Systemic Delivery of Extracellular Vesicles Attenuates Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction.

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Publication Year:
2023
Authors:
Rui Zhang, Thassio Mesquita, Jae Hyung Cho, Chang Li, Lizbeth Sanchez, Kevin Holm, Akbarshakh Akhmerov, Weixin Liu, Yigang Li, Ahmed G Ibrahim, Eugenio Cingolani
PubMed ID:
36858679
Funding Grants:
Public Summary:
This study tested a new treatment for a common irregular heartbeat called atrial fibrillation (AF) that happens in some people with a certain type of heart failure (HFpEF). Using rats with this heart problem, researchers gave them tiny particles made from heart cells called extracellular vesicles. These particles helped fix the heart’s electrical signals, reduced harmful scarring and inflammation, and greatly lowered the chances of the irregular heartbeat happening—without affecting blood pressure or how well the heart pumps. This shows promise for a new way to prevent AF in people with this kind of heart failure.
Scientific Abstract:
BACKGROUND: Atrial fibrillation (AF) is a common comorbidity in heart failure with preserved ejection fraction (HFpEF) patients. To date, treatments for HFpEF-related AF have been limited to anti-arrhythmic drugs and ablation. Here we examined the effects of immortalized cardiosphere-derived extracellular vesicles (imCDCevs) in rats with HFpEF. OBJECTIVES: This study sought to investigate the mechanisms of AF in HFpEF and probe the potential therapeutic efficacy of imCDCevs in HFpEF-related AF. METHODS: Dahl salt-sensitive rats were fed a high-salt diet for 7 weeks to induce HFpEF and randomized to receive imCDCevs (n = 18) or vehicle intravenously (n = 14). Rats fed a normal-salt diet were used as control animals (n = 26). A comprehensive characterization of atrial remodeling was conducted using functional and molecular techniques. RESULTS: HFpEF-verified animals showed significantly higher AF inducibility (84%) compared with control animals (15%). These changes were associated with prolonged action potential duration, slowed conduction velocity (connexin 43 lateralization), and fibrotic remodeling in the left atrium of HFpEF compared with control animals. ImCDCevs reversed adverse electrical remodeling (restoration of action potential duration to control levels and reorganization of connexin 43) and reduced AF inducibility (33%). In addition, fibrosis, inflammation, and oxidative stress, which are major pathological AF drivers, were markedly attenuated in imCDCevs-treated animals. Importantly, these effects occurred without changes in blood pressure and diastolic function. CONCLUSIONS: Thus, imCDCevs attenuated adverse remodeling, and prevented AF in a rat model of HFpEF.