Torsades de pointes during complete atrioventricular block: Genetic factors and electrocardiogram correlates

INTRODUCTION:

Atrioventricular (AV) block is infrequently associated with QT prolongation and torsades de pointes (TdP). It was hypothesized that patients with AV block-mediated QT-related arrhythmia may have latent congenital long QT syndrome or a vulnerable genetic polymorphism.

METHODS:

Eleven patients with complete AV block and TdP were prospectively identified. Patients underwent assessment, resting electrocardiography and telemetry at baseline, during AV block and pre-TdP. Genetic testing of KCNH2, KCNQ1, KCNE1, KCNE2 and SCN5A was performed. Thirty-three patients with AV block without TdP were included for comparison.

RESULTS:

