Quantitative Aspects of Ventricular Repolarization

Introduction: QT dispersion assesses repolarization inhomogeneity on 12-lead standard ECG. However, the implications of the electrical cardiac vector during the repolarization phase (the T wave loop) with the genesis of this phenomenon are unknown. Methods and Results: The aim of this study was to explore conventional 12-lead resting ECG QT dispersion and the corresponding morphology of the spatial three-dimensional (3-D) T wave loop in 25 normals subjects, 30 postmyocardial infarction (Ml) patients, and in 17 individuals with congenital long QT syndrome (LQTS). Standard and XYZ ECG leads were simultaneously digitized (250 Hz) and automatically analyzed. Ventricular repolarization dispersion was estimated by the range (RAN12o) and standard deviation (SD12o) of the 12 rate corrected QTo intervals (between the Q wave onset and the T wave offset). Spatial T wave loops were extracted from XYZ data and analyzed with a 3-D algorithm which provides quantitative parameters related to the loop morphology. All scalar measurements of dispersion were significantly larger in the two pathological populations; however none of them could discriminate post-MI from LQTS groups (RAN12o = 33.3, 61.4, and 62.7 ms respectively, for the three populations). Conversely, a loss of planarity and an increased roundness of the T wave loop were observed in the two pathological groups, with the former effect more pronounced in the LQTS (P = 0.04 compared to post-MI) and the latter in the post-MI group (P = 0.02 compared to LQTS). Furthermore, multiple regression and principal component analyses showed that planarity and roundness are independently involved with QT dispersion. Conclusion: Changes in the morphology of the spatial T wave loop associated with QT dispersion were identified. These changes discriminate different substrates of repolarization inhomogeneity. The use of a 3-D technique to assess repolarization inhomogeneity may bring additional information on the intrinsic nature of this disorder.     

Effect of Heart Rate on Ventricular Repolarization in Healthy Individuals Applying Vectorcardiographic T Vector and T Vector Loop Analysis

Background: Ventricular repolarization (VR) is strongly influenced by heart rate (HR) and autonomic nervous activity, both of which also are important for arrhythmogenesis. Their relative influence on VR is difficult to separate, but might be crucial for understanding while some but not other individuals are at risk for life‐threatening arrhythmias at a certain HR. This study was therefore designed to assess the “pure” effect of HR increase by atrial pacing on the ventricular gradient (VG) and other vectorcardiographically (VCG) derived VR parameters during an otherwise unchanged condition. Methods: In 19 patients with structurally normal hearts, a protocol with stepwise increased atrial pacing was performed after successful arrhythmia ablation. Conduction intervals were measured on averaged three‐dimensional (3D) QRST complexes. In addition, various VCG parameters were measured from the QRS and T vectors as well as from the T loop. All measurements were performed after at least 3 minutes of rate adaptation of VR. Results: VR changes at HR from 80 to 120 bpm were assessed. The QRS and QT intervals, VG, QRSarea, Tarea, and Tamplitude were markedly rate dependent. In contrast, the Tp‐e/QT ratio was rate independent as well as the T‐loop morphology parameters Tavplan and Teigenvalue describing the bulginess and circularity of the loop. Conclusions: In healthy individuals, the response to increased HR within the specified range suggests a decreased heterogeneity of depolarization instants, action potential morphology, and consequently of the global VR. Ann Noninvasive Electrocardiol 2011;16(3):287–294     

Dynamics of Ventricular Repolarization in Patients with Dilated Cardiomyopathy Versus Healthy Subjects

