Myocarditis: more specific diagnosis thanks to molecular imaging
Myocarditis: more specific diagnosis thanks to molecular imaging
Interview with Prof. Ali Yilmaz, Peter Lancier Endowed Chair in Cardiovascular Imaging, Department of Cardiology and Angiology, University Hospital Münster
There are many causes of myocarditis or inflammation of the heart muscle. Oftentimes, the culprits are viruses or bacteria and sometimes even an acute heart attack. Regardless of the cause, it creates a challenge for cardiologists: a diagnosis tends to be only nonspecific without a biopsy. A cardiac MRI and molecular imaging promise to provide assistance.
Prof. Ali Yilmaz
In this interview with MEDICA-tradefair.com, Prof. Ali Yilmaz talks about the causes, consequences, and diagnosis of myocarditis, discusses the advantages of an MRI compared to other imaging techniques and reveals what renders molecular imaging visible.
Prof. Yilmaz, what exactly is "myocarditis"?
Prof. Ali Yilmaz: Regardless of the causes, we consider almost all inflammations of the heart muscle myocarditis. They are frequently completely harmless and do not affect the patient. Occasionally, during a later exam such as an MRI, for example, we detect that the patient suffered from myocarditis at some point in the past. In this case, we notice residual signs such as a fibrosis or scarring from the inflammation. Having said that, there are also disease courses that can manifest as acute heart failure during the initial acute phase for instance.
How does the heart muscle change as a result of myocarditis?
Yilmaz: There are several factors that determine the degree in which myocarditis can manifest in the heart and the types of complications or subsequent diseases. Is the contagious virus aggressive to where it is able to destroy cardiac muscle tissue? Is the immune system able to quickly eliminate the pathogen or is the virus able to spread quickly?
Oftentimes, myocarditis leads to an autoimmune response. Even though the immune system removes the virus, the immune defense continues and increasingly attacks the body’s own cardiac muscle tissue and causes damages even past the acute phase of myocarditis.
How do you typically diagnose this disease today?
Yilmaz: The gold standard for establishing the diagnosis is the invasive removal of a sampling of heart muscle tissue and the confirmation of inflammation by a pathologist.
The approach is somewhat inconsistent when it comes to non-invasive methods. The problem here is that myocarditis can have very different manifestations, for instance, heart palpitations or shortness of breath during exercise or exertion but also sudden strong pain as is the case in an acute cardiac infarction. It is crucial for health professionals to also always consider myocarditis as a possible cause.
As a diagnostic test, an ECG is a top choice, followed by an ultrasound scan of the heart and a blood test to look for specific cardiac enzymes and inflammation markers. That being said, these procedures generally tend to deliver nonspecific findings that do not conclusively indicate myocarditis. That is why a cardiac MRI has also become a popular procedure in recent years. Not only does it allow us to analyze the heart muscle performance, we are also able to see its morphology. We can identify minute structural changes and especially inflammatory changes that are typical of specific factors that trigger myocarditis and reliably confirm suspected myocarditis.
Today's MRI technology allows for very precise and specific images of the heart muscle.
What is the benefit of an MRI compared to other imaging methods when it comes to cardiac tests?
Yilmaz: We are ultimately able to essentially examine all cardiac muscle aspects. We can inspect the function, its blood supply and most notably its structure. And we are able to determine whether we are dealing with an active inflammation or an earlier fibrosis. We are also able to assess the conditions of the heart valves, the aorta and indirectly the coronary blood vessels.
MRI scans are constantly being improved. New techniques are added that enable an even more accurate and more specific diagnosis.
How does molecular imaging work?
Yilmaz: First we have to define what we mean by "molecular" or rather what we want to uncover at the molecular level. Oftentimes, this refers to a type of cellular imaging, that is to say, we want to illustrate individual cells or cell components. Many types of myocarditis are associated with a macrophage accumulation in the inflamed cardiac muscle area. These macrophages can, in turn, be made visible with certain molecular imaging techniques.
One relatively simple process is based on MRI pulse sequences that account for increased water content in the cardiac muscle. This would be an indirect and nonspecific statement about inflammatory changes at the molecular level. Another option is the use of superparamagnetic contrast agents such as iron oxide nanoparticles for example. They cause minor magnetic field inhomogeneity if they accumulate in a specific tissue. Today we are able to prepare the surfaces of these nanoparticles to where they are being absorbed by the macrophages for example. This allows us to see macrophage accumulation in the cardiac muscle as a nanoparticle accumulation in the MRI.
What are your research findings to date?
Yilmaz: Our task force has conducted studies with iron oxide nanoparticles in patients with myocardial infarction. The cardiac muscle is damaged during the acute phase of a heart attack, which causes inflammation. We took a closer look at the distribution pattern of these damages with an MRI scan. We detected that we could pinpoint these areas after intravenous administration of nanoparticles, which was still possible during the first three to four days after the contrast agent had been administered.
However, we were also able to show that we acquire additional information about the texture of the damaged tissue, which we were unable to obtain with previous MRI options. In doing so, contrast agents containing iron oxide make a more sensitive and more specific diagnosis of inflammation of the heart muscle possible.
How do you plan to continue your research?
Yilmaz: We first take a look at the functionalization of iron oxide particles. Macrophages generally absorb these particles in a very nonspecific manner because they are very thirsty for foreign objects. However, functionalization allows us to visualize specific molecular structures, such as myosin or actin filaments of cardiac muscle cells for example. This is done with an antibody that is specifically opposed to the filaments and that we link to the nanoparticles. When we inject a patient or model with these particles, these should accumulate in the area where the heart muscle is damaged and where the filaments are able to come into direct contact with the antibodies.
As a second objective, we focus on the possibility of navigating the particles from the outside using magnetic fields and taking them into the targeted region of the body since iron oxide nanoparticles exhibit unique properties to this effect. In this case, it is only logical to also link substances to the particles and accumulate them where they should work – for instance, in the cardiac muscle tissue after a heart attack. This increases the effectiveness of the substance in the target tissue, while it also reduces its adverse effects on other organs. This is a so-called "theranostic" approach, i.e., the combination of diagnostic and therapeutic applications using particles.