Long-Term Follow-Up of Idiopathic Ventricular Fibrillation in a Pediatric Population: Clinical Characteristics, Management, and Complications.

Background The natural history and long-term outcome in pediatric patients with idiopathic ventricular fibrillation ( IVF ) are poorly characterized. We sought to define the clinical characteristics and long-term outcomes of a pediatric cohort with an initial diagnosis of IVF . Methods and Results Patients were included from an International Registry of IVF (consisting of 496 patients). Inclusion criteria were: (1) VF with no identifiable cause following comprehensive analysis for ischemic, electrical or structural heart disease and (2) age ≤16 years. These included 54 pediatric IVF cases (age 12.7±3.7 years, 59% male) among whom 28 (52%) had a previous history of syncope (median 2 syncopal episodes [interquartile range 1]). Thirty-six (67%) had VF in situations associated with high adrenergic tone. During a median 109±12 months of follow-up, 31 patients (57%) had recurrence of ventricular arrhythmias, mainly VF . Two patients developed phenotypic expression of an inherited arrhythmia syndrome during follow-up (hypertrophic cardiomyopathy and long QT syndrome, respectively). A total of 15 patients had positive genetic testing for inherited arrhythmia syndromes. Ten patients (18%) experienced device-related complications. Three patients (6%) died, 2 due to VF storm. Conclusions In pediatric patients with IVF , a minority develop a definite clinical phenotype during long-term follow-up. Recurrent VF is common in this patient group.

High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Previous studies suggested that genetic status affects the clinical course of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. The aim of this study was to compare the outcome of desmoglein-2 (DSG2) mutation carriers to those who carry the plakophilin-2 (PKP2) mutation, the most common ARVC/D-associated gene. METHODS AND RESULTS: Consecutive ARVC/D patients carrying a pathogenic mutation in PKP2 or DSG2 were selected from a national ARVC/D registry. The cumulative freedom from sustained ventricular arrhythmia and cardiac transplantation/death from heart failure (HF) during follow-up was assessed, compared between PKP2 and DSG2, and predictors for ventricular arrhythmia and HF events determined. Overall, 118 patients from 78 families were included: 27 (23%) carried a DSG2 mutation and 91 (77%) a PKP2 mutation. There were no significant differences between DSG2 and PKP2 mutation carriers concerning gender, proband status, age at diagnosis, T-wave inversion, or right ventricular dysfunction at baseline. DSG2 patients displayed more frequent epsilon wave (37% vs. 17%, P = 0.048) and left ventricular dysfunction at diagnosis (54% vs. 10%, P < 0.001). During a median follow-up of 5.6 years (2.5-16), DSG2 and PKP2 mutation carriers displayed a similar risk of sustained ventricular arrhythmia (log-rank P = 0.20), but DSG2 mutation carriers were at higher risk of transplantation/HF-related death (log-rank P < 0.001). The presence of a DSG2 mutation vs. PKP2 mutation was a predictor of transplantation/HF-related death in univariate Cox analysis (P = 0.0005). CONCLUSIONS: In this multicentre cohort, DSG2 mutation carriers were found to be at high risk of end-stage HF compared to PKP2 mutation carriers, supporting careful haemodynamic monitoring of these patients. The benefit of early HF treatment needs to be assessed in DSG2 carriers.

Rationale and Design for a Monocentric Prospective Study: Sleep Apnea Diagnosis Using a Novel Pacemaker Algorithm and Link With Aldosterone Plasma Level in Patients Presenting With Diastolic Dysfunction (SAPAAD Study).

Previous studies showed good agreement between pacemaker respiratory disturbance index (RDI) and polysomnography for diagnosis of severe sleep apnea (SA). The aim of this study is to investigate the diagnostic accuracy of RDI compared with apnea-hypopnea index (AHI) from a cardiorespiratory sleep study for the diagnosis of severe SA within patients requiring a pacemaker and meeting diastolic dysfunction criteria. Secondary objectives are as follows: correlation between plasma aldosterone level and SA severity, diagnostic accuracy of RDI for moderate SA, prevalence of SA among patients with diastolic dysfunction, occurrence of arrhythmias, and improvement of RDI with continuous positive airway pressure therapy. We designed a monocentric prospective nonrandomized study of prevalent cases to include 68 patients with a 6-month follow-up. Both RDI and AHI will be compared 2 months after implantation and after 1 month of continuous positive airway pressure treatment in patients with severe SA. This is the first study that examines diagnostic accuracy of pacemaker algorithm for the diagnosis of SA and correlation with plasma aldosterone levels in patients with diastolic dysfunction. Protocol version: V04. 04/04/2017 Trial registration: ClinicalTrials.gov NCT02751021.