Background: Patients with impaired left ventricular function have a high risk of developing ventricular arrhythmias and sudden death. Among different markers of risk, the prolongation and regional heterogeneity of repolarization are of increasing interest. However, there are limited data regarding feasibility of analyzing repolarization parameters and their dynamics in 24‐hour Holter ECG recordings. Methods: Dynamic behavior of repolarization parameters was studied with a new automatic algorithm in digital 24‐hour Holter recordings of 60 healthy subjects and 55 patients with idiopathic dilated cardiomyopathy (IDC). Repolarization parameters included the mean value of QT and QTc durations, QT dispersion, and peaks of QT duration and QT dispersion above prespecified thresholds. Results: In comparison to healthy subjects, patients with IDC had lower heart rate variability, longer mean QT and QTc durations, higher content of QTc peaks >500 ms, longer QT dispersion and its standard deviation, and a higher content of peaks >100 ms of QT dispersion (P < 0.01 for all comparisons). These repolarization parameters were significantly higher in IDC patients after adjustment for age, sex, and heart rate variability. The parameters of repolarization dynamics correlated with SDNN in healthy subjects but not in dilated cardiomyopathy patients. Conclusions: The automatic assessment of repolarization parameters in 24‐hour digital ECG recordings is feasible and differentiates dilated cardiomyopathy patients from healthy subjects. Patients with dilated cardiomyopathy have increased QT duration, QT dispersion, and increased variability of QT dispersion reflecting variations in T‐wave morphology, the factors which might predispose them to the development of arrhythmic events.     

Electrocardiographic Quantitation of Heterogeneity of Ventricular Repolarization

Background: QT interval dispersion (QT_d) measured from the surface ECG has emerged as the most common noninvasive method for assessing heterogeneity of ventricular repolarization. Although QT_d correlates with dispersion of monophasic action potential duration at 90% repolarization and with dispersion of recovery time recorded from the epicardium, total T‐wave area, representing a summation of vectors during this time interval, has been shown to have the highest correlation with these invasive measures of dispersion of repolarization. However, recent clinical studies suggest that the ratio of the second to first eigenvalues of the spatial T‐wave vector using principal component analysis (PCA ratio) may more accurately reflect heterogeneity of ventricular repolarization. Methods: To better characterize the ECG correlates of surface ECG measures of heterogeneity of ventricular repolarization and to establish normal values of these criteria using an automated measurement method, the relations of QRS onset to T‐wave offset (QT_od) and to T‐wave peak (QT_pd) dispersion and the PCA ratio to T‐wave area and amplitude, heart rate, QRS axis and duration, and the QT_o interval were examined in 163 asymptomatic subjects with normal resting ECGs and normal left ventricular mass and function. QT_od and QT_pd were measured by computer from digitized ECGs as the difference between the maximum and minimum QT_o and QT_p intervals, respectively. Results: In univariate analyses, a significant correlation was found between the sum of the T‐wave area and the PCA ratio (R =?0.46, P < 0.001), but there was no significant correlation of the sum of T‐wave area with QT_od (R = 0.11, P = NS) or QT_pd (R=0.09, P = NS). There were only modest correlations between QT_od and QT_pd (R = 0.45) and between the PCA ratio and QT_od (R = 0.29) and QT_pd (R = 0.49) (each P < 0.001). In stepwise multivariate linear regression analyses, the PCA ratio was significantly related to the sum of T‐wave area, T‐wave amplitude in aVL, and to female gender (overall R = 0.54, P < 0.001), QT_od correlated only with the maximum QT_o0 interval (R = 0.39, P < 0.001), and QT_pd was related to heart rate and QRS axis (overall R = 0.36, P <0.001). In addition, the normal interlead dispersion of repolarization as measured by QT_od was significantly greater than dispersion measured by QT_od (23.5 ± 11.5 ms vs 18.3 ± 11.2 ms, P < 0.001). Conclusions: These findings provide new information on ECG measures of heterogeneity of repolarization in normal subjects, with a significantly higher intrinsic variability of Q to T‐peak than Q to T‐offset dispersion and only modest correlation between these wo measures. The independent relation of the PCA ratio to the sum of T‐wave area suggests that the PCA ratio may be a more accurate surface ECG reflection of the heterogeneity of ventricular repolarizat on. A.N.E. 2000;5(1):79–87     

