Genetics in cardiac arrhythmias wins second and third best oral abstracts at ECAS


Researchers studying the genetic aspects of cardiac arrhythmias have won second and third prizes for the best oral abstracts at the 10th Annual Congress of the European Cardiac Arrhythmia Society meeting in Munich, Germany.

Moritz Sinner (Ludwig Maximilian University Munich, Munich, Germany) and colleagues (from Denmark, Canada, Iceland, Japan, The Netherlands, Sweden, UK and USA) won second prize for their presentation explaining their discovery of five novel genetic loci for atrial fibrillation, while Anneline te Riele (University Medical Center Utrecht, Utrecht, The Netherlands and John Hopkins Hospital, Baltimore, USA) and colleagues won third prize for their study shedding light on successful screening for relatives of family members with arrhythmogenic right ventricular dysplasia/cardiomyopathy.


Given that atrial fibrillation has a heritable component, Sinner et al aimed to identify additional susceptibility loci on top of nine already identified in recent genome-wide association studies. Their analysis of 6,691 atrial fibrillation cases and 17,144 controls of European descent found four novel susceptibility loci exceeding genome-wide significance in the atrial fibrillation cases (NEURL, TBX5, CAND2, and GJA1). A further analysis of 8,373 atrial fibrillation cases and 17,190 controls of Japanese descent found two novel loci exceeding genome-wide significance (NEURL and CUX2).

Sinner told delegates that TBX-5 was a transcription factor heavily involved in the cardiac conduction system, while GJA1 was a gap junction protein encoding connexin 43 which was abundant in the heart. However, he said the involvement of the other loci in atrial fibrillation pathophysiology was as yet unknown.

Sinner commented: “Atrial fibrillation is common and confers high morbidity. It is a heritable disease, where several genetic loci have been described before by gene association studies. Here we were able to identify five novel association signals by systematic large-scale, multi-ethnic genetic replication analyses, and hopefully functional analyses will elucidate the possible role of these candidate genes in atrial fibrillation pathophysiology in the future.”

He said further investigation of the findings would include looking at gene expression in close to 300 human left atrial tissue samples, along with functional analysis of animal models.

The study by te Riele and colleagues, which won third prize, indicated that longer screening intervals and focus on ECG and Holter monitoring may be appropriate for family members of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy.


Te Riele et al recognised that although family screening is now part of clinical practice, incomplete penetrance and variable expressivity of arrythmogenic right ventricular dysplasia/cardiomyopathy complicate family screening, and optimal screening intervals and screening strategies in at-risk relatives remains to be elucidated.

Over four years of follow-up of 33 relatives (24.4±14.1 years, 61% male) of 22 patients with arrythmogenic right ventricular dysplasia/cardiomyopathy, te Riele et al found that disease progression was minimal and that electrical progression preceded detectable structural changes. During the follow-up period, 11 (33%) of subjects experienced disease progression, of whom four (36%) fulfilled arrythmogenic right ventricular dysplasia/cardiomyopathy diagnosis by last follow-up. Electrical progression was observed in 10 patients (30%) while structural progression was observed in only one (3%).

Te Riele said: “Arrythmogenic right ventricular dysplasia/cardiomyopathy relatives without a diagnosis at first evaluation have a good short-term prognosis, their disease progression during four years of follow-up is minimal and longer screening intervals may be justified. We should focus on ECG monitoring and Holter screening during follow-up when evaluating these patients.”

Award judge Massimo Santini told Cardiac Rhythm News that the genetic research abstracts were of particular interest at this meeting: “Genetics is very important for us, there are at least three or four illnesses which are congenital and can kill children. For example when they are exercising or while they are sleeping in cases of Brugada syndrome. The long QT syndrome and arrythmogenic right ventricular dysplasia are also genetic. We look very carefully at genetics, because the more we understand the more we will be able to treat them.”

He added: “The challenge of the future will be to look at the gene which is altered and then to have a genetic therapy to modify that gene. We still do not have that today.”

The jury, blinded to researchers and teams, comprised Gunter Breithardt, John Camm, David Cannom, Kenzo Hirao, Neil Kay, Giles Lascaut, Massimo Santini and Gerhardt Steinbeck. Abstracts on pharmacological and non-pharmacological management of atrial fibrillation, sudden cardiac death, ICD therapy, diagnosis and management of ventricular tachycardia/ventricular fibrillation, antiarrhythmic drug therapy among others were also presented.


The first prize was awarded to Fu Siong Ng who presented a study titled: “Do M-Cells play a functional role in humans? Insights from high-resolution optical mapping of explanted human hearts”. A commentary on the subject written by Ng can be found here.