Multi-omics tests reveal immune system response to heart attack

Improving patient outcomes after myocardial infarction is one of the main goals of cardiology. This includes a comprehensive understanding of pathophysiology and early identification of patients at high risk of poor outcome.

Researchers from LMU Hospital, Helmholtz Munich and other institutions used high-tech biomedical and bioinformatics methods to comprehensively map the immune response to myocardial infarction in humans and identify signatures that correlate with clinical course of the disease.

The results were published in the journal Nature Medicine.

In Germany alone, about 300,000 people suffer a heart attack every year. Treatment of patients has improved significantly over recent decades. However, many of those affected develop heart failure after the event because the heart muscle does not recover.

According to animal studies, the inflammatory response plays an important role after a heart attack and has a decisive influence on the restoration of cardiac muscle function.

“An abnormal or excessive immune response may compromise the recovery of heart function,” says Dr. Kami Pekaivaz, lead author of the new study and clinical scientist from the Department of Medicine I at LMU Hospital, LMU Munich.

A team led by him, including Victoria Knottenberg, PD Dr. Leo Nicolai and Prof. Constantin Stark from the Department of Medicine I at LMU Hospital and Corinne Loesert and Dr. Matthias Heinig from Helmholtz Munich, analyzed for the first time how the immune systemreacts to myocardial infarction in humans.

Researchers studied blood samples from heart attack patients who were treated at LMU Hospital and showed varying clinical outcomes.

Atlas of immune responses

Immune cells in the blood were analyzed individually for their RNA expression. RNA is produced when cells translate the information from their genes into proteins - so-called transcriptomic analysis can reveal the current state and characteristics of the cell.

In addition, blood plasma has been studied for various substances using protein assays, which provide detailed information about inflammatory and other processes. These analyzes belong to the most modern methods, the so-called multi-omics methods.

A specific bioinformatics technique (MOFA, for multi-omics data factor analysis) recognized common patterns in the mass of data obtained.

“This method is ideal for identifying and summarizing many smaller effects that are coordinated in one direction,” says Dr. Matthias Heinig, head of the bioinformatics working group at Helmholtz Munich. This made it possible to create an atlas of immune responses after myocardial infarction.

“These patterns may explain differences between clinical and time courses in patients,” says Professor Constantin Stark, senior consultant in cardiology at LMU Hospital. This means that certain "immune signatures" are associated with better recovery of cardiac function, while others are associated with worse recovery.

This atlas of the immune response to myocardial infarction is highly relevant for further basic research in the field of cardiovascular disease and potentially indicates that multi-omics analyzes of blood samples can be used to predict the clinical course of a patient's infarction. However, the concept of MOFA-based diagnostics for cardiovascular diseases should be tested in further studies - and this is what the Munich researchers plan to do in the coming years.