QT Dispersion in Healthy Chinese Children and Adolescents

Background: QT dispersion (QT_d) reflects the interlead difference in QT interval. It may provide a measure of repolarization inhomogeneity. Studies on QT_d mainly involve adults, while QT_d in children are less well studied. The aim of this study was to evaluate QT_d in healthy children and assess the relationship of gender, age, and anthropometric parameters, viz. weight (W), height (H), body mass index (BMI), and body surface area (BSA) to QT_d. Methods: Five hundred and one Chinese children and adolescents (243 boys, 258 girls) with no history of cardiovascular diseases were studied. Their ages ranged from 6.3 to 17.5 years. Surface 12-lead electrocardiograms were measured in each child at rest. QT and R-R intervals in each of the 12 leads were manually measured at a magnification of 2X. QT was corrected to QT_c according to Bazett's formula. QT_d was calculated as the difference between the maximum and minimum QT of the measured leads, while corrected QT_d (QT_cd) was the difference between the maximum and minimum QT_c of the measured leads. Adjusted QT_d was QT_cd divided by the square root of the number of measurable leads. Results: Mean QT_d of all subjects was 34 ms (95% Cl 33.6–35.1 msl. Mean QT_d for boys and girls was 35 ms and 34 ms, respectively (P = 0.18). Mean QT_cd for the whole group was 47 ms (95% Ci 45.8–48.2 ms), while mean adjusted QT_cd was 14 ms (95% Cl 13.8–14.5 ms). There were no significant gender differences in QT_cd or adjusted QT_cd. Weak negative correlation existed between age and QT_d, QT_d and adjusted QT_cd (r =?0.22, r =?0.26, r =?0.21, respectively, P < 0.001 Similarly, QT_cd also had a weak significant negative correlation with W (r =?0.20), H (r =?0.21) and BSA (r =?0.22), P < 0.001. However, multiple stepwise regression analysis revealed that only age was significantly related to QT_cd (R2 = 0.066) and QT_d (R2 = 0.059), P < 0.001. Conclusions: The results of this study indicate a trend of decreasing QT_d and QT_cd with increasing age, supported by multiple regression analysis. However indices of QT_d in children are not influenced by anthropometry. This information may be useful for the clinical application of QT_d in children. A.N.E. 1999;4(3):281–285     

Electrocardiographic Findings at Initial Diagnosis in Children with Isolated Left Ventricular Noncompaction

Background: The aim of this study was to comprehensively evaluate electrocardiographic (ECG) findings of isolated left ventricular noncompaction (IVNC) patients at initial diagnosis and to explore the correlation between them and the clinical, echocardiographic, and magnetic resonance imaging (MRI) findings. Methods: Twenty‐three patients diagnosed with IVNC by echocardiography and cardiac MRI between January 2006 and June 2010 were enrolled in this study. The patients were examined with standard ECG and 24‐hour Holter ECG. For comparison purpose, ECGs of 50 healthy children of similar ages and demographic characteristics were taken. Results: In 87% of patients, ECG abnormalities were found. The most frequently seen ECG findings were left ventricular hypertrophy, ST‐segment depression, and negative T wave related to abnormal repolarization particularly in DII, DIII, and V_4–6 leads, as well as prolonged PR and QTc intervals. No ECG features or patterns were found that were specific to the disease. In contrast to adult patients, while no intraventricular conduction defects (particularly in the left bundle brach) were found in any of our patients, 13% had considerable bradycardia and one required a pacemaker. The Holter ECG recordings showed supraventricular tachycardia attacks in two patients and a short ventricular tachycardia attack in one. Patients whose echocardiograms and MRI showed left ventricular systolic dysfunction and left ventricular dilatation had signs of left ventricular hypertrophy and repolarization abnormality on their ECGs, but there was no significant difference in PR, QRS, and QTc intervals. Conclusion: Regardless of how frequently left ventricular hypertrophy and repolarization abnormalities are found on IVNC patients’ initial ECGs, we think that they are not unique to the disease but are related to the severity of the cardiomyopathy. Ann Noninvasive Electrocardiol 2011;16(2):184–191     

Electrocardiographic Markers of Late Sudden Death Risk in Postoperative Tetralogy of Fallot Children

