表征心室复极不一致有效参数的仿真研究

建立了从心内膜到心外膜的一维心肌几何模型,采用心肌双域模型建立心电电位的仿真模型,通过改变缺血程度构造不同的心室复极不一致状态,利用有限差分法求解控制方程,模拟了心电兴奋在心室复极不一致状态下形成的心电电位,并从中提取QT离散度和兴奋恢复间期(activation-recovery interval,ARI)离散度。分析结果显示：缺血区与正常区电位的QT间期没有明显差异,QT离散度接近于零,不能有效地表征心室肌复极不一致;缺血区ARI明显区别于正常区,ARI离散度与缺血程度有很好的对应关系,可以用来表征心室复极不一致。     

In silico study of action potential and QT interval shortening due to loss of inactivation of the cardiac rapid delayed rectifier potassium current

The rapid delayed rectifier K(+) current, I(Kr), plays a key role in repolarisation of cardiac ventricular action potentials (APs). In recent years, a novel clinical condition denoted the short QT syndrome (SQTS) has been identified and, very recently, gain in function mutations in the gene encoding the pore-forming sub-unit of the I(Kr) channel have been proposed to underlie SQTS in some patients. Here, computer simulations were used to investigate the effects of the selective loss of voltage-dependent inactivation of I(Kr) upon ventricular APs and on the QT interval of the electrocardiogram. I(Kr) and inactivation-deficient I(Kr) were incorporated into Luo-Rudy ventricular AP models. Inactivation-deficient I(Kr) produced AP shortening that was heterogeneous between endocardial, mid-myocardial, and epicardial ventricular cell models, irrespective of whether heterogeneity between these sub-regions was incorporated of slow delayed rectifier K(+) current (I(Ks)) alone, or of I(Ks) together with that of transient outward K(+) current. The selective loss of rectification of I(Kr) did not augment transmural dispersion of AP repolarisation, as AP shortening was greater in mid-myocardial than in endo- or epicardial cell models. Simulated conduction through a 1 D transmural ventricular strand was altered by incorporation of inactivation-deficient I(Kr) and the reconstructed QT interval was shortened. Collectively, these results substantiate the notion that selective loss of I(Kr) inactivation produces a gain in I(Kr) function that causes QT interval shortening.     

QT interval variability and cardiac norepinephrine spillover in patients with depression and panic disorder

Suggestions were made that increased myocardial sympathetic activity is reflected by elevated QT variability (dynamic changes in QT interval duration). However, the relationship between QT variability and the amount of norepinephrine released from the cardiac sympathetic terminals is unknown. We thus attempted to assess this relationship. The study was performed in 17 subjects (12 with major depressive disorder and 5 with panic disorder). Cardiac norepinephrine spillover (measured by direct catheter technique coupled with norepinephrine isotope dilution methodology) was assessed before and 4 mo after treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants. The distribution of the cardiac norepinephrine spillover was bimodal, with the majority of patients having values of < or =10 ng/min. There was a positive correlation between cardiac norepinephrine spillover and corrected QT interval (r = 0.7, P = 0.03) but not with any of the QT variability measures. However, in a subgroup of five patients who had high levels of cardiac norepinephrine spillover (>20 ng/min) a tendency for a strong positive correlation with variance of QT intervals (r = 0.9, P = 0.08) was observed. There were significant correlations between the severity of depression and QT variability indexes normalized to the heart rate [QTVi and QT interval/R-R interval (QT/RR) coherence] and between the severity of anxiety and the QT/RR residual and regression coefficient, respectively. Treatment with SSRI antidepressants substantially reduced depression score but did not affect any of the QT variability indexes. We conclude that in depression/panic disorder patients with near-normal cardiac norepinephrine levels QT variability is not correlated with cardiac norepinephrine spillover and is not affected by treatment with SSRI.     

