Scientist From John Hopkins Find That Fat Intermingling With Heart Scar Tissue Triggers Ventricular Arrhythmias That Can Be Fatal!
: A new study led by researcher from Johns Hopkins University along with support from researchers at University of Pennsylvania has found that fat intermingling with heart scar tissue triggers ventricular arrhythmias that can be fatal!
Infiltrating adipose tissue (inFAT) has been recently found to co-localize with scar in infarcted hearts and may contribute to ventricular arrhythmias (VAs), a life-threatening heart rhythm disorder.
The contribution of Infiltrating adipose tissue (inFAT) to ventricular arrhythmias (VA) however has not been well-established.
The study team investigated the role of inFAT versus scar in ventricular arrhythmias (VA) through a combined prospective clinical and mechanistic computational study.
Utilizing personalized computational heart models and comparing the results from simulations of ventricular arrhythmias (VA) dynamics with measured electrophysiological abnormalities during the clinical procedure, the study team demonstrated that inFAT, rather than scar, is a primary driver of arrhythmogenic propensity and is frequently present in critical regions of the VA circuit.
The study team determined that, within the ventricular arrhythmias (VA) circuitry, inFAT, as opposed to scar, is primarily responsible for conduction slowing in critical sites, mechanistically promoting ventricular arrhythmias (VA).
The study findings hence implicate inFAT as a dominant player in infarct-related ventricular arrhythmias (VA), challenging existing paradigms and opening the door for unexplored anti-arrhythmic strategies.
The study findings were published in the peer reviewed journal: Nature Cardiovascular Research and also covered in various Cardiology News
Typically, heart attacks scar the heart, leaving patients vulnerable to heart rhythm disorders that can lead to sudden death.
Although not all who have experienced a cardiac infarction will develop an arrhythmia, if they do, it will typically happen about three years post-attack.
It was found that in these patients, fat penetrates the heart wall in the region of the scar after three years, as well.
However, until now, the relationship between those fat deposits and the development of arrhythmias was unclear.
The research team conducted a computational study that revealed fat intermingling with scar tissue was the driving force behind the development of heart rhythm disturbances.
Dr Natalia Trayanova, a Professor of Biomedical Engineering at Johns Hopkins and co-director of the Alliance for Cardiovascular Diagnostic and Treatment Innovation, and a member of the Institute for Computational Medicine partnered with Dr Jonathan Chrispin, assistant professor of medicine and director of ventricular arrhythmia research at the Johns Hopkins School of Medicine, and Dr Saman Nazarian, professor of medicine at the at the Hospital of the University of Pennsylvania for the study.
Dr Trayanova is a pioneer in the use of 3D virtual replicas of the heart and its electrical functions, which are personalized to patients with various heart conditions.
The study team commented, “We needed to understand whether scarring in the heart or the presence of fat in the heart wall or both contribute to arrhythmias in post-infarction patients. In order to do so, we needed to first analyze images of patients' hearts and see where scarring and fat penetration occur. However, since scarring in the heart is visualized on contrast-enhanced MRI, while fat can only be seen on contrast-enhanced CT scans, there were no patient records that had both types of imaging data already available. Hence, we decided to conduct a prospective clinical study, where post-infarction patients who were scheduled to undergo an invasive treatment for their arrhythmias had both an MRI and a CT scan taken.”
The study team utilizing funds from a U.S. NIH grant between researchers at the University of Pennsylvania and those at Johns Hopkins, enrolled 24 patients both institutions. Dr Trayanova’s lab was used to create the first-of-their-kind CT- and MRI-based digital models of the patients' hearts using existing patients' MRI and CT images.
The digital models were then used to understand how heart rhythm disorders arise in these patients.
The study findings from the simulations, together with the electrical recordings acquired from the hearts of the patients during the treatment procedure, helped the study team figure out the role of the penetrating fat in lethal arrhythmias.
The research was a true combined clinical and computational study, with patients prospectively enrolled at two different clinical centers.
The study team using the personalized digital heart models determined that larger amounts of fat in a patient's heart wall was predictive of an increased likelihood of arrhythmias; in contrast, a larger amount of scarring was not associated with an increased arrhythmia likelihood.
By utilizing both the patient digital heart models and the clinical recordings acquired during the procedure, the presence of fat in the heart wall was found to slow down conduction of electrical signals that underlie heart rhythm, making them more likely to behave in a disorderly fashion.
The study findings demonstrated that penetrating fat rather than scarring in the heart is the primary reason for arrhythmia occurrence in these patients.
The study findings implicate the fat that penetrates the walls of the heart as a new, significant player in post-infarct arrhythmias.
Importantly, this study finding challenges the conventional wisdom, which considers scarring in the heart as the main reason for heart rhythm disorders in patients with infarction.
The study team envisions that this new study findings will motivate novel, patient-specific therapeutic strategies to mitigate heart rhythm disorders.
For example, knowledge of how fat is distributed in the heart will affect how catheter ablations are delivered to treat arrhythmias.
The study team also also envisions the implementation of new pharmacological strategies to decrease the extent of penetrating fat in post-infarct patients, thus decreasing the occurrence of arrhythmic events.
The study team plans to continue enrolling patients to increase the size of the patient cohort and ensure that their study findings remain valid.
The study team also intends to examine whether penetrating fat plays a role in heart rhythm disturbances in other heart diseases.
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