Late Sudden Death Risk in Postoperative TOF. Following surgery for tetralogy of Fallot (TOP), children may develop late onset ventricular arrhythmias. Many patients have both depolarization and repolarization abnormalities, including right bundle branch block (RBBB) and QT prolongation. The goal of this study was to improve prospective risk-assessment screening for late onset sudden death. Resting ECG markers including QRS duration, QTc, JTc, and interlead QT and JT dispersion were statistically analyzed to identify those patients at risk for ventricular arrhythmias and sudden cardiac death. To determine predictive markers for future development of arrhythmia, we examined 101 resting ECGs in patients (age 12 ± 6 years) with postoperative TOF and RBBB, 14 of whom developed late ventricular tachycardia (VT) or sudden death. These ECGs were also compared with an additional control group of 1000 age- and gender-matched normal ECGs. The mean QRS (± SD) in the VT group was 0.18 ± 0.02 seconds versus 0.14 ± 0.02 seconds in the non-VT group (P < 0.01). QTc and JTc in the VT group was 0.53 ± 0.05 seconds and 0.33 ± 0.03 seconds compared with 0.50 ± 0.03 seconds and 0.32 ± 0.03 seconds in the non-VT group (P = NS). There was no increase in QT dispersion among TOF patients with VT or sudden death compared with control patients or TOF patients without VT, although JT dispersion was more common in the TOF groups. A prolonged QRS duration in postoperative TOF with RBBB is more predictive than QTc, JTc, or dispersion indexes for identifying vulnerability to ventricular arrhythmias in this population, while retaining high specificity. The combination of both QRS prolongation and increased JT dispersion had very good positive and negative predictive values. These results suggest that arrhythmogenesis in children following TOF surgery might involve depolarization in addition to repolarization abnormalities. Prospective identification of high-risk children may be accomplished using these ECG criteria.     

Comparison of ECG Variables of Dispersion of Ventricular Repolarization with Direct Myocardial Repolarization Measurements in the Human Heart

Validation of ECG Variables of Dispersion. Introduction: QT dispersion (QTD) from the 12-tead ECG has been widely adopted as a noninvasive index of dispersion of ventricular repolarization (DVR). QTD, however, has never been validated by direct comparison with myocardial DVR in the human heart. Methods and Results: Monophasic action potential (MAP) recordings obtained in an earlier study were retrospectively matched with 12-lead ECGs available from within 24 hours of the invasive procedure. MAPs were available from an average of 8 ± 3 left endocardial sites in 4 patients with left ventricular hypertrophy (LVH) and 7 patients with normal ECGs, and 6 ± 2 epicardial sites in 3 patients of each group during normal ventricular activation. Local repolarization time (RT) was determined as MAP duration at 90% repolarization plus the local activation time. Dispersion of RT was calculated as the difference between the earliest and latest RT. ECGs were digitized and analyzed with recently described interactive QTD analysis software. In addition to standard QTD (defined as QT_max– QT_min), all currently proposed ECG dispersion variables were compared and correlated with the invasive measurements of DVR. QTD exhibited a reasonable correlation with dispersion of RT (R = 0.67; P < 0.01). Several other variables designed to measure DVR exhibited a similar, but not better, correlation. Among them, the QT peak/QT end ratio in V₃ (R =?0.72; P < 0.01) and averaged over all analyzableleads (R =?0.59; P < 0.01) exhibited a good correlation with dispersion of RT, which was further improved when endocardial measurements were considered alone. T area measures did not correlate with dispersion of RT, but discriminated LVH. Conclusion: DVR can he assessed by means of a 12-lead surface ECG. Several of the variables under study exhibit a similar accuracy in determination of true myocardial dispersion of repolarization. Variables involving the terminal part of repolarization, such as the QT peak/QT ratio, even from a single lead, may add to the determination of DVR from the human heart.     

Ibutilide-Induced Changes in the Temporal Lability of Ventricular Repolarization in Patients with and without Structural Heart Disease