QT interval prolongation and decreased heart rates after intravenous bolus oxytocin injection in male and female conscious rabbits

The aim of this study was to evaluate changes in heart rate (HR), QT and RR intervals and corrected QT (QTc) values in conscious male and female New Zealand rabbits which intravenously received oxytocin (OXT) at different dosages. Animals were divided into 6 equal groups: group I (n = 6 male, received 0.75 U OXT per animal); group II (n = 6 male, received 1.5 U OXT per animal); group III (n = 6 male, received 3 U OXT per animal); group IV (n = 6 female, received 0.75 U OXT per animal); group V (n = 6 female, received 1.5 U OXT per animal); group VI (n = 6 female, received 3 U OXT per animal). ECG recording were taken from all animals before injection and then at 2, 4, 6, 8, 10, 15 and 20 min of OXT administration. QT and RR intervals obtained at 2 min of OXT administration were significantly prolonged in all groups (p < 0.05) with one exception that is the 1.5 U OXT injected female group where only QT interval did not change. The prolongation of QT and RR intervals persisted for 20 min in 1.5 U OXT injected male group while only QT interval prolongation was obvious for 20 min in 3 U OXT injected female group as for the other groups the prolonged interval were observed for 8-10 min and then returned to baseline values. Generally, a significant prolongation of QTc was noticed in both male and female rabbits at the 2 and 4 min in all groups and bradycardia was noticed at 2 min of OXT administration in all groups. Heart beats returned to normal values in all groups after 8 min of OXT administration. The change of HR, RR, QT and QTc was gender- but not dose-dependent (p < 0.001). The male rabbits were more sensitive to OXT effect then female rabbits. In conclusion, OXT used in therapeutic dosages decreased heart rate and prolonged QT and QTc intervals. Although cardiovascular effect of OXT are of short duration, its use in patient with risk factors for malignant arrhythmias requires more attention.     

Increased ventricular repolarization heterogeneity in patients with ventricular arrhythmia vulnerability and cardiomyopathy: a human in vivo study

Increased repolarization heterogeneity can provide the substrate for reentrant ventricular arrhythmias in animal models of cardiomyopathy. We hypothesized that ventricular repolarization heterogeneity is also greater in patients with cardiomyopathy and ventricular arrhythmia vulnerability (inducible ventricular tachycardia or positive microvolt T wave alternans, VT/TWA) compared with a similar patient population without ventricular arrhythmia vulnerability (no VT/TWA). Endocardial and epicardial repolarization heterogeneity was measured in patients with (n = 12) and without (n = 10) VT/TWA by using transvenous 26-electrode catheters placed along the anteroseptal right ventricular endocardium and left ventricular epicardium. Local activation times (AT), activation-recovery intervals (ARI), and repolarization times (RT) were measured from unipolar electrograms. Endocardial RT dispersion along the apicobasal ventricle was greater (P < 0.005) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion (P < 0.005). AT dispersion was similar between the two groups. Epicardial RT dispersion along the apicobasal ventricle was greater (P < 0.05) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion (P < 0.05). AT dispersion was similar between the two groups. A plot of AT as a function of ARI revealed an inverse linear relationship for no VT/TWA such that progressively later activation was associated with progressively shorter ARI. The AT-ARI relationship was nonlinear in VT/TWA. In conclusion, patients with cardiomyopathy and VT/TWA have greater endocardial and epicardial repolarization heterogeneity than those without VT/TWA without associated conduction slowing. The steep repolarization gradients in VT/TWA may provide the substrate for functional conduction block and reentrant ventricular arrhythmias.     

The effect of L-citrulline ingestion on ECG QT interval and autonomic nervous system activity

The purpose of this study was to investigate the effect of L-citrulline ingestion on ECG QT interval. To accomplish this purpose, nine male subjects (age: 23.4±0.5 years, weight: 57.7±5.6 kg) participated, who had no history of cardiovascular or respiratory function disorders. Each subject performed two tests (L-citrulline and placebo ingestion) on a separate day. ECG was taken before, and 60 min and 90 min after L-citrulline ingestion. The heart-rate-corrected QT interval (QTc) decreased significantly 60 min (p=0.0004) and 90 min (p=0.011) after L-citrulline ingestion. However, there were no significant changes after placebo ingestion. In addition, the interaction between L-citrulline ingestion and placebo was significant (two-way ANOVA: interaction, p=0.010). Our major finding was that L-citrulline ingestion decreases the QT interval in healthy subjects. This result suggests that transient L-citrulline ingestion may shorten the time required to complete myocardial depolarization and repolarization.     

Steeper restitution slopes across right ventricular endocardium in patients with cardiomyopathy at high risk of ventricular arrhythmias

Steep action potential duration (APD) restitution slopes (>1) and spatial APD restitution heterogeneity provide the substrate for ventricular fibrillation in computational models and experimental studies. Their relationship to ventricular arrhythmia vulnerability in human cardiomyopathy has not been defined. Patients with cardiomyopathy [left ventricular (LV) ejection fraction <40%] and no history of ventricular arrhythmias underwent risk stratification with programmed electrical stimulation or T wave alternans (TWA). Low-risk patients (n = 10) had no inducible ventricular tachycardia (VT) or negative TWA, while high-risk patients (n = 8) had inducible VT or positive TWA. Activation recovery interval (ARI) restitution slopes were measured simultaneously from 10 right ventricular (RV) endocardial sites during an S1-S2 pacing protocol. ARI restitution slope heterogeneity was defined as the coefficient of variation of slopes. Mean ARI restitution slope was significantly steeper in the high-risk group compared with the low-risk group [1.16 (SD 0.31) vs. 0.59 (SD 0.19), P = 0.0002]. The proportion of endocardial recording sites with a slope >1 was significantly larger in the high-risk patients [47% (SD 35) vs. 13% (SD 21), P = 0.022]. Spatial heterogeneity of ARI restitution slopes was similar between the two groups [29% (SD 16) vs. 39% (SD 34), P = 0.48]. There was an inverse linear relationship between the ARI restitution slope and the minimum diastolic interval (P < 0.001). In cardiomyopathic patients at high risk of ventricular arrhythmias, ARI restitution slopes along the RV endocardium are steeper, but restitution slope heterogeneity is similar compared with those at low risk. Steeper ARI restitution slopes may increase the propensity for ventricular arrhythmias in patients with impaired left ventricular function.     

Modulated dispersion of activation and repolarization by premature beats in patients with cardiomyopathy at risk of sudden death

Premature beats can trigger ventricular arrhythmias in heart disease, but the mechanisms are not well defined. We studied the effect of premature beats on activation and repolarization dispersion in seven patients with cardiomyopathy (57 ± 10 yr, left ventricular ejection fraction 31 ± 7%). Activation time (AT), activation-recovery interval (ARI), and total repolarization time (TRT) were measured from 26 unipolar electrograms during right ventricle (RV) endocardial (early) to left ventricle epicardial (late) activation in response to RV apical extrastimulation (S1S2). Early TRT dispersion increased significantly with shorter S1S2 (1.0 ± 0.2 to 2.3 ± 0.4 ms/mm, P < 0.0001), with minimal change in late TRT dispersion (0.8 ± 0.1 to 1.0 ± 0.3 ms, P = 0.02). This was associated with an increase in early AT dispersion (1.0 ± 0.1 to 1.5 ± 0.2 ms/mm, P = 0.05) but no change in late AT dispersion (0.6 ± 0.1 to 0.7 ± 0.2 ms/mm, P = 0.4). Early and late ARI dispersion did not change with shorter S1S2. AT restitution slopes were similar between early and late sites, as was slope heterogeneity. ARI restitution slope was greater in early vs. late sites (1.3 ± 0.6 vs. 0.8 ± 0.6, P = 0.03), but slope heterogeneity was similar. With shorter S1S2, AT-ARI slopes became less negative (flattened) at both early (-0.4 ± 0.1 to +0.04 ± 0.2) and late (-1.5 ± 0.2 to +0.3 ± 0.2) sites, implying less activation-repolarization coupling. There was no difference in AT-ARI slopes between early and late sites at short S1S2. In conclusion, high-risk patients with cardiomyopathy have greater TRT dispersion at tightly coupled S1S2 due to greater AT dispersion and activation-repolarization uncoupling. Modulated dispersion is more pronounced at early vs. late activated sites, which may predispose to reentrant ventricular arrhythmias.     

