Mutations in the TGFβR2 gene have been associated with a life threatening risk of aortic dissection but no arrhythmic death has been previously reported. Two young females carrying a TGFβR2 mutation, ...initially diagnosed as Marfan syndrome or Loeys Dietz syndrome, presented sudden death with autopsy ruling out dissection. The ECGs of the 2 Sudden Cardiac Deaths revealed profound ventricular repolarization abnormalities with a sinusoidal T-U morphology associated with normal left ventricular ejection fraction. These data strongly suggest sudden cardiac arrhythmic deaths and prompted us to systematically study the repolarization pattern in the patients with TGFβR2 mutations. ECG findings from 58 mutation carriers patients (TGFβR2 group) were compared with those of 46 non-affected first degree relatives (control group). TGFβR2 mutation was associated with ventricular repolarization abnormalities in 47% of patients (p < 0.001 vs. controls), including a 19.6 ms (95%CI 8.7; 30.5) QTc interval prolongation compared to the non-affected first degree relatives (p < 0.001), higher prevalence of abnormal U waves (16% vs. 2%), and sinusoidal T-U morphology (10% vs. 0%). TGFβR2 mutations can be associated with abnormal ventricular repolarization pattern, longer QT interval than non-carrier relatives and an increased risk for sudden death.
Inappropriate therapy delivered by implantable cardioverter defibrillators (ICDs) remains a challenge. The OPERA registry measured the times to, and studied the determinants of, first appropriate ...(FAT) and inappropriate (FIT) therapies delivered by single-, dual- and triple-chamber cardiac resynchronization therapy defibrillator (CRT-D) ICD.
We entered 636 patients (mean age = 62.0 ± 13.5 years; 88% men) in the registry, of whom 251 received single-, 238 dual-, and 147 triple-chamber ICD, for primary (30.5%) or secondary (69.5%) indications. We measured times to FAT and FIT as a function of multiple clinical characteristics, examined the effects of various algorithm components on the likelihood of FAT and FIT delivery, and searched for predictors of FAT and FIT. Over 22.8 ± 8.8 months of observation, 184 patients (28.9%) received FAT and 70 (11.0%) received FIT. Ventricular tachycardia (VT) was the trigger of 88% of FAT, and supraventricular tachycardia was the trigger of 91% of FIT. The median times to FIT (90 days; range 49-258) and FAT (171 days; 50-363) were similar. The rate of FAT was higher (P <0.001) in patients treated for secondary than primary indications, while that of FIT were similar in both groups. Out of 57 analysable FIT, 27 (47.4%) could have been prevented by fine tuning the device programming like the sustained rate duration or the VT discrimination algorithm.
First inappropriate therapy occurred in 11% of 636 ICD recipients followed for ∼2 years. Nearly 50% of FIT could have been prevented by improving device programming.
The 2 genes KCNQ1 (LQT1) and HERG (LQT2), encoding cardiac potassium channels, are the most common cause of the dominant long-QT syndrome (LQTS). In addition to QT-interval prolongation, notched T ...waves have been proposed as a phenotypic marker of LQTS patients.
The T-wave morphology of carriers of mutations in KCNQ1 (n=133) or HERG (n=57) and of 100 control subjects was analyzed from Holter ECG recordings. Averaged T-wave templates were obtained at different cycle lengths, and potential notched T waves were classified as grade 1 (G1) in case of a bulge at or below the horizontal, whatever the amplitude, and as grade 2 (G2) in case of a protuberance above the horizontal. The highest grade obtained from a template defined the notch category of the subject. T-wave morphology was normal in the majority of LQT1 and control subjects compared with LQT2 (92%, 96%, and 19%, respectively, P:<0.001). G1 notches were relatively more frequent in LQT2 (18% versus 8% LQT1 and 4% control, P:<0.01), and G2 notches were seen exclusively in LQT2 (63%). Predictors for G2 were young age, missense mutations, and core domain mutations in HERG.
This study provides novel evidence that Holter recording analysis is superior to the 12-lead ECG in detecting G1 and G2 T-wave notches. These repolarization abnormalities are more indicative of LQT2 versus LQT1, with G2 notches being most specific and often reflecting HERG core domain missense mutations.
