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Background: Active smoking is the main risk factor for COPD. Here, epigenetic mechanisms may play a role, since cigarette smoking is associated with differential DNA methylation in whole blood. So far, it is unclear whether epigenetics also play a role in subjects with COPD who never smoked. Therefore, we aimed to identify differential DNA methylation associated with lung function in never smokers.Methods: We determined epigenome-wide DNA methylation levels of 396,243 CpG-sites (Illumina 450 K) in blood of never smokers in four independent cohorts, LifeLines COPD&C (N = 903), LifeLines DEEP (N = 166), Rotterdam Study (RS)-III (N = 150) and RS-BIOS (N = 206). We meta-analyzed the cohort-specific methylation results to identify differentially methylated CpG-sites with FEV1/FVC. Expression Quantitative Trait Methylation (eQTM) analysis was performed in the Biobank-based Integrative Omics Studies (BIOS).Results: A total of 36 CpG-sites were associated with FEV1/FVC in never smokers at p-value< 0.0001, but the meta-analysis did not reveal any epigenome-wide significant CpG-sites. Of interest, 35 of these 36 CpG-sites have not been associated with lung function before in studies including subjects irrespective of smoking history. Among the top hits were cg10012512, cg02885771, annotated to the gene LTV1 Ribosome Biogenesis factor (LTV1), and cg25105536, annotated to Kelch Like Family Member 32 (KLHL32). Moreover, a total of 11 eQTMS were identified.Conclusions: With the identification of 35 CpG-sites that are unique for never smokers, our study shows that DNA methylation is also associated with FEV1/FVC in subjects that never smoked and therefore not merely related to smoking. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common long-term arrhythmia in adults. Rhythm control in patients with AF involves efforts to restore and maintain sinus rhythm and is accomplished by medication, catheter ablation, or electrical cardioversion. Amiodarone represents one of the most commonly used antiarrhythmic medications. Prolonged use of amiodarone can lead to many side effects. One of the most severe side effects is drug-induced long QT syndrome (LQTS), which can cause malignant arrhythmias and sudden cardiac death. We presented a case of a 52-year-old male who was admitted to the Coronary Unit due to first diagnosed AF with a rapid ventricular response. After amiodarone infusion was administrated the patient lost consciousness and the monitor displayed torsades de pointes (TdP) ventricular tachycardia with rapid conversion to ventricular fibrillation (VF). Cardiac resuscitation with two direct current (DC) shocks was performed. The patient was stabilized, and restoration of sinus rhythm with significant QT prolongation on the ECG was noted. This is a rare case of short-term amiodarone administration causing LQTS, TdP, and VF. The findings or observations emphasize the significance of diligent ECG monitoring during amiodarone treatment., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Stojanovic et al.)

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2×)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted., (© The Author(s) 2019. Published by Oxford University Press.)

Introduction: The aim of this study was to evaluate oxidative stress markers (OSM) and catecholamine levels in patients with dilated cardiomyopathy (DCM) before and after cardiopulmonary exercise testing, and to investigate the association between changes in these markers and the New York Heart Association classification (NYHA) and left ventricular ejection fraction (LVEF) in these patients., Methods: We evaluated 74 patients with DCM and 80 control subjects without DCM. Patients were grouped according to NYHA stages I/II or III/IV. Eligible participants were considered to be those with LVEF values <45%. The OSM analysed included superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPX). The catecholamines analysed included adrenaline, noradrenaline, and dopamine. Vitamin C was also evaluated. All values were obtained before and after cardiopulmonary exercise testing., Results: There was a significant increase in GR, adrenaline, and noradrenaline after testing in the DCM patients. A significant difference between controls and patients in CAT and evaluated catecholamines was observed after testing. A significant increase in GR, GPX, adrenaline, and noradrenaline for patients in NYHA I/ II, and in CAT, GR, adrenaline, noradrenaline, and dopamine for patients in NYHA III/IV, was found between the different times of observation. LVEF before testing showed a significant positive correlation with GPX, and a negative correlation with noradrenaline and adrenaline. After testing a significant negative correlation was found with SOD and GR., Conclusions: The results of our study demonstrate the complexity of the neurohumoral mechanisms and physiological alterations in the failing heart in DCM patients. Further studies are needed, including other biomarkers and larger samples of patients, in order to improve our understanding of the aetiopathogenesis of DCM development and progression.

Background and Aim of the Study: Risk stratification is particularly complex in asymptomatic patients with significant aortic stenosis (AS). The study aim was to assess which hemodynamic/Doppler-echocardiographic parameter best predicts mortality in asymptomatic patients with severe AS and a normal left ventricular ejection fraction (LVEF)., Methods: This prospective study included 128 consecutive asymptomatic patients (75 males, 53 females; mean age 66.35 ± 10.51 years) with severe AS (aortic valve area (AVA) ± 1.0 cm2) and a normal LVEF (55%). The patients were followed up for 47 months (median 35.5 months, IQR 7 months). Clinical data at follow up were obtained from all patients by either direct examination or telephone interview., Results: During the follow up, 55 patients (43.0%) underwent aortic valve replacement (AVR) surgery due to AS-related symptoms. Of the 12 patients that died (9.4%), eight deaths occurred before surgery (four patients refused operation), and one patient died after surgery due to postoperative infection. Those patients who died had a significantly higher valvulo-arterial impedance (Z(va)) (7.81 versus 4.86 mmHg x ml/m2, p < 0.001), a higher N-terminal pro-brain natriuretic peptide (NT-proBNP) level (1708.5 versus 376.5 pg/ml, p = 0.003) and a lower AVA (0.65 versus 0.86 cm2, p = 0.002), but there were no differences in LVEF, P(mean) or age between the groups (69.68% versus 72.24%, p = 0.206; 44.95 versus 41.75 mmHg; and 69 versus 66 years, p = 0.332, respectively). When parameters that were predictors of mortality according to univariate analysis were further analyzed with Cox multivariate analysis, Z(va) was found to be the best independent predictor (B = 0.460, HR = 1.584, 95% CI = 1.064-2.359, p = 0.024). A Z(va) value of 6.1 mmHg x ml/m2 was identified as the best (cut-off) predictive value for the occurrence of death, with a sensitivity 61.1% and a specificity 86.0%., Conclusion: Z(va) is the best mortality predictor in asymptomatic patients with severe AS and a normal LVEF. Future studies are required to focus further on predictors of outcome, the aim being to achieve an optimal selection of asymptomatic patients considered to be at risk and who would benefit from early AVR.

Coronary microcirculatory function after primary percutaneous coronary intervention (pPCI) in patients with acute myocardial infarction is important determinant of infarct size (IS). Our aim was to investigate the utility of coronary flow reserve (CFR) and diastolic deceleration time (DDT) of the infarct artery (IRA) assessed by transthoracic Doppler echocardiography after pPCI for final IS prediction. In 59 patients, on the 2nd day after pPCI for acute anterior myocardial infarction, transthoracic Doppler analysis of IRA blood flow was done including measurements of CFR, baseline DDT and DDT during adenosine infusion (DDT adeno). Killip class, myocardial blush grade, resolution of ST segment elevation, peak creatine kinase-myocardial band and conventional echocardiographic parameters were determined. Single-photon emission computed tomography myocardial perfusion imaging was done 6 weeks later to define final IS (percentage of myocardium with fixed perfusion abnormality). IS significantly correlated with CFR (r = -0.686, p < 0.01), DDT (r = -0.727, p < 0.01), and DDT adeno (r = -0.780, p < 0.01). CFR and DDT adeno in multivariate analysis remained independent IS predictors after adjustment for other covariates and offered incremental prognostic value in models based on conventional clinical, angiographic, electrocardiographic and enzymatic variables. In predicting large infarction (IS > 20 %), the best cut-off for CFR was <1.73 (sensitivity 65 %, specificity 96 %) and for DDT adeno ≤720 ms (sensitivity 81 %, specificity 96 %). CFR and DDT during adenosine are independent and powerful early predictors of final IS offering incremental prognostic information over conventional parameters of myocardial and microvascular damage and tissue reperfusion.

Background: Patients in chronic phase of myocardial infarction (MI) have decreased coronary flow reserve (CFR) in infarct related artery (IRA) that is proportional to the extent of microvascular/myocardial damage. We proposed a novel model for the assessment of microvascular damage and infarct size using Doppler echocardiography evaluation of CFRs of the IRA (LAD) and reference artery (RCA)., Methods: Our study included 34 consecutive patients (28 men, mean age 50 ± 11 years) with first anterior STEMI and single vessel disease successfully treated with primary PCI. All patients underwent SPECT MPI for the assessment of infarct size (expressed as a percentage of myocardium with fixed perfusion abnormalities) and CFR evaluation of LAD and RCA. CFR derived percentage of microvascular damage (CFR PMD) was calculated as: CFR PMD=(CFR RCA-CFR LAD)/(CFR RCA-1)×100 (%)., Results: CFR PMD correlated significantly with all parameters evaluating the severity of myocardial damage including: peak CK activity (r=0.632, p<0.001), WMSI (r=0.857, p<0.001), ejection fraction (r=-0.820, p<0.001), left ventricular end diastolic (r=0.757, p<0.001) and end systolic volume (r=0.794, p<0.001). Most importantly, CFR PMD (22 ± 17%) correlated significantly with infarct size by SPECT MPI (21 ± 17%) (r=0.874, p<0.001)., Conclusions: CFR PMD derived from the proposed model was significantly related to echocardiographic and enzymatic parameters of infarct size, as well as to myocardial damage assessed by SPECT MPI in patients with successfully reperfused first anterior STEMI., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Evaluation of coronary pressures during angioplasty may functionally quantify collateral circulation. The aim of the study was to evaluate the relation between the amount of collateral circulation and development of myocardial ischemia during balloon occlusion, anatomic degree of collaterals, and functional improvement of myocardium. Study population consisted of 31 pts (mean age 53 +/- 7 years; 25 male) with previous myocardial infarction and significant one-vessel stenosis undergoing angioplasty. Collateral circulation was calculated as the ratio between distal coronary pressure during balloon occlusion (P(w)) and aortic pressure (P(a)). Angiographic appearance of collaterals was evaluated by Rentrop classification. Patients were evaluated by echo for functional improvement of myocardium in the follow-up period. Mean P(w)/P(a) was 0.24 +/- 0.10 (range of 0.07-0.51). Rentrop grade 0 of collaterals was present in 16 patients (52%), grade 1 in11 patients (35%), and grade 2 in 4 patients (13%). A mild correlation between angio and hemodynamic evaluation of collaterals was observed (r = 0.38, P = 0.035). In patients without ECG changes during angioplasty (21 pts, 68%), P(w)/P(a) was significantly higher in comparison to patients with ECG changes (0.28 +/- 0.09 vs. 0.15 +/- 0.06, P < 0.001; area under the curve 0.93). In patients with myocardial functional improvement during follow-up (21 pts, 68%), P(w)/P(a) was significantly higher than in the patients without echo improvement (0.26 +/- 0.10 vs. 0.18 +/- 0.08, P = 0.035). The amount of recruitable collaterals is not negligible even in the patients with no angio visible collaterals. Low values of P(w)/P(a) are associated with ECG changes during balloon occlusion. Higher P(w)/P(a) was associated with better functional improvement of myocardium.