Novel miRNAs predict heart failure, mortality in severe FTR patients

Circulating microRNAs (miRNAs) have been observed in patients with severe functional tricuspid regurgitation (FTR), reveals a study presented at ESC 2023.

The investigators, led by Rocio Hinojar Baydes from Ramon and Cajal University Hospital (RCUH) in Madrid, Spain, have also found that several miRNAs are significantly associated with heart failure (HF) and all-cause mortality, independently of right ventricular (RV) dimension and symptomatic status.

“These novel biomarkers may help to identify those patients that benefit from earlier valve interventions,” the investigators said.

To explore the potential role of circulating miRNAs as prognostic biomarkers, Baydes and her team assessed consecutive patients with severe FTR, who underwent a comprehensive clinical protocol. They also recruited those with nonvalvular permanent atrial fibrillation (AF; and no TR) undergoing anticoagulant therapy as a control group.

In the screening phase, 16 participants (eight atrial FTR and eight AF controls) were included to identify candidate miRNAs differentially expressed in a qPCR panel containing 192 specific miRNAs. In the validation phase, the investigators screened selected miRNAs for further validation by qRT-PCR in 118 additional patients (77 FTR and 41 controls).

Based on the initial screening, Baydes and colleagues found 16 differentially expressed miRNAs in atrial FTR patients relative to those with AF matched by age, gender, and atrial dimensions. Subsequently, they validated the candidate miRNAs in 188 individuals. [Baydes, et al, ESC 2023]

Twenty-five patients (32 percent) reached the combined endpoint of hospital admission due to HF and all-cause mortality over a median follow-up of 20.4 months. Those who had events demonstrated different levels of miR-15a-5p, miR-152-3p, miR101-3p, miR-92a-3p, miR-363-3p, miR-324-3p and miR-22-3p (p<0.05 for all).

Predictors of events

Baydes and her team then stratified the patients based on the high or low relative expression of selected miRNAs (below or above the median value). Those with low relative expression of miR-15a-5p, miR-92a-3p, miR101-3p, and miR-363-3p, miR-324-3p, and miR-22-3p were more likely to experience cardiovascular events (log rank test for all, p<0.01).

Multivariate analysis further revealed that the level of miR-15a-5p (hazard ratio [HR], 3.97, 95 percent confidence interval [CI], 1.58-9.96), miR-92a-3p (HR, 2.64,95 percent CI, 1.13-6.13), and miR-363-3p (HR, 2.41, 95 percent CI, 1.04-5.60) predicted events regardless of New York Heart Association functional class and RV dimensions (p<0.05 for all).

“FTR is associated with high risk of cardiovascular events, in particular HF, but optimal timing for intervention remains controversial,” the investigators said. “Surgery is often performed late mainly because symptoms might go unnoticed until advance stage of the disease.”

In a related study, Luis Rincon and colleagues from RCUH in Spain showed the capability of several miRNAs to independently predict long-term hospitalization for HF and cardiovascular death in patients following an acute myocardial infarction. Based on an independent profiling-validation process, circulating miRNAs such as miR‐210‐3p, miR‐221‐3p, and miR‐23a‐3p demonstrated a robust prognostic value. [ESC Heart Fail 2022;9:3367-3379]