Study flow chart.

HTX: heart transplantation, LTX: lung transplantation, ECMO: extracorporeal membrane oxygenation, VAD: ventricular assist device.</p

Scatterplot of lactate and base excess levels at admission on ICU after cardiac surgery.

1st group: Lactate ≤3.9mmol/l and BE > -6.7 (n = 887): r = -0.1, p = 0.002, 95%-CI -0.17 to –0.04 2nd group: Lactate ≤3.9mmol/l and BE ≤ -6.7 (n = 28): r = -0.06, p = 0.78, 95%-CI -0.42 to 0.32 3rd group: Lactate >3.9mmol/l and BE > -6.7 (n = 96): r = -0.06, p = 0.58, 95%-CI -0.27 to 0.15. 4th group: Lactate >3.9mmol/l and BE ≤ -6.7 (n = 47): r = -0.36, p = -0.01, 95%-CI -0.59 to -0.08 Overall correlation (n = 1058): r = -0.48, p<0.0001, 95%-CI -0.52 to -0.43.</p

Expression of microRNAs in patients with and without aortopathy progression.

Normalized delta Ct values are shown.</p

Univariate and multivariate Cox proportional hazard regression models for patients variables.

Univariate and multivariate Cox proportional hazard regression models for patients variables.</p

MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy

<div><p>MicroRNAs (miRNAs) may serve as elegant tool to improve risk stratification in bicuspid aortic valve (BAV)-associated aortopathy. However, the exact pathogenetic pathway by which miRNAs impact aortopathy progression is unknown. Herewith, we aimed to analyze the association between circulating miRNAs and rare variants of aortopathy-related genes. 63 BAV patients (mean age 47.3±11.3 years, 92% male) with a root dilatation phenotype, who underwent aortic valve+/-proximal aortic surgery at a single institution (mean post-AVR follow-up 10.3±6.9 years) were analyzed. A custom-made HaloPlex HS panel including 20 aortopathy-related genes was used for the genetic testing. miRNAs were extracted from whole blood and miRNA analysis was performed using miRNA-specific assay. Study endpoint was the association between circulating miRNAs and rare genetic variants in the aortopathy gene panel. The study cohort was divided into a subgroup with rare variants vs. a subgroup without rare variants based on the presence of rare variants in the respective genes (i.e., at least one variant present). The genetic analysis yielded n = 6 potentially and likely pathogenic rare variants within the <i>NOTCH1</i> gene as being the most common finding. Univariate analysis between blood miRNAs and <i>NOTCH1</i> variants revealed a significantly lower expression of miR-145 in the subgroup of patients with <i>NOTCH1</i> variants vs. those without <i>NOTCH1</i> variants (i.e., delta Ct 4.95±0.74 vs. delta Ct 5.57±0.78, p = 0.04). Our preliminary data demonstrate a significant association between blood miR-145 expression and the presence of rare <i>NOTCH1</i> variants. This association may be indicative of a specific pathogenetic pathway in the development of genetically-triggered bicuspid aortopathy.</p></div

Patient demographics and perioperative data.

Patient demographics and perioperative data.</p

Hazard ratios with 95% confidence intervals and medians for combinations of lactate and base excess.

Hazard ratios with 95% confidence intervals and medians for combinations of lactate and base excess.</p

Comparison of receiving operating curves (ROC) for prediction ICU-mortality.

Comparison of receiving operating curves (ROC) for prediction of ICU-mortality. Lactate AUROC = 0.79 (95%-CI 0.77–0.82); base excess AUROC = 0.72 (95%-CI 0.69–0.74), p = 0.27.</p

Expression of miR-145 in patients with and without rare <i>NOTCH1</i> variants.

<p>Expression of miR-145 in patients with and without rare <i>NOTCH1</i> variants.</p

Demographics and intraoperative variables.

<p>Demographics and intraoperative variables.</p