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Funding Acknowledgements Type of funding sources: None. Background The 2010 Task Force Criteria (TFC), although representing the current gold standard to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC), have not been tested to differentiate ARVC from the athlete’s heart. Furthermore, not all 6 diagnostic categories are easy to obtain. Purpose We hypothesized that atrial dimensions are useful to differentiate between both entities. Therefore, we developed a new diagnostic score based upon readily available clinical parameters including atrial dimensions on TTE to help distinguishing the athlete’s heart from ARVC in daily clinical practice. Methods In this observational study, 37 patients with definite ARVC (from the Zurich ARVC Program) were compared to 68 athletes. Base on ROC analysis, the following echocardiographic, laboratory and electrocardiographic parameters were included in the final score: indexed right/left atrial volumes (RAVI/LAVI ratio), NT-proBNP, RVOT measurements (PLAX and PSAX adjusted for BSA) on TTE, tricuspid annular motion velocity (TAM) on TTE, precordial electrocardiographic T-wave inversions and depolarization abnormalities according to the TFC. Results ARVC patients had a higher RAVI/LAVI ratio (1.78 ± 1.6vs0.95 ± 0.3,p Conclusions ARVC patients present with significantly larger RA as compared to athletes, resulting in a greater RAVI/LAVI ratio. Our novel diagnostic score includes readily available clinical parameters and has a high diagnostic accuracy to differentiate between ARVC and the athlete´s heart. Abstract Figure. Novel clinical score

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement of the myocardium and ventricular arrhythmias. Biventricular (BiV) involvement in ARVC may lead to heart failure. Purpose This study aimed to investigate the role of novel plasma biomarkers soluble (s)ST2, Galectin-3 (Gal-3) and GDF-15 in predicting BiV involvement and adverse outcomes in ARVC patients. Methods ARVC patients from two independent cohorts were studied. 108 patients were included from the discovery cohort and 47 patients were included from a second validation cohort. All patients had a definite ARVC diagnosis at time of blood withdrawal. sST2, Gal-3 and GDF-15 were independently correlated with NT-proBNP, left ventricular (LV) ejection fraction, late gadolinium enhancement by cardiac magnetic resonance (CMR) imaging and clinical outcome. Results ARVC patients with LV involvement had higher levels of sST2 and GDF-15 as compared to controls and patients with isolated right ventricular involvement. sST2 and GDF-15 significantly correlated to late gadolinium enhancement on CMR and also correlated to adverse heart failure outcomes. Gal-3 was elevated in ARVC patients with and without LV involvement as compared to controls. The combined use of the three biomarkers (NT-proBNP, sST2 and GDF-15) showed the best performance in predicting LV involvement in both the discovery and the validation cohort. Plasma drawn from coronary arteries and coronary sinus showed a transmyocardial elevation of sST2. Conclusion Our study shows that sST2 and GDF-15 may predict BiV involvement and the combined use of NT-proBNP, sST2 and GDF-15 shows the best prediction of LV involvement in ARVC. Transmyocardial elevation of sST2 suggests that this biomarker is produced by myocardial tissue in ARVC. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Fuwai ARVC Program was supported by CAMS Innovation Fund for Medical Sciences and the National Natural Science Foundation of China, Zurich ARVC Program was supported by grants from the Schwyzer Foundation and Baugarten Foundation

Introduction Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited condition, which is associated with potentially life-threatening ventricular arrhythmias in the young. Approximately 60% of patients carry a possibly disease-causing genetic variant. Purpose The aim of this study was to investigate the impact of the 2015 American College of Medical Genetics (ACMG) Criteria on ARVC diagnosis based on the 2010 Modified Task Force Criteria (TFC). Methods The study included 79 patients from the Swiss ARVC Registry who harbored a genetic variant deemed to be associated with the disease at initial screening, and classified them as definite, borderline or possible ARVC. Every variant found was re-classified on Varsome Genetics, based on the 2015 ACMG Criteria. Clinical information was then assessed at last available follow-up of every patient and ARVC diagnosis was reclassified based on the newest genetic evidence available. Results In 42 out of 79 patients (53.2%), genetic variants were reclassified. Out of these, 33 variants (41.8%) were downgraded from pathogenic (P) / likely pathogenic (LP) to either variants of unknown significance (VUS) or benign (B) / likely benign (LB). Three patients (3.8%) were upgraded from VUS / LP to P. Out of the 12 variants initially classified as VUS, 9 (75%) were reclassified as B or LB. Overall, 13 patients (16.5%) were downgraded from their initial diagnosis (11 from definite to borderline and 2 from borderline to possible). Conclusion A significant proportion of patients with ARVC diagnosed based on the 2010 TFC were reclassified when the 2015 ACMG Criteria were taken into consideration. These findings may have clinical consequences, particularly for genetic cascade screening of family members of ARVC patients and necessitate reassessment of genetic variants of index patients who were previously diagnosed with ARVC. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University Hospital Zurich

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is frequently associated with mutations in genes coding for desmosomal proteins. In this study, we investigated the association of genetic status with ARVC progression as defined by echocardiographic parameters. Methods We tested 62 ARVC patients for their genetic profile. Accordingly, they were grouped in mutation positive (48 (77%) patients; median age 48.5 years; 33 (69%) males), and mutation negative (14 (23%) patients; median age 45 years; 10 (71%) males). Prevalent mutations were Desmoglein-2 (DSG2) in 16 (26%), Desmoplakin (DSP) in 14 (23%), and Plakophilin-2 (PKP2) in 9 (15%) patients. Results At baseline, there were no significant differences in clinical characteristics between the two groups. Patients were followed-up for a median time period of 1420 days, and there was no significant difference in the duration of follow-up between the two groups (p=0.05). In the mutation positive group, there was a significant increase in right ventricular end-diastolic area (p=0.002), right atrial short (p=0.008) and long (p=0.002) diameter, left atrial diameter (p=0.014), and a decrease in left ventricular ejection fraction (p=0.014) during follow up. Right ventricular functial parameters did not change significantly (tricuspid annular plane systolic excursion: p=0.24; fractional area change: p=0.088). In the mutation negative group, none of the aforementioned echocardiographic findings exhibited any significant difference during follow-up: right ventricular end-diastolic area (p=0.1); right atrial short (p=0.7) and long (p=0.9) diameter, left atrial diameter (p=0.6), and left ventricular ejection fraction (p=0.3). Similarly, right ventricular functional parameters did not change significantly (tricuspid annular plane systolic excursion: p=0.77; fractional area change: p=0.80. Results are summarized in the figure. Change in echocardiographic findings. Conclusions There is a strong association between echocardiographic progression of ARVC phenotype and the presence of a pathogenic mutation. Such mutations should be searched in all patients with an ARVC phenotype, and mutation positive individuals should be followed-up in shorter intervals.

AIMS: Patients with isolated left ventricular non-compaction (IVNC) are at high risk for developing ventricular tachyarrhythmias. However, no analysis of invasive electrophysiological (EP) findings in these patients has yet been performed. METHODS AND RESULTS: We performed a retrospective analysis of EP findings in 24 patients with IVNC. Ventricular tachyarrhythmias were inducible in nine patients; of these, two patients had sustained monomorphic ventricular tachycardia (VT) and two patients had ventricular fibrillation. No specific electrocardiographic or echocardiographic finding was predictive of VT inducibility. Three of the 9 patients with inducible VT experienced ventricular tachyarrhythmias during the follow-up of 61.4+/-50 months, whereas no tachyarrhythmias or sudden deaths were noted in 12 patients without inducible VT during the follow-up of 30+/-19 months (3 patients in the latter group were lost to follow-up). Supraventricular tachyarrhythmias were inducible in seven patients. CONCLUSION: Our present study provides the first comprehensive analysis of EP findings in patients with IVNC. Ventricular and supraventricular arrhythmias can readily be induced in these patients, whereas the inducibility of a sustained monomorphic VT is relatively low. Further studies including long-term follow-up are required to investigate the role of EP testing for arrhythmic risk stratification in these patients.