Chronic atrial fibrillation (AF) is associated with an increased frequency of embolic events and negative impact on cardiac function, and therefore, an increased morbidity and mortality risk in patients with rheumatic mitral valve stenosis (RMS). In the present study, the clinical, 2-D and Doppler echocardiographic, and left-and right-heart hemodynamic data were evaluated for 92 patients (68 women) with RMS and AF and compared with data from 118 patients (88 women) with RMS with sinus rhythm. The clinical, echocardiographic, and hemodynamic evaluations were performed within 1 to 7 days of each other. Patients with AF were older (45.7+/-13.4 vs 38.6+/-12.0 years, p < 0.01) and had a longer symptomatic period (108.2+/-117.9 vs 50.6+/-53.1 months, p < 0.01) compared with those with sinus rhythm. Most of the patients with AF were in NYHA functional capacity 3-4 (74% vs 19%), whereas most of the patients with sinus rhythm were in NYHA functional capacity 2. Patients with AF had a higher mitral valve score based on morphologic features ranging from 4 to 16 depending on the severity of disease (8.3+/-2.1 vs 6.5+/-1.9, p < 0.01) and greater left ventricular end-diastolic diameter (LVEDD) (52.3+/-8.7 vs 47.7+/-8.7 mm, p < 0.02), and end-systolic diameter (LVESD) (34.4+/-7.5 vs 30.9+/-7.5 mm, p < 0.01). Organic tricuspid valve involvement was diagnosed more frequently in patients with AF (61% vs 32%, p < 0.01). Mild mitral regurgitation was also more frequent in patients with AF (71%vs 51%, p < 0.03). The mitral valve area was similar in patients with and without AF (1.30+/-0.39 vs 1.39+/-0.41 cm2, p > 0.05). Mean diastolic mitral valve gradient and pulmonary artery pressure did not differ in patients with and without AF. Right atrial pressures were higher in patients with AF (7.6+/-3.3 vs 6.3+/-1.9 mm Hg, p < 0.02). The authors suggest that (1) AF occurred in older patients, who had a longer disease process and more serious symptoms; (2) hemodynamic derangements (mitral valve gradient, pulmonary artery pressure) did not differ in patients with and without AF; (3) greater mitral valve score, more tricuspid valve involvement, higher LVEDD, which are suggestive of greater rheumatic activity process were more frequently seen in patients with AF than in those without AF. These findings support the opinion that AF is a marker of widespread rheumatic damage in patients with RMS.
CUMYL-4CN-BINACA(1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3-carboxamide) is a recently introduced indazole-3-carboxamide-type synthetic cannabinoid (SC) that was detected in herbal incense seized by of the Council of Forensic Medicine, Istanbul Narcotics Department, in May 2016 in Turkey. Recently introduced SCs are not detected in routine toxicological analysis; therefore, analytical methods to measure these compounds are in demand. The present study aims to identify urinary marker metabolites of CUMYL-4CN-BINACA by investigating its metabolism in human liver microsomes and to confirm the results in authentic urine samples (n = 80). In this study, 5 μM CUMYL-4CN-BINACA was incubated with human liver microsomes (HLMs) for up to 3 hours, and metabolites were identified using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Less than 21% of the CUMYL-4CN-BINACA parent compound remained after 3 hours of incubation. We identified 18 metabolites that were formed via monohydroxylation, dealkylation, oxidative decyanation to aldehyde, alcohol, and carboxylic acid formation, glucuronidation or reaction combinations. CUMYL-4CN-BINACA N-butanoic acid (M16) was found to be major metabolite in HLMs. In urine samples CUMYL-4CN-BINACA was not detected; CUMYL-4CN-BINACA N-butanoic acid (M16) was major metabolite after β-glucuronidase hydrolysis. Based on these findings, we recommend using M16 (CUMYL-4CN-BINACA N-butanoic acid), M8 and M11 (hydroxylcumyl CUMYL-4CN-BINACA) as urinary marker metabolites to confirm CUMYL-4CN-BINACA intake.
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