Prolonged QT interval is associated with blood pressure rather than left ventricular mass in spontaneously hypertensive rats

QT interval is prolonged in hypertensive individuals, although the factors responsible for this increase are not completely understood. We questioned whether enhanced left ventricular mass (LVM) or increased systemic blood pressure represents the principal factor determining QT prolongation in the period of development of hypertension and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). In 12-and 20-week-old SHR (SHR12 and SHR20) and age-matched normotensive Wistar-Kyoto rats (WKY12 and WKY20), arterial systolic blood pressure (sBP) was measured using tail-cuff technique. Orthogonal Frank ECG was registered in anaesthetized animals in vivo, and bipolar ECG was measured in spontaneously beating isolated hearts in vitro. Progressive increase of sBP and LVM resulted in significant QT prolongation in SHR20 as compared to WKY12, WKY20, and also to SHR12 in vivo (WKY12: 82 +/- 9 ms, WKY20: 81 +/- 9 ms, SHR12: 88 +/- 15 and SHR20: 100 +/- 10, respectively; p < 0.05) but not in isolated hearts (WKY20: 196 +/- 39 ms and SHR20: 220 +/- 55, respectively; NS). In whole animals, QT duration was positively related to sBP (r = 0.6842; p < 0.001) but not to LVM (r = 0.1632, NS) in SHR20. The results suggest that QT prolongation in SHR developing hypertension and LVH depends on blood pressure rather than increase in LVM. In this period, myocardial hypertrophy is probably the predisposition for QT prolongation, but the significant change manifests only in the presence of elevated systemic factors.     

The Initial Stage of Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats is Manifested by a Decrease in the QRS Amplitude/Left Ventricular Mass Ratio

In this study we tested the hypothesis of the relative voltage deficit, i.e. the discrepancy between increased left ventricular mass (LVM) and QRS amplitudes, in an experimental model of spontaneously hypertensive rats (SHR) during the period of a moderate increase in blood pressure. To address this issue we recorded orthogonal electrocardiograms of male SHR at the age of 12 and 20 weeks. During this period the systolic blood pressure (sBP) increased from 165 ± 3 mmHg to 195 ± 1 mmHg (p < 0.001). Age and sex matched WKY rats were used as control groups. The sBP values in WKY normotensive control groups were within normal limits (122 ± 8 mmHg and 130 ± 4mmHg, respectively). The maximum QRS spatial vector magnitude (QRSmax) was calculated from X, Y, Z amplitudes of the orthogonal electrocardiograms. The animals were sacrificed and the left ventricular mass was weight. The specific potential of myocardium (SP) was calculated as a ratio of QRSmax to LVM. The LVM in SHR (0.86 ± 0.05 g and 1.05 ± 0.07 g, respectively) was significantly higher as compared to WKY (0.65 ± 0.07 g and 0.70 ± 0.02 g), and the increase of LVM closely correlated with the sBP increase. On the other hand, QRSmax in SHR did not follow either the increase of sBP, or LVM. The QRSmax values in SHR did not differ from those of WKY at the age of 12 weeks (0.59 ± 0.14 mV compared to 0.46 ± 0.05 mV), and they were even lower in SHR at the age of 20 weeks (0.74 ± 0.08 mV compared to 0.44 ± 0.05 mV, p < 0.001). The values of SP, quantifying the relative voltage deficit, were significantly lower in SHR as compared to the WKY control. The values decreased significantly in SHR with increasing age, sBP and LVM, i.e., with the progression of hypertrophic remodeling of the left ventricle. The results of this study support the hypothesis of the relative voltage deficit in LVH. These results are consistent with the finding of a high number of false negative ECG results in clinical ECG diagnostics of LVH, and could contribute to an understanding of the diagnostic importance of the false negative ECG results, their re‐evaluation and utilization for clinical diagnosis and prognosis.     

