was not treated due to end of the therapeutic sequence, and the patient died. The causes of the dysfunction are discussed.

The role of stress test for predicting genetic mutations and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular tachycardia probands

AIMS Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmic disorder with a highly malignant clinical course. Exercise-stress test is the first-line approach to diagnose suspected individuals. We sought to elucidate the value of exercise-stress test for predicting mutations and future cardiac events in CPVT-family relatives. METHODS AND RESULTS The present study included 67 asymptomatic relatives (24 ± 15 years) of 17 genetically positive CPVT probands, who underwent exercise-stress test without any medication and genetic testing. Exercise-stress test, which was considered positive with the induction of ventricular tachycardia or premature ventricular contractions consisting of bigeminy or couplets, was positive in 17 relatives (25%). Genetic analysis disclosed mutations in 16 of these 17 relatives (94%) and in 16 of the 50 relatives (32%) with negative exercise-stress test; the sensitivity and specificity for a positive genotype were 50 and 97%, respectively (P< 0.001). Among 32 mutation carriers, cardiac events occurred in 7 of the 16 relatives with positive and 2 of the 16 relatives with negative exercise-stress test during the follow-up period of 9.6 ± 3.8 years, and four with positive and two with negative stress test were not on regular beta-blocker treatment at these events. In the 16 relatives with positive stress test, those on beta-blocker treatment demonstrated a trend of lower cardiac event rate (Log-rank P= 0.054). CONCLUSION In asymptomatic relatives of CPVT probands, exercise-stress test can be used as a simple diagnostic tool. Nevertheless, because of the low sensitivity for predicting mutations and future cardiac events in those with negative stress test, genetic analysis should be performed to improve patient management.

Long-term follow-up of asymptomatic Brugada patients with inducible ventricular fibrillation under hydroquinidine

AIMS To evaluate the long-term efficacy and safety of an electrophysiologically guided therapy, based on a strategy of treatment using hydroquinidine (HQ) among asymptomatic Brugada patients with inducible ventricular fibrillation (VF). METHODS AND RESULTS In two French reference centres, consecutive asymptomatic type 1 Brugada patients with inducible VF were treated with HQ (600 mg/day, targeting a therapeutic range between 3 and 6 µmol/L) and enroled in a specific follow-up (mean 6.6 ± 3 years), including a second programmed ventricular stimulation (PVS) under HQ. An implantable cardioverter defibrillator (ICD) was eventually implanted in patients inducible under HQ, or during follow-up in case of HQ intolerance, as well as occurrence of arrhythmic events. From a total of 397 Brugada patients, 44 were enroled (47 ± 10 years, 95% male). Of these, 34 (77%) were no more inducible (Group PVS-), and were maintained under HQ alone during a mean follow-up of 6.2 ± 3 years. In this group, an ICD was eventually implanted in four patients (12%), with occurrence of appropriate ICD therapies in one. Among the 10 other patients (22%), who remained inducible and received ICD (Group PVS+), none of them received appropriate therapy during a mean follow-up of 7.7 ± 2 years. The overall annual rate of arrhythmic events was 1.04% (95% confidence interval 0.00-2.21), without any significant difference according to the result of PVS under HQ. One-third of patients experienced device-related complications. CONCLUSION Our long-term follow-up results emphasize that the rate of arrhythmic events among asymptomatic Brugada patients with inducible VF remains low over time. Our results also suggest that residual inducibility under HQ is of limited value to predict events during follow-up.

Ventricular Repolarization Restitution Properties in Patients Exhibiting Type 1 Brugada Electrocardiogram With and Without Inducible Ventricular Fibrillation

OBJECTIVES This study aimed to elucidate the contribution of the repolarization restitution property to the sustained ventricular fibrillation (VF) in Brugada syndrome. BACKGROUND Although phase 2 re-entry develops as the trigger of VF, the other precipitating factors have remained unclear. METHODS Twenty-one patients with a type 1 Brugada electrocardiogram underwent programmed electrical stimulation. Before the VF induction, single extrastimuli were delivered at 3 basic drive cycle lengths (BCLs) (400 ms, 600 ms, and 750 ms) from the right ventricular apex (RVA) and outflow tract (RVOT), and the activation recovery interval (ARI) was measured at 5-mm vicinity of the pacing site. The maximum ARI restitution slope was determined using the overlapping least-squares linear segments. RESULTS We found that VF was inducible in 10 patients. A repeated-measure analysis of variance revealed that the slope in the RVA was steeper in patients with inducible VF than in those without but that in the RVOT was similar. The slope was steeper at longer BCLs and also steeper in the RVA than RVOT at BCLs of 600 and 750 ms. In patients with inducible VF, the percentage of patients exhibiting a slope >1 was 0%, 20%, and 75% in the RVA and 0%, 0%, and 14% in the RVOT at BCLs of 400 ms, 600 ms, and 750 ms, respectively. No patients without inducible VF had a slope >1. CONCLUSIONS These results suggest the repolarization restitution property is a contributing factor to the propensity for VF in Brugada syndrome and, regarding this property, the RVA plays more important role than the RVOT.

Beat-to-beat T-wave amplitude variability in the long QT syndrome.

AIMS Long QT syndrome (LQTS) is a primary electrical disease characterized by QT prolongation and increased repolarization dispersion leading to T-wave amplitude beat-to-beat changes. We aimed to quantify beat-to-beat T-wave amplitude variability from ambulatory Holter recordings in genotyped LQTS patients. METHODS AND RESULTS Seventy genotyped LQTS patients (mean age 23 +/- 15 years, 42 males, 50% LQT1, 39% LQT2, and 11% LQT3) and 70 normal matched control subjects underwent a 24-h digital Holter recording. Using the Tvar software (Ela Medical, Sorin group), the beat-to-beat variance of the T-wave amplitude (TAV in microV) [corrected] was assessed on 50-ms consecutive clusters during three 1-h periods: one with around average diurnal heart rate (Day Fast), one nocturnal period (Night), and one diurnal period with around average nocturnal heart rate (Day Slow). TAV was increased in LQTS patients during the two diurnal periods but not at night (during the Day Fast period, mean TAV was 34 +/- 20 microV [corrected] in LQTS patients vs. 27 +/- 10 microV [corrected] in controls, P < 0.05). This effect depended on the genotype. In LQT1, TAV was larger when compared with controls for both Day Fast and Slow periods, but in LQT2 only Day Fast shows higher TAV. Oppositely, in LQT3 the TAV was higher than in the control group during the Day slow period (mean TAV = 34 +/- 20 vs. 25 +/- 8 microV [corrected] in controls, P < 0.05). CONCLUSION In genotyped LQTS patients beat-to-beat T-wave amplitude variability was increased when compared with control subjects. That pattern was modulated by circadian influences in a gene-dependent manner.

High take-off left inferior pulmonary vein as an obstacle in creating a conduction block at the lateral mitral isthmus.

AIMS Creation of complete linear lesions in the lateral mitral isthmus (LMI) by catheter ablation for treating atrial fibrillation remains technically challenging. We aimed to clarify whether a high take-off left inferior pulmonary vein (LIPV) can hamper the creation of a complete block at the LMI. METHODS AND RESULTS We included 81 consecutive patients who underwent linear ablation at the LMI and cardiac computed tomography (CT) before ablation. We defined a high take-off LIPV when the level of the lower edge of the LIPV ostium was higher than that of the top of mitral annulus on CT. The clinical backgrounds, parameters, and long-term follow-up were then compared between the success (successful creation of a complete LMI block) and failure groups. A complete LMI block was obtained in 60/81 (76%) patients. In the failure group, a high take-off LIPV was noted more commonly and the LMI tended to be longer than the success group. Multivariate analysis revealed that a high take-off LIPV was an independent predictor of failure to achieve a complete LMI block. The sinus rhythm maintenance rate was not different between the success and failure groups. CONCLUSION A high take-off LIPV hampered the creation of complete linear lesions in the LMI.

La fibrillation atriale est-elle un marqueur indépendant de risque cardio-vasculaire ?

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia and its prevalence rises with age. AF may cause stroke and heart failure but the relationship between AF and mortality is less clear. It is difficult to determine if cardiovascular events in patients with AF are attributable to the arrhythmia itself or if they are merely related to the comorbidities frequently associated with AF. Review of the literature suggests that lone AF (without structural heart disease), a rare clinical entity except in young patients, is not an independent risk factor for mortality. On the other hand, if illnesses usually associated with AF are present (hypertension, heart failure...), AF has a negative impact on outcome in terms of survival and morbidity. Current antiarrhythmic medications have not shown reduction in mortality of AF patients, but new agents and catheter ablation are promising paths to explore in order to decrease AF burden.

Short-long-short sequence caused by ventricular safety pacing inducing ventricular tachycardia in a patient with a dual-chamber implantable cardioverter defibrillator.

Ventricular safety pacing (VSP) is an algorithm used to prevent crosstalk inhibition and ventricular capture during the vulnerable period. We report a 78-year-old man with implantable dual-chamber defibrillator, in whom clusters of ventricular tachycardias (VTs) were provoked by the VSP. During rapid DDDR pacing, the delivery of the VSP after every other atrial-paced beat resulted in short-long-short ventricular sequences and induced VTs. An atrial-based lower rate timing, long atrioventricular pacing interval, and automatic gain control also accounted for this arrhythmogenic ventricular sequence. The VSP and the subsequent VT were eliminated by decreasing the pacing rate.

Spectrum and Outcome of Patients Who Have Undergone Implantation of an Implantable Cardioverter Defibrillator After Aborted-Sudden Cardiac Arrest

Most of implantable cardioverter defibrillator (ICD) secondary prevention studies have been published 2 decades ago. We aimed to describe a contemporary cohort of patients who have undergone implantation of an ICD after an aborted-sudden cardiac arrest (SCA). We retrospectively evaluated consecutive patients referred to our centers between 2005 and 2013. Predictors of overall mortality or heart transplant were analyzed using Cox proportional hazards models. A total of 250 patients (76.4% male, 48.7 ± 16.7 years) were included (mean follow-up = 49.6 ± 35 months). The presence of a structural heart disease (SHD) was considered as the primary cause of the aborted-SCA in 160 patients (64%). In 90 patients (36%), no SHD was observed, with patients much younger (40.9 ± 16.2 years vs 53.0 ± 15.5 years in the SHD group, p < 0.0001). The 5-year estimated rates of death or heart transplant were 14.3% and 5.2% in the group with and without SHD, respectively (hazard ratio = 4.65, 95% confidence interval 1.40 to 15.6, p = 0.014). The 5-year estimated rates of appropriate ICD therapy in the ventricular fibrillation zone were 16.7% and 25.1% in patients without and with SHD (p = 0.24), respectively. Only left ventricular ejection fraction remained independently associated with mortality or heart transplant (hazard ratio = 0.94, 95% confidence interval 0.90 to 0.97, p = 0.0004). Overall, 69 patients (27.6%) experienced at least 1 ICD-related complication. In conclusion, compared with secondary prevention pivotal studies, the current patients who have undergone implantation of an ICD after aborted-SCA are younger, with a high proportion of structurally normal hearts. Compared with patients without SHD, who depicted a relatively favorable outcome, patients with SHD present a fourfold higher risk of death during follow-up. Reduced left ventricular ejection fraction remains the major influencing factor.