The Netherlands Arrhythmogenic Cardiomyopathy Registry: design and status update.

BACKGROUND: Clinical research on arrhythmogenic cardiomyopathy (ACM) is typically limited by small patient numbers, retrospective study designs, and inconsistent definitions. AIM: To create a large national ACM patient cohort with a vast amount of uniformly collected high-quality data that is readily available for future research. METHODS: This is a multicentre, longitudinal, observational cohort study that includes (1) patients with a definite ACM diagnosis, (2) at-risk relatives of ACM patients, and (3) ACM-associated mutation carriers. At baseline and every follow-up visit, a medical history as well information regarding (non-)invasive tests is collected (e. g. electrocardiograms, Holter recordings, imaging and electrophysiological studies, pathology reports, etc.). Outcome data include (non-)sustained ventricular and atrial arrhythmias, heart failure, and (cardiac) death. Data are collected on a research electronic data capture (REDCap) platform in which every participating centre has its own restricted data access group, thus empowering local studies while facilitating data sharing. DISCUSSION: The Netherlands ACM Registry is a national observational cohort study of ACM patients and relatives. Prospective and retrospective data are obtained at multiple time points, enabling both cross-sectional and longitudinal research in a hypothesis-generating approach that extends beyond one specific research question. In so doing, this registry aims to (1) increase the scientific knowledge base on disease mechanisms, genetics, and novel diagnostic and treatment strategies of ACM; and (2) provide education for physicians and patients concerning ACM, e. g. through our website ( www.acmregistry.nl ) and patient conferences.

VT Recurrence After Ablation: Incomplete Ablation or Disease Progression? A Multicentric European Study.

AIM: To determine whether ventricular tachycardia (VT) recurrences in arrhythmogenic RV cardiomyopathy (ARVC) and nonischemic cardiomyopathy (NICM) are related to incomplete ablation or disease progression. METHODS: ARVC and NICM patients with two substrate maps of the same diseased ventricle with an interprocedural delay of ≥12 months were included. Disease progression was defined as ≥1 factor: scar area progression (PROG, +5%), ventricular remodeling (dilatation [+25 mL] or decreased ejection fraction [-5%EF]). Incomplete ablation was defined as index VT recurrence or ablation in previously unablated regions inside index scar without PROG. RESULTS: Twenty patients from nine centers were included (80% male 55 ± 16 years, 7 ARVC and 13 NICM, LVEF 43 ± 14%). Mean delay was 28 ± 18 months. Disease progression occurred in 75% with ventricular remodeling in 70%: ventricular dilation in 45% (ARVC [71%]; NICM [38%]), decreased EF in 60% [RVEF in ARVC (71%); LVEF in NICM (54%)], and scar progression in 50% (in ARVC [57%] and NICM [46%]). Index VT recurrence was observed in 40%. Redo ablation sites were located in previously unablated regions inside the index scar in 70% of patients. VT recurrence following the second procedure was seen in 25%. Fifteen percent died during a follow-up of 17 ± 17 months. CONCLUSION: Disease progression is the rule in ARVC and NICM while scar progression occurs in half. However, even if disease progression is frequently observed, incomplete index ablation is the most common finding, strongly suggesting the need for more extensive ablation.

Outcome of stand-alone thoracoscopic epicardial left atrial posterior box isolation with bipolar radiofrequency energy for longstanding persistent atrial fibrillation.