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.
Abstract
Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): Ministère de la Santé Française
Background
Arrhythmic risk stratification remains a major ...challenge in asymptomatic Brugada patients. Many studies have evaluated risk stratification performance based on a single or a few ECG-derived parameters measured manually. We aimed to assess the predictive value of multi ECG parameters measured automatically in patients with Brugada syndrome.
Materials and Methods
We performed a prospective, multicenter cohort study including Brugada patients with at least one available type 1 ECG (either spontaneously or drug-induced) between January 2005 and November 2021. Paper ECG were first digitized and then automatically analyzed using the Glasgow and Bravo algorithms (included in the logiciel CalECG). Clinical data and Brugada related events at diagnosis and during follow-up were collected. Sudden cardiac death, aborted cardiac arrest and appropriate ICD therapy in the VF zone were considered as major events. The predictive value of clinical and ECG parameters for symptomatic status was assessed using uni- and multivariate Cox models.
Results
ECGs from 301 Brugada patients (77% male, mean age at diagnosis 43 years, follow-up 7±5.6 years) were analyzed. Brugada-related symptoms (cardiac syncope or major event) occurred in 23% of patients before diagnosis and 11% during follow-up (incidence: 1.57%/year).
After multivariate Cox analysis, only 2 baseline ECG (without Ajmaline) parameters were significantly associated with major events: RR interval (HR=1.01 (95%CI 1-1.01), p=0.002) and QRS duration in lead V1 (HR=1.04 (95%CI 1-1.07), p=0.038).
QRS prolongation in lead V1 >113 ms (AUROC 0.69 (95% CI 0.58-0.8)) was associated with a 3-fold increased risk of major event (HR =3.49 (95% CI 1.72-7.09), p=0.001).
Conclusion
Many previously described ECG parameter were not associated with major event in Brugada patients after multi-parameter evaluation. Sinus rate and QRS duration on lead V1 were independent risk factor. These results need to be validated on an external cohort. The predictive value of ECG parameters in Brugada syndrome should be assessed using automated multiparametric quantification.
Roc curve of QRS duration in V1
Cumulative incidence of QRS dur in V1
Torsade de pointes is characterized not only by its particular ECG pattern but by its context of congenital or acquired long QT syndrome and the long coupling interval of the initial premature beat.
...We observed 14 patients aged 34.6 +/- 10 years (mean +/- SD) with no structural heart disease who presented with syncope related to a typical ECG aspect of torsade de pointes. However, there was no evidence of long QT syndrome, and the torsade had the unusual particularity of an extremely short coupling interval of the first beat or of the isolated premature beats (245 +/- 28 milliseconds). In 10 cases they deteriorated into ventricular fibrillation. Four patients had a familial history of sudden death. Only 2 patients had a tachyarrhythmia inducible by programmed stimulation. At Holter recordings the heart rate variability was globally and significantly depressed, the vagal limb of the autonomic nervous system being predominantly affected. During a mean follow-up of 7 years there were 5 deaths (4 sudden). Nine patients are alive, 3 with implanted defibrillators and 6 treated with verapamil alone. Unlike the other types of antiarrhythmic agents including beta-blockers and amiodarone, verapamil is in our experience the only drug apparently active on the arrhythmias; however, it does not prevent sudden death.
The short-coupled variant of torsade de pointes should be identified because of their ECG pattern and the risk of sudden death in young adults with no structural heart disease.
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.
Abstract
Funding Acknowledgements
Type of funding sources: Public hospital(s). Main funding source(s): Assistance Publiques Hôpitaux de Paris (APHP)
Background
Congenital long QT syndrome (LQTS) is ...still associated with syncope and a risk of sudden cardiac death despite the dramatic reduction in mortality associated with beta-blocker therapy. Current risk stratification tools are imperfect.
Objective
To assess the contribution of automated scalar ECG descriptors of ventricular repolarization for arrrhythmic risk stratification in genotyped LQTS patients.
Methods
Patients with genotyped type 1, 2 or 3 LQTS with at least 1 digital ECG recording have been included in the study. History at diagnosis, and follow-up data were collected. Cardiac events included syncope, aborted cardiac arrest, appropriate implantable cardioverter-defibrillator therapy in VF zone, and sudden death.
