A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

Abstract

Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients.

Methods and results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001).

Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).

Keywords: Arrhythmogenic right ventricular cardiomyopathy; Implantable cardioverter-defibrillators; Sudden cardiac death; Ventricular arrhythmias.

Figure 1

Cumulative survival free from sustained ventricular arrhythmia. Plotted is the cumulative event-free survival for any ventricular arrhythmia with 95% confidence intervals (shaded area). Dotted line represents cumulative 5-year survival.

Figure 2

Calibration plot showing the agreement between predicted (x axis) and observed (y axis) 5-year risk of the primary outcome. Triangles represent binned Kaplan–Meier estimates with 95% confidence intervals for quintiles of predicted risk. Straight line is the continuous calibration hazard regression. Dotted line represents perfect calibration. Spike histogram on the x axis reflects the number of patients with a predicted risk corresponding to the x axis value. VA, ventricular arrhythmia.

Figure 3

Outcomes of patients associated with model-based implantable cardioverter-defibrillator implantation thresholds. The implications of implanting an implantable cardioverter-defibrillator in all (left bar) or none (second-to-right bar) of the patients are shown, as well as the implications of treating all patients as per International Task Force Consensus Statement (far right bar). The rest of the bars show the impact of using different implantable cardioverter-defibrillator placement thresholds based on the risk calculated by our model. Each bar represents the complete cohort (n = 528) and colour coding represents the proportion of patients experiencing sustained ventricular arrhythmia (red) or absence thereof (blue) as well as the placement (solid colours) vs. the non-placement (striped colours) of an implantable cardioverter-defibrillator. The black triangles represent the number of implantable cardioverter-defibrillators needed to protect one patient developing ventricular arrhythmia, with a horizontal dotted line for the reference value (i.e. treatment as per International Task Force Consensus Statement). Left y axis denotes proportion of patients (corresponding to the colour coding); right y axis denotes the number of implantable cardioverter-defibrillators needed to protect one patient (corresponding to the black triangles). ICD, implantable cardioverter-defibrillator; ICD:VA, ratio of implantable cardioverter-defibrillator placements required to protect one patient developing ventricular arrhythmia; ITFC, International Task Force Consensus Statement.

Figure 4

Decision curve analysis comparing the clinical utility of our model (red dotted line) to the International Task Force Consensus Statement algorithm (blue dotted line). The clinical utility of both treatment strategies is compared by plotting the net benefit (y axis) for a range of potential implantable cardioverter-defibrillator placement thresholds based on the 5-year risk of VA (x axis). Our model showed the highest net benefit for all potential thresholds (ranging from 2.5% to 27.5%). This indicates that our model would result in the highest weighted balance of appropriate vs. inappropriate implantable cardioverter-defibrillator placements, regardless of the clinically preferred risk threshold. ICD, implantable cardioverter-defibrillator; ITFC, International Task Force Consensus Statement.

Take home figure

Prediction of sustained ventricular arrhythmia in arrhythmogenic right ventricular dysplasia/cardiomyopathy. ARVC, arrhythmogenic right ventricular dysplasia/cardiomyopathy; inv., inversion; PVC, premature ventricular complex; RVEF, right ventricular ejection fraction; VT, ventricular tachycardia.