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Background/Introduction Recently, a variant-specific prediction model for PLN p.Arg14del variant carriers was developed to predict individual malignant ventricular arrhythmia (VA) risk to inform decision-making for primary prevention implantable cardioverter defibrillator (ICD) implantation. This model predicts malignant VA risk from data at diagnosis, but iterative evaluation of malignant VA risk may be warranted considering that the risk factors for malignant VA are progressive. Purpose To evaluate the diagnostic performance of the PLN p.Arg14del risk model. Methods/Results Date were collected of 278 PLN p.Arg14del variant carriers at 3 year follow-up. This was considered the new baseline for the survival analysis. Patients with history of malignant VA at both baseline and during the first 3 years after baseline were excluded. At 3 year patients were aged 40.1±18.0 year and 40.7% was male. Median left ventricular ejection fraction (LVEF) was 53% and percentage with microvoltages was 10.3. During a median follow-up of 4 years (Interquartile range 1.8–6.5) 31 (11%) carriers experienced malignant VA, defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. Reevaluation of the predictors with the 3 year follow-up data revealed hazard rates that were similar to those in the original PLN p.Arg14del risk model; LVEF per 1% decrease (hazard ratio (HR) 1.10 [95% confidence interval (CI), 1.06–1.12]; p Conclusion The PLN p.Arg14del risk model is valid at 3 year follow-up in PLN p.Arg14del variant carriers with no history of malignant VA and can therefore be used to inform decision-making for primary prevention ICD implantation not merely at diagnosis, but also during follow-up and can be seen as a type of validation in a cohort where no other large cohort is present to perform external validation. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): 1. PSIDER: From pluripotent stem cells to prime editing gene therapy for inheritedcardiomyopathies. ZOn-MW.2. PREDICT2: Predicting sudden cardiac arrest. The Dutch Heart Foundation.

Background The Task Force Criteria (TFC) for ARVC are highly sensitive, but lack specificity. Patients with atypical RV-involvement (aRVi) may have different underlying aetiologies and prognosis, requiring specific therapeutic interventions. Purpose We aimed to evaluate the role of the baseline ECG for initial suspicion of aRVi. Methods From the Netherlands Heart Institute Arrhythmogenic Cardiomyopathy (NHI-ACM) registry, patients were selected who 1) fulfilled TFC for definite ARVC, 2) presented with sustained VT, 3) underwent genetic testing. The first available ECG after VT was evaluated for AV-conduction and the presence and surface area (SA) of an R'-wave in V1-V3. ECGs with AV-conduction disturbances or an R'-wave with SA ≥1.65 mm2 were classified as suspicious for `atypical RV-involvement' (aRVi-ECG). Patients with ARVC-related pathogenic/likely pathogenic variant (P/LP+) were classified as “typical ARVC”. Data of patients without an ARVC-related pathogenic/likely pathogenic variant (P/LP−) were reviewed by an expert panel and classified as either “typical ARVC” or “suggestive for another aetiology” based on consensus. Results In total 124 P/LP+ patients and 35 P/LP− patients were included. Nineteen patients had an aRVi-ECG, which appeared significantly more predominant in the P/LP− group (11 (9%) P/LP+ vs. 8 (22%) P/LP−, p=0.019). Of the P/LP− patients, seventeen (49%) were classified as “suggestive for another aetiology” (e.g. myocarditis, ischemia, sarcoid), including all 8 patients with an aRVI-ECG. Among P/LP+ patients with an aRVi-ECG, 46% carried the Arg14del phospolamban variant and 64% died, versus 15% and 18% of P/LP+ patients without aRVi-ECG, respectively (Table 1). Conclusion For patients presenting with sustained VT and fulfilling the TFC for ARVC diagnosis, a baseline ECG suggestive for atypical RV-involvement should raise suspicion for a different underlying aetiology in patients without an ARVC-related P/LP variant. In P/LP+ patients, an aRVi-ECG may identify those with poor outcome. Funding Acknowledgement Type of funding sources: None.