ECG were analyzed using the BRAVO algorithm embedded in the CalECG software, version 4.1.0. QT interval duration was manually checked but ECG descriptors of Ventricular Repolarization were fully automatic.
Multivariate cox regression analysis were performed to identify parameters associated with cardiac events.
Results
467 patients (58% female, median age at diagnosis=25, LQT1,2,3 54%, 39%, 7%) were followed-up during 15.2±9.2 years. Rate of cardiac event was 1.2/100 patients-year before diagnosis and 0.9/100 patients-year during follow-up.
QTc duration was associated with the occurrence of cardiac events in the whole study population (HR=1.01 95%CI 1.0-1.01, p=0.03). Ventricular repolarization parameters associated with cardiac events were different according to LQTS type. Cardiac events were associated with increased time to accumulate 50% of T-wave energy (HR=1.53 95%CI 1.04-2.26, p=0.03) in LQT1 but with a decrease in T-wave slopes (ascending slope HR=0.63 95%CI 0.17-0.75, p<0.01) in type 2 LQTS patients. QTc duration was not independently associated with cardiac events in genotype specific multivariate models.
Conclusions
T-wave morphology parameters are associated with cardiac events in a gene-specific manner. Change in T-wave symmetry and T-wave flattening are associated with cardiac events in type 1 and type 2 LQTS respectively. The descriptors of ventricular repolarization are promising parameters or risk stratification beyond QTc duration in LQTS patients.
Abstract
Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the ZonMW Priority Medicines for Rare Diseases ...and Orphan Drugs (grant 113304045 to Dr Van der Werf) and the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences (PREDICT2 to Dr. Wilde).
Background
In patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), β-blocker may be insufficiently protective. A randomized clinical trial showed that flecainide reduces ventricular arrhythmias (VAs) in CPVT and small retrospective cohort studies suggest that this translates into a reduction of arrhythmic events.
Objective
To evaluate the efficacy of flecainide when added to β-blockers for the prevention of arrhythmic events (AE) in a large cohort of patients with CPVT using paired analysis.
Methods
From two international registries, this multicentre retrospective cohort study included patients with a clinical and/or genetic diagnosis of CPVT using flecainide as an adjunct to β-blockers. The study period, which comprised a pre- and on-flecianide period, was defined as the period in which background therapy, i.e. β-blocker type (β1-selective or nonselective), left cardiac sympathetic denervation (LCSD), and implantable cardioverter-defibrillator (ICD) treatment status, remained unchanged within individual patients. The primary endpoint was AEs, defined as SCD, sudden cardiac arrest (SCA), appropriate ICD shock, and arrhythmic syncope. The effect of flecainide on AE rates was assessed using a generalized linear mixed model assuming Poisson distribution and random effects for patients.
Results
Two-hundred forty-seven patients (median age at start of flecainide 18 years IQR 14-29, 123 50% female, median flecainide dose 2.2 mg/kg/day IQR 1.7-3.1) were included. At baseline, 70 (28%) patients had an ICD and 21 (9%) had a LCSD performed. Nonselective β-blockers were used by 133 (54%) patients. During a median pre-flecainide follow-up of 2.1 years (IQR 0.4-7.2), 41 patients experienced 58 AEs. During a median on-flecainide follow-up of 2.9 years (IQR 1.0-6.0), 23 patients experienced 38 AEs. There was a significant reduction in AEs after initiation of flecainide (OR 0.55 0.38-0.83; p=0.007). Among patients who were symptomatic before diagnosis or before the initiation of flecainide (n=167), flecainide was associated with a significant reduction in AEs (OR 0.49 0.31-0.77; p=0.002). Among patients with ≥1 AE on β-blocker therapy (n=41), adding flecainide was associated with a significant reduction in AEs (OR 0.25 0.14-0.45; p<0.001).
Conclusion
Flecainide was associated with a reduction in AEs when added to β-blockers in patients with CPVT in the overall cohort, symptomatic patients, and particularly in patients with breakthrough AEs on β-blocker therapy.
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