The initial stage of left ventricular hypertrophy in spontaneously hypertensive rats is manifested by a decrease in the QRS amplitude/left ventricular mass ratio

In this study we tested the hypothesis of the relative voltage deficit, i.e. the discrepancy between increased left ventricular mass (LVM) and QRS amplitudes, in an experimental model of spontaneously hypertensive rats (SHR) during the period of a moderate increase in blood pressure. To address this issue we recorded orthogonal electrocardiograms of male SHR at the age of 12 and 20 weeks. During this period the systolic blood pressure (sBP) increased from 165 +/- 3 mmHg to 195 +/- 1 mmHg (p < 0.001). Age and sex matched WKY rats were used as control groups. The sBP values in WKY normotensive control groups were within normal limits (122 +/- 8 mmHg and 130 +/- 4mmHg, respectively). The maximum QRS spatial vector magnitude (QRSmax) was calculated from X, Y, Z amplitudes of the orthogonal electrocardiograms. The animals were sacrificed and the left ventricular mass was weight. The specific potential of myocardium (SP) was calculated as a ratio of QRSmax to LVM. The LVM in SHR (0.86 +/- 0.05 g and 1.05 +/- 0.07 g, respectively) was significantly higher as compared to WKY (0.65 +/- 0.07 g and 0.70 +/- 0.02 g), and the increase of LVM closely correlated with the sBP increase. On the other hand, QRSmax in SHR did not follow either the increase of sBP, or LVM. The QRSmax values in SHR did not differ from those of WKY at the age of 12 weeks (0.59 +/- 0.14 mV compared to 0.46 +/- 0.05 mV), and they were even lower in SHR at the age of 20 weeks (0.74 +/- 0.08 mV compared to 0.44 +/- 0.05 mV, p < 0.001). The values of SP, quantifying the relative voltage deficit, were significantly lower in SHR as compared to the WKY control. The values decreased significantly in SHR with increasing age, sBP and LVM, i.e., with the progression of hypertrophic remodeling of the left ventricle. The results of this study support the hypothesis of the relative voltage deficit in LVH. These results are consistent with the finding of a high number of false negative ECG results in clinical ECG diagnostics of LVH, and could contribute to an understanding of the diagnostic importance of the false negative ECG results, their re-evaluation and utilization for clinical diagnosis and prognosis.     

Relation Between QRS Amplitude and Left Ventricular Mass in the Initial Stage of Exercise-Induced Left Ventricular Hypertrophy in Rats

The aim of the study was to analyze the relationship between QRS amplitude and left ventricular mass (LVM) in early stages of two different experimental models of left ventricular hypertrophy (LVH) in rats: in exercise-induced hypertrophy and pathological hypertrophy due to genetically conditioned pressure overload. Three groups of experimental animals were studied: healthy control Wistar-Kyoto rats (WKYs), spontaneously hypertensive rats (SHRs), and WKY rats exposed to training by intermittent swimming (SWIM). Orthogonal electrocardiograms were recorded in each group at the age of 12 and 20 weeks, and the maximum spatial QRS vector (QRSmax) was calculated. Then the animals were sacrificed and LVM was measured. The specific potential of myocardium (SP) was calculated as a ratio of QRS_max to LVM. The QRSmax values did not follow the changes in LVM. At the end of the follow-up period, the highest values of QRSmax were recorded in the control WKY rats (0.80 ± 0.05 mV). The QRSmax values in both groups with experimental LVH were significantly lower as compared with control animals (SHR 0.44 ± 0.02 mV, p < 0.001; SWIM 0.53 ± 0.04 mV, p < 0.001). Similarly, the SP values were significantly lower in both groups with experimental LVH as compared with control animals (SHR 0.42 ± 0.02 mV/g, p < 0.001; SWIM 0.55 ± 0.05 mV/g, p < 0.001). A decrease in QRSmax and SP was observed in both models of experimental LVH. We attributed these findings to the changes in electrogenetic properties of myocardium in the early stage of developing LVH. In other words, it is changes of nonspatial determinants that influence the resultant QRS voltage in terms of the solid angle theory.     

Impact of QT Variables on Clinical Outcome of Genotyped Hypertrophic Cardiomyopathy

Background: Although QT variables such as its interval and/or dispersion can be clinical markers of ventricular tachyarrhythmia, few data exist regarding the role of QT variables in genotyped hypertrophic cardiomyopathy (HCM). Therefore, we analyzed QT variables in genotyped subjects with or without left ventricular hypertrophy (LVH). Methods: QT variables were analyzed in 111 mutation and 43 non‐mutation carriers who were divided into three groups: A, those without ECG abnormalities and echocardiographically determined LVH (wall thickness ≥13 mm); B, those with ECG abnormalities but LVH; and C, those with ECG abnormalities and LVH. We also examined clinical outcome of enrolled patients. Results: Maximal LV wall thickness in group C (19.0 ± 4.3 mm, mean ±SD) was significantly greater than that in group A (9.2 ± 1.8) and group B (10.4 ± 1.8). Under these conditions, maximum QTc interval and QT dispersion were significantly longer in group C than those in group A (438 ± 38 ms vs 406 ± 30 and 64 ± 31 vs 44 ± 18, respectively; P < 0.05). QTc interval and QT dispersion in group B (436 ± 50 and 64 ± 22 ms) were also significantly greater than those in group A. During follow‐up periods, four sudden cardiac deaths and one ventricular fibrillation were observed in group C, and two nonlethal ventricular tachyarrhythmias were observed in group B. Conclusions: Patients with HCM‐related gene mutation accompanying any ECG abnormalities frequently exhibited impaired QT variables even without LVH. We suggest that careful observation should be considered for those genotyped subjects.     

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension

Aims: Non-dipper hypertension is associated with increased cardiovascular morbidity and mortality. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension.

Materials and method: This study included 80 hypertensive patients. Hypertensive patients were divided into two groups: 50 dipper patients (29 male, mean age 51.5?±?8 years) and 30 non-dipper patients (17 male, mean age 50.6?±?5.4 years). Tp-e interval and Tp-e/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared between groups.

Results: No statistically significant difference was found between two groups in terms of basic characteristics. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in non-dipper patients compared to the dippers (39.4?±?11.5 versus 27.3?±?7.5?ms and 37.5?±?9.5 versus 29.2?±?6.5?ms, p?=?0.001 and p?=?0.01, respectively). Tp-e interval and Tp-e/QT ratio were also significantly higher in non-dipper patients (97.5?±?11.2 versus 84.2?±?8.3?ms and 0.23?±?0.02 versus 0.17?±?0.02, all p value <0.001).

Conclusion: Our study revealed that QTd, Tp-e interval and Tp-e/QT ratio are prolonged in patients with non-dipper hypertension.     

Immediate and short term effects of percutaneous atrial septal defect device closure on cardiac electrical remodeling in children

Background

The beneficial effects of atrial septal defect (ASD) device closure on electrical cardiac remodeling are well established. The timing at which these effects starts to take place has yet to be determined.

Effect of amiodarone on qt dispersion in the 12-lead standard electrocardiogram and its significance for subsequent arrhythmic events

Background and hypothesis: QT dispersion, measured as interlead variability of QT intervals in the surface electrocardiogram, has been demonstrated to provide an indirect measurement of the inhomogeneity of myocardial repolarization. The purpose of the present study was twofold: (1) to analyze the effect of amiodarone on QT dispersion measured in the 12-lead standard ECG, and (2) to examine the association between QT dispersion on amiodarone and subsequent arrhythmic events. Methods: To determine the effect of amiodarone on QT dispersion and its clinical significance for subsequent arrhythmic events, QT dispersion was measured in the 12-lead standard electrocardiogram (ECG) in 52 patients before and after administration of empiric amiodarone for ventricular tachyarrhythmias. Results: QT intervals increased from 401 ± 44 ms before amiodarone to 442 ± 53 ms after amiodarone therapy, and rate corrected QT intervals (QTc) increased from 452 ± 43 ms to 477 ± 37 ms, respectively (p<0.01). QT dispersion, QTc dispersion, and adjusted QTc dispersion, which take account of the number of leads measured, were not significantly different before and after initiation of amiodarone therapy (58 ± 24 ms vs. 61 ± 26 ms, 68 ± 29 vs. 66 ± 26 ms, and 22 ± 8 vs. 22 ± 8 ms, respectively, p = NS). During 31 ± 25 months follow-up after initiation of amiodarone therapy, arrhythmic events defined as sustained ventricular tachycardia, ventricular fibrillation, or sudden death occurred in 11 of 52 study patients (21%). QT dispersion, QTc dispersion, and adjusted QTc dispersion on amiodarone were not different between patients with and without arrhythmic events during follow-up (65 ± 14 vs. 59 ± 29 ms, 73 ± 15 vs. 64 ± 28 ms, and 25 ± 6 vs. 21 ± 8 ms, respectively, p=NS). Conclusions: We conclude that (1) amiodarone increases QT intervals and QTc intervals during sinus rhythm but does not significantly change measures of QT dispersion; and (2) QT dispersion measured in the 12-lead standard ECG after initiation of amiodarone therapy does not appear to be a useful marker for subsequent arrhythmic events.     

Comparing Methods of Measurement for Detecting Drug‐Induced Changes in the QT Interval: Implications for Thoroughly Conducted ECG Studies

Background: The aim of this study was to compare the reproducibility and sensitivity of four commonly used methods for QT interval assessment when applied to ECG data obtained after infusion of ibutilide. Methods: Four methods were compared: (1) 12‐lead simultaneous ECG (12‐SIM), (2) lead II ECG (LEAD II), both measured on a digitizing board, (3) 3‐LEAD ECG using a manual tangential method, and (4) a computer‐based, proprietary algorithm, 12SL? ECG Analysis software (AUT). QT intervals were measured in 10 healthy volunteers at multiple time points during 24 hours at baseline and after single intravenous doses of ibutilide 0.25 and 0.5 mg. Changes in QT interval from baseline were calculated and compared across ECG methods, using Bland–Altman plots. Variability was studied using a mixed linear model. Results: Baseline QT values differed between methods (range 376–395 ms), mainly based on the number of leads incorporated into the measurement, with LEAD II and 3‐LEAD providing the shortest intervals. The 3‐LEAD generated the largest QT change from baseline, whereas LEAD II and 12‐SIM generated essentially identical result within narrow limits of agreement (0.4 ms mean difference, 95% confidence interval ± 20.5 ms). Variability with AUT (standard deviation 15.8 ms for within‐subject values) was clearly larger than with 3‐LEAD, LEAD II, and 12‐SIM (9.6, 10.0, and 11.3 ms). Conclusion: This study demonstrated significant differences among four commonly used methods for QT interval measurement after pharmacological prolongation of cardiac repolarization. Observed large differences in variability of measurements will have a substantial impact on the sample size required to detect QT prolongation in the range that is currently advised in regulatory guidance.     

Patterns of QT Dispersion in Athletic and Hypertensive Left Ventricular Hypertrophy

Objective: The objective of this article is to assess whether left ventricular hypertrophy (LVH) due to physical training or of hypertensive patients shows similarities in QT length and QT dispersion. Methods: A total of 51 subjects were studied: 17 essential hypertensive patients (27.7 ± 5.6 years), 17 athletes involved in agonistic activity (canoeing) (24.8 ± 6.1 years), and 17 normotensive healthy subjects as control group (24.8 ± 3.6 years). The testing protocol consisted of (1) clinic BP measurement, (2) echocardiography, (3) 12‐lead electrocardiographic examination (QT max, QTc max, QT min, QTc min, ΔQT, ΔQTc). Results: There were no significant differences between the body surface area, height, and age of the three groups. Clinic blood pressure was higher in hypertensives (146.5 ± 45.2/93.5 ± 4.9 mmHg) versus athletes (120.9 ± 10.8/77.1 ± 6.0 mmHg) and controls (123.5 ± 4.8/78.8 ± 2.9 mmHg) by definition. Indexed left ventricular mass (LVM/BSA) was significantly greater in both athletes (148.9 ± 21.1 g/m²) and hypertensives (117.1 ± 15.2 g/m²) versus controls (81.1 ± 14.5 g/m²; P < 0.01), there being no statistical difference among them. LVH (LVMI > 125 g/m²) was observed in all athletes, while the prevalence in hypertensives was 50%. In spite of this large difference in cardiac structure there were no significant differences in QT parameters between athletes and the control group, while hypertensive patients showed a significant increase in QT dispersion versus the two other groups (ΔQT 82 ± 2.1, 48 ± 1.3, 49 ± 2.3 ms; P < 0.01; ΔQTc 88 ± 2.0, 47 ± 1.4, 54 ± 2.7; P < 0.01). Conclusions: LVH induced by physical training activity is not associated with an increase in QT dispersion, whereas pathological increase in LVM secondary to hypertension is accompanied by an increased QT dispersion.     

高盐饮食对大鼠左室肥厚的影响

目的　观察高盐饮食对原发性高血压大鼠 (SHR)及正常血压大鼠 (WKY)左室肥厚的影响 ,并探讨其可能机制。方法　SHR和WKY各 2 0只分别分为两组 :( 1)高盐饮食组SHRSL(n =10 )和WKYSL(n =10 )饮用含 2 %NaCl盐水 ;( 2 )正常盐饮食组SHRNS(n =10 )和WKYNS(n =10 )饮用不含NaCl清水 ,共饲养 6周。测量左室重量指数 (LVI) ,心肌细胞直径(CMD) ,放免测定循环ANP以及心肌局部ET 1含量。结果　 ( 1)左室重量指数及心肌细胞直径SHRSL较SHRNS显著增加(P <0 0 1) ,WKYSL较WKYNS有所增加 ,但差异不显著 (P >0 0 5 ) ;( 2循环中ANP浓度WKYSL较WKYNS明显升高 (P <0 0 1) ,SHRSL较SHRNS无明显差别 (P >0 0 5 ) ;( 3 )左室局部ET 1:SHRSL较SHRNS显著增加 (P <0 0 1) ,WKYSL较WKYNS无明显差别 (P >0 0 5 )。结论　高盐饮食可引起SHR左室肥厚 ,盐负荷后SHR心肌局部ET 1含量的增加可能是SHR左室肥厚的原因之一     

跨室壁复极离散变化及其对心电图T波影响的在体实验研究

为探讨在体情况下心肌跨室壁复极离散变化及其对心电图T波影响的可能机制。运用单相动作电位 (MAP)记录技术 ,同步记录 2 1只开胸兔的左室心肌心外膜层 (Epi) ,中层 (Mid) ,内膜层 (Endo)的MAP ,分别予以减慢心率、静脉注射索他洛尔 (dl sotalol)、海葵毒素 (ATX Ⅱ )后 ,观察跨室壁复极离散的变化以及心电图T波的相应改变。结果 :①慢频率导致Mid层细胞MAP复极时间 (RT)显著延长 (从 2 0 2± 19ms到 370± 34ms,P <0 .0 5 ) ,跨壁复极离散度 (TDR)增大 (从 11± 4ms到 40± 2 1ms,P <0 .0 5 ) ,QT间期延长 (从 2 0 5± 2 1ms到 371± 30ms,P <0 .0 5 ) ,T波增宽。②dl sotalol导致Mid层细胞MAP的RT显著的延长 (从 2 0 2± 19ms到 395± 34ms,P <0 .0 5 ) ,TDR增大 (从 10± 3ms到 75± 2 5ms ,P <0 .0 5 ) ,QT间期延长 (从 2 0 8± 16ms到 397± 33ms,P <0 .0 5 ) ,三层心肌MAP的 3相复极不同程度的延长 ,使复极电位梯度变化 ,产生增宽、低幅有切迹的T波。③ATX Ⅱ导致Mid层细胞MAP的RT显著的延长 (从370± 34ms到 473± 35ms,P <0 .0 5 ) ,TDR增大 (从 40± 2 1ms到 6 2± 19ms,P <0 .0 5 ) ,QT间期延长 (从 372± 33ms到 479± 33ms,P <0 .0 5 ) ,三层心肌MAP的 2相平台期不同程度延长 ,使复极电位梯     

Absence of Gender Difference in Circadian Trends of QT Interval Duration

Background: The long-term circadian behavior of the QT interval duration was comparatively evaluated in females and in males. The corrected QT interval duration is known to be longer in females than in males, and this gender difference persists after double autonomic blockade. Methods: Our population consisted of 32 young healthy subjects (16 males). Twenty-four-hour ambulatory ECG recordings were processed by QT analysis software. All sinus complexes were averaged on a 30-second time basis. The averaged template was defined by a single QT apex (QTa) interval and its mean RR interval. The circadian behavior of ventricular repolarization was assessed by the nocturnal lengthening of QTa at an identical RR interval, and by the respective diurnal and nocturnal QT/AR relationship in both genders. Results: The corrected QTa was longer in females (318 ± 20 vs 294 ± 13 ms, P = 0.0003). The correlation coefficients of the QTa/RR regression lines were >0.75, whatever the gender and the circadian period considered. In both genders, diurnal slopes were higher than nocturnal ones (0.15 ± 0.01 vs 0.09 ± 0.03 in males and 0.18 ± 0.04 vs 0.09 ± 0.05, P = NS), and the nocturnal lengthening of QTa was on the same range (25 ± 12 vs 17 ± 12 ms, P = NS). Conclusion: The longer corrected QT interval in females is not associated with a specific static or dynamic circadian behavior of QT interval.     

ECG low QRS voltage and wide QRS complex predictive of centenarian 360-day mortality

We examined the electrocardiographic (ECG) findings of centenarians and associated them with >360-day survival. Physical and functional assessment, resting electrocardiogram and laboratory tests were performed on 86 study participants 101.9?±?1.2 years old (mean?±?SD) (70 women, 16 men) and followed for at least 360 days. Centenarian ECGs were assessed for left ventricular hypertrophy (LVH) according to the Romhilt–Estes score, Sokolow–Lyon criteria and Cornell voltage criteria which were positive for 12.8, 6.98, and 10.5 % of participants, respectively. Fifty-two study participants (60 %) survived ≥360 days. Multivariate logistic regression analysis revealed a negative relationship between 360-day survival and the following: R II <0.45 mV adjusted for CRP (odds ratio (OR)?=?0.108, 95 % confidence interval (CI)?=?0.034–0.341, P?<?.001), R aVF?<?0.35 mV adjusted for CRP (OR?=?0.151, 95 % CI?=?0.039–0.584, P?<?.006), Sokolow–Lyon voltage <1.45 mV adjusted for CRP (OR?=?0.178, 95 % CI?=?0.064–0.492, P?=?.001), QRS ≥90 ms adjusted for CRP (OR?=?0.375, 95 % CI?=?0.144–0.975, P?=?.044), and Romhilt–Estes score ≥5 points adjusted for sex and Barthel Index (OR?=?0.459, 95 % CI?=?0.212–0.993, P?=?.048) in single variable ECG models. QRS voltage correlated positively with systolic and pulse pressure, serum vitamin B12 level, sodium, calcium, phosphorous, TIMP-1, and eGFR. QRS voltage correlated negatively with BMI, WHR, serum leptin, IL-6, TNF-α, and PAI-1 levels. QRS complex duration correlated positively with CRP; QTc correlated positively with TNF-α. Results suggest that Romhilt–Estes LVH criteria scores ≥5 points, low ECG QRS voltages (Sokolow–Lyon voltage <1.45 mV), and QRS complexes ≥90 ms are predictive of centenarian 360-day mortality.     

QT Interval Length and Diabetic Autonomic Neuropathy

QT interval length was measured in ECG recordings from three groups of age-matched male subjects: 36 normal subjects, 41 diabetic patients without (DAN-ve), and 34 with (DAN+ve) autonomic neuropathy. ECG samples were selected from previously recorded 24-h ECGs on the basis of a clearly defined T wave and a steady RR interval over 2 min of around 750 ms (80 beats min^?1). There were no significant differences in RR interval between the groups. The two diabetic groups had slightly longer QT measurements (normal 365 ± 14 (±SD) ms, DAN-ve 373 ± 18 ms, DAN+ve 375 ± 23 ms, p = 0.05), and corrected QT (QTc) values (normal 423 ± 15 ms, DAN-ve 430 ± 20 ms, DAN+ve 435 ± 24 ms, p = 0.05). Ten diabetic patients fell above our defined upper limit of normal for QTc (>mean + 2SD). There was a significant correlation in the DAN-ve group between the QT indices and 24-h RR counts (QT r = ?0.38, p < 0.01; QTc r = ?0.40, p < 0.01). We conclude that there are some small alterations in QT interval length in the steady state in diabetic autonomic neuropathy. The changes appear to be due to autonomic impairment, rather than diabetes per se.     

Dispersion of the QT Interval in Subjects with Frequent Nonsustained Ventricular Arrhythmias and No Underlying Heart Disease: Arrhythmogenic Substrate or Mechanoelectrical Feedback of Arrhythmias?

Background: QT dispersion (QTd) on the ECG is thought to reflect the temporal and spatial inhomogeneity of repolarization in the underlying myocardium. In myocardial infarction, ischemia, and long QT syndromes, an increased QTd is associated with a propensity for malignant ventricular arrhythmias and sudden cardiac death. We investigated this feature of the repolarization process in subjects with frequent ventricular arrhythmias and structurally normal hearts. Methods: Forty‐nine patients referred for frequent, nonsustained ventricular arrhythmias (45 ± 14 years, ×± SD, 61% female) had normal ventricular dimensions and function, no late potentials, and normal ECG. They were compared with 30 controls (42 ± 13 years, 50% female). QTd was measured as the difference between the longest and the shortest QT in the six precordial leads at a paper speed of 50 mm/s. Results: In patients, QTc was similar to that of controls: 395 ± 21 versus 386 ± 20. However, QTd was greater: 49 ± 20 ms versus 32 ± 14 ms, P < 001. Moreover, 18 patients (36%) had QTd exceeding 60 ms—a value superior to the mean normal value of 2 SD—compared to only 1 control (3%) (P < 0.01). Finally, patients with more frequent ventricular arrhythmias had larger QTd. Conclusions: In patients with frequent nonsustained ventricular arrhythmias and otherwise normal hearts, QT interval dispersion is increased. We speculate that, instead of representing a specific electrophysiological substrate of arrhythmias, QT dispersion in this specific population could result from arrhythmias themselves through a possible mechanoelectrical feedback.     

Left ventricular mass and hypertrophy assessment by means of the QRS complex voltage-independent measurements

ECG QRS-complex voltage-based criteria are relatively insensitive for detection of increased left ventricular mass (LVM). We developed and evaluate a new ECG index for LV hypertrophy (LVH) detection regardless of the QRS voltage. METHODS: Study population consisted of 106 patients (73 m, 33 f, aged 60 +/- 10 years) with established coronary artery disease (CAD). All patients had LVM assessed echocardiographically and indexed to BSA (LVMI(ECHO)). LVH was diagnosed if LVMI(ECHO) >117 g/m2 in men and >104 g/m2 in women. LV geometry was also determined. Analysed ECG variables, obtained from 12 leads recorded simultaneously, were: the QRS complex duration (QRSd, ms), the average 12-lead time to maximal deflection (TMD, ms), the average 12-lead QRS complex voltage (12QRSV, mV), the average product of 12 lead QRS voltage and duration (12QRSVd, mV ms), Sokolow-Lyon voltage and V-d product (SLV, SLVd), Cornell voltage and V-d product (CV, CVd). A newly developed index, LVM(ECG), was calculated, as LVM(ECG) = [(2 x TMD+QRSd/pi)3-(QRSd/pi)3]*0.0001 (ms3), and indexed to BSA (LVMI(ECG), ms3/m2). RESULTS: Means of the QRS voltage-related parameters were similar in patients with LVH and normal LVM. Greater differences existed between both groups when the QRS voltage-duration products were compared. LVMI(ECG) was most powerful in distinguishing between groups (130 +/- 33 LVH vs 91 +/- 21 normal LVM, p < 0.001). LVMI(ECG) correlated with LVMI(ECHO) better (r = 0.77, p < 0.001) than other indices (r coefficients between 0.24 for SLV and 0.49 for CVd). None of the examined indices allowed for distinction between eccentric and concentric LVH. The new index showed better statistical performance (area under ROC = 0.861) compared to the other indices (AUC range 0.545-0.697, p<0.001 vs LVMI(ECG)). At the specificity level of 92%, the value of LVMI(ECG) > 120 ms3/m2 had the sensitivity of 64% for detection of increased LVM. The sensitivities of the other parameters were significantly lower (sensitivity range 18-42%). Relative intra- and interobserver errors and correlation coefficients for LVMI(ECG) calculation were 0.4% and 1.6% and r = 0.94 and 0.98, respectively. CONCLUSIONS: In patients with CAD an assessment of LV mass and detection of hypertrophy using the QRS complex time-dependent index is feasible. The new index correlated well with echocardiographically-determined LVM and showed better statistical performance than indices which include QRS-voltage measurements. The results are promising and warrant further studies to evaluate the utility of the new index as a risk predictor.     

Relation between QRS amplitude and left ventricular mass in the initial stage of exercise-induced left ventricular hypertrophy in rats

The aim of the study was to analyze the relationship between QRS amplitude and left ventricular mass (LVM) in early stages of two different experimental models of left ventricular hypertrophy (LVH) in rats: in exercise-induced hypertrophy and pathological hypertrophy due to genetically conditioned pressure overload. Three groups of experimental animals were studied: healthy control Wistar-Kyoto rats (WKYs), spontaneously hypertensive rats (SHRs), and WKY rats exposed to training by intermittent swimming (SWIM). Orthogonal electrocardiograms were recorded in each group at the age of 12 and 20 weeks, and the maximum spatial QRS vector (QRSmax) was calculated. Then the animals were sacrificed and LVM was measured. The specific potential of myocardium (SP) was calculated as a ratio of QRSmax to LVM. The QRSmax values did not follow the changes in LVM. At the end of the follow-up period, the highest values of QRSmax were recorded in the control WKY rats (0.80 +/- 0.05 mV). The QRSmax values in both groups with experimental LVH were significantly lower as compared with control animals (SHR 0.44 +/- 0.02 mV, p < 0.001; SWIM 0.53 +/- 0.04 mV, p < 0.001). Similarly, the SP values were significantly lower in both groups with experimental LVH as compared with control animals (SHR 0.42 +/- 0.02 mV/g, p < 0.001; SWIM 0.55 +/- 0.05 mV/g, p < 0.001). A decrease in QRSmax and SP was observed in both models of experimental LVH. We attributed these findings to the changes in electrogenetic properties of myocardium in the early stage of developing LVH. In other words, it is changes of nonspatial determinants that influence the resultant QRS voltage in terms of the solid angle theory.     

QT间期及其离散度测定的方法学研究和正常值

报告１００例健康成人同步体表１２导联心电图的ＱＴ间期和ＱＴ间期离散度（ＱＴｄ）：（１）各参数测量结果（±ｓ）：ＱＴｄ、ＱＴｃｄ（矫正ＱＴｄ）、ＪＴｄ（ＪＴ离散度）、ＱＴｐｄ（ＱＴ顶点离散度）、ＪＴｐｄ（ＪＴｐ离散度）、Ｔｐ－ＴＥｄ（Ｔ波顶点至Ｔ波终点间期离散度）、ＱＲＳｄ（ＱＲＳ间期离散度）和Ｏ－Ｑｄ（ＱＲＳ起始时间离散度）分别为２５．６±１１．２，２６．８±１２．６，２６．１±１２．５，２４．６±１４．７，３２．０±１５．６，３１．０±１４．６，２０．６±８．８和１２．５±７．３ｍｓ，其范围均在５～５０ｍｓ以内，与国际上研究结果一致。笔者认为ＱＴｄ的正常值可暂定为＜５０ｍｓ；（２）体表１２导联心电图同步记录方法，比常规非同步记录更能反映ＱＴｄ的实际情况，并且可测量同步１２导联ＱＲＳ起始部时间（Ｑ－ＱＴ）及其离散度（Ｑ－ＱＴｄ）；（３）本文资料由国内和国外三组不同人员测量结果相同，表明ＱＴ、ＱＴｄ测定的可重复性好；（４）性别差异，ＱＴ间期女性比男性长，而ＱＲＳ间期男性比女性长，其机理尚待进一步研究探讨。     

Sildenafil Citrate Does Not Affect QT Intervals and QT Dispersion: An Important Observation for Drug Safety

Background: Sildenafil is an effective and widely used therapeutic agent for erectile dysfunction. Deaths have been reported due to sildenafil use and most of them are attributed to concurrent use of nitrates. However, the effects of sildenafil on QT intervals, QT dispersion, and the possible risk of ventricular arrhythmia have not been studied before. Our aim in this study was to evaluate the effect of sildenafil citrate on QT intervals and QT dispersion. Methods: Thirty‐six patients with erectile dysfunction were included in this study. Twenty‐one patients had coronary artery disease whereas 12 of them also had accompanying diabetes mellitus. Standard 12‐lead electrocardiograms (ECG) were recorded three times: before, and at the first and fourth hours of 50 mg sildenafil citrate ingestion. All QT parameters were corrected for heart rate. Results: Mean age of the patients was 54 ± 12 years. The mean heart rate did not differ significantly between the three ECG examinations. The corrected and uncorrected maximum and minimum QT intervals were not significantly different between the three ECG examinations. The QT dispersion and corrected QT dispersion before and 1 hour and 4 hours after sildenafil ingestion were 31 ± 9 ms, 36 ± 10 ms; 32 ± 11 ms, 37 ± 14 ms; 27 ± 8 ms, 32 ± 9 ms, respectively (P > 0.05) . Conclusions: Sildenafil does not prolong QT intervals or increase QT dispersion in patients with erectile dysfunction. Our results suggest that the risk of ventricular arrhythmia does not increase with ingestion of 50 mg sildenafil.