A 24-HOUR AMBULATORY ECG MONITORING IN ASSESSMENT OF QT INTERVAL DURATION AND DISPERSION IN ROWERS WITH PHYSIOLOGICAL MYOCARDIAL HYPERTROPHY

Myocardial hypertrophy (MH) due to cardiac pathology is characterized by an increase in QT interval duration and dispersion, while the findings for exercise-induced myocardial hypertrophy are contradictory. The majority of published research findings have not explored this relationship, but there have only been a few conducted studies using 24-hour ECG monitoring. The aim of the study was to determine the QT interval duration and dispersion in short-term and 24-hour ECG in endurance athletes with myocardial hypertrophy and without it. Methods: A total of 26 well-trained rowers underwent a resting 12-lead ECG, 24-hour ECG monitoring and echocardiography. Results: Athletes with MH (n = 7) at rest did not show any increase in QTc interval duration and dispersion, or mean and maximal QTc duration in Holter monitoring compared to athletes without MH (n = 19). Left ventricular mass was not significantly correlated with any QTc characteristics. Furthermore, athletes with MH had significantly longer mean QT (P = 0.01) and maximal QT (P = 0.018) intervals in Holter monitoring and higher 24-hour heart rate variability indexes due to stronger vagal effects. Conclusions: The present study demonstrated that athlete''s heart syndrome with myocardial hypertrophy as a benign phenomenon does not lead to an increase in QT interval duration, or increases in maximal and mean duration in a 24-hour ECG. An increase in QT interval duration in athletes may have an autonomic nature.     

Sympathetic stimulation increases dispersion of repolarization in humans with myocardial infarction

The sympathetic nervous system is thought to play a key role in genesis and maintenance of ventricular arrhythmias. The myocardial effect of sympathetic stimulation on myocardial repolarization in humans is poorly understood. The purpose of this study was to evaluate the effects of direct and reflex sympathetic stimulation on ventricular repolarization in patients with postinfarct cardiomyopathy (ICM). The effects of direct sympathetic stimulation were assessed using isoproterenol, while those of reflex sympathetic stimulation were assessed with nitroprusside infusion in ICM patients (n = 5). Five patients without cardiomyopathy were also studied. Local repolarization was measured from intracardiac electrograms that were used to calculate the activation recovery interval (ARI), a surrogate of action potential duration. Isoproterenol significantly increased heterogeneity in repolarization in patients with ICM; the decrease in ARI from baseline was 72.9 ± 9.1 ms in more viable regions, 64.5 ± 8.9 ms in the scar, and 54.9 ± 9.1 ms in border zones (P = 0.0002 and 0.014 comparing normal and scar to border zones, respectively). In response to nitroprusside, the ARI at the border zones decreased significantly more than either scar or surrounding viable myocardium, which showed an increase in ARI (P = 0.014 and 0.08 comparing normal tissue and scar to border zones, respectively). Furthermore, isoproterenol increased ARI dispersion by 70%, while nitroprusside increased ARI dispersion by 230% when ICM patients were compared to those with structurally normal hearts (P = 0.0015 and P < 0.001, respectively). In humans, both direct and reflex sympathetic stimulations increase regional differences in repolarization. The normal tissue surrounding the scar appears denervated. Dispersion of ARI in response to sympathetic stimulation is significantly increased in patients with ICM.     

Effect of an increase in coronary perfusion on transmural ventricular repolarization

The effect of increased coronary flow on transmural ventricular repolarization was investigated in six pentobabital-anesthetized sheep. Fresh blood at 10 ml/min was injected into the left circumflex coronary artery (LCX) in addition to the normal coronary flow. Unipolar electrocardiograms were simultaneously registered from epicardium, mid-myocardium and endocardium with fine plunge needles. Activation-recovery interval (ARI) was measured from the unipolar electrocardiograms and was used for estimating the ventricular repolarization duration. It was found that intracoronary blood injection (n=3) prolonged ARI in the epicardium, mid-myocardium and endocardium by an average of 34 +/- 16, 28 +/- 18 and 25 +/- 13 ms, respectively (p<0.01). Pretreatment with nitro-L-arginine (n=3), a nitric synthase inhibitor, diminished the flow-induced ARI prolongation across the ventricular wall. In conclusion, an increase in coronary flow lengthens the duration of transmural ventricular repolarization. These effects appear to be mediated by nitric oxide from the coronary endothelium.     