Introduction: Ibutilide has been shown to prolong repolarization times and increase the risk of ventricular tachyarrhythmias particularly in patients with structural heart disease. The mechanisms underlying its proarrhythmic effects remain incompletely understood. We sought to define the effects of ibutilide on the temporal lability of ventricular repolarization in patients with and without structural heart disease.
Methods: Twenty-four patients referred for electrophysiology study underwent monophasic action potential (MAP) recordings in the right ventricle during sinus rhythm and random interval right atrial pacing (RIAP). Ibutilide was subsequently administered and the recordings repeated both in sinus rhythm and with RIAP. Digitized recordings were analyzed offline for calculation of the QT variability index (QTVI) based on surface ECG, and the MAP duration variability index (MAPDVI) based on the intracardiac MAP signal.
Results: Of 24 patients enrolled, analyses were performed in 21 patients (mean age 59 ± 15 years, 38% women). In three patients, the data were not analyzed due to frequent premature ventricular complexes. Ibutilide resulted in significant changes in heart rate (mean difference: −7.4 ± 0.91 bpm, P < 0.0001) and the surface QT interval (mean difference: 59.6 ± 12.2 ms, P = 0.0001) during sinus rhythm. After ibutilide, QTVI remained unchanged from baseline during sinus rhythm but was significantly different in the setting of RIAP (mean difference: 0.345 ± 0.098, P = 0.0022). With subgroup analyses, these differences remained significant regardless of the presence or absence of heart disease.
Conclusion: Ibutilide results in overall prolongation of ventricular repolarization and reductions in baseline sinus rates. Ibutilide increases temporal lability of repolarization only with enriched fluctuations in heart rate.     

Impact of Left Ventricular Remodeling on Ventricular Repolarization and Heart Rate Variability in Patients after Myocardial Infarction Treated with Primary PCI: Prospective 6 Months Follow‐up

Background: The relation between postinfarction left ventricle remodeling (LVR), autonomic nervous system and repolarization process is unclear. Purpose of the study was to assess the influence of LVR on the early (QTpeak) and late (TpeakTend) repolarization periods in patients after myocardial infarction (MI) treated with primary PCI. The day‐to‐night differences of repolarization parameters and the relation between QT and heart rate variability (HRV) indices, as well left ventricle function were also assessed. Methods: The study cohort of 104 pts was examined 6 months after acute MI. HRV and QT indices (corrected to the heart rate) were obtained from the entire 24‐hour Holter recording, daytime and nighttime periods. Results: LVR was found in 33 patients (31.7%). The study groups (LVR+ vs LVR?) did not differ in age, the extent of coronary artery lesions and treatment. Left ventricle ejection fraction (LVEF) was lower (38%± 11% vs 55%± 11%, P < 0.001), both QTc (443 ± 26 ms vs 420 ± 20 ms, P < 0.001) and TpeakTendc (98 ± 11 ms vs 84 ± 12 ms, P < 0.005) were longer in LVR + patients, with no differences for QTpeakc. Trends toward lower values of time‐domain (SDRR, rMSSD) HRV parameters were found in LVR+ pts. Day‐to‐night difference was observed only for SDRR, more marked in LVR‐group. Remarkable relations between delta LVEF (6 months minus baseline), delta LVEDV and TpeakTendc were found, with no such relationships for QTpeakc. Conclusions: The patients with LVR have longer repolarization time, especially the late phase‐ TpeakTend, which represents transmural dispersion of repolarization. Its prolongation seems to be related to local attributes of myocardium and global function of the left ventricle but unrelated to the autonomic nervous influences. Remodeling with moderate LV systolic dysfunction is associated with insignificant decrease in HRV indices and preserved circadian variability.     

Electrocardiographic Transmural Dispersion of Repolarization in Patients with Inherited Short QT Syndrome

Background : Short QT syndrome (SQTS) carries an increased risk for sudden cardiac death. However, only a short QT interval does not express the risk of ventricular arrhythmias. Thus, additional evaluation of the repolarization abnormality in SQTS patients is essential. In experimental models of SQTS, increased transmural dispersion of repolarization (TDR) and its electrocardiographic counterpart T‐wave peak to T‐wave end interval (TPE) appeared critical for induction of polymorphic ventricular tachycardia (PMVT). In a clinical study with acquired long QT syndrome patients, TPE/QT ratio > 0.28 indicated arrhythmia risk. We hypothesized that the TPE/QT ratio would be greater in SQTS patients than in control subjects. Methods and Results : We compared the behavior of the electrocardiographic TDR in three seriously symptomatic SQTS patients of unknown genotype presenting baseline QTc values <320 ms and in nine healthy age‐matched control subjects. We determined QT and TPE intervals as well as TPE/QT ratio from 24‐hour ECG recordings using a computer‐assisted program. Diurnal average of TPE/QT ratio was 0.28 ± 0.03 in SQTS patients and 0.21 ± 0.02 in control subjects (P = 0.01). SQTS patients had also lesser capacity to change TPE intervals from steady‐state conditions to abrupt maximal values than control subjects. Conclusion : SQTS patients have increased and autonomically uncontrolled electrocardiographic TDR. According to experimental SQTS models, the present results may in part explain increased vulnerability of SQTS patients to ventricular arrhythmias.     