INTRODUCTION: Catheter ablation of longstanding (> 1 year) persistent atrial fibrillation (AF) is associated with poor outcome. This might be due to remodelling and fibrosis formation, mainly located in the posterior left atrial (LA) wall. Therefore, we adopted a thoracoscopic epicardial box isolation of the posterior left atrium using bipolar RF energy with intraoperative testing of conduction block. METHODS AND RESULTS: Bilateral thoracoscopic box isolation was performed with a bipolar RF clamp. Entrance block was defined as absence of a conducted electrogram within the box, while exit block was confirmed by pacing at 10.0 V/2 ms. Ablation outcome was evaluated after 3, 6, 12 and 24 months with 12-lead ECGs and 24-hour Holter recordings. Twenty-five consecutive patients were included (58 ± 7 years, persistent AF duration 1.8 ± 0.9 years). Entrance block was achieved in all patients and exit block confirmed if sinus rhythm was achieved. After 17 ± 7 months, 76 % of the patients (n = 19) were free of AF recurrence. One patient died within 1 month and was considered an ablation failure. Four patients with AF recurrences regained sinus rhythm with additional catheter ablation or antiarrhythmic drugs. CONCLUSIONS: Treatment of longstanding persistent AF with thoracoscopic epicardial LA posterior box isolation using bipolar RF energy with intraoperative testing of conduction block is feasible and highly effective.

Founder mutations in the Netherlands: familial idiopathic ventricular fibrillation and DPP6.

In this part of a series on founder mutations in the Netherlands, we review familial idiopathic ventricular fibrillation linked to the DPP6 gene. Familial idiopathic ventricular fibrillation determines an intriguing subset of the inheritable arrhythmia syndromes as there is no recognisable phenotype during cardiological investigation other than ventricular arrhythmias highly associated with sudden cardiac death. Until recently, it was impossible to identify presymptomatic family members at risk for fatal events. We uncovered several genealogically linked families affected by numerous sudden cardiac deaths over the past centuries, attributed to familial idiopathic ventricular fibrillation. Notably, ventricular fibrillation in these families was provoked by very short coupled monomorphic extrasystoles. We were able to associate their phenotype of lethal arrhythmic events with a haplotype harbouring the DPP6 gene. While this gene has not earlier been related to cardiac arrhythmias, we are now able, for the first time, to identify and to offer timely treatment to presymptomatic family members at risk for future fatal events solely by genetic analysis. Therefore, when there is a familial history of unexplained sudden cardiac deaths, a link to the DPP6 gene may be explored as it may enable risk evaluation of the remaining family members. In addition, when closely coupled extrasystoles initiate ventricular fibrillation in the absence of other identifiable causes, a link to the DPP6 gene should be suspected.

Ventricular tachycardia ablation: indications and techniques.

Over the last decades indications have broadened and techniques have been developed resulting in an increasing use of catheter ablation for different types of ventricular tachycardia (VT). Due to the high ablation success for non scar-related ventricular arrhythmia (VA) catheter ablation has become a first line therapy for symptomatic idiopathic VA or VA presumed to cause ventricular dysfunction. For the ablation of scar-related VTs individual patient factors and operator experience play an important role in risk-benefit considerations. However, the development of substrate based techniques, irrigated tip catheter ablation and the introduction of a percutaneous epicardial approach in selected patients has greatly enhanced the treatment of VTs in patients with structural heart disease. Understanding of the VT substrate in different diseases and individual patients is important for mapping and ablation. Advances in substrate imaging technologies and their integration during ablation procedures may provide more insights into the substrates and may guide VT ablation in the future. The distinction between scar-related and non scar-related VT is relevant because it may affect treatment and prognosis. Distinction between these entities may be facilitated by identification of the VT substrate during catheter mapping. Failure of catheter ablation is often due to the anatomical localization of the arrhythmic source or reentry circuit. However, evolving new catheter techniques and energy sources may overcome these limitations.

Reversed polarity of bipolar electrograms for predicting a successful ablation site in focal idiopathic right ventricular outflow tract arrhythmias.

