Abstract Objectives. Galectin-3 (gal-3) is a mediator of extracellular matrix metabolism and reflects an ongoing cardiac fibrotic process. The aim of this study was to determine the potential use of gal-3 in evaluating the structural and functional parameters of the right ventricle as determined by echocardiography. Design. Ninety-one patients undergoing routine echocardiography were prospectively enrolled in this monocentric study. Serum samples for gal-3 and aminoterminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 h of echocardiographic examination. Patients were arbitrarily divided into subgroups based on right ventricular function as measured by tricuspid annular plane systolic excursion (TAPSE) and these included TAPSE >24 mm (n = 23); TAPSE 18–24 mm (n = 55); TAPSE ≤17 mm (n = 13); permitting the detailed statistical analysis of derived data. Results. Serum levels of gal-3 in all patients correlated with age (r = 0.36. p < .001), creatinine (r = 0.60, p < .001), NT-proBNP (r = 0.53, p < .001), RA area (r = 0.38, p < .001) and TAPSE (r = −0.3. p < .01). The distribution of echocardiographic indices according to TAPSE subgroups revealed an association between gal-3 and its ability to identify patients with right ventricular failure (RVF) as diagnosed by a TAPSE ≤17 mm (r = 0.04, p < .001). The multivariable logistic regression model with adjusted odds ratio showed the ability of gal-3 to identify RVF when adjusted to age and gender (adjusted odds ratio 3.60, 95% CI 1.055–12.282, p < .05). Conclusion. Gal-3 correlated with echocardiographic indices of RVF and could effectively diagnose these patients. The supplementary use of NT-proBNP strengthened the diagnostic capability of each biomarker. Trial Registration: The ‘Cardiovascular Imaging and Biomarker Analyses’ (CIBER Study), clinicaltrials.gov identifier: NCT03074253. Registered 3/8/2017. https://www.clinicaltrials.gov/ct2/show/NCT03074253

Background This study evaluates the associations between high-sensitivity troponin I and T (hs-TnI/hs-TnT) and the stages of heart failure with preserved ejection fraction (HFpEF)/diastolic dysfunction. Methods Blood samples for biomarker measurements (hs-TnI/hs-TnT/NT-proBNP) were collected within 24 h of routine echocardiographic examination. Patients with left ventricular ejection fraction <50%, right ventricular dysfunction and moderate-to-severe valvular heart disease were excluded. Graduation of diastolic dysfunction was determined according to current guidelines. Results A total of 70 patients were included. Hs-TnT concentrations increased significantly according to the progression of diastolic dysfunction ( P = 0.024). Hs-TnT was able to discriminate patients with diastolic dysfunction grade III (AUC = 0.737; P = 0.013), while NT-proBNP revealed a greater AUC (AUC 0.798; P = 0.002). Concentrations of hs-TnI increased only numerically according to the increasing stages of diastolic dysfunction ( P = 0.353). In multivariable logistic regression models, hs-TnT concentrations > 28 ng/L were associated with diastolic dysfunction grade III (OR = 4.7, P = 0.024), even after adjusting for NT-proBNP. Conclusion Increasing concentrations of hs-TnT may reflect the stages of diastolic dysfunction being assessed by echocardiography, whereas hs-TnI does not show any association with diastolic dysfunction.

Background: The level of Galectin-3 (Gal-3) protein purportedly reflects an ongoing cardiac fibrotic process and has been associated with ventricular remodeling, which is instrumental in the development of heart failure with preserved ejection fraction (HFpEF) syndrome. The aim of this study was to investigate the potential use of Gal-3 in improved characterization of the grades of diastolic dysfunction as defined by echocardiography. Methods: Seventy HFpEF patients undergoing routine echocardiography were prospectively enrolled in the present monocentric study. Blood samples for measurements of Gal-3 and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 hours pre-or post-echocardiographic examination. The classification of patients into subgroups based on diastolic dysfunction grade permitted detailed statistical analyses of the derived data. Results: The Gal-3 serum levels of all patients corresponded to echocardiographic indices, suggesting HFpEF (E/A, P = 0.03 and E/E', P = 0.02). Gal-3 was also associated with progressive diastolic dysfunction, and increased levels corresponded to the course of disease (P = 0.012). Detailed analyses of ROC curves suggested that Gal-3 levels could discriminate patients with grade III diastolic dysfunction (area under the curve [AUC]= 0.770, P = 0.005). Conclusions: Gal-3 demonstrates remarkable effectiveness in the diagnosis of patients suffering from severe grade diastolic dysfunction. Increasing levels of Gal-3 possibly reflect the progressive course of HFpEF, as classified by the echocardiographic grades of diastolic dysfunction.

Background Left atrial function (LAF) plays an interactive role between pulmonary and systemic circulation. Cardiac biomarkers, such as amino-terminal pro-brain natriuretic peptide (NT-proBNP) and troponins, might reflect cardiac function. This study aims to evaluate the association between high sensitivity troponins (hsTn) and left atrial function in patients undergoing cardiac magnetic resonance imaging (cMRI). Methods Patients undergoing cardiac magnetic resonance imaging (cMRI) were enrolled prospectively. Patients with right ventricular dysfunction (<50%) were excluded. Blood samples for measurements of hsTn and NT-proBNP were collected at the time of cMRI. Results Eighty-four patients were included. Median LVEF was 59% (IQR 51–64%). HsTn correlated inversely with LAF within multivariable linear regression models (hsTnI: Beta −0.46; T −4.44; P = 0.0001; hsTnT: Beta −0.29; T −3.06; P = 0.003). High sensitivity troponins increased significantly according to decreasing stages of impaired LAF ( P = 0.0001). High sensitivity troponins discriminated patients with impaired LAF < 55% (hsTnT: AUC = 0.80; P = 0.0001; hsTnI: AUC = 0.74; P = 0.0001) and <45% (hsTnT: AUC = 0.75; P = 0.0001; hsTnI: AUC = 0.73; P = 0.001) and were still significantly associated in multivariable logistic regression models (LAF < 55%: hsTnT: OR = 21.78; P = 0.0001; hsTnI: OR = 5.96; P = 0.009; LAF < 45%: hsTnT: OR = 10.27; P = 0.0001; hsTnI: OR = 12.56; P = 0.001). Conclusions This study demonstrates that hsTn are able to reflect LAF being assessed by cardiac magnetic resonance imaging.

BACKGROUND This study aims to evaluate the association between galectin-3 and left atrial function (LAF) in patients undergoing cMRI. METHODS Patients undergoing cMRI were prospectively enrolled. Right ventricular dysfunction (< 50%) was excluded. Blood samples for biomarker measurements of galectin-3 and NT-proBNP were collected at the time of cMRI examination. RESULTS A total of 84 patients were included. Median LVEF was 59% (IQR 51 - 64%). Galectin-3 was inversely correlated with overall LAF within a multivariable linear regression model (Beta -0.27; T -2.54; p = 0.01). Galectin-3 increased significantly according to the different stages of impaired LAF (p = 0.003) and was able to discriminate both patients with impaired LAF < 55% (AUC = 0.70, p = 0.002) and LAF < 45% (AUC = 0.69, p = 0.004). In multivariable logistic regression models, galectin-3 was still associated with impaired LAF (LAF < 55%: OR = 2.64, p = 0.07; LAF < 45%: OR = 6.65, p = 0.007). CONCLUSIONS This study demonstrates that galectin-3 is able to reflect LAF being assessed by cMRI.

Background. This study evaluates the association between high sensitivity troponin I (hsTnI) and T (hsTnT) and the morphology of coronary artery plaques detected by coronary computed tomography angiography (CCTA) in patients with suspected coronary artery disease (CAD). Methods. Patients undergoing CCTA were prospectively enrolled. CCTA was indicated by a low to intermediate pretest probability for CAD during routine clinical care. Within 24 hours of CCTA examination, peripheral blood samples were taken to measure hsTnI, hsTnT, and N-terminal probrain natriuretic peptide (NT-proBNP). Results. A total of 99 patients were enrolled with 43% without CAD, 9% with noncalcified plaques, 28% with calcified plaques, and 19% with mixed type plaque lesions. Both hsTnI and hsTnT levels were able to discriminate significantly between the groups, especially in the presence of mixed coronary plaques (AUC range: 0.741–0.752; p = 0.0001). In multivariate logistic regression models, hsTnT, but not hsTnI, was still significantly associated with mixed coronary plaque morphology (odds ratio = 8.968; 95% CI 1.999–40.241; p = 0.004). Conclusions. Both hsTnI and hsTnT are able to discriminate between different coronary artery plaques morphologies, whereas hsTnT was significantly associated with mixed coronary plaques in patients with suspected CAD. This trial is registered with NCT03074253 .

Following publication of the original article [1], the authors reported that there was a mistake in the Methods section → Measurements of biomarkers (page 6, line 3): 2000g should read 2500g. So, the correct sentence should be “All samples were obtained by venipuncture into serum monovettes® and centrifuged at 2500g for 10 min at 20 °C.”

Background This study evaluates the association between high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) and coronary calcium concentration (CAC) detected by coronary computed tomography (CCT) and evaluated with the Agatston score in patients with suspected coronary artery disease (CAD). Methods Patients undergoing CCT during routine clinical care were enrolled prospectively. CCT was indicated for patients with a low to intermediate pretest probability for CAD. Within 24 h of CCT examination, peripheral blood samples were taken to measure cardiac biomarkers hs-cTnI and hs-cTnT. Results A total of 76 patients were enrolled including 38% without detectable CAC, 36% with an Agatston score from 1 to 100, 17% from 101 to 400, and 9% with values ≥ 400. hs-cTnI was increasing alongside Agatston score and was able to differentiate between different groups of Agatston scores. Both hs-cTn discriminated values greater than 100 (hs-cTnI, AUC = 0.663; p = 0.032; hs-cTnT, AUC = 0.650; p = 0.048). In univariate and multivariate logistic regression models, hs-cTnT and hs-cTnI were significantly associated with increased Agatston scores. Patients with hs-cTnT ≥ 0.02 µg/l and hs-cTnI ≥ 5.5 ng/l were more likely to reveal values ≥ 400 (hs-cTnT; OR = 13.4; 95% CI 1.545–116.233; p = 0.019; hs-cTnI; OR = 8.8; 95% CI 1.183–65.475; p = 0.034). Conclusion The present study shows that the Agatston score was significantly correlated with hs cardiac troponins, both in univariable and multivariable linear regression models. Hs-cTnI is able to discriminate between different Agatston values. The present results might reveal potential cut-off values for hs cardiac troponins regarding different Agatston values. Trial registration Cardiovascular Imaging and Biomarker Analyses (CIBER), NCT03074253 https://clinicaltrials.gov/ct2/show/record/NCT03074253

Background. This study investigates whether serum levels of galectin-3 may reflect impaired mitral annular plane systolic excursion (MAPSE) in patients undergoing cardiac magnetic resonance imaging (cMRI). Methods. Patients undergoing cMRI during routine clinical care were included prospectively within an all-comers design. Blood samples for biomarker measurements were collected within 24 hours following cMRI. Statistical analyses were performed in all patients and in three subgroups according to MAPSE (MAPSE I: ≥11 mm, MAPSE II: ≥8 mm–<11 mm, and MAPSE III: <8 mm). Patients with right ventricular dysfunction (<50%) were excluded. Results. 84 patients were included in the study. Median LVEF was 59% (IQR 51–64%). Galectin-3 correlated significantly with NT-proBNP (r = 0.42, p = 0.0001). Galectin-3 increased significantly according to the different stages of impaired MAPSE (p = 0.006) and was able to discriminate both patients with impaired MAPSE <11 mm (area under the curve (AUC) = 0.645, p = 0.024) and <8 mm (AUC = 0.733, p = 0.003). Combining galectin-3 with NT-proBNP improved discrimination of MAPSE <8 mm (AUC 0.803, p = 0.0001). In multivariable logistic regression models galectin-3 was still associated with impaired MAPSE (MAPSE < 11 mm: odds ratio (OR) = 3.53, p = 0.018; MAPSE < 8 mm: OR = 3.18, p = 0.06). Conclusions. Galectin-3 reflects MAPSE being assessed by cardiac MRI.

U2OS cells harbor a circadian clock but express only a few rhythmic genes in constant conditions. We identified 3040 binding sites of the circadian regulators BMAL1, CLOCK and CRY1 in the U2OS genome. Most binding sites even in promoters do not correlate with detectable rhythmic transcript levels. Luciferase fusions reveal that the circadian clock supports robust but low amplitude transcription rhythms of representative promoters. However, rhythmic transcription of these potentially clock-controlled genes is masked by non-circadian transcription that overwrites the weaker contribution of the clock in constant conditions. Our data suggest that U2OS cells harbor an intrinsically rather weak circadian oscillator. The oscillator has the potential to regulate a large number of genes. The contribution of circadian versus non-circadian transcription is dependent on the metabolic state of the cell and may determine the apparent complexity of the circadian transcriptome.