Myocardial infarction

There are approximately 3.8 million cases of death annually in Europe that are related to cardiovascular diseases (CVD). This represents approximately 40% of all causes of death.

In the US, approximately 940,000 people die every year due to a cardiovascular disease. Through the implementation of improved and more effective treatments the last decades mortality rates have decreased, but despite of this cardiovascular diseases are still the number one cause of death globally.

There are different types of cardiovascular disease. One type is when the condition is caused by lack of oxygen, so called ischemic cardiovascular disease. Myocardial infarction is the most severe and acute form of ischemic cardiovascular disease, commonly referred to as heart attack. A myocardial infarction means that the coronary artery is blocked by a thrombosis, which blocks the blood flow in the heart leading to a lack of oxygen. Myocardial infarction is further divided into ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), based on if the coronary artery is blocked completely or partially. STEMI is the most severe type of myocardial infarction, with a complete blockage of the coronary artery. The symptom of STEMI is intense chest pains and the condition is acute and requires immediate medical treatment.

Treatment of STEMI

Standard-of-care for treatment of STEMI is to conduct a percutaneous coronary intervention (PCI) in combination with pain killing and anti-platelet drugs. PCI is an intervention through which the blocked coronary artery is opened with a ballon, covered by a stent. The stent ensures that the coronary artery is widened and remains open after the removal of the ballon. The purpose of the intervention is to re-oxygenate the heart, so called reperfusion.

High unmet medical need in STEMI

PCI was introduced in the treatment of STEMI about thirty years ago and has, in combination with the introduction of more effective drugs, contributed to significantly improved survival. However despite this, the risk of major adverse cardiovascular events (MACE) has remained at a high level: within twelve months from PCI in STEMI the risk of death is 10%, heart failure 9% and re-infarction 10%. Hence, the unmet medical need of more effective treatment in STEMI is significant.

Ischemic reperfusion injury

PCI in STEMI is usually a successful intervention through which the oxygenation of the heart is restored, a so-called reperfusion. However, the intervention itself can cause damage to the cardiac tissue, as the heart is “shocked” by the sudden restored blood flow after a long period of oxygen shortage. This phenomenon is called ischemic reperfusion injury (IRI). IRI is a common complication following PCI and is linked to an excessive inflammatory response where certain immune cells that are expressing fractalkine are involved.

Intramyocardial hemorrhage

Several clinical studies have shown that IRI post PCI is a common complication which can lead to cardiac tissue damage on the microvascular level. The severity of this cardiac tissue damage is assessed in a four graded scale. The most severe type of tissue damage (grade 4) means that the endothelial cell layer is damaged and red blood cells are infiltrated into the cardiac tissue, referred to as intramyocardial hemorrhage (IMH). IMH leads to larger final infarct size and adverse re-modelling, which is associated with an increased risk of MACE (death, heart failure and re-infarct). Today there are no available drugs to prevent or reduce the risk of IMH.

Fractalkine and ischemic reperfusion injury

o Individuals with cardiovascular disease have higher levels of fractalkine vs healthy individuals. In STEMI patients, the levels of fractalkine are raising rapidly following PCI, which is associated with an increased risk of ischemic reperfusion injury and cardiovascular events (death, heart failure or myocardial infarction).