A new study reveals how metabolic syndrome remodels the heart and leads to cardiac arrhythmias

## A new study reveals how metabolic syndrome remodels the heart and leads to cardiac arrhythmias

Experimental Cardiac Electrophysiology Research Group, with M. Zarzoso, in the center, and F.J. Chorro, second from the right.

A study led by the University of Valencia (UV) and the INCLIVA Health Research Institute has identified the mechanisms by which metabolic syndrome — mainly caused by a diet high in fats and sugars — could be promoting the development of life-threatening ventricular arrhythmias such as ventricular fibrillation. The findings, obtained using panoramic optical mapping techniques and published in The Journal of Physiology, open up new avenues for research into preventive and therapeutic strategies.

Metabolic syndrome encompasses a range of physiological, biochemical, clinical and metabolic risk factors whose combined presence is associated with an increased risk of cardiovascular disease. Although it has been linked to lethal ventricular arrhythmias such as ventricular fibrillation, the underlying mechanisms of this syndrome with truly serious health implications are not yet fully understood.

Metabolic syndrome includes various disorders such as central obesity, high blood pressure, insulin resistance and blood lipid abnormalities, including elevated LDL cholesterol and triglycerides. Its onset is associated with sedentary lifestyles and inappropriate, high-calorie diets rich in fats and sugars.

The multidisciplinary scientific team behind the study recently published in *The Journal of Physiology* carried out an investigation into the cardiovascular remodelling caused by metabolic syndrome, with a particular focus on the changes occurring in the heart. Using an experimental rabbit model that faithfully replicates the key alterations of this disease in humans, the research group identified electrical changes in the heart that increase an individual’s vulnerability to rhythm disturbances. Specifically, the results reveal electrical remodelling in the left ventricle — and more markedly in the right ventricle — which, according to the article, could largely explain the increased risk of arrhythmias in patients with metabolic syndrome.

This discovery represents a significant step forward in understanding the cardiovascular pathophysiology associated with metabolic syndrome and provides a solid foundation for future research into the prevention and treatment of its arrhythmic complications.

One of the most innovative aspects of the study was the use of high-resolution panoramic optical mapping, which allows for the simultaneous and highly precise study of the electrical properties of different areas of the heart. The scientific and technical equipment used for this mapping was acquired through research funding from both the University of Valencia and the Generalitat Valenciana, as well as through FEDER funds.

The study was led by Manuel Zarzoso Muñoz (Department of Physiotherapy, UV-INCLIVA-CIBERCV) and coordinated by Francisco Javier Chorro Gascó (Department of Medicine, UV-INCLIVA-CIBERCV). It was conducted within the Experimental Cardiac Electrophysiology Research Group, a multidisciplinary team from INCLIVA and the University of Valencia, which forms part of the Centre for Networked Biomedical Research on Cardiovascular Diseases (CIBERCV) under the Carlos III Health Institute. Researchers from the Polytechnic University of Valencia, CEU Cardenal Herrera University of Valencia and the University of Auckland (New Zealand) also contributed to the study.

**Reference:**

Arias-Mutis ÓJ, Calvo CJ, Bizy A, Ortiz-Guzmán JE, Such-Miquel L, Such L, Alberola A, Zhao J, Chorro FJ, Zarzoso. **Ventricular arrhythmogenic remodelling in diet-induced metabolic syndrome driven by right-to-left regional differences in action potential duration and dominant frequency gradients**. J Physiol. 2025 May 5. doi: 10.1113/JP286516. Epub ahead of print. PMID: 40320918.

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