Differential microRNA expression in atrial vs. ventricular functional tricuspid regurgitation. New insights into TR pathophysiology

Abstract Background Functional tricuspid regurgitation (FTR) is associated with poor cardiovascular outcomes. Different pathophysiologic process can lead to the onset and progression of tricuspid valve disease. While atrial FTR (A-FTR) is a recently defined phenotype associated with permanent atrial fibrillation, ventricular FTR (V-FTR) has classically been related to leaflet tethering in the context of RV remodelling due to pulmonary hypertension. Although the correct identification of both phenotypes carry important therapeutic and prognostic implications, A-FTR and V-FTR overlap in a significant number of patients. Purpose The present work study aims to study the differential expression of serum miRNAs in A-FTR vs V-FTR Methods Consecutive patients with severe A-FTR and V-FTR evaluated in the Heart Valve Clinic were prospectively recruited. Patients with non-valvular permanent atrial fibrillation without TR undergoing anticoagulant therapy unit were prospectively recruited as a control group. The experimental design included a first screening phase in 16 subjects ((8 A-FTR and 8 AF controls) to identify candidate miRNAs differentially expressed in a miRNA qPCR panel containing 192 specific miRNAs, and a second validation phase in which selected miRNAs were screened for further validation by qRT-PCR in 118 additional patients (40 A-FTR, 37 V-FTR and 41 controls). Results The initial screening revealed 16 differentially expressed miRNAs in atrial FTR vs. AF subjets matched by age, gender and atrial dimensions (figure 1). Table 1 demonstrates differential miRNA expression in atrial and ventricular TR compared to controls in the validation phase (n=118). Among all the miRNAs, miR-152-3p, miR 22-3p, miR-324-3p and miR-29c-3p were differentially expressed in the A-FTR compared to V-FTR (p<0.05 for both). A-FTR exhibited significantly different levels of expression of miR-29b-3p, miR-152-3p, miR-30e-5p, miR-186-5p and miR-126-5p (p<0.05), whereas V-FTR expressed differentially miR-15a-5p, miR-152-3p, miR-30e-5p and miR-186-5p, miR-22-3p respectively (p<0.05). Conclusions The current study shows for the first time differential miRNA expression in patients with FTR. It further shows a different expression of several miRNA in atrial compared to ventricular FTR. These findings provide needed insights on the pathophysiological pathway of the atrial vs. the ventricular phenotype of FTR, and important implications towards specific therapeutic options.miRNA in A-FTR and V-FTR