Рабочая группа по диабету, предиабету и сердечно-сосудистым заболеваниям европейского общества кардиологов (ESC) в сотрудничестве с европейской ассоциацией по изучению диабета (EASD).

Background There is a paucity of global data on cardiovascular disease (CVD) prevalence in people with type 2 diabetes (T2D). The primary objective of the CAPTURE study was to estimate the prevalence of established CVD and its management in adults with T2D across 13 countries from five continents. Additional objectives were to further characterize the study sample regarding demographics, clinical parameters and medication usage, with particular reference to blood glucose-lowering agents (GLAs: glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) with demonstrated cardiovascular benefit in randomized intervention trials. Methods Data were collected from adults with T2D managed in primary or specialist care in Australia, China, Japan, Czech Republic, France, Hungary, Italy, Argentina, Brazil, Mexico, Israel, Kingdom of Saudi Arabia, and Turkey in 2019, using standardized methodology. CVD prevalence, weighted by diabetes prevalence in each country, was estimated for the overall CAPTURE sample and participating countries. Country-specific odds ratios for CVD prevalence were further adjusted for relevant demographic and clinical parameters. Results The overall CAPTURE sample included 9823 adults with T2D (n = 4502 from primary care; n = 5321 from specialist care). The overall CAPTURE sample had median (interquartile range) diabetes duration 10.7 years (5.6–17.9 years) and glycated hemoglobin 7.3% (6.6–8.4%) [56 mmol/mol (49–68 mmol/mol)]. Overall weighted CVD and atherosclerotic CVD prevalence estimates were 34.8% (95% confidence interval [CI] 32.7–36.8) and 31.8% (95% CI 29.7–33.8%), respectively. Age, gender, and clinical parameters accounted for some of the between-country variation in CVD prevalence. GLAs with demonstrated cardiovascular benefit were used by 21.9% of participants, which was similar in participants with and without CVD: 21.5% and 22.2%, respectively. Conclusions In 2019, approximately one in three adults with T2D in CAPTURE had diagnosed CVD. The low use of GLAs with demonstrated cardiovascular benefit even in participants with established CVD suggested that most were not managed according to contemporary diabetes and cardiology guidelines. Study registration NCT03786406 (registered on December 20, 2018), NCT03811288 (registered on January 18, 2019).

Background and purpose: Assessing the proarrhythmic potential of compounds during drug development is essential. However, reliable prediction of drug-induced torsades de pointes arrhythmia (TdP) remains elusive. Along with QT interval prolongation, assessment of the short-term variability of the QT interval (STV(QT)) may be a good predictor of TdP. We investigated the relative importance of I Ks and I Kr block in development of TdP together with correlations between QTc interval, QT interval variability and incidence of TdP. Experimental approach: ECGs were recorded from conscious dogs and from anaesthetized rabbits given the I Kr blocker dofetilide (DOF), the I Ks blocker HMR-1556 (HMR) and their combination, intravenously. PQ, RR and QT intervals were measured and QTc and short-term variability of RR and QT intervals calculated. Key results: DOF increased QTc interval by 20% in dogs and 8% in rabbits. HMR increased QTc in dogs by 12 and 1.9% in rabbits. Combination of DOF þ HMR prolonged QTc by 33% in dogs, by 16% in rabbits. DOF or HMR given alone in dogs or HMR given alone in rabbits induced no TdP. Incidence of TdP increased after DOF þ HMR combinations in dogs (63%) and following HMR þ DOF (82%) and DOF þ HMR combinations (71%) in rabbits. STV(QT) markedly increased only after administration of DOF þ HMR combinations in both dogs and rabbits. Conclusion and implications: STV(QT) was markedly increased by combined pharmacological block of I Kr and I Ks and may be a better predictor of subsequent TdP development than the measurement of QTc interval prolongation.

No abstract

1 The eects of I Ks block by chromanol 293B and L-735,821 on rabbit QT-interval, action potential duration (APD), and membrane current were compared to those of E-4031, a recognized I Kr blocker. Measurements were made in rabbit Langendor-perfused whole hearts, isolated papillary muscle, and single isolated ventricular myocytes. 2 Neither chromanol 293B (10 mM) nor L-735,821 (100 nM) had a signi®cant eect on QTc interval in Langendor-perfused hearts. E-4031 (100 nM), on the other hand, signi®cantly increased QTc interval (35.6+3.9%, n=8, P50.05).3 Similarly both chromanol 293B (10 mM) and L-735,821 (100 nM) produced little increase in papillary muscle APD (less than 7%) while pacing at cycle lengths between 300 and 5000 ms. In contrast, E-4031 (100 nM) markedly increased (30 ± 60%) APD in a reverse frequency-dependent manner. 4 In ventricular myocytes, the same concentrations of chromanol 293B (10 mM), L-735,821 (100 nM) and E-4031 (1 mM) markedly or totally blocked I Ks and I Kr , respectively. 5 I Ks tail currents activated slowly (at +30 mV, t=888.1+48.2 ms, n=21) and deactivated rapidly (at 740 mV, t=157.1+4.7 ms, n=22), while I Kr tail currents activated rapidly (at +30 mV, t=35.5+3.1 ms, n=26) and deactivated slowly (at 740 mV, t 1 =641.5+29.0 ms, t 2 =6531+343, n=35). I Kr was estimated to contribute substantially more to total current density during normal ventricular muscle action potentials (i.e., after a 150 ms square pulse to +30 mV) than does I Ks . 6 These ®ndings indicate that block of I Ks is not likely to provide antiarrhythmic bene®t by lengthening normal ventricular muscle QTc, APD, and refractoriness over a wide range of frequencies.