Longitudinal Prediction of Ventricular Arrhythmic Risk in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

Abstract

Background: The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator stratifies risk for incident sustained ventricular arrhythmias (VA) at the time of ARVC diagnosis. However, included risk factors change over time, and how well the ARVC risk calculator performs at follow-up is unknown. Methods: This was a retrospective analysis of patients with definite ARVC and without prior sustained VA. Risk factors for VA including age, nonsustained ventricular tachycardia, premature ventricular complex burden, T-wave inversions on electrocardiogram, cardiac syncope, right ventricular function, therapeutic medication use, and exercise intensity were assessed at the time of 2010 Task Force Criteria based ARVC diagnosis and upon repeat evaluations. Changes in these risk factors were analyzed over 5-year follow-up. The 5-year risk of VA was predicted longitudinally using (1) the baseline ARVC risk calculator prediction, (2) the ARVC risk prediction calculated using updated risk factors, and (3) time-varying Cox regression. Discrimination and calibration were assessed in comparison to observed VA event rates. Results: Four hundred eight patients with ARVC experiencing 132 primary VA events were included. Matched comparison of risk factors at baseline versus at 5 years of follow-up revealed decreased burdens of premature ventricular complexes (−1200/day) and nonsustained ventricular tachycardia (−14%). Presence of significant right ventricular dysfunction and number of T-wave inversions on electrocardiogram were unchanged. Observed risk for VA decreased by 13% by 5 years follow-up. The baseline ARVC risk calculator’s ability to predict 5-year VA risk worsened during follow-up (C statistics, 0.83 at diagnosis versus 0.68 at 5 years). Both the updated ARVC risk calculator (C statistics of 0.77) and time-varying Cox regression model (C statistics, 0.77) had strong discrimination. The updated ARVC risk calculator overestimated 5-year VA risk by an average of +6%. Conclusion: Risk factors for VA in ARVC are dynamic, and overall risk for incident sustained VA decreases during follow-up. Up-to-date risk factor assessment improves VA risk stratification.

AAV-Mediated Delivery of Plakophilin-2a Arrests Progression of Arrhythmogenic Right Ventricular Cardiomyopathy in Murine Hearts: Preclinical Evidence Supporting Gene Therapy in Humans

“…ARVC is a disease with incomplete penetrance. 2 While significant progress has been made in risk stratification of patients suspect of ARVC, [30][31][32] it remains unpredictable whether or when the disease will present in an asymptomatic gene carrier. 2 As such, any future implementation of gene therapy in PKP2 pathogenic variant carriers will likely not be in an asymptomatic individual as a preventive measure, but as a therapeutic procedure for a patient with an overt disease.…”

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe

“…In keeping with this, recent data tracking ARVC patients longitudinally over time have also suggested that 5-year VA risk drops by nearly 50% between the time of initial diagnosis and 5-year follow-up. 24 , 25 It is therefore possible that enrolment of European patients later in the disease process may have contributed to their observed lower rate of VA events. Importantly, prior studies have demonstrated adequate calibration of the ARVC risk calculator in both European and North American patients, 9 , 10 and thus, these phenotypic discrepancies are accounted for during calculation of VA risk.…”

Evolution and triggers of defibrillator shocks in patients with arrhythmogenic right ventricular cardiomyopathy

“…This highlights the high persisting arrhythmic risk within this population, as patients may receive their first appropriate ICD shock more than 10 years after ICD implantation, which is important for patient counselling concerning lifestyle and ongoing ICD indication in case of battery depletion, even without prior documentation of VA. Interestingly, even though ARVC is a progressive disease, the amount of appropriate ICD shocks seems to decline over time (figure 2), which reflects optimisation of treatment including the generous use of antiarrhythmic drugs, heart failure medication, catheter ablation, physical restriction and optimised ICD programming as previously reported. VT with a cycle length of <240 ms (>250 bpm) is described as potentially life-threatening (life-threatening ventricular arrhythmia (LTVA)) 16 17. It may be speculated that by treatment of such an episode, a life is potentially saved.…”