Search

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): PSIDER (ZOn-MW) PREDICT2 (Hartstichting) Background: The PLN p.Arg14del risk model is a mutation-specific risk model developed to predict individual malignant ventricular arrhythmia (VA) risk to inform decision-making for primary prevention implantable cardioverter defibrillator (ICD) implantation. While the risk model has proven to be valid, two main points of criticisms remain to be discussed: first, the risk model is only validated at baseline and second, appropriate ICD therapy and sustained ventricular tachycardia (VT) Purpose: To evaluate the diagnostic performance of the PLN p.Arg14del risk model longitudinal at 3 year follow-up and to reevaluate the predictors regarding SCD. Methods: Clinical data of 278 PLN p.Arg14del mutation carriers with no history of malignant VA at both baseline and 3 year follow-up were collected. During a median follow-up of 4 years (Interquartile range (IQR) 1.8-6.5), 31 (11%) carriers experienced malignant VA, defined as sustained VA, appropriate ICD intervention, or (aborted) SCD. The reevaluation of the predictors with the 3 year follow up data revealed hazard ratio’s (HR) that were similar to the baseline PLN p.Arg14del risk model for left ventricular ejection fraction (HR 1.10 [95% CI, 1.06-1.12], p To reevaluate the predictive performance of the PLN p.Arg14del risk model for a more strict surrogate of SCD we redefined the outcome as VT >250 beats per minute sustained (lasting ≥30 seconds) or terminated by ICD, ventricular fibrillation, aborted SCD and SCD. We included 669 PLN p.Arg14del carriers with no presentation or history of sustained VA or (aborted) SCD. During a median follow-up of 4.75 years (IQR 1.9-7.9), 33 (5%) carriers experienced the outcome. Results of the univariable analysis are shown in table 1. The PLN p.Arg14del risk model yielded a C-statistic of 0.75 (95% CI 0.70-0.80). Adding risk factors sex, age and sustained VT Conclusion: The PLN p.Arg14del risk model was validated longitudinal at 3 year follow-up and it held its performance with a more strict definition of SCD.

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.

An extract has been prepared from the suprarenal cortex, which, when injected into rabbits, lowers the blood calcium to the extent of about 30 per cent. ; the maximum fall occurs after 24 hours, and returns to normal in about 48 hours. The extract prepared from the suprarenal cortex resembles that obtained from ovary and corpus luteum, both in physical characteristics, and in the production of a typical response on the part of the blood calcium. It would appear that the hormone of the suprarenal cortex that is capable of lowering the blood calcium is very similar and possibly identical with the hormone of the ovary, having the same function. A definite relationship has been established between the suprarenal cortex and the ovary, justifying the long-suspected connection between the two glands.

It has long been recognised that the testis has an influence upon growth in general, and especially upon the growth of bone. This was the basis for the generalisation formulated by the early observers that growth and reproduction are essentially opposed to one another. Later investigations indicated, however, that the changes produced by castration are not due to the abolishing of spermatogenesis but to the fact that the normal internal secretion of the testis is not available for controlling the growth of bone.