CRT_D介导室性心动过速的研究进展

心室再同步心脏转复除颤器（CRT）可有效改善心力衰竭（CHF）患者的运动耐量和生活质量,预防猝死,提高生存率,但_DCHFCRTD植入后由于心室激动顺序的改变,使QT间期延长、跨室壁复极离散度（TDR）增加,潜在致室性心律失常风险;且CHF患者通常存在心肌解剖改变,传导的不均一性,也为折返性心动过速的发生提供了维持的机制;而多次电击也可导致肌钙蛋白升高,引起心肌损伤,局部心肌复极离散度增加（DRVR）和QT间期延长,以及电除颤后心肌纤维化和急性细胞损伤,反复室速、室颤也会引起进行性左心功能不全、心肌细胞凋亡、恶化心律失常基质和增加心律失常易感性。CRT_D潜在致室性心律失常作用逐渐引起人们的重视,本文就近年来CRTD致室性心律失常的电生理机制与临床防治对策等做一综述。     

Electrical Inhomogeneity in Left Ventricular Hypertrophy

Recent studies designed to assess the relationship between aortic compliance and heterogeneity of heart electrical activity has shown that hypertrophy aggravates repolarization disturbances in the myocardium. Numerous mechanisms of electrical instability and inhomogeneity associated with left ventricular hypertrophy are now under investigation. Most of the studies have been found to be focused on ventricular Gradient, QT dispersion, amplitudes of isointegral maps during ventricular repolarization, abnormally low-QRST areas, dispersion of the QT interval, and spatial QRS-T _angle. These studies point to marked repolarization abnormalities in left ventricular hypertrophy and the dispersion of the QT interval as a valuable index for inhomogeneity of repolarization and the subsequent heart rate variability. The heart rate-corrected QT dispersion and QT apex dispersion seem to be significantly longer in the patients with left ventricular hypertrophy than in normal individuals. The review study has also identified QRST isointegral map as a valuable technique in assessment of the electro-cardiac events in LVH.     

Relation between QT interval variability and cardiac sympathetic activity in hypertension

Elevated QT interval variability is a predictor of malignant ventricular arrhythmia, but the underlying mechanisms are incompletely understood. A recent study in dogs with pacing-induced heart failure suggests that QT variability is linked to cardiac sympathetic nerve activity. The aim of this study was to determine whether increased cardiac sympathetic activity is associated with increased beat-to-beat QT interval variability in patients with essential hypertension. We recorded resting norepinephrine (NE) spillover into the coronary sinus and single-lead, short-term, high-resolution, body-surface ECG in 23 patients with essential hypertension and 9 normotensive control subjects. To assess beat-to-beat QT interval variability, we calculated the overall QT variability (QTVN) as well as the QT variability index (QTVi). Cardiac NE spillover (12.2 ± 6.5 vs. 20.7 ± 14.7, P = 0.03) and QTVi (-1.75 ± 0.36 vs. -1.42 ± 0.50, P = 0.05) were significantly increased in hypertensive patients compared with normotensive subjects. QTVN was significantly correlated with cardiac NE spillover (r(2) = 0.31, P = 0.001), with RR variability (r(2) = 0.20, P = 0.008), and with systolic blood pressure (r(2) = 0.16, P = 0.02). Linear regression analysis identified the former two as independent predictors of QTVN. In conclusion, elevated repolarization lability is directly associated with sympathetic cardiac activation in patients with essential hypertension.     

