Dr. Gladden Willis / Visuals Unlimited, Inc. / SPL / Latinstock
Microscopic image of myocardial infarction: fibrosis (lighter areas) damages the functioning of the heartDr. Gladden Willis / Visuals Unlimited, Inc. / SPL / LatinstockMagnetic resonance imaging (MRI) may provide a useful tool for early diagnosis of small changes to the heart caused by chronic obesity and other health problems. Because these changes are still at a very early stage, they are not detected by the usual exams for evaluating the condition of the heart, like electrocardiograms and ultrasounds. Working with colleagues from Harvard University, where he finished his Master’s degree five years ago, cardiologist Otávio Rizzi Coelho-Filho, now professor at the School of Medical Sciences of the University of Campinas (FCM-Unicamp), developed a new protocol for the technique, which identifies two types of subtle changes to the heart muscle: increased cell size and the amount of interstitial fibrosis, a condition where collagen-rich tissue forms in the space between cells, making it harder for the heart to work.
These changes occur at a subcellular level, before the shape of the heart displays any visible alterations. At this stage, in general terms, the heart muscle remains functional and looks completely healthy, but inside it shows signs of incipient degeneration. “Only an MRI lets us see that the heart is not completely healthy, while other diagnostic methods show the organ to be normal,” explains Coelho-Filho, who is on the team of the Obesity and Comorbidities Research Center (OCRC), one of 17 FAPESP-funded Research, Innovation and Dissemination Centers (RIDC). Cellular hypertrophy and spreading fibrosis are factors that increase the risk of cardiac arrhythmia, heart attack, and even sudden death. According to Coelho-Filho, MRIs are the only non-invasive method able to detect both changes simultaneously. At present, interstitial fibrosis can be detected only through a heart tissue biopsy, which is an invasive technique that is hard to employ.
By capturing multiple images of the myocardial fibers to make a kind of movie of the functioning of the heart, an MRI makes it possible to calculate cardiac muscle cell size and the amount of fibrosis. The larger the cells and the more widespread the collagen, the greater the damage. During testing, researchers take measurements before and after administering gadolinium, a chemical element that is used as a contrast in MRIs. Gadolinium does not penetrate heart cells but spreads through the extracellular space where interstitial fibrosis occurs. The distribution of the contrast provides an idea of the extent of the area presenting collagen. Another parameter that is analyzed is how long it takes water molecules to cross the myocardial cells. Longer times indicate larger cells, a sign that some change is underway.
Ataxia and chagas disease
According to physician Wilson Nadruz, a Unicamp professor who is taking part in the cardiac MRI studies, the new protocol for this technique allows for early identification of cardiac remodeling, before more significant changes to heart shape and functioning have developed. “We could identify changes to the heart that might be completely or at least partly reversible if we treated underlying diseases, like obesity and diabetes,” says Nadruz, doctoral advisor to Coelho-Filho, who defended his dissertation on the topic in 2013. “Based on data obtained with this methodology so far, cellular hypertrophy seems to be an even earlier event than interstitial fibrosis,” he states. There is usually a correlation between fibrosis and hypertrophy, but the two processes are not necessarily related.
Eduardo CesarMRI of the heart: exam measures increased myocardial cell size and interstitial fibrosisEduardo Cesar
In recent years, Coelho-Filho has been testing the methodology on mice, obese humans, and humans with other heart-damaging illnesses. One of his more recent studies dealt with individuals who suffer from Friedreich’s ataxia, a genetic neurodegenerative disease that hampers motor coordination and causes heart problems and sometimes diabetes. Heart failure is the most common cause of death among these patients. RIDC researchers used the new protocol to check for the presence of fibrosis and heart cell size in 27 patients with the disease and in a control group of 30 healthy individuals. The MRIs showed that indicators of fibrosis and expansion of the size and area of heart cells in people with ataxia were higher than in non-sufferers. The study was published in January 2016 in the Journal of Cardiovascular Magnetic Resonance.
Cardiac MRIs are not performed routinely but can be helpful in monitoring the earliest changes in the myocardial cells of patients who have diseases like Friedreich’s ataxia, which will eventually damage the heart muscles. Physician Carlos Eduardo Rochitte, professor with the cardiovascular MRI and CT-scan service at the Heart Institute (InCor), of the University of São Paulo School of Medicine (FMUSP), researches the use of this technology on patients with Chagas disease, who suffer an inflammation of the heart caused by the protozoan Trypanosoma cruzi.
By administering MRIs to a group of 20 people with what is known as the indeterminate form of the disease – where a carrier of the pathogen is clinically healthy and presents no symptoms or changes caused by Chagas disease – Rochitte found that 30% already displayed interstitial fibrosis. “The technique is good for quantifying these changes at an early stage,” says Rochitte, whose studies are funded in part by FAPESP. “However, we still don’t know the clinical relevance of these data for patients with Chagas disease. Does the presence of fibrosis in these carriers of the protozoan mean they will soon start displaying the symptoms of the disease?” he asks. This is one of the still unanswered questions now being studied by the InCor researcher.
Projects
1. OCRC – Obesity and Comorbidities Research Center (nº 2013/07607-8); Grant Mechanism Research, Innovation and Dissemination Center (RIDC); Principal Investigator Lício Velloso (FCM-Unicamp); Investment R$14,579,597.41 (for the entire RIDC).
2. Evaluation of myocardial fibrosis by cardiac magnetic resonance in risk stratification in Chagas disease (nº 2014/17643-4); Grant Mechanism Regular Research Grant; Principal Investigator Carlos Eduardo Rochitte (InCor/FMUSP); Investment R$175,938.00.
Scientific article
COELHO-FILHO, O. R. et al. Characterization of both myocardial extracellular volume expansion and myocyte hypertrophy by CMR detect early signs of myocardial tissue remodeling in Friedreich’s ataxia patients without heart failure. Journal of Cardiovascular Magnetic Resonance. V. 18, suppl. 1, Jan. 27, 2016.