Prevalence and significance of rare RYR2 variants in arrhythmogenic right ventricular cardiomyopathy/dysplasia: results of a systematic screening.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic disease predominantly caused by desmosomal gene mutations that account for only ~50% of cases. Ryanodine receptor 2 (RYR2) gene mutations usually cause catecholaminergic polymorphic ventricular tachycardia but have been associated with a peculiar phenotype named ARVC2. OBJECTIVE: We aimed to determine the prevalence and phenotype associated with RYR2 mutations in a large ARVC/D population. METHODS: We analyzed the whole RYR2 coding sequence by Sanger sequencing in 64 ARVC/D probands without desmosomal gene mutations. RESULTS: We have identified 6 rare missense variants: p.P1583S, p.A2213S, p.G2367R, p.Y2932H, p.V3219M, and p.L4670V. It corresponds to a 9% prevalence of rare RYR2 variants in the ARVC/D population (6 of 64 probands), which is significantly higher than the estimated frequency of rare RYR2 variants in controls (Fisher exact test, P = .03). Phenotypes associated with RYR2 variants were similar to desmosome-related ARVC/D, associating typical electrocardiographic abnormalities at rest, frequent monomorphic ventricular tachycardia, right ventricular dilatation, wall motion abnormalities, and fibrofatty replacement when histopathological examination was available. CONCLUSION: In this first systematic screening of the whole coding region of the RYR2 gene in a large ARVC/D cohort without mutation in desmosomal genes, we show that putative RYR2 mutations are frequent (9% of ARVC/D probands) and are associated with a conventional phenotype of ARVC/D, which is in contrast with previous findings. The results support the role of the RYR2 gene in conventional ARVC/D.

Scar extent as a predictive factor of ventricular tachycardia cycle length after myocardial infarction: implications for implantable cardioverter-defibrillator programming optimization.

AIMS: After an old myocardial infarction (MI), patients are at risk for reentrant ventricular tachycardia (VT) due to scar tissue that can be accurately identified by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Although the ability of LGE-CMR to predict sustained VT in implantable cardioverter-defibrillator (ICD) recipients has been well established, its use to predict monomorphic VT (sustained or not) cycle length (CL) and so, optimize ICD programming has never been investigated. METHODS AND RESULTS: We included retrospectively 49 consecutive patients with an old MI who had undergone LGE-CMR before ICD implantation over a 4-year period (2006-09). Patients with amiodarone used were excluded. Scar extent was assessed by measuring scar mass, percent scar, and transmural scar extent. The endpoint was the occurrence of monomorphic VT, requiring an ICD therapy or not. The endpoint occurred in 26 patients. The median follow-up duration was 31 months. Scar extent parameters were significantly correlated with the study endpoint. With univariate regression analysis, the scar mass had the highest correlation with the VT CL (R = 0.671, P = 0.0002). Receiver-operating characteristic curve showed that scar mass can predict VT CL (area under the curve = 0.977, P < 0.0001). For a cut-off value of scar mass at 17.6 g, there is 100% specificity and 94.4% sensitivity. CONCLUSION: In this observational and retrospective study, scar mass studied by LGE-CMR was specific and sensitive to predict VT CL and so could be a promising option to improve ICD post-implantation programming and decrease appropriate and inappropriate shocks. These conclusions must now be confirmed in a large and prospective study.

Scar extent evaluated by late gadolinium enhancement CMR: a powerful predictor of long term appropriate ICD therapy in patients with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) patients are at risk for life-threatening ventricular arrhythmias (VA) related to scar tissue. Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) can accurately identify myocardial scar extent. It has been shown that scar extent, particularly scar transmurality, percent scar and scar mass, are associated with the occurrence of appropriate implantable cardioverter-defibrillator (ICD) therapy. However, quantification of transmurality extent has never been studied. The purpose of our study was to evaluate whether different methods quantifying scar transmurality, percent scar and scar mass (assessed with LGE-CMR) can predict appropriate ICD therapy in CAD patients with a long term follow-up period. METHODS AND RESULTS: We enrolled retrospectively 66 patients with chronic CAD referred for primary or secondary preventive ICD implantation and LGE-CMR before ICD implantation. Using LGE-CMR, scar extent was assessed by measuring scar mass, percent scar and transmural scar extent using four different methods. The median follow-up duration was 41.5 months (interquartile range 22-52). The endpoint was the occurrence of appropriate device therapy and occurred in 14 patients. Pre-ICD revascularization and transmural scar extent were significantly associated with the study endpoint but the latter was especially highly dependent on the method used. Patients with appropriate device therapy had also larger scar mass (29.6 ± 14.5 g vs 17.1 ± 8.8 g, p = 0.004), and larger percent scar (15.1 ± 8.2% vs 9.9 ± 5.6%, p = 0.03) than patients without appropriate device therapy. In multivariate analysis, scar extent variables remained significantly associated with the study end-point. CONCLUSIONS: In this study of CAD patients implanted for primary or secondary preventive ICD, pre-ICD revascularization and scar extent studied by LGE-CMR were significantly associated with appropriate device therapy and can identify a subgroup of CAD patients with an increased risk of life-threatening VA. Depending of the method used, transmural scar extent may vary significantly and needs further studies to obtain a validated and consensual study method.

