Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international study in ischemic cardiomyopathy: international DERIVATE-ICM Registry
Authors: Fusini L , Volpe A , Baggiano A , Mushtaq S , Annoni A , Carerj M L , Cilia F , Fazzari F , Formenti A , Mancini M E , Marchetti F , Maragna R , Tassetti L , Guaricci A I , Pontone G 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Implantable cardioverter–defibrillator (ICD) therapy is the most effective sudden cardiac death (SCD) event prophylactic-strategy in ischemic cardiomyopathy (ICM) patients with transthoracic echocardiographic (TTE) left ventricular ejection fraction (LVEF) ≤35%. This approach has been recently questioned due to the low rate of ICD interventions in patients who received implantation and the not negligible percentage of patients who experienced SCD event despite not fulfilling criteria for implantation.

Purpose
The DERIVATE-ICM registry (RCT#NCT03352648) is an international, multicenter and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to standard of care based on TTE in ICM patients.

Methods
We enrolled 861 ICM patients (mean age 65±11 years, 86% male) with chronic heart failure and TTE-LVEF&lt;50%. Major adverse arrhythmic cardiac events (MAACE), defined as the combination of SCD, aborted SCD event, and sustained ventricular tachycardia were the primary endpoint. Independent predictors were used to calculate a CMR risk score for each patient. Risk levels were defined as low (quantile 1 [Q1]), medium (Q2 and Q3) and high (Q4).

Results
During a median follow-up of 1054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007, 95%CI:1.000–1.011, p = 0.050), CMR-LVEF (HR: 0.972, 95%CI: 0.945–0.999, p = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010, 95%CI: 1.002–1.018, p = 0.015) were independent predictors of MAACE. Based on the multivariable analysis, CMR weighted risk score was developed according to the following equation [0.005 * EDV/BSA (mL/m²) – 0.029 * LVEF (%) + 0.010 * LGE ischemic mass (g)]. Figure 1 (top) shows the Kaplan-Meier curves according to the guidelines-based TTE-LVEF model and the CMR risk score. Moreover, the table of reclassification of the CMR versus TTE predictive model is reported in Figure 1 (bottom). This multiparametric CMR weighted predictive derived score effectively identifies subjects at high risk for MAACE as compared to TTE-LVEF cut-off of 35% with a NRI of 31.7% (p = 0.007). The distribution of CMR predictive score in patients with TTE-LVEF≤35% (panel A) and with TTE LVEF&gt;35% (panel C) is represented in Figure 2, together with the event rate redistribution according to the CMR risk score (panel B and panel D).

Conclusions
The DERIVATE-ICM study is the first large multicenter registry testing the additional value of CMR to stratify the risk for MAACE in a large cohort of ICM patients as compared to standard of care. This model identifies a large number of patients with TTE-LVEF&lt;35% at low risk of SCD event and on the other side it identifies a subset of patients who are at high risk of MAACE despite TTE-LVEF≥35%. Further randomized trials to test a CMR guided strategy for ICD implantation versus standard of care are now needed.