Marcus Carlsson

Aims: The specific aims of the pilot study is to provide data to prepare for a future national, open-label proof of concept clinical treatment study assessing the safety and efficacy  interleukin 6 inhibition (IL6i) for the treatment of immune checkpoint inhibitor (ICI) related myocarditis (ICIrM). Background:  ICIrM is a rare complication to ICI cancer therapy but  the increasing number of patients in combination with a reported mortality of 30-40% summons up to a significant clinical problem. Current treatment guidelines with high dose cortisone are based on retrospectiv data. IL6 is used for  other irAEs, and we suggest a national open -label proof of concept clinical treatment study to asses early IL6i in the treatment of ICIrM. Methods: We will perform a systematic review covering clinical data on IL6 blockade for ICIrM treatments  according to the PRISMA framework (2024) and a retrospective single center study of diagnosis, management and cardiovascular och cancer outcome i patients with ICIrM at Karolinska University Hospital (2024). These subprojects will be the base for planning and preparing the future treatment study, The project organisation and steering committe is a multidisciplinary team to secure all aspects of optimal dimensioning, patient eligbility, outcome measures. This group will also be the steering committe for the national ICIrM network to provide a base for future treatment study.

Impaired cardiac function often results in heart failure which represents a major burden of morbidity and mortality. Cardiac magnetic resonance imaging (MRI) is considered to be the reference method for assessment of cardiac function. However, the relatively long scan times makes MRI sensitive to motion. Most current cardiac MRI techniques require multiple breath holds, which many patients with heart failure are unable to perform., resulting in non-diagnostic image quality. The aim of this project is to develop a novel framework for adaptive image acquisition, where the pulse sequence is controlled by online motion estimators. This will enable acquisition that is robust to respiratory motion and arrhythmia, as well as fetal motion during examination of fetal hearts. The methods will be evaluated both in healthy volunteers, heart failure patients, and in pregnant women. The pulse sequence and corresponding image reconstruction will be implemented directly on the clinical scanner platform, making it immediately available for clinical use. The research will take place immersed in a clinical environment at the Karolinska University Hospital, with full access to dedicated cardiac MRI scanners and relevant patient populations. The proposed approach is highly original, fills an important unmet clinical need in medicine, and involves novel approaches that push the technical limits of image acquisition and reconstruction beyond state-of-the-art.