Relaxin-2 exerts many favourable cardiovascular effects in pathological circumstances such as atrial fibrillation (AF) and heart failure, but the mechanisms underlying its actions are not completely understood. Since inflammation and fibrosis are pivotal processes in the pathogenesis of AF, our aim was to study the relationship between relaxin-2 plasma levels in left atrium (LA) and peripheral vein with molecules implicated in fibrosis, inflammation and oxidative stress in AF patients, and to evaluate the anti-fibrotic ability of relaxin-2 in normal human atrial cardiac fibroblasts (NHCF-A). Peripheral vein relaxin-2 plasma levels were higher than LA relaxin-2 plasma levels in men while, in women, peripheral vein relaxin-2 levels were increased compared to men. AF patients with higher levels of relaxin-2 exhibited a reduction in H₂O₂ plasma levels and in mRNA levels of alpha-defensin 3 (DEFA3) and IL-6 in leucocytes from LA plasma. Relaxin-2-in-vitro treatment inhibited NHCF-A migration and decreased mRNA and protein levels of the pro-fibrotic molecule transforming growth factor-β1 (TGF-β1). Our results support an association between relaxin-2 and molecules involved in fibrosis, inflammation and oxidative stress in AF patients, and reinforce an anti-fibrotic protective role of this hormone in NHCF-A; strengthening the relevance of relaxin-2 in AF physiopathology, diagnosis and treatment.

Atrial fibrillation is the most prevalent tachyarrhythmia in clinical practice, with very high cardiovascular morbidity and mortality with a high-cost impact in health systems. Currently, it is one of the main causes of stroke and subsequent heart failure and sudden death. miRNAs mediate in several processes involved in cardiovascular disease, including fibrosis and electrical and structural remodeling. Several studies suggest a key role of miRNAs in the course and maintenance of atrial fibrillation. In our study, we aimed to identify the differential expression of circulating miRNAs and their predictive value as biomarkers of recurrence in atrial fibrillation patients undergoing catheter pulmonary vein ablation. To this effect, 42 atrial fibrillation patients were recruited for catheter ablation. We measured the expression of 84 miRNAs in non-recurrent and recurrent groups (45.2%), both in plasma from peripheral and left atrium blood. Expression analysis showed that miRNA-451a is downregulated in recurrent patients. Receiver operating characteristic curve analysis showed that miR-451a in left atrium plasma could predict atrial fibrillation recurrence after pulmonary vein isolation. In addition, atrial fibrillation recurrence is positively associated with the increment of scar percentage. Our data suggest that miRNA-451a expression plays an important role in AF recurrence by controlling fibrosis and progression.

Cardiac resynchronization therapy represents a therapeutic option for heart failure drug-refractory patients. However, due to the lack of success in 30% of the cases, there is a demand for an in-depth analysis of individual heterogeneity. In this study, we aimed to evaluate the prognostic value of circulating miRNA differences. Responder patients were defined by a composite endpoint of the presence of left ventricular reverse remodelling (a reduction ≥15% in telesystolic volume and an increment ≥10% in left ventricular ejection fraction). Circulating miRNAs signature was analysed at the time of the procedure and at a 6-month follow-up. An expression analysis showed, both at baseline and at follow-up, differences between responders and non-responders. Responders presented lower baseline expressions of miR-499, and at follow-up, downregulation of miR-125b-5p, both associated with a significant improvement in left ventricular ejection fraction. The miRNA profile differences showed a marked sensitivity to distinguish between responders and non-responders. Our data suggest that miRNA differences might contribute to prognostic stratification of patients undergoing cardiac resynchronization therapy and suggest that preimplant cardiac context as well as remodelling response are key to therapeutic success.

This study aims to determine the predictive value of the soluble suppression of tumorigenicity 2 (sST2) biomarker in atrial fibrillation (AF) recurrence. This prospective, observational study included patients with AF referred for electrical cardioversion (ECV) or pulmonary vein isolation (PVI) procedures. Baseline characteristics were collected, and sST2 was determined at baseline and at 3 and 6 months of follow-up. sST2 was determined at baseline in a matched control group. Left atrial voltage mapping was performed in patients undergoing PVI. The sST2 maximal predictive capacity of AF recurrence was at the 3-month FU in the cohort of patients undergoing ECV with respect to 6-month AF recurrence with an AUC of 0.669, a cut-off point of 15,511 pg/mL, a sensitivity of 60.97%, and a specificity of 69.81%. The ROC curve of the sST2 biomarker at baseline and 3 months in the cohort of patients undergoing PVI showed AUCs of 0.539 and 0.490, respectively. The logistic regression model identified the rhythm (AF) and the sST2 biomarker at 3 months as independent factors for recurrence at 6 months in the ECV cohort. In the logistic regression model, sST2 was not an independent factor for recurrence at 6 months of follow-up in the PVI cohort. In patients who underwent ECV, sST2 values at 3 months may provide utility to predict AF recurrence at 6 months of follow-up. In patients who underwent PVI, sST2 had no value in predicting AF recurrence at 6 months of follow-up.

Cardiotoxicity (CDTX) is a critical side effect of many cancer therapies, leading to increased morbidity and mortality if not addressed. Early detection of CDTX is essential, and while echocardiographic measures like global longitudinal strain offer promise in identifying early myocardial dysfunction, the search for reliable biomarkers continues. MicroRNAs (miRNAs) are emerging as important non-coding RNA molecules that regulate gene expression post-transcriptionally, influencing key biological processes such as the cell cycle, apoptosis, and stress responses. In cardiovascular diseases, miRNAs have demonstrated potential as biomarkers due to their stability in circulation and specific expression patterns that reflect pathological changes. Certain miRNAs have been linked to CDTX and hold promise for early detection, prognosis, and therapeutic targeting. These miRNAs not only assist in identifying early cardiac injury, but also offer opportunities for personalized interventions by modulating their expression to influence disease progression. As research advances, integrating miRNA profiling with traditional diagnostic methods could enhance the management of CDTX in cancer patients, paving the way for improved patient outcomes and more tailored therapeutic strategies. Further clinical studies are essential to validate the clinical utility of miRNAs in managing CDTX.

Atrial fibrillation (AF) is the most common arrhythmia worldwide, affecting 1% of the population over 60 years old. The incidence and prevalence of AF are increasing globally, representing a relevant health problem, suggesting that more advanced strategies for predicting risk stage are highly needed. miRNAs mediate several processes involved in AF. Our aim was to identify miRNAs with a prognostic value as biomarkers in patients referred for AF ablation and its association with LVA extent, based on low-voltage area (LVA) maps. In this study, we recruited 44 AF patients referred for catheter ablation. We measured the expression of 84 miRNAs in plasma from peripheral blood in 3 different groups based on LVA extent. Expression analysis showed that miR-486-5p was significantly increased in patients with broader LVA (4-fold, p = 0.0002; 5-fold, p = 0.0001). Receiver operating characteristic curve analysis showed that miR-486-5p expression could predict atrium LVA (AUC, 0.8958; p = 0.0015). Also, miR-486-5p plasma levels were associated with AF-type (AUC, 0.7137; p = 0.0453). In addition, miR-486-5p expression was positively correlated with LVA percentage, left atrial (LA) area, and LA volume (r = 0.322, p = 0.037; r = 0.372, p = 0.015; r = 0.319, p = 0.045, respectively). These findings suggest that miR-486-5p expression might have prognostic significance in LVA extent in patients with AF.