Signatures of heart attack

Giving patients even better treatment after a heart attack is one of the goals of cardiology. This includes comprehensively understanding and punctually recognizing those patients at risk of poorer disease outcomes after a coronary. Researchers at LMU University Hospital, Helmholtz Munich, and other institutions have now used high-tech biomedical and bioinformatics methods to comprehensively map the human immune response to heart attacks and have identified signatures that correlate with the clinical progression of the disease. The results of their pioneering work have been published in the prestigious journal Nature Medicine.

In Germany alone, some 300,000 people suffer a heart attack every year. The treatment of patients has reached a high level, with falling mortality rates. However, many patients subsequently develop heart failure because their cardiac muscle does not recover optimally.

We know mainly from animal studies that the inflammatory response plays an important role after a heart attack and has a decisive influence on whether the functions of the heart muscle are restored. “A misdirected or overshooting immune response can endanger this recovery of cardiac function,” says Dr. Kami Pekayvaz, lead author of the new study and clinician scientist at Medical Clinic I at LMU University Hospital.

For the first time, a team led by Dr. Kami Pekayvaz, Viktoria Knottenberg, PD Dr. Leo Nicolai, and Prof. Konstantin Stark from Medical Clinic I at LMU University Hospital and Corinna Losert and Dr. Matthias Heinig from Helmholtz Munich has analyzed how the human immune system “behaves” after a heart attack. The researchers investigated blood samples from heart attack patients who were treated at LMU University Hospital and had different subsequent disease progressions.

Atlas of immune responses

The researchers analyzed immune cells located in the blood cell by cell in relation to their RNA composition. RNA is formed when cells translate the information in their genes into proteins – and this allows a transcriptome analysis to reveal the current state and properties of a cell. In addition, the scientists used protein analyses to study the blood plasma for various messengers that could be indicators of inflammations. These so-called multi-omics methods are at the cutting edge of this medical field.

A specific bioinformatics technique called multi-omics factor analysis (MOFA) recognized overarching patterns in the mass of data obtained. “This method is optimal for identifying and summarizing many smaller effects that move in the same direction in a coordinated fashion,” says Dr. Matthias Heinig, leader of a bioinformatics research group at Helmholtz Munich. This allowed the team to create a sort of atlas of immune responses after a heart attack. “These patterns can explain differences between the clinical and temporal courses of a disease in patients,” says Prof. Konstantin Stark, Senior Consultant in Cardiology at LMU University Hospital. In other words, some of these “immune signatures” are associated with a better recovery of cardiac function, while others are associated with a poorer one.

This atlas of immune responses for heart attacks is hugely significant for further cardiovascular basic research and potentially indicates that the clinical progression of heart attack patients could be evaluated using multi-omics analyses of blood samples. Before this can happen, however, the concept of MOFA-based diagnostics in cardiovascular diseases has to be assessed in further studies – something the Munich researchers intend to do over the coming years.