Re-defining clinical care and reasoning in ST-elevation myocardial infarction (STEMI) by shifting focus to ischemic myocardial stunning - Mechanisms prognostic implications and a new treatment

Informations projet

De-StunHeartAttacks

N° de convention de subvention: 948665

DOI

10.3030/948665

Date de signature de la CE 27 Octobre 2020

Date de début 1 Novembre 2020

Date de fin 30 Avril 2027

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 500 000,00

Contribution de l’UE

€ 1 500 000,00

Coordonné par

GOETEBORGS UNIVERSITET
Sweden

Periodic Reporting for period 3 - De-StunHeartAttacks (Re-defining clinical care and reasoning in ST-elevation myocardial infarction (STEMI) by shifting focus to ischemic myocardial stunning - Mechanisms prognostic implications and a new treatment)

Période du rapport: 2023-11-01 au 2025-04-30

Résumé du contexte et des objectifs généraux du projet

Acute myocardial infarction (AMI) remains a leading cause of death. Among patients admitted to hospital with an AMI, 10% develop acute ischemic heart failure (AIHF) and account for 50% of those who die within 30 days. The prognosis for patients with AIHF has not improved over the past decade, since neither currently available drugs nor assist devices reduce mortality; and despite considerable efforts, cardioprotective therapies to limit myocardial injury in AMI have not been successful. Myocardial stunning (MS) refers to the sudden but reversible loss of myocardial function that occurs alongside irreversible necrosis in AMI. MS is not limited to AMI but can also occur in other cardiac conditions, including takotsubo in which patients develop pronounced stunning without significant myocardial necrosis in response to stress.

MS is thought to be caused by myocardial injury, but I hypothesize that it is a means of preserving energy for vital processes by shutting down energy-demanding contractile functions in settings of oxygen deprivation. The overarching aim of my projects is to understand how MS can be manipulated to optimize cardiac function and survival in AMI and takotsubo. To achieve this goal, I am conducting studies in a cohort of Swedish patients with AMI or takotsubo and a rat model of myocardial stunning as well as via the extensive Swedish healthcare registries with patient records. My integrated research approach allows me to easier translate findings in animals to clinical research, and investigate interesting findings in humans more in-depth in the rat model. My research could change how researchers and clinicians approach the pathophysiology, prognosis, and treatment of AMI and takotsubo and help mitigate the sex gap in the evidence supporting the use and benefit of current treatments.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The first years of my studies have focused on establishing my research group and infrastructure. This includes enrolling AMI and takotsubo patients into my clinical cohort STAMI (“Stunning in Takotsubo versus Acute Myocardial Infarction”), creating a new rat model simulating myocardial stunning, and developing a new technique to accurately measure myocardial stunning via echocardiography. My published results so far have generated new information on different diagnostic parameters, such as echocardiography, electrocardiography, and bloodborne biomarkers for AMI and takotsubo, as well as comparisons of the risk for severe consequences in the two conditions.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

By the end of the projects, I expect to have thoroughly investigated several parameters of the myocardial stunning phenomenon in our recruited patients and the Swedish healthcare registries with a particular focus on potential sex differences. Examples of such parameters include the resolution of stunning between different conditions and the relationship between myocardial stunning and prognosis. I will also have made progress towards a potential new treatment for AMI. On the preclinical side, my new rat model of myocardial stunning will have been characterized in-depth via several studies investigating the pathophysiology of myocardial stunning.

Preclinical results from a substudy using a rat model of ischemia-reperfusion