Age,Gender, and Autonomic Tone Effects on Surface Electrocardiographic Indices of Ventricular Repolarization

Background: Prolonged QT offset dispersion (QToD), an index of heterogeneity of ventricular repolarization, is thought to be an independent predictor of all‐cause and cardiovascular mortality. However the influence of gender and autonomic tone in healthy adults on age‐related changes in measures of ventricular repolarization are not well characterized. Methods: QToD and T wave complexity were measured in 56 healthy subjects with no detectable heart disease (by echo and stress test)—38 young subjects with a mean age of 28 ± 4 years and 18 old subjects with a mean age of 71 ± 7 years. QToD and T wave complexity were computed from 12‐lead ECGs using the GE Marquette QT Guard automated analysis program with manual over‐reading at rest (baseline), following exercise, and double autonomic blockade with atropine and propranolol. Data was analyzed using factorial ANOVA. Results: Young males had a significantly greater QToD than young and old females at baseline (28 ± 5 ms, 23 ± 5 ms, and 22 ± 5 ms, respectively, P < 0.01), an intrinsic effect independent of changes in autonomic tone. In contrast, females had significantly greater T wave complexity than males following exercise and double autonomic blockade with a definite trend at baseline. There was no correlation between T wave complexity and QToD. Conclusions: Age and gender demonstrate a complex interaction on indices of myocardial repolarization with different measures behaving differently. These findings have implications for better understanding age and gender effects on myocardial electrophysiology. A.N.E. 2001;6(4):290–297     

Early Repolarization Syndrome: Electrocardiographic Signs and Clinical Implications

Early repolarization syndrome (ERS) was previously considered as a benign variant, but it has recently emerged as a risk marker for idiopathic ventricular fibrillation (VF) and sudden death. As measured by electrocardiogram (ECG), early repolarization is characterized by an elevation of the J point and/or ST segment from the baseline by at least 0.1 mV in at least two adjoining leads. In particular, early repolarization detected by inferior ECG leads was found to be associated with idiopathic VF and has been termed as ERS. This condition is mainly observed in young men, athletes, and blacks. Also, it has become evident that electrocardiographic territory, degree of J‐point elevation, and ST‐segment morphology are associated with different levels of risk for subsequent ventricular arrhythmia. However, it is unclear whether J waves are more strongly associated with a depolarization abnormality rather than a repolarization abnormality. Several clinical entities can cause ST‐segment elevation. Therefore, clinical and ECG data are essential for differential diagnosis. At present, the data set is insufficient to allow risk stratification in asymptomatic individuals. ERS, idiopathic VF, and Brugada syndrome (known as J‐wave syndromes) are three clinical conditions that share many common ECG features; however, their clinical consequences are remarkably different. This review summarizes the current electrocardiographic data concerning ERS with clinical implications.     

Epinephrine Bolus Test in Detecting Long QT Syndrome Mutation Carriers with Indeterminable Electrocardiographic Phenotype

