The Usefulness of Magnetic Resonance Imaging of the Cardiovascular System in the Diagnostic Work-Up of Patients With Turner Syndrome.

Cardiovascular defects occur in 50% of patients with Turner syndrome (TS). The aim of the study was to estimate the usefulness of cardiac magnetic resonance imaging (CMR) and magnetic resonance angiography (angio-MR) as diagnostics in children and adolescents with TS. Forty-one females with TS, aged 13.9 ± 2.2 years, were studied. CMR was performed in 39 patients and angio-MR in 36. Echocardiography was performed in all patients. The most frequent anomalies diagnosed on CMR and angio-MR were as follows: elongation of the ascending aorta (AA) and aortic arch, present in 16 patients (45.7%), a bicuspid aortic valve (BAV), present in 16 patients (41.0%), and partial anomalous pulmonary venous return (PAPVR), present in six patients (17.1%). Aortic dilatation (Z-score > 2) was mostly seen at the sinotubular junction (STJ) (15 patients; 42.8%), the AA (15 patients; 42.8%), the thoracoabdominal aorta at the level of a diaphragm (15 patients; 42.8%), and the transverse segment (14 patients; 40.0%). An aortic size index (ASI) above 2.0 cm/m2 was present in six patients (17.1%) and above 2.5 cm/m2 in three patients (8.6%). The left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and stroke volume (SV) were diminished (Z-score < -2) in 10 (25.6%), 9 (23.1%), and 8 patients (20.5%), respectively. A webbed neck was correlated with the presence of vascular anomalies (p = 0.006). The age and body mass index (BMI) were correlated with the diameter of the aorta. Patients with BAV had a greater aortic diameter at the ascending aorta (AA) segment (p = 0.026) than other patients. ASI was correlated with aortic diameter and descending aortic diameter (AD/DD) ratio (p = 0.002; r = 0.49). There was a significant correlation between the right ventricular (p = 0.002, r = 0.46) and aortic diameters at the STJ segment (p = 0.0047, r = 0.48), as measured by echocardiography and CMR. Magnetic resonance can identify cardiovascular anomalies, dilatation of the aorta, pericardial fluid, and functional impairment of the ventricles not detected by echocardiography. BMI, age, BAV, and elongation of the AA influence aortic dilatation. The ASI and AD/DD ratio are important markers of aortic dilatation. The performed diagnostics did not indicate a negative influence of GH treatment on the cardiovascular system.

Analysis of retinol, α-tocopherol, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in plasma of patients with cardiovascular disease by HPLC-MS/MS method.

Fat-soluble vitamins play a pivotal role in the progression of atherosclerosis and the development of cardiovascular disease. Therefore, plasma monitoring of their concentrations may be useful in the diagnosis of these disorders as well as in the process of treatment. The study aimed to develop and validate an HPLC-MS/MS method for determination of retinol, α-tocopherol, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in plasma of patients with cardiovascular disease. The analytes were separated on an HPLC Kinetex F5 column via gradient elution with water and methanol, both containing 0.1% (v/v) formic acid. Detection of the analytes was performed on a triple-quadrupole MS with multiple reaction monitoring via electrospray ionization. The analytes were isolated from plasma samples with liquid-liquid extraction using hexane. Linearity of the analyte calibration curves was confirmed in the ranges 0.02-2 µg/mL for retinol, 0.5-20 µg/mL for α-tocopherol, 5-100 ng/mL for 25-hydroxyvitamin D2 and 2-100 ng/mL for 25-hydroxyvitamin D3. Intra- and inter-assay precision and accuracy of the method were satisfactory. Short- and long-term stabilities of the analytes were determined. The HPLC-MS/MS method was applied for the determination of the above fat-soluble vitamin concentrations in patient plasma as potential markers of the cardiovascular disease progression.

Influence of genetic co-factors on the population pharmacokinetic model for clopidogrel and its active thiol metabolite.

PURPOSE: A high interindividual variability is observed in the pharmacokinetics of clopidogrel, a widely used antiplatelet drug. In the present study, a joint parent-metabolite population pharmacokinetic model was developed to adequately describe observed concentrations of clopidogrel and its active thiol metabolite (H4). METHODS: The study included 63 patients undergoing elective coronarography or percutaneous coronary intervention. The population pharmacokinetic model was developed in the NONMEM 7.3 software, and first-order conditional estimation method with interaction was applied. Also, the influence of covariates was evaluated (age, weight, body mass index (BMI), obesity defined as BMI ≥ 30 kg/m2, sex, diabetes mellitus, co-administration of PPI or statins, presence of CYP2C19*2, CYP2C19*17, CYP3A4*1G alleles, and ABCB1 3435 TT genotype). RESULTS: It was found that the only significant covariate was the presence of CYP2C19*2 allele, which had an impact on lower conversion of clopidogrel to H4. As a result, predicted area under the time-concentration curve values was lower in carriers of this allele, with median 5.94 ng h/ml (interquartile range 3.92-12.51 [ng∙h/ml]) vs. 12.70 ng h/ml in non-carriers (interquartile range, 7.00-19.39 [ng∙h/ml]), respectively (p = 0.004). CONCLUSIONS: Developed model predicts that the only significant covariate influencing the observed concentrations and therefore the exposure to the active H4 metabolite is the presence of CYP2C19*2 allele.

Determinants of high on-treatment platelet reactivity and agreement between VerifyNow and Multiplate assays.

Dual antiplatelet therapy with clopidogrel is a regimen used before and after drug-eluting stent (DES) implantation. Point-of-care platelet reactivity assays are easy-to-use methods to determine adequate response to the drug. The aim of this study was a comparison of the two platelet reactivity assays: Multiplate® and VerifyNow® and an identification of factors potentially influencing the results of these tests, including common genetic polymorphisms. The study included 39 patients receiving 75 mg clopidogrel daily before angioplasty with DES implantation. Platelet reactivity was measured with Multiplate and P2Y12 VerifyNow assays. Genetic polymorphisms of CYP2C19*2, ABCB1 3435C > T, and CYP3A4*1G were determined with PCR-RFLP method and CYP2C19*17 was determined by means of an allele-specific PCR. Agreement between Multiplate and VerifyNow assays was poor (Cohen's κ = 0.056, p = .273). Hematocrit significantly negatively correlated with VerifyNow assayed platelet reactivity (r = -.487, p = .002). Female sex was significantly associated with higher VerifyNow assay results after adjustment to hematocrit (253.2 ± 47.6 PRU vs. 195.9 ± 56.9 PRU, p = .013) and the prevalence of high-on-treatment platelet reactivity (OR: 8.50; 95% CI 1.13-77.60, p = .024). Reactivity measured with Multiplate was lower in women (82.3 vs. 175.6 AU·min, p = .037) and in patients who received calcium channel blockers (74.7 vs. 191.7 AU·min, p = .002). None of the studied polymorphisms significantly influenced platelet aggregation measurements. In conclusion, different aspects modify between-patient variability of the Multiplate and VerifyNow assays and agreement between those two assays was poor.