ENIGMA-shock: protocol for a study framEwork for aN InteGrated assessMent of cArdiac rehabilitation programmes in...

The treatment of patients with cardiogenic shock (CS) has been focused historically on single interventions (medical treatments, percutaneous and surgical interventions and, more recently, various temporary mechanical circulatory supports). However, none of these interventions has significantly changed the short-term prognosis of CS. Moreover, considerable interest in interventions applied in the acute setting has not been matched with comprehensive assessment of patients' long-term follow-up, not only for survival and rehospitalisation but also for quality of life and functional status, recovery from critical illness and its destructive sequelae, and a global evaluation of the overall sustainability of pathways of care. To fill this knowledge gap, the ENIGMA study will be conducted.

This is a prospective and retrospective multicentre registry conducted under the scientific coordination of the IRCCS Fondazione Don Gnocchi and funded by the Italian Ministry of Health (PNRR-MCNT2-2023-12377767). Data referring to 2000 patients included in the Altshock registry, the largest multicentre CS registry in Italy, will be analysed. A standardised protocol of high-intensity cardiac rehabilitation has been defined and will be followed by the involved institutions after the inclusion of the first 1000 patients. Where feasible, this new pathway will be implemented in every institution. All the patients enrolled will be evaluated according to the Long-Term Conditions Questionnaire, the Kansas City Cardiomyopathy Questionnaire and a questionnaire on the patient experience at 6-month follow-up, to evaluate real-life comparative effects on patient outcomes and experiences. In conclusion, a health technology assessment (HTA) analysis, grounded in the EUnetHTA Core Model, will be conducted to define the potential multidimensional benefits and effects with regard to the overall economic, organisational and social sustainability of the innovative dedicated pathway. Various data sources will be used to conduct the HTA: (1) literature evidence, to define the evidence-based comparative indicators considering both surgical approaches; (2) real-world anonymised data from the hospitals included in the study, to enable costing of the rehabilitative pathways; and (3) healthcare professionals' perceptions, defining the perceived added value of the innovative pathway versus the historical one, based on an evaluation scale ranging from -3 to +3.

The study was approved by the ethical committee (EC) of Lombardy Region (CET 44/24), on 28 May 2024, and is under evaluation by the EC of three other centres. The study protocol will be evaluated for ethics by 10 more centres in January 2025. Study results will be published in peer-reviewed publications and disseminated through conference presentations. The Associazione Nazionale Scompensati Cardiaci (AISC; 'National Association of Patients with Heart Failure'), the Progetto Vita initiative and the non-profit organisation 'Heart Helps Heart' have endorsed the project and will be involved in disseminating information about the project and its outcomes to the general public.

The ENIGMA-shock study has been registered at ClincialTrials.gov: NCT06572826.