Background: In long QT syndrome (LQTS), prolonged and heterogeneous ventricular repolarization predisposes to serious arrhythmias. We examined how QT intervals are modified by epinephrine bolus in mutation carriers of three major LQTS subtypes with indefinite QT interval. Methods: Genotyped, asymptomatic subjects with LQTS type 1 (LQT1; n = 10; four different KCNQ1 mutations), type 2 (LQT2; n = 10; three different HERG mutations), and type 3 (LQT3; n = 10; four different SCN5A mutations), and healthy volunteers (n = 15) were examined. Electrocardiogram was recorded with body surface potential mapping system. After an epinephrine 0.04 μg/kg bolus QT end, QT apex, and T‐wave peak‐to‐end (Tpe) intervals were determined automatically as average of 12 precordial leads. Standard deviation (SD) of the 12 channels was calculated. Results: Heart rate increased 26 ± 10 bpm with epinephrine bolus, and similarly in all groups. QT end interval lengthened, and QT apex interval shortened in LQTS and normals, leading to lengthening of Tpe interval. However, the lengthening in Tpe was larger in LQTS than in normals (mean 32 vs 18 ms; P < 0.05) and SD of QT apex increased more in LQTS than in normals (mean 23 vs 7 ms; P < 0.01). The increase in Tpe was most pronounced in LQT2, and in SD of QT apex in LQT1 and LQT2. Conclusions: Abrupt adrenergic stimulation with a moderate dose of exogenous epinephrine affects ventricular repolarization in genotype‐specific fashion facilitating distinction from normals. This delicate modification may help in diagnosing electrocardiographically silent mutation carriers when screening LQTS family members. Ann Noninvasive Electrocardiol 2011;16(2):172–179     

交感神经调节失衡与缺血性心律失常关系的研究

为探讨急性心肌缺血后 ,交感神经对心室肌不同部位复极时程的调节及其与缺血性心律失常的关系 ,制备兔急性心肌缺血模型 ,分离、结扎并剪断双侧颈迷走、心交感神经 ,电刺激心交感神经远端。心室复极时程以心外膜电图 (EPG)的QT间期及采用玻璃微电极技术记录的动作电位时程 (APD90 、APD50 )表示。结果 :交感神经刺激使正常心室肌不同部位的QT间期、APD90 、APD50 均有明显缩短 (P <0 .0 5 ) ;不同部位心肌复极时程对交感神经刺激的反应性没有明显区别。急性心肌缺血后 ,交感神经刺激使缺血区QT间期、APD90 明显缩短 ,而非缺血区则无明显变化 ;非缺血区的QT间期、APD90 对交感神经刺激的反应性较缺血区明显减小 (P <0 .0 5 )。心肌缺血后心室易损期明显延长 ,交感神经刺激后更为延长 (P <0 .0 5 )。结论 :急性心肌缺血后 ,交感神经对非缺血区心室复极的调节作用减弱 ,交感神经兴奋导致心肌复极的不同步性更进一步增加 ,心室易损性增加 ,引起缺血性心律失常。     

Shock-Induced Dispersion of Ventricular Repolarization:

Shock-induced Dispersion and VF Induction. Introduction: Shock-induced dispersion of ventricular repolarization (SIDR) caused by an electrical field stimulus has been suggested as a mechanism of ventricular fibrillation (VF) induction: however, this hypothesis has not been studied systematically in the intact heart. Likewise, the mechanism underlying the upper (ULV) and lower (LLV) limit of vulnerability remains unclear.
Methods and Results: In eight Langendorff-perfused rabbit hearts, monophasic action potentials were recorded simultaneously from ten different sites of both ventricles. Truncated biphasic T wave shocks were randomly delivered at various coupling intervals and strengths, exceeding the vulnerable window, ULV, and LLV. SIDR, defined as the difference between the longest and shortest postshock repolarization times, was 64 ± 15 msec for sbocks inducing VF. SIDR was 41 ± 17 msec for shocks delivered above the ULV, and 33 ± 14 and 27 ± 8 msec for shocks delivered 10 msec before and after the vulnerable window, respectively (all P < 0.01 vs VF-inducing shocks). Although SIDR was larger for shocks delivered below the LLV(93 ± 24 msec, P < 0.01 vs VF-inducing shocks), the repolarization extension was significantly smaller for shocks below the LLV (10.3%± 3.9% vs 16.3%± 4.9%, P < 0.01).
Conclusion: SIDR is influenced by the shock timing and intensity. Large SIDR within the vulnerable window and an SIDR decrease toward its borders suggest that SIDR is essential for VF induction. The decrease in SIDR toward greater shock strengths may explain the ULV. Small repolarization extension for shocks below the LLV may explain why these shocks, despite producing large SIDR, fail to induce VF.     