Apical aneurysm and myocardial bridging in a patient with hypertrophic cardiomyopathy: association or consequence of the myocardial bridging?

The identification of high-risk patients with hypertrophic cardiomyopathy (HC) for primary prevention of sudden cardiac death (SCD) remains a challenging issue, since major risk factors sometimes lack specificity. We report the case of a patient with HC and association of apical aneurysm and myocardial bridging who had been initially not implanted because she had only one major risk factor. She subsequently experienced a sustained ventricular tachycardia that finally motivated the implantation. We conclude that it is never an easy decision to implant a preventive implantable cardioverter-defibrillator (ICD). Nevertheless, additional criteria for a better selection of patients who would benefit from an ICD implant are certainly useful.

Primary prevention with a defibrillator: are therapies always really optimized before implantation?

AIMS: Left ventricle ejection fraction (LVEF) ≤ 30-35% is widely accepted as a cut-off for primary prevention with an implantable cardiac defibrillator (ICD) in patients with both ischaemic and non-ischaemic cardiomyopathy supposedly on optimal medical therapy. This study reports evolutions of LVEF and treatments of patients implanted in our institution with an ICD for primary prevention of sudden death, after 2 years of follow-up. METHODS AND RESULTS: Among 84 patients with LVEF under 35% implanted between 2005 and 2007, 28 (33%) had improved their LVEF >35% after the 2 years of follow-up. During this period, even if Beta-blockers (98%) and renin-angiotensin system (RAS) blockers (95%) were already initially prescribed, treatments were significantly optimized with improvement of maximal doses of beta-blockers and RAS blockers at 2 year follow-up compared with initial prescription (62 vs. 37% and 68 vs. 45%, respectively). In patients with improved LVEF, a trend toward a better treatment optimization and revascularization procedures (in the sub-group of ischaemic patients) were observed compared with non-improved LVEF patients. CONCLUSIONS: In our study of patients with prophylactic ICD, one-third of them have improved their LVEF after a 2 year follow-up. Despite an optimal medical therapy at the time of implantation, we were able to further improve the maximal treatment doses after implantation. This study highlights the issue of what should be considered as 'optimal' therapy and the possibility of improvement of LVEF related to a real optimized treatment before implantation.

Comparison of outcomes in patients with abandoned versus extracted implantable cardioverter defibrillator leads.

BACKGROUND: Despite the increased number of implantable cardioverter defibrillator (ICD) recipients and the frequent need for device upgrading and/or occurrence of lead malfunction, the optimal approach to managing abandoned leads remains debated. AIMS: To determine the rate and type of complications related to either abandoned or extracted ICD leads. METHODS: Patients with abandoned or extracted leads were identified retrospectively. Patient medical records were reviewed to assess long-term lead or device malfunction, defibrillation test values before and after lead abandonment or extraction, and appropriateness of delivered shocks and subsequent surgical procedures related to devices or leads. RESULTS: A total of 58 ICD patients with 47 extracted and 34 abandoned leads were identified. After a mean follow-up of 3.2 ± 2.6 years, the defibrillation test was not affected by either abandoned or extracted leads (23.4 ± 6.6 J vs 25.4 ± 4.9 J, respectively; P = 0.24). There were no differences in the number of ICD-related surgical procedures after extracting versus abandoning leads (22% vs 12%, respectively; P = 0.3) or in the thromboembolic event rate (7.7% vs 6.3%; P = 0.83). During follow-up, no differences in the occurrence of major complications or appropriate/inappropriate shocks were observed between patients with or without abandoned leads. CONCLUSION: We observed no difference in rates of immediate or medium-term complications between extracting versus abandoning leads. Lead abandonment remains an alternative and safe option when extraction does not appear mandatory according to the age of the leads or experience of the operating centre.

[Management of a first recent episode of atrial fibrillation in clinical practice]. / Que faire devant un premier passage récent en fibrillation atriale?

Atrial fibrillation (AF) is the most frequent supraventricular arrhythmias with an approximative prevalence of 1 % in the general population and above 6 % in the elderly. Management of a first AF episode is different depending on the clinical status of patients. Practice guidelines developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society are available for the management of these patients. A four-step decisional scheme must be followed in the management of a first recent AF episode: need for a short- and long-term anticoagulation, define a rythmologic strategy (rhythm or rate control), select the weapon (drug, device or ablation) and reconsider the strategy if needed. After a first uncomplicated paroxysmal AF episode, guidelines recommend that prescription of antiarrhythmics must be avoided and anticoagulation is optional. After a first persistent AF episode, guidelines recommend to either respect or reduce the arrhythmia. Prescription of antiarrhythmics and anticoagulation is also optional depending on the patients condition. In case of the AF reduction decision, anticoagulation must be tailored preliminary to this reduction. AF recurrence rate varies depending on the patients condition, and the risk of stroke assessed by the CHADS(2) score might be similarly considered for both paroxysmal and persistent AF.

Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice.

AIMS: Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping. METHODS AND RESULTS: Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135 unrelated patients with ARVD/C. We identified 41 different disease-causing mutations, including 28 novel ones, in 62 patients (46%). In addition, a genetic variant of unknown significance was identified in nine additional patients (7%). Distribution of genes was 31% (PKP2), 10% (DSG2), 4.5% (DSP), 1.5% (DSC2), and 0% (JUP). The presence of desmosomal mutations was not associated with familial context but was associated with young age, symptoms, electrical substrate, and extensive structural damage. When compared with other genes, DSG2 mutations were associated with more frequent left ventricular involvement (P = 0.006). Finally, complex genetic status with multiple mutations was identified in 4% of patients and was associated with more frequent sudden death (P = 0.047). CONCLUSION: This study supports the use of genetic testing as a new diagnostic tool in ARVC/D and also suggests a prognostic impact, as the severity of the disease appears different according to the underlying gene or the presence of multiple mutations.

Sudden cardiac arrest associated with early repolarization.

BACKGROUND: Early repolarization is a common electrocardiographic finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest. METHODS: We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of electrocardiographic early repolarization. The latter was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects. RESULTS: Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P<0.001). Among case subjects, those with early repolarization were more likely to be male and to have a history of syncope or sudden cardiac arrest during sleep than those without early repolarization. In eight subjects, the origin of ectopy that initiated ventricular arrhythmias was mapped to sites concordant with the localization of repolarization abnormalities. During a mean (+/-SD) follow-up of 61+/-50 months, defibrillator monitoring showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without such an abnormality (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008). CONCLUSIONS: Among patients with a history of idiopathic ventricular fibrillation, there is an increased prevalence of early repolarization.

Contributions of high resolution electrograms memorized by DDDR pacemakers in the interpretation of arrhythmic events.

The accuracy of information retrievable from the memories of DDDR pacing systems has been limited by the absence of actual electrograms confirming the proper sensing of spontaneous cardiac activity versus that of extraneous signals. This study examined the diagnostic power of a new arrhythmia interpretation scheme, which includes the recording and storage of high resolution endocavitary atrial and ventricular electrograms (HREGM). HREGM stored in the memories of new generation pacemakers (PM) in response to nonsustained ventricular tachycardia (NSVT), sustained VT, and atrial arrhythmias were analyzed in a follow-up registry of 520 patients at 1 month, and 3 to 6 months after implantation of a PM for standard indications. For each sequence of stored HREGM, the accuracy of the PM response was examined, classified as accurate (true positive), versus inaccurate (false positive), versus undetermined, and the relative contribution of the HREGM in verifying the PM diagnosis was measured. During a follow-up of 4.9 +/- 2 months, 256 (49%) of the 520 patients had an event recorded, which was confirmed to be arrhythmic on the basis of HREGM. Overall, approximately 34% of atrialtachy response (ATR) episodes were confirmed to be appropriate. Similar percentages of episodes were prompted by oversensing of signals unrelated to cardiac arrhythmias, while nearly 12% of the episodes could not be clarified because of such brief duration as to preclude recording of their onset. Approximately one-third of NSVT, and one-half of VT detections were false positive. Ventricular oversensing, most often due to myopotential interference in presence of unipolar sensing, and atrial undersensing were both identified as sources of false-positive detections of ventricular events. The proportion of true-positive detections was significantly higher in the bipolar (83%) than unipolar configuration. Among 520 PM recipients, miscellaneous episodes of atrial arrhythmias were confirmed by HREGM in 37% of patients within 3 to 6 months of follow-up. Atrial fibrillation was confirmed in only 6% of patients, of whom over 50% already had histories of atrial fibrillation. The prevalence of unsuspected atrial arrhythmia in this unselected population was lower than previously reported.