Circulating microRNA changes in heart failure patients treated with cardiac resynchronization therapy: responders vs. non‐responders

Abstract

AimsMicroRNAs (miRNAs) play an important role in the pathogenesis of structural alterations of the failing heart through their ability to regulate negatively the expression levels of genes that govern the process of adaptive and maladaptive cardiac remodelling. We studied whether LV reverse remodelling after CRT was associated with changes of circulating miRNAs in patients with heart failure (HF) and dyssynchrony. Methods and resultsA prospective, non-randomized self-control trial was performed in 81 patients with HF eligible for CRT. At baseline, to select the HF miRNA profile, we evaluated the expression of 84 miRNAs (implicated in the pathogenesis of structural alterations of the failing heart) in three groups of patients: healthy subjects (healthy group, n ¼ 15); patients with HF (HF group, n ¼ 81); and patients without HF matched for age, sex, and concomitant disease with HF patients (control group, n ¼ 60). At 12 months, the selected miRNA profile was evaluated in plasma from responder (n ¼ 55) and non-responder HF patients (n ¼ 26) to CRT. In the test cohort, the HF patients were characterized by lower expression of 48 miRNAs (all P , 0.04) as compared with healthy subjects. In the validation cohort, the HF patients were characterized by lower expression of 24 miRNAs (all P , 0.03) as compared with control patients. At 12 months, 55 patients (68%) were considered responders and 26 non-responders to CRT (32%). Responders showed an increase in expression of 19 miRNAs (all P , 0.03) compared with baseline expression, whereas in the non-responders we observed an increase of six miRNAs (all P , 0.05) compared with baseline expression. At follow-up, miRNAs were differentially expressed between responders and non-responders. The responders were characterized by higher expression of five miRNAs (miRNA-26b-5p, miRNA-145-5p, miRNA-92a-3p, miRNA-30e-5p, and miRNA-29a-3p; P , 0.01 for all) as compared with non-responders. ConclusionsIn responders, reverse remodelling is associated with favourable changes in miRNAs that regulate cardiac fibrosis, apoptosis, and hypertrophy.--

Local microRNA‐133a downregulation is associated with hypertrophy in the dyssynchronous heart

“…COL1A1 is not the only factor that does not show local differences in expression in the dyssynchronous heart and that does not recover upon CRT. Studies have shown that, in hearts with LBBB and heart failure, a number of proteins and genes behave similarly 6, 26. The incomplete recovery upon CRT may simply indicate that conditions during CRT are still inferior to those with an intact ventricular conduction system.…”

microRNAs in cardiovascular disease – clinical application

“…Analogous to cT, NT-proBNP has a high sensitivity but brings along a considerable false-positive rate, which illustrates the usefulness of novel HF biomarkers. Five miRNAs down-regulated in HF patients were inversely correlated with NT-proBNP and directly correlated with EF [92]. Receiver operating characteristics (ROC) analysis revealed strong AUC values between 0.84 and 0.91 for predicting the diagnosis of HF, suggesting these miRNAs as strong circulating biomarkers for HF [92].…”

“…For example, a set of 24 miRNAs was significantly down-regulated in a group of HF patients compared with healthy controls [92]. Important from a clinical point of view is the diagnostic power of miRNAs as potential novel circulating biomarkers for HF in terms of sensitivity and specificity.…”

“…Five miRNAs down-regulated in HF patients were inversely correlated with NT-proBNP and directly correlated with EF [92]. Receiver operating characteristics (ROC) analysis revealed strong AUC values between 0.84 and 0.91 for predicting the diagnosis of HF, suggesting these miRNAs as strong circulating biomarkers for HF [92]. In an interesting study, Goren and co-workers performed a screening of circulating miRNAs in patients with HF and identified a set of four circulating miRNAs [93].…”

Biological Markers to Predict Cardiac Resynchronization Therapy Effect

“…5, 15 First, reductions in the plasma levels of natriuretic peptides appear to be a short-term effect occurring within the first 3 months after CRT. Reduction of plasma levels of these markers supposes a beneficial hemodynamic effect of reduced volume overload and pressures in the cardiac chambers.…”