Methods of assessment and clinical relevance of QT dynamics

The dependence on heart rate of the QT interval has been investigated for many years and several mathematical formulae have been proposed to describe the QT interval/heart rate (or QT interval/RR interval) relationship. While the most popular is Bazett's formula, it overcorrects the QT interval at high heart rates and under-corrects it at slow heart rates. This formulae and many others similar ones, do not accurately describe the natural behaviour of the QT interval. The QT interval/RR interval relationship is generally described as QT dynamics. In recent years, several methods of its assessment have been proposed, the most popular of which is linear regression. An increased steepness of the linear QT/RR slope correlates with the risk of arrhythmic death following myocardial infarction. It has also been demonstrated that the QT interval adapts to heart rate changes with a delay (QT hysteresis) and that QT dynamics parameters vary over time. New methods of QT dynamics assessment that take into account these phenomena have been proposed. Using these methods, changes in QT dynamics have been observed in patients with advanced heart failure, and during morning hours in patients with ischemic heart disease and history of cardiac arrest. The assessment of QT dynamics is a new and promising tool for identifying patients at increased risk of arrhythmic events and for studying the effect of drugs on ventricular repolarisation.     

Serum leptin and adiponectin concentrations in patients infected with human immunodeficiency virus type 1 (HIV-1) on antiretroviral therapy

The lipodystrophy syndrome with dyslipidaemia and insulin resistance is side-effect of combined antiretroviral therapy (CART). Aim of the study: to describe the influence of CART on leptin and adiponectin concentration in connection with lipids levels in HIV-infected patients on antiretroviral therapy. BMI, serum leptin, adiponectin, triglycerides, total cholesterol, HDL- and LDL-cholesterol concentrations were measured in 56 HIV(+) patients before and on CART; average of treatment duration 38.4 +/-13.2 months. Significant increase of BMI (p=0.0268) of (22.6 +/- 3.3 before and 23.5 +/- 3.4 kg/m2 on therapy, respectively) and all analyzed lipids were found. Mean adiponectin concentration in treated patients was significantly (7.256 +/- 3.551 microg/ml) lower than mean value before treatment (8.395 +/- 3.568 microg/ml; p=0.0011). Mean values of leptin concentrations did not differ significantly (before therapy 3.721 +/- 0.347 log10; on therapy 3.1737 +/- 0.353 log10). Significant positive correlation between BMI and leptin concentrations was found before, as well as during CART (r=0.5333; p<0.0001), but negative correlation between adiponectin and leptin concentrations (r=-0.2677; p=0.042). Leptin and adiponectin concentrations did not revealed significant correlation with lipids levels before therapy. The decrease of adiponectin concentration on CART correlated negatively with total (r=-0.2912; p=0.0310) and LDL-cholesterol (r=-0.310; p=0.0225). CART lasting longer than 2 years resulted in the decrease of adiponectin concentration, with lack of influence on leptin concentration in analyzed group. The increase of total cholesterol and LDL-cholesterol in correlation with the decrease of adiponectin concentration confirms that CART induces metabolic disturbances related to higher risk of atherosclerosis and its sequel.     

The electrocardiogram of the Beagle dog: reference values and effect of sex, genetic strain, body position and heart rate

The aim of the study was to establish a database for electrocardiographic parameters of Beagle dogs used for toxicological studies and to evaluate the influence of supplier, sex, heart rate (HR) and body position for electrocardiogram (ECG) recording on ECG parameters. Peripheral ECG leads were recorded from 934 female and 946 male dogs from Marshall Farms and 27 females and 30 males from Harlan, either standing on a table or restrained in a hammock. HR, RR, PQ and QT intervals, P and QRS duration and P-wave amplitude were measured. There were no major differences between sexes for ECG parameters. The axis of the heart was shifted to the left when the animals were restrained in a hammock compared to when they were standing on a table. The PQ interval was higher (about 9%) in Harlan than in Marshall dogs. HR was negatively correlated with QT (coefficient of linear correlation: r=-0.61 to -0.74), which emphasizes the need for a formula correcting QT interval for HR when interpreting changes in QT interval. HR was also negatively correlated with PQ intervals (r=-0.26 to -0.11), whereas a positive correlation was found between HR and the amplitude of the P wave (r=0.21-0.34). The level of the respiratory sinus arrhythmia (SA) was quantified by calculating the ratio of maximum to minimum RR interval measured over a 10 s period. This ratio was negatively correlated with HR (r =-0.49 to -0.33). Therefore, at high HRs, SA was less marked than at low HRs, but it did not completely disappear. Analysis of beat-to-beat variation indicated that QT and PQ intervals and the amplitude of P wave fluctuated over time and the degree of this variability was positively correlated with the level of SA. In conclusion, we have established reference values for the duration and/or amplitude of some ECG parameters both in terms of means and variability over the recording period, and we have evaluated the influence of body position, genetic strain and HR on the ECG parameters. These data can be used as baseline for the interpretation of the ECG of Beagle dogs.     

Effect Of Levothyroxine Treatment On Qt Dispersion In Patients With Subclinical Hypothyroidism

ObjectiveTo examine the effect of levothyroxine treatment in patients with subclinical hypothyroidism on electrocardiographic variables, especially on ventricular repolarization-related factors.Methods:Sixteen women (mean age, 48.2 years) with subclinical hypothyroidism were treated with levothyroxine for 16 weeks. All standard 12-lead electrocardiograph-ic recordings were scanned and transferred to a computer, and the QT intervals were measured on 300 times magnified recordings. QT dispersion, which reflects the heterogeneity of the ventricular repolarization, was calculated by the difference between the QT maximum and the QT minimum.ResultsWe found that, after 16 weeks of levothyroxine treatment, the QT interval decreased from 387.2 ± 10.8 ms to 345.6 ± 13.0 ms (P < 40.0001). The study patients exhibited a significant reduction of QT dispersion from 46.5 ± 5.3 ms to 30.7 ± 5.8 ms (P < 0.0001). On linear regression analysis, a positive relationship was found between QT dispersion and logarithmic serum TSH levels (r = 0.492; P < 0.0001).ConclusionWe conclude that serum TSH concentration has a role in ventricular inhomogeneity and, therefore, that subclinical hypothyroidism may predispose to ventricular arrhythmias. A large-scale, multicenter, randomized trial should be undertaken to address the benefit-to-risk ratio of levothyroxine treatment on cardiac inhomogeneity in patients with subclinical hypothyroidism. (Endocr Pract. 2007;13:711-715)     

Markers of ventricular repolarization as an additional non-invasive electrocardiography parameters for predicting ventricular tachycardia/fibrillation in patients with Brugada Syndrome – A systematic review and meta-analysis

BackgroundControversies surrounded the management of asymptomatic Brugada syndrome. Prognostication using electrophysiology study (EPS) is disputable. Non-invasive parameters may be a valuable additional tool for risk stratification. We aim to evaluate the use markers of ventricular repolarization including Tpeak-to-Tend (TpTe), Tpe Dispersion, TpTe/QT ratio, and QTc interval as additional non-invasive electrocardiography parameters for predicting ventricular tachycardia/fibrillation in patients with Brugada syndrome.MethodsWe performed a comprehensive search on TpTe, Tpe Dispersion, TpTe/QT ratio, and QTc interval as a predictor for ventricular tachycardia(VT)/fibrillation(VF)/aborted sudden cardiac death/appropriate ICD shock in patients with Brugada syndromes up until October 2018.ResultsWe included ten studies in the qualitative synthesis and eight studies in meta-analysis. There were a total of 2126 subjects from ten studies. We found that TpTe interval (mean difference 11.97 m s [5.02–18.91]; p < 0.001; I² 80% possibly on ≥80–100 m s and maximum QTc interval (mean difference 11.42 m s [5.90–16.93], p < 0.001; I² 28%) were the most potential ECG parameters to predict VT/VF/AT/SCD. Tpe dispersion and TpTe/QT ratio have a high heterogeneity. Upon sensitivity analysis, there is no single study found to markedly affect heterogeneity of Tpe dispersion and TpTe/QT ratio. Removal of a study reduced maximum QTc interval heterogeneity to 0%.ConclusionsMeasurement of TpTe interval, Tp-e dispersion, TpTe/QT ratio, and QTc interval on ECG emerge as a promising prognostication tool which needs further investigations with a more standardized method, outcome, and cut-off points. As for now, only maximum QTc interval has a reliable result with low heterogeneity sufficiently reliable for prognostication.     

Retinol-binding protein 4 (RBP-4) levels do not change after oral glucose tolerance test and after dexamethasone, but correlate with some indices of insulin resistance in humans

Introduction: Secretory products from adipocytes may contribute to deterioration in glycaemic control and increased insulin resistance (IR). Retinol-binding protein 4 (RBP-4) may increase IR in mice, with elevated levels in insulin-resistant mice and humans with obesity and type 2 diabetes. However, the mechanisms regulating RBP-4 synthesis remain not fully understood. It is not clear whether short-term glucose-induced hyperglycaemia and hyperinsulinaemia as well as glucocorticosteroid-induced increase in IR might be reflected in alterations in serum RBP-4 levels in humans. In order to investigate this, we measured serum RBP-4, glucose and insulin concentrations during 75.0 gram oral glucose tolerance test (OGTT) - Study 1, as well as before and after oral administration of dexamethasone - Study 2. Material and methods: Both studies included 35 subjects (8 males), age (mean +/- SD) 39.1 +/- 15.6 years, BMI 35.8 +/- 8.7 kg/m(2). Twenty-four of those subjects (5 males), age 38.7 +/- 15.1 years, BMI 34.4 +/- 8.3 kg/m(2), had 75 gram oral glucose tolerance test (OGTT) - Study 1. Blood samples were taken before (0 minutes), and at 60 and 120 minutes of OGTT. 17 subjects (3 males, 4 subjects with type 2 diabetes), age 43.1 +/- 18.1 years, BMI 36.7 +/- 9.0 kg/m(2) underwent screening for Cushing's disease/syndrome (Study 2). Dexamethasone was administered in a dose of 0.5 mg every 6 hours for 48 hours. Fasting serum concentrations of RBP-4, glucose and insulin were assessed before (D0) and after 48 hours of dexamethasone administration (D2). IR was assessed by HOMA in all non-diabetic subjects and in subjects participating in study 1 also by Insulin Resistance Index (IRI), which takes into account glucose and insulin levels during OGTT. Results: Glucose administration resulted in significant increases in insulin and glucose (p < 0.0001). There was, however, no change in RBP-4 concentrations (124.1 +/- 32 mg/ml at 0 minutes, 123 +/- 35 mg/ml at 60 minutes and 126.5 +/- 37.5 mg/ml at 120 minutes of OGTT, p = ns). All subjects in Study 2 achieved suppression of cortisol below 50 nmo/l. Dexamethasone administration resulted in an increase in fasting insulin (from 11.6 +/- 6.8 to 17.1 +/- 7.2 muU/ml; p = 0.003), and an increase in HOMA (from 2.73 +/- 1.74 to 4.02 +/- 2.27; p = 0.015), although without a significant change in RBP-4 levels (119 +/- 26.8 vs. 117.5 +/- 24.8 mg/ml, p = ns). RBP-4 correlated with fasting insulin (r = 0.40, p = 0.025), fasting glucose (r = 0.41, p = 0.02) and HOMA (r = 0.43, p = 0.015), but not with IRI (r = 0.19, p = 0.31). There was, however, only a moderate correlation between HOMA and IRI (r = 0.49 [r(2) = 0.24]; p = 0.006, Spearman rank correlation), while the best correlation was obtained between the product of glucose and insulin levels at 60 min of OGTT and IRI in a non-linear model (r = 0.94 [r(2) = 0.88]; p<0.00001). In subjects who received dexamethasone, a positive correlation between RBP-4 and HOMA (p = 0.01) was lost after two days of dexamethasone administration (p = 0.61). Conclusions: RBP-4 levels do not change during oral glucose tolerance test or after a dexamethasone-induced increase in insulin resistance. This implies that it is highly unlikely that RBP-4 is involved in short-term regulation of glucose homeostasis in humans and that it responds to short-term changes in insulin resistance. A moderate correlation between RBP-4 and some insulin resistance indices (HOMA) does not exclude the fact that RBP-4 might be one of many factors that can influence insulin sensitivity in humans.