Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death

Abstract

Aims This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation. Methods and results We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1–2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0–3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality. Conclusion Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.

Ventricular Arrhythmias in Ischemic Cardiomyopathy—New Avenues for Mechanism-Guided Treatment

“…Repolarisation parameters derived from standard 12-lead electrocardiogram (ECG) analysis include QT-interval and its dispersion, T-peak to T-end and microvolt T-wave alternans, which may reflect the dynamic substrate for arrhythmias as well as depolarisation, and parameters such as QRS duration and QRS fragmentation that reflect conduction abnormalities [36,37]. These new parameters still need to be assessed comprehensively before recommendation to clinical practice [38].…”

Rationale and design of the SafeHeart study: Development and testing of a mHealth tool for the prediction of arrhythmic events and implantable cardioverter-defibrillator therapy

“…trialregister.nl) 1 Shared co-first authorship. 2 Shared senior authorship. Address reprint requests and correspondence: Dr Diana M. Frodi, Department of Cardiology, Copenhagen University Hospital-Rigshospitalet, Inge Lehmanns Vej 7, DK-2100 Copenhagen, Denmark.…”

“…External validation of 3 previously developed risk stratification models for benefit of ICD implantation (ie, risk of death before first ICD intervention) rendered C statistics between 0.66 and 0.75. 2 , 7 , 8 , 9 The recently published Multicentre Autonomic Defibrillator Implantation Trial-ICD and The Dutch outcome in ICD therapy prediction scores have demonstrated similar discriminative performance; the external validation of both scores yielded C statistics of 0.75 and 0.60, respectively. 2 , 10 Although these models could aid in the risk stratification for ICD implantation, there are considerable differences in these models in terms of the included variables and predictive performance.…”

“…Implantable cardioverter-defibrillator (ICD) implantation is the cornerstone of the prevention of sudden cardiac death through the termination of ventricular arrhythmias for either primary prevention or secondary prevention. 1 Despite improvements in pharmacological and nonpharmacological treatments, 2 , 3 a meta-analysis of 5 clinical trials with 5516 participants showed that 18% received appropriate ICD therapy and 10% received inappropriate ICD therapy during an average follow-up time period of 2.4 years. 4 Aside from the potential harm related to ICD shock on the myocardium itself, ICD therapy has an adverse psychological impact and may reduce quality of life (QoL).…”

Myocardial Scar Characterization and Future Ventricular Arrhythmia in Patients With Ischemic Cardiomyopathy and an Implantable Cardioverter-Defibrillator

“…Several predictors of appropriate ICD shock have been found, including male gender, non-sustained VT, and a history of atrial fibrillation (7). Wide QRS and VT as presenting arrhythmia are other examples of predictors of VAs in secondary prevention ICD recipients (8).…”