Repolarization abnormality in idiopathic ventricular fibrillation: assessment using 24-hour QT-RR and QaT-RR relationships

INTRODUCTION: We evaluated the characteristics of QT-RR and QaT (apex of T wave)-RR relationships in patients with idiopathic ventricular fibrillation (IVF) compared with control subjects. We hypothesized that IVF patients have unique repolarization dynamics related to a reduced fast Na current and a prominent transient outward current. METHODS AND RESULTS: The study group consisted of 9 men (age 47 +/- 10 years) with IVF (6 with Brugada type and 3 with non-Brugada type) who had experienced nocturnal episodes of VF. The control group consisted of 28 healthy age-matched men (age 44 +/- 12 years). The relationships between QT and RR intervals and between QaT and RR intervals were analyzed from 24-hour Holter ECG data using an automatic measurement system. Both QT and QaT at RR intervals of 0.6, 1.0, and 1.2 seconds were determined from QT-RR and QaT-RR linear regression lines. Both QT-RR and QaT-RR slopes were lower in the IVF group than in the control group (QT-RR: 0.092 +/- 0.023 vs 0.137 +/- 0.031, P < 0.001; QaT-RR: 0.109 +/- 0.025 vs 0.153 +/- 0.028, P < 0.001). QT at an RR interval of 0.6 second did not differ between two groups, but QT at RR intervals of either 1.0 or 1.2 seconds was significantly shorter in the IVF group than in the control group (RR 1.0 s: 0.384 +/- 0.018 vs 0.399 +/- 0.017, P < 0.05; RR 1.2 s: 0.402 +/- 0.019 vs 0.426 +/- 0.020, P < 0.01). QaT at RR intervals of either 1.0 or 1.2 seconds also was shorter in the IVF group (RR 1.0 s: 0.289 +/- 0.022 vs 0.312 +/- 0.021, P < 0.01; RR 1.2 s: 0.311 +/- 0.024 vs 0.343 +/- 0.024, P < 0.01). In four patients, oral administration of disopyramide (300 mg/day) was effective in suppressing VF episodes and increased slopes of QT-RR and QaT-RR relationships. CONCLUSION: IVF patients had lower slopes of QT-RR and QaT-RR regression lines and impaired prolongation of QT and QaT at longer RR intervals compared with control subjects. These unique repolarization dynamics may be related to the frequent occurrence of VF episodes at night.     

Repolarization dynamics in patients with long QT syndrome

INTRODUCTION: Dynamics of ventricular repolarization may contribute to cardiac arrhythmias in subjects with the long QT syndrome (LQTS). The aim of the present study was to assess the dynamics of repolarization duration and the dynamics of repolarization complexity in LQTS patients and their unaffected family members. METHODS AND RESULTS: Twelve-lead 24-hour ambulatory ECG recordings were obtained from LQTS patients (n = 38) and unaffected family members (n = 20). The 24-hour dynamics of the QT interval, T wave complexity (TWC) index measured by principal component analysis, and the RR interval were analyzed using standard deviation (SD) and square root of the mean squared differences of successive values of the parameters (RMSSD). QT variability, mean TWC, and TWC variability were increased in the LQTS patients compared with unaffected family members (QT-SD: 38 +/- 20 msec vs 19 +/- 7 msec, P = 0.0001; QT-RMSSD: 36 +/- 20 msec vs 14 +/- 8 msec, P = 0.0001; TWC: 27.7% +/- 11.1% vs 20.4% +/- 6.7%, P = 0.003; TWC-SD: 6.7% +/- 2.8% vs 4.6% +/- 1.8%, P = 0.003; TWC-RMSSD: 5.3% +/- 2.8% vs 3.7% +/- 1.2%, P = 0.004, respectively). At the same time, the measures of heart rate variability were similar between the affected and unaffected LQTS subjects (SD of normal-to-normal RR intervals [SDNN]: 94 +/- 25 msec vs 89 +/- 37 ms, P = 0.56; RMSSD: 49 +/- 26 msec vs 49 +/- 34 ms, P = 0.97, respectively). CONCLUSION: Despite similar heart rate variability, QT variability and the variability of TWC are significantly increased in LQTS patients compared with unaffected family members, suggesting that disturbances in temporal dynamics of repolarization and repolarization complexity in LQTS patients possibly increase vulnerability to arrhythmias.