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.

Recurrent and founder mutations in the Netherlands : Plakophilin-2 p.Arg79X mutation causing arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiac disease with reduced penetrance and a highly variable expression. Mutations in the gene encoding the plakophilin-2 gene (PKP2) are detected in about 50% of ARVC/D patients. The p.Arg79X mutation in PKP2 has been identified in Europe and North America and has been functionally characterised. We evaluated the prevalence of the p.Arg79X mutation in PKP2 in the Dutch population. METHODS: Twelve index patients and 41 family members were evaluated in three university hospitals in the Netherlands. The diagnosis of ARVC/D was established according to the recently revised Task Force Criteria. Segregation of the p.Arg79X mutation was studied and haplotypes were reconstructed to determine whether the p.Arg79X mutation was a recurrent or a founder mutation. RESULTS: The p.Arg79X mutation in PKP2 was identified in 12 index patients. Haplotype analysis revealed a shared haplotype among Dutch p.Arg79X mutation carriers, indicating a common founder. Six index patients (50%) had a first- or second-degree relative who had died of sudden cardiac death below 40 years of age. At age 60, only 60% of the mutation carriers had experienced any symptoms. There was no significant difference in symptom-free survival and event-free survival between men and women. CONCLUSION: We have identified the largest series of patients with the same desmosome gene mutation in ARVC/D reported to date. This p.Arg79X mutation in PKP2 is a founder mutation in the Dutch population. The phenotypes of PKP2 p.Arg79X mutation carriers illustrate the clinical variability and reduced penetrance often seen in ARVC/D. (Neth Heart J 2010;18:583-91.).

Ablación del sustrato de arritmias cardíacas con catéter de radiofrecuencia / Radiofrequency catheter ablation of the substrate of cardiac arrhythmias

Este trabajo presenta los resultados de siete años de experiencia de ablación con catéter de radiofrecuencia en el Hospital de la Universidad de Utrecht, Holanda. 448 pacientes fueron tratados por una variedad de taquiarritmias supraventriculares y ventriculares. Los porcentajes de éxito fueron excelentes en pacientes con vías accesorias aurículoventriculares y taquicardia aurículoventricular por reentrada nodal, con un 95 por ciento y 93 por ciento respectivamente. La incidencia de bloqueo aurículoventricular completo accidental en el último grupo fue bajo: 5,4 por ciento para la aproximación anteriory 1,5 por ciento para la posterior. La ablación del haz de His se efectuó predominantemente en pacientes con fibrilación auricular refractaria a las drogas, con 100 por ciento de éxito. En pacientes con taquiarritmia ventricular idiopática, 5 de 6 pacientes están libres de recurrencia. La ablación por radiofrecuencia es una modalidad segura y potencialmente curativa de tratamiento. Los hallazgos subrayan la enorme importancia de una cuidadosa localización del blanco y de la localización del catéter para el éxito y el uso racional de la ablación por radiofrecuencia