BACKGROUND: Radiofrequency catheter ablation (RFCA) for idiopathic right ventricular outflow tract (RVOT) arrhythmias is typically guided by local activation time (LAT) mapping and unipolar electrogram morphology (QS configuration). However, LAT mapping is limited by the large variation among patients, and the area demonstrating a QS configuration of the unipolar electrogram may be larger than the focal source. Reversed polarity has been proposed as a criterion for guiding RFCA. OBJECTIVE: The purpose of this study was to investigate the value of reversed polarity of adjacent bipolar electrograms for predicting a successful ablation site in idiopathic RVOT arrhythmias. METHODS: Twenty-five consecutive patients (12 men [48%], age 43 ± 15 years) undergoing RFCA for RVOT arrhythmia were studied. Electrograms of ablation sites and of points within a 15-mm radius to the successful site were evaluated for LAT, unipolar electrogram morphology, and the presence of reversed polarity of adjacent bipolar electrograms. Electrogram characteristics of successful ablation sites were compared to those of nonsuccessful ablation sites. The spatial distribution of each electrogram characteristic was studied. RESULTS: Successful ablation sites more often demonstrated reversed polarity and had an earlier LAT than nonsuccessful sites. A wide spatial distribution was observed for unipolar electrograms with a QS configuration around the successful ablation site. Mapping based on LAT and reversed polarity had a higher predictive value for a successful ablation site than mapping based on LAT and QS configuration. CONCLUSION: The presence of reversed polarity has a high predictive value for successful ablation sites in focal idiopathic RVOT arrhythmias and is likely to reduce the number of RFCA applications.

Risk factors and time delay associated with cardiac device infections: Leiden device registry.

AIMS: A nested case-control study of 75 patients with cardiac device infections (CDI) and 75 matched controls was conducted to evaluate time course, risk factors, culture results and frequency of CDI. METHODS AND RESULTS: CDI occurred in 75/3410 (2.2%) device implantation and revision procedures, performed between 2000 and 2007. The time delay between device procedure and infection ranged from 0 to 64 months (mean 14 (SD 16)), 21 patients (28%) had an early infection (<1 month), 26 (35%) a late infection (1-12 months) and 28 (37%) a delayed infection (>12 months). Of interest, 18 (24%) patients presented with an infection >24 months after the device-related procedure. Time delay until infection was significantly shorter when cultures were positive for micro-organisms compared to negative cultures (8 (12) vs 18 (18) months, p = 0.03). Pocket cultures in delayed infections remained more often negative (61% vs 23%, p = 0.01). Independent CDI risk factors were: device revision (odds ratio (OR) 3.67; 95% confidence interval (CI), 1.51 to 8.96), renal dysfunction defined as glomerular filtration rate <60 ml/min (OR 4.64; CI, 1.48 to 14.62) and oral anticoagulation use (OR 2.83; CI 1.20 to 6.68). CONCLUSION: CDI occurred in 2.2% of device procedures, with 24% occurring more than two years after the device-related procedure. Renal dysfunction, device revisions and oral anticoagulation are potent risk factors for CDI.

Cardiac resynchronisation therapy in chronic atrial fibrillation: impact on left atrial size and reversal to sinus rhythm.

OBJECTIVE: To evaluate the impact of long term cardiac resynchronisation therapy (CRT) on left atrial and left ventricular (LV) reverse remodelling and reversal to sinus rhythm (SR) in patients with heart failure with atrial fibrillation (AF). PATIENTS: 74 consecutive patients (age 68 (8) years; 67 men) with advanced heart failure and AF (20 persistent and 54 permanent) were implanted with a CRT device. MAIN OUTCOME MEASURES: Patients were evaluated clinically (New York Heart Association (NYHA) class, quality of life, six minute walk test) and echocardiographically (LV ejection fraction, LV diameters, and left atrial diameters) before and after six months of CRT. Additionally, restoration of SR was evaluated after six months of CRT. RESULTS: NYHA class, quality of life score, six minute walk test, and LV ejection fraction had improved significantly after six months of CRT. In addition, left atrial and LV end diastolic and end systolic diameters had decreased from 59 (9) to 55 (9) mm, from 72 (10) to 67 (10) mm, and from 61 (11) to 56 (11) mm, respectively (all p < 0.01). During implantation 18 of 20 (90%) patients with persistent AF were cardioverted to SR. At follow up 13 of 18 (72%) patients had returned to AF and none had spontaneously reverted to SR; thus, only 5 of 74 (7%) were in SR. CONCLUSION: Six months of CRT resulted in significant clinical benefit with significant left atrial and LV reverse remodelling. Despite these beneficial effects, 93% of patients had not reverted to SR.

[Radiofrequency catheter ablation for treating children with cardiac arrhythmias: favourable results after a mean of 4 years]. / Katheterablatie met radiofrequente energie ter behandeling van kinderen met hartritmestoornissen: gunstige resultaten na gemiddeld 4 jaar.

OBJECTIVE: Analysis of long-term results with radiofrequency catheter ablation (RF ablation) in children. DESIGN: Retrospective. METHOD: Data were analysed from all 118 paediatric patients < or =18 years old who underwent RF ablation at the Leiden University Medical Centre (LUMC), the Netherlands, during the period 1 December 1992-31 May 2004. RESULTS: The group consisted of 6o boys and 58 girls with a mean age of 12.7 years (SD: 4.6). They underwent 140 RF ablation procedures for 122 disorders. Indications for RF ablation were: failure or side-effects of antiarrhythmic medication (45%), patient/parent choice (45%), cardiomyopathy or life-threatening arrhythmia (8%), and impending surgery for a congenital heart defect (2%). The mean follow-up interval was 4 years (SD: 3.2; range: 1.2 months-11.3 years). The final total success rate for RF was 93% (n = 110). 19 patients (16%) underwent a total of 22 repeat procedures. Recurrences occurred after a mean period of 2.3 months (SD: 2.5) following successful RF ablation. Major complications (2nd degree AV block) occurred in 2 patients. During follow-up, no evidence was found of new arrhythmias or of coronary artery lesion development as the result ofRF ablation. There was no difference between the < 10 years of age group and the > or = 10 years of age group in terms of final success rate (93% vs. 93%; p = 0.914) and complication rate (3% vs. 7%, p = 0.680). CONCLUSION: The long-term outcome of paediatric patients who underwent RF ablation was good. RF ablation in young children (< 10 years) was found to be safe and effective. These results demonstrate that it is also possible to curatively treat this group of patients with RF ablation in specialized centres.

Multislice computed tomography versus intracardiac echocardiography to evaluate the pulmonary veins before radiofrequency catheter ablation of atrial fibrillation: a head-to-head comparison.

OBJECTIVES: The purpose of this study was to perform a head-to-head comparison between multislice computed tomography (MSCT) and intracardiac echocardiography (ICE). BACKGROUND: Different imaging techniques have been used to visualize the pulmonary veins (PV) before radiofrequency ablation of atrial fibrillation. METHODS: The PV and their atrial insertion were evaluated in 42 patients (35 men, 49 +/- 9 years) admitted for ablation of PV ostia. Ostia were measured in two directions (anterior-posterior and superior-inferior) with MSCT. Two-dimensional (2-D) measurements of PV ostia were performed with ICE. Results were compared, considering MSCT as the gold standard. Venous ostium indexes were calculated by dividing MSCT measurements in the anterior-posterior direction and the superior-inferior direction. RESULTS: Common ostia of left PV were observed in 33 (79%) patients with MSCT and 31 (74%) patients with ICE. Common ostia of right PV were observed in 13 (31%) and 16 (38%) patients, respectively. Additional PV were observed in 13 (31%) patients with MSCT and in 7 (17%) patients with ICE. Ostial diameters by MSCT in the anterior-posterior direction were similar to 2-D measurements by ICE. By contrast, diameters by MSCT in the superior-inferior direction were significantly larger than 2-D diameters measured with ICE. Venous ostium indexes were 0.77 +/- 0.18 and 0.90 +/- 0.15 (p < 0.01) for left and right PV respectively, indicating an oval shape of particularly left PV ostia. CONCLUSIONS: Variation in PV anatomy is frequently observed with both techniques. The sensitivity for detection of additional branches is higher for MSCT. Results of measurements of PV ostia suggest an underestimation of ostial size by ICE. Three-dimensional imaging techniques, such as MSCT, are required to demonstrate an oval shape of PV ostia.