Takotsubo syndrome (TTS) is an acute heart failure, typically triggered by high adrenaline during physical or emotional stress. It is distinguished from myocardial infarction (MI) by a characteristic pattern of ventricular basal hypercontractility with hypokinesis of apical segments, and in the absence of culprit coronary occlusion. We aimed to understand whether recently discovered circulating biomarkers miR-16 and miR-26a, which differentiate TTS from MI at presentation, were mechanistically involved in the pathophysiology of TTS. miR-16 and miR-26a were co-overexpressed in rats with AAV and TTS induced with an adrenaline bolus. Untreated isolated rat cardiomyocytes were transfected with pre-/anti-miRs and functionally assessed. Ventricular basal hypercontraction and apical depression were accentuated in miR-transfected animals after induction of TTS. In vitro miR-16 and/or miR-26a overexpression in isolated apical (but not basal), cardiomyocytes produced strong depression of contraction, with loss of adrenaline sensitivity. They also enhanced the initial positive inotropic effect of adrenaline in basal cells. Decreased contractility after TTS-miRs was reproduced in non-failing human apical cardiomyocytes. Bioinformatic profiling of miR targets, followed by expression assays and functional experiments, identified reductions of CACNB1 (L-type calcium channel Ca_vβ subunit), RGS4 (regulator of G-protein signalling 4), and G-protein subunit Gβ (GNB1) as underlying these effects. miR-16 and miR-26a sensitize the heart to TTS-like changes produced by adrenaline. Since these miRs have been associated with anxiety and depression, they could provide a mechanism whereby priming of the heart by previous stress causes an increased likelihood of TTS in the future.

This study aimed to investigate the association of circulating biomarkers with echocardiographic parameters of atrial remodelling and their potential for predicting atrial fibrillation (AF). In patients with and without AF (n = 21 and n = 60) the following serum biomarkers were determined: soluble ST2 (sST2), Galectin−3 (Gal-3), N-terminal pro-brain natriuretic peptide (NT-proBNP), microRNA (miR)−21, −29a, −133a, −146b and −328. Comprehensive transthoracic echocardiography was performed in all participants. Biomarkers were significantly altered in patients with AF. The echocardiographic parameter septal PA-TDI, indicating left atrial (LA) remodelling, correlated with concentrations of sST2 (r = 0.249, p = 0.048), miR−21 (r = −0.277, p = 0.012), miR−29a (r = −0.269, p = 0.015), miR−146b (r = −0.319, p = 0.004) and miR−328 (r = −0.296, p = 0.008). In particular, NT-proBNP showed a strong correlation with echocardiographic markers of LA remodelling and dysfunction (septal PA-TDI: r = 0.444, p < 0.001, LAVI/a’: r = 0.457, p = 0.001, SRa: r = 0.581, p < 0.001). Multivariate Cox regressions analysis highlighted miR−21 and NT-proBNP as predictive markers for AF (miR−21: hazard ratio (HR) 0.16; 95% confidence interval (CI) 0.04–0.7, p = 0.009; NT-proBNP: HR 1.002 95%CI 1.001–1.004, p = 0.006). Combination of NT-proBNP and miR−21 had the best accuracy to discriminate patients with AF from those without AF (area under the curve (AUC)= 0.843). Our findings indicate that miR−21 and NT-proBNP correlate with echocardiographic parameters of atrial remodeling and predict AF, in particular if combined.

Background MicroRNAs (miRNAs) can regulate gene expression, controlling numerous cellular processes. Dysregulation of miRNA function is linked to various diseases, making them attractive diagnostic and therapeutic targets. Examples include hsa-miR-92a-3p, hsa-miR-126-3p, hsa-miR-143-3p, hsa-miR-145-5p and hsa-miR-204-5p, which are associated with endothelial function. Their prevalence in Sjögren’s disease (SjD) is unknown. We assessed the prevalence of these miRNAs in serum of patients with SjD, correlating levels with cardiovascular risk factors and carotid intima-media thickness (cIMT) to evaluate their utility in risk stratification. Methods 199 patients with SjD and 100 age and sex-matched healthy controls (HC) were included in the study. Five different miRNAs (hsa-miR-92a-3p; hsa-miR-126-3p; hsa-miR143-3p; hsa-miR-145-5p; hsa-miR-204-5p) were analysed by quantitative real-time PCR. The miRNA results were compared with known clinical and disease-related parameters. Results Four miRNAs showed significantly different expressions compared with HC. MiR-92a-3p was upregulated (p=0.025) and miR-126-3p (p=0.044), miR-143-3p (p=0.006) and miR-204-5p (p=0.009) downregulated in SjD compared with HC. The comparison between HC and SjD with/without organ involvement revealed descriptively increased miR-92a-3p levels in patients with SjD with organ involvement (p=0.087). Furthermore, miR-92a-3p levels correlated positively with cIMT as an expression of subclinical atherosclerosis (r=0.148, p=0.04). Conclusion In conclusion, patients with SjD demonstrated differences in their expression of miRNAs linked to regulation of endothelial function. Reduction of specific miRNAs was associated with increased cardiovascular risk, suggesting a potentially protective role for these miRNAs. Furthermore, miR-92a-3p could be helpful for molecular detection of early-stage atherosclerosis and increased cardiovascular risk in SjD.

Background: The diagnostic and prognostic roles of cardiovascular biomarkers in chronic coronary syndrome remain unclear. Methods: Patients undergoing coronary angiography for suspected chronic coronary syndrome were prospectively enrolled (n=2251; median follow‐up 12.6 years). Obstructive coronary artery disease was defined as ≥50% stenosis in ≥1 major epicardial vessel. HsTnT (high‐sensitivity cardiac troponin T), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity C‐reactive protein, interleukin‐6, and copeptin were measured. Receiver operating characteristic analysis and Cox regression with biomarker × treatment interaction testing were performed. Results: Overall, 888 patients (39.4%) had obstructive coronary artery disease. Only hsTnT showed meaningful diagnostic capacity (area under the curve 0.669; risk factor‐weighted clinical likelihood area under the curve 0.663), with incremental benefit inversely proportional to risk factor‐weighted clinical likelihood category (Δ area under the curve: very low 10.4%, low 8.0%, intermediate/high 5.0%). NT‐proBNP was the strongest mortality predictor across optimal medical therapy (hazard ratio [HR], 1.488 [95% CI, 1.288–1.720], P <0.001), percutaneous coronary intervention (HR, 1.220 [95% CI, 1.020–1.458], P =0.029), and coronary artery bypass grafting (HR, 1.220 [95% CI, 1.049–1.420], P =0.010). Interaction analysis validated a data‐derived 150 pg/mL threshold ( P =0.032): below it, mortality was comparably low regardless of revascularization (HR, 0.98 [95% CI, 0.67–1.43], P =0.910); above it, baseline risk was markedly elevated (HR, 5.75 [95% CI, 4.10–8.00], P <0.001) and revascularization associated with 40% mortality reduction, with substantial residual risk (HR, 3.43 [95% CI, 2.70–4.40], P <0.001). Conclusions: HsTnT provides risk factor‐weighted clinical likelihood category‐specific incremental diagnostic value. NT‐proBNP is a universal prognostic marker identifying patients with distinct revascularization‐associated mortality reduction driven by differential baseline risk. Registration: URL: https://clinicaltrials.gov/study/NCT00497887 ; Unique Identifier: NCT00497887.