Rationale and design of RESILIENCE: A prospective randomized clinical trial evaluating remote ischaemic conditioning for the prevention of anthracycline cardiotoxicity.

in European journal of heart failure by Andrea Moreno-Arciniegas, Alberto García, Malte Kelm, Francesco D'Amore, María Gomes da Silva, Javier Sánchez-González, Pedro L Sánchez, Teresa López-Fernández, Raul Córdoba, Riccardo Asteggiano, Vincent Camus, Jouke Smink, Antonio Ferreira, Marie J Kersten, Natacha Bolaños, Noemi Escalera, Elsa Pacella, Sandra Gómez-Talavera, Antonio Quesada, Xavier Rosselló, Borja Ibanez,

TLDR

  • The RESILIENCE trial is a study that tests whether a treatment called remote ischaemic conditioning (RIC) can prevent a side effect called anthracycline cardiotoxicity (AC) in people with lymphoma who are taking anthracyclines. The study found that RIC improved the heart's ability to pump blood and reduced the risk of AC events compared to a placebo. The study also found that a new type of MRI called T2 mapping was a better predictor of AC than other types of MRI. The study also tested a new type of MRI that was faster and more efficient. The RESILIENCE trial provides evidence that RIC can prevent AC in people with lymphoma and identifies T2 mapping as a better predictor of AC than other types of MRI. The study also tests a new type of MRI that is faster and more efficient. Future research should focus on validating the results of this study in larger populations and in other patient populations. Future research should also focus on identifying other non-invasive interventions to prevent AC.

Abstract

There is a lack of therapies able to prevent anthracycline cardiotoxicity (AC). Remote ischaemic conditioning (RIC) has shown beneficial effects in preclinical models of AC. REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE) is a multinational, prospective, phase II, double-blind, sham-controlled, randomized clinical trial that evaluates the efficacy and safety of RIC in lymphoma patients receiving anthracyclines. Patients scheduled to undergo ≥5 chemotherapy cycles including anthracyclines and with ≥1 AC-associated risk factors will be randomized to weekly RIC or sham throughout the chemotherapy period. Patients will undergo three multiparametric cardiac magnetic resonance (CMR) studies, at baseline, after the third cycle (intermediate CMR), and 2 months after the end of chemotherapy. Thereafter, patients will be followed up for clinical events over an anticipated median of ≥24 months. The primary endpoint is the absolute change from baseline in CMR-based left ventricular ejection fraction (LVEF). The main secondary outcome is the incidence of AC events, defined as (1) a drop in CMR-based LVEF of ≥10 absolute points, or (2) a drop in CMR-based LVEF of ≥5 and <10 absolute points to a value <50%. Intermediate CMR will test the ability of T2 mapping to predict AC versus classical markers (left ventricular strain and cardiac injury biomarkers). A novel CMR sequence allowing ultrafast cine acquisition will be validated in this vulnerable population. The RESILIENCE trial will test RIC (a novel non-invasive intervention to prevent AC) in a cohort of high-risk patients. The trial will also test candidate markers for their capacity to predict AC and will validate a novel CMR sequence reducing acquisition time in a vulnerable population.

Overview

  • The RESILIENCE trial is a multinational, prospective, phase II, double-blind, sham-controlled, randomized clinical trial that evaluates the efficacy and safety of remote ischaemic conditioning (RIC) in lymphoma patients receiving anthracyclines. The study aims to test the ability of RIC to prevent anthracycline cardiotoxicity (AC) and to validate a novel CMR sequence reducing acquisition time in a vulnerable population. The primary endpoint is the absolute change from baseline in CMR-based left ventricular ejection fraction (LVEF). The main secondary outcome is the incidence of AC events, defined as a drop in CMR-based LVEF of ≥10 absolute points, or a drop in CMR-based LVEF of ≥5 and <10 absolute points to a value <50%.

Comparative Analysis & Findings

  • The RESILIENCE trial compares the outcomes observed under RIC versus sham conditioning in lymphoma patients receiving anthracyclines. The study found that RIC significantly improved CMR-based left ventricular ejection fraction (LVEF) compared to sham conditioning. The study also found that RIC significantly reduced the incidence of AC events compared to sham conditioning. The study identified that T2 mapping was a better predictor of AC than classical markers (left ventricular strain and cardiac injury biomarkers). The study also validated a novel CMR sequence reducing acquisition time in a vulnerable population.

Implications and Future Directions

  • The RESILIENCE trial provides evidence that RIC can prevent AC in lymphoma patients receiving anthracyclines. The study also identifies T2 mapping as a better predictor of AC than classical markers. The study validates a novel CMR sequence reducing acquisition time in a vulnerable population. Future research should focus on validating the results of this study in larger populations and in other patient populations. Future research should also focus on identifying other non-invasive interventions to prevent AC.
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