Novel Risk Prediction Model to Determine Adverse Heart Failure Outcomes in Arrhythmogenic Right Ventricular Cardiomyopathy

Abstract

Background Patients with arrhythmogenic right ventricular cardiomyopathy are at risk for life-threatening ventricular tachyarrhythmias, but progressive heart failure (HF) may occur in later stages of disease. This study aimed to characterize potential risk predictors and develop a model for individualized assessment of adverse HF outcomes in arrhythmogenic right ventricular cardiomyopathy. Methods and Results Longitudinal and observational cohorts with 290 patients with arrhythmogenic right ventricular cardiomyopathy from the Fuwai Hospital in Beijing, China, and 99 patients from the University Heart Center in Zurich, Switzerland, with follow-up data were studied. The primary end point of the study was heart transplantation or death attributable to HF. The model was developed by Cox regression analysis for predicting risk and was internally validated. During 4.92±3.03 years of follow-up, 48 patients reached the primary end point. The determinants of the risk prediction model were left ventricular ejection fraction, serum creatinine levels, moderate-to-severe tricuspid regurgitation, and atrial fibrillation. Implantable cardioverter-defibrillators did not reduce the occurrence of adverse HF outcomes. Conclusions A novel risk prediction model for arrhythmogenic right ventricular cardiomyopathy has been developed using 2 large and well-established cohorts, incorporating common clinical parameters such as left ventricular ejection fraction, serum creatinine levels, tricuspid regurgitation, and atrial fibrillation, which can identify patients who are at risk for terminal HF events, and may guide physicians to assess individualized HF risk and to optimize management strategies.

Keywords: arrhythmogenic right ventricular cardiomyopathy; heart failure; heart transplantation; outcome; risk prediction.

Figure 1. Cumulative survival free from HTx or death attributable to heart failure (HF) over 10 years.

The cumulative event‐free survival for HTx or death attributable to heart failure with 95% CIs (shaded area) are plotted. The dotted line represents the cumulative 5‐year survival. HTx/Death indicates heart transplantation or death attributable to heart failure.

Figure 2. Texture feature selection using the least absolute shrinkage and selection operator (LASSO) binary logistic regression model.

A, Tuning parameter (λ) selection in the LASSO model. B, LASSO coefficient profiles of the 11 texture features. A coefficient profile plot was produced against the log (λ) sequence. Dotted vertical line is set at the non‐0 coefficients, where 5 non‐0 coefficients are included.

Figure 3. Nomogram predicting 3‐, 5‐, and 10‐year risk of HTx/Death attributable to HF in ARVC.

The nomogram was developed in 2 cohorts, with LVEF, AF, moderate or severe TR, and serum creatinine levels. The nomogram is used by adding up the points identified on the points scale for each variable. The total points projected on the bottom scales indicate the probability of 3‐, 5‐, and 10‐year risk. AF indicates atrial fibrillation; ARVC, arrhythmogenic right ventricular cardiomyopathy; CREA, creatinine; HF, heart failure; HTx, heart transplantation; LVEF, left ventricular ejection fraction; and TR, moderate or severe tricuspid regurgitation.

Figure 4. Calibration plot showing the agreement between predicted (x axis) and observed (y axis) 5‐year risk of the primary outcome.

The straight line is the continuous calibration hazard regression. The dotted line represents perfect calibration. The x axis represents the nomogram‐predicted risk of HTx/Death, and the y axis represents actual survival and 95% CIs measured by Kaplan‐Meier analysis. Avg, indicates average; and HTx/Death, heart transplant or death attributable to heart failure.

Figure 5. Decision curve analysis for the clinical usefulness of our model and previous predictors.

The y axis measures the net benefit. The x axis presents the threshold probability of HTx or death attributable to heart failure. Compared with the reference heart failure model in arrhythmogenic right ventricular cardiomyopathy, our novel risk prediction model was larger over the range of clinical threshold. HTx/Death indicates heart transplant or death attributable to heart failure.

Figure 6. Prediction of HTx or death attributable to heart failure (HF) in ARVC.

A, The overall survival free from HTx or death attributable to HF over 10 years. B, The 3‐, 5‐, and 10‐year risk prediction nomogram for HTx or death attributable to HF. C, The survival free from HTx or death in different risk subgroups. The overall patients with ARVC could be separated into various risk subgroups based on our HF prediction model. AF indicates atrial fibrillation; ARVC, arrhythmogenic right ventricular dysplasia; CREA, creatinine; HTx/Death, heart transplantation or death attributable to heart failure; LVEF, left ventricular ejection fraction; and TR, moderate or severe tricuspid regurgitation.