DUOX1 Gene Missense Mutation Confers Susceptibility on Type 2 Amiodarone-Induced Thyrotoxicosis.

Possible triggers and genetic markers involved in pathogenesis of amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH) are currently unknown. This study aimed to analyze the association between polymorphisms in the genes involved in thyroid hormones biosynthesis and metabolism. Thirty-nine consecutive patients with confirmed type 2 amiodarone-induced thyrotoxicosis were enrolled; 39 patients on the same therapy for at least 6 months without thyroid pathology were included as a control group. A comparative study was carried out to determine the distribution and genotypes of polymorphic markers of the (Na)-iodide symporter (NIS) genes (rs7250346, C/G substitution), thyroid stimulating hormone receptor (TSHR) (rs1991517, C/G substitution), thyroid peroxidase (TPO) (rs 732609, A/C substitution), DUOX 1-1 (C/T substitution), DUOX 1-2 (G/T substitution), DUOX 1-3 (C/T substitution), glutathione peroxidase 3 (GPX3) (C/T substitution), glutathione peroxidase 4 (GPX4) (C/T substitution). Statistical analysis was performed using Prism (Version 9.0.0 (86)). This study showed that the risk of AIT2 is 3.18 times higher in the G/T of the DUOX1 gene carriers. This study is the first report of genetic markers associated with amiodarone-related adverse events conducted in humans. The obtained results indicate the necessity for a personalized approach to amiodarone administration.

The Profile of Circulating Blood microRNAs in Outpatients with Vulnerable and Stable Atherosclerotic Plaques: Associations with Cardiovascular Risks.

Non-coding RNAs reflect many biological processes in the human body, including athero-sclerosis. In a cardiology outpatient department cohort (N = 83), we aimed to compare the levels of circulating microRNAs in groups with vulnerable plaques (N = 22), stable plaques (N = 23) and plaque-free (N = 17) depending on coronary computed tomography angiography and to evaluate associations of microRNA levels with calculated cardiovascular risks (CVR), based on the SCORE2 (+OP), ACC/AHA, ATP-III and MESA scales. Coronary computed tomography was performed on a 640-slice computed tomography scanner. Relative plasma levels of microRNA were assessed via a real-time polymerase chain reaction. We found significant differences in miR-143-3p levels (p = 0.0046 in plaque-free vs. vulnerable plaque groups) and miR-181b-5p (p = 0.0179 in stable vs. vulnerable plaques groups). Analysis of microRNA associations with CVR did not show significant differences for SCORE2 (+OP) and ATPIII scales. MiR-126-5p and miR-150-5p levels were significantly higher (p < 0.05) in patients with ACC/AHA risk >10% and miR-145-5p had linear relationships with ACC/AHA score (adjusted p = 0.0164). The relative plasma level of miR-195 was higher (p < 0.05) in patients with MESA risk > 7.5% and higher (p < 0.05) in patients with zero coronary calcium index (p = 0.036). A linear relationship with coronary calcium was observed for miR-126-3p (adjusted p = 0.0484). A positive correlation with high coronary calcium levels (> 100 Agatson units) was found for miR-181-5p (p = 0.036). Analyzing the biological pathways of these microRNAs, we suggest that miR-143-3p and miR-181-5p can be potential markers of the atherosclerosis process. Other miRNAs (miR-126-3p, 126-5p, 145-5p, 150-5p, 195-5p) can be considered as potential cardiovascular risk modifiers, but it is necessary to validate our results in a large prospective trial.

Remote Screening for Atrial Fibrillation by a Federal Cardiac Monitoring System in Primary Care Patients in Russia: Results from the Prospective Interventional Multicenter FECAS-AFS Study.

Background: Screening for atrial fibrillation has the potential to significantly reduce cardiovascular morbidity and mortality. However, questions in regard to how to screen, on whom to screen, and the optimal setting of screening remain unanswered. Objective: To assess the applicability of a federal cardiac monitoring for atrial fibrillation (AF) screening and remote heart rhythm monitoring in patients at high cardiovascular risk in a mixed urban and rural population in Russia. Methods: This is a prospective multicenter cohort study including 3249 individuals with high cardiovascular risk (mean age 56 ± 12.8 years) from the larger Moscow region who were screened for AF using a smartphone-case based single-lead ECG monitor over a period of 18 month. The endpoints were considered as number of newly diagnosed AF; mean time to diagnosis; number of patients for the first time assigned to anticoagulation therapy; frequency of adverse events. Results: A trial fibrillation was diagnosed in 126 patients, 36 of them for the first time. The mean time to diagnosis was 3 ± 2 days. Of 36 patients, the CHA2DS2-VASc score was ≥1 in 34 cases, ≥2 in 29 cases. Anticoagulant therapy was first induced in 31 patients. One death in newly diagnosed group and two deaths in chronic group were registered. There were a total of eight hospitalizations: one in newly diagnosed and seven in chronic AF patients. Conclusion: Our results indicate that a Federal AF screening system in patients at high cardiovascular risk by using a smartphone-case based single lead ECG which is supported by centrally located ECG specialist and central data management is feasible and reliable when performed in a mixed urban and rural area. Further studies are needed to evaluate the full potential of this approach.

Noninvasive Assessment of the Fractional Flow Reserve with the CT FFRc 1D Method: Final Results of a Pilot Study.

Background: Until recently, Russia did not utilize noninvasive fractional flow reserve (FFR) assessment. We developed an automated algorithm for noninvasive assessment of FFR based on a one-dimensional (1D) mathematical modeling. Objective: The research aims to evaluate the diagnostic accuracy of this algorithm. Methods: The study enrolled 80 patients: 16 of them underwent 64-slice computed tomography - included retrospectively, 64 - prospectively, with a 640-slice CT scan. Specialists processed CT images and evaluated noninvasive FFR. Ischemia was confirmed if FFR < 0.80 and disproved if FFR ≥ 0.80. The prospective group of patients was hospitalized for invasive FFR assessment as a reference standard. If ischemic, patients underwent stent implantation. In the retrospective group, patients already had invasive FFR values.Statistical analysis was performed using GraphPad Prism 8. We compared two methods using a Bland-Altman plot and per-vessel ROC curve analysis. Considering the abnormality of distribution by the Kolmogorov-Smirnov test, we have used Spearman's rank correlation coefficient. Results: During data processing, three patients of the retrospective and 46 patients of the prospective group were excluded. The sensitivity of our method was 66.67% (95% CI: 46.71-82.03); the specificity was 78.95% (95% CI: 56.67-91.49), p = 0.0052, in the per-vessel analysis. In per-patient analysis, the sensitivity was 69.57% (95% CI: 49.13-84.40); the specificity was 87.50% (95% CI: 52.91-99.36), p = 0.0109. The area under the ROC curve in the per-vessel analysis was 77.52% (95% CI: 66.97-88.08), p < 0.0001. Conclusion: The obtained indices of sensitivity, specificity, PPV, and NPV are, in general, comparable to those in other studies. Moreover, the noninvasive values of FFR yielded a high correlation coefficient with the invasive values. However, the AUC was not high enough, 77.52 (95% CI: 66.97-88.08), p < 0.0001. The discrepancy is probably attributed to the initial data heterogeneity and low statistical power.

One-Dimensional Mathematical Model-Based Automated Assessment of Fractional Flow Reserve in a Patient with Silent Myocardial Ischemia.

BACKGROUND Noninvasive assessment of the fractional flow reserve (FFR) in patients with coronary artery disease plays an important role in determining the need for revascularization. It is particularly relevant for patients with a borderline stenoses and painless myocardial ischemia. Our article describes the first clinical experience in the Russian Federation of using an automated method of noninvasive assessment of the fractional flow reserve (FFRct) with a one-dimensional (1-D) mathematical model in a patient with painless myocardial ischemia. CASE REPORT A 58-year-old male patient who underwent stent implantation in the left circumflex coronary artery (LCX) due to an acute non-ST-elevation posterior myocardial infarction had borderline stenoses of the left anterior descending artery (LAD). After stent implantation, there were no relapse angina symptoms on drug treatment, and according to our examination guideline for patients with borderline stenoses, a treadmill test was performed. The test was positive; therefore, FFR assessment was recommended, with coronary multi-slice CT being performed. The following results were obtained: FFRct LAD - 0.57; FFRct LCX - 0.88. An invasive assessment of FFR was also performed as a reference standard and revealed: FFR LAD - 0.6; FFR LCX - 0.88, and simultaneously a LAD percutaneous coronary intervention (PCI) was performed. Three months later, the patient underwent a stress test, which revealed no evidence of induced ischemia. CONCLUSIONS Our method of noninvasive assessment of FFR has shown encouraging results, but we believe that larger-scale studies are needed to establish it as common clinical practice.