Short summary

During the last 10 years there has been a great re-organization in Denmark on how the patient with a heart attack is handled from symptom onset to treatment. Today diagnostics and pre-medication takes place in the ambulance where from the patient is transferred directly to a highly specialized coronary intervention unit. Earlier the patient was taken to a smaller hospital for diagnosis. We wish to investigate how this streamlining of patient-transportation has influenced the risk of developing the most serious complication to a heart attack - cardiogenic shock. Also, we wish to compare two advanced assist devices used in the treatment, in an experimental animal model of cardiogenic shock.
There is a lack of knowledge on how many people suffer from the gravest complication to a heart attack - cardiogenic shock, what the mortality is and how it is best treated. We wish to address these questions in a Ph.D. dissertation including a population based study on heart attacks and an animal study comparing two advanced mechanical assist devices used in the treatment. 

Rationale

Background:

Historically cardiogenic shock is seen in approximately 5% of patients suffering from a heart attack corresponding to 150 cases per year nationwide in Denmark. However, during the last 10 to 15 years management of heart attacks has undergone major improvements in Denmark including the introduction of acute angioplasty and prehospital diagnosis which has reduced the time from symptom onset to treatment dramatically.  This streamlining of patient handling has been showed to reduce the overall mortality but whether this is also the case for cardiogenic shock is unknown.

Cardiogenic shock develops when the volume of blood ejected from the heart (cardiac output) is critically reduced, which may occur after an extensive heart attack. The consequence is poor tissue perfusion, decreased oxygen delivery and potentially end-organ damage and multi-organ failure, with death occurring in more than half of the cases. Thus, circulatory support is necessary to maintain organ perfusion and avoid death. Traditionally this has been done by a combination of pharmacological support and mechanical circulatory support by intra-aortic balloon counterpulsation. However, a recent randomized study has demonstrated no benefit of aortic counterpulsation and pharmacological support alone is often inadequate to restore cardiac output, which has led to a rapid increase in the utility of alternative circulatory support systems. Most commonly used are the Impella device or extracorporeal veno arterial support (VA-ECMO). ECMO offers full circulatory and respiratory support like a heart-lung machine, whereas the Impella offloads the heart by ejecting blood from the left ventricle into the aorta. Although VA-ECMO offers partial or full circulatory support, it has been suggested to cause less unloading of the heart conversely the Impella device is less powerful in restoring cardiac output. Today there is expert agreement that mechanical assist devices are feasible and may be used, but there is a lack of agreement on which device should be used, and there are very few studies with head to head comparison of the technologies

The objective:

Is to investigate the incidence of cardiogenic shock relative to system- and patient delay in a large retrospective population study based on review of individual patient data. Further the study will in a comprehensive experimental design compare the impact of the Impella device versus VA-ECMO in terms of unloading the heart.

Methods:

1. Population study: Patients with a heart attack treated at Rigshospitalet or Odense University hospital in the period January 1st 2010 to December 31st 2017 will be identified by undergoing a primary screening process followed by individual chart review to establish whether they had suffered from cardiogenic shock. Relevant data will be registered anonymously in an online based database.
2. Animal study: We will induce cardiogenic shock in 20 animals and randomize to either Impella or VA-ECMO. Primary endpoints are measurements of work performed by the heart and hereby the ability of the devices to offload the heart. Secondary endpoints will by oxygenation of the brain and kidneys, myocardial infarct size and impact on biomarkers.

This Ph.D. will contribute with important knowledge about cardiogenic shock following a heart attack and how the condition has been influenced by the changes in patient handling that has occurred over the last decade. The results will potentially have significant influence on how the condition should be treated in the future.

Description of the cohort

People admitted to Odense University Hospital (OUH) and Rigshospitalet (RH) during the last 10 years with an ST-segment elevation myocardial infarction and suffering from cardiogenic shock.

Data and biological material

This is a retrospective study using data from the heart databases in eastern Denmark as well as patient charts. 

Collaborating researchers and departments

Department of Cardiology, Odense University Hospital

• PhD-student Ole Kristian Møller-Helgestad, MD
• Professor Jacob Eifer Møller, MD, DMSc, PhD
• Lisette Okkels Jensen, MD, DMSc, PhD

Department of Anaesthesiology and Intensive Care, Odense University Hospital

• Henrik Schmidt, MD, DMSc

Department of Cardiothoracic Anaesthesiology, Copenhagen University Hospital, Rigshospitalet

• Professor Hanne Berg Ravn. MD, DMSc, PhD

Department of Cardiology, Copenhagen University Hospital, Rigshospitalet

• Christian Hassager, MD, DMSc
• Lene Holmvang, MD, DMSc
• PhD-student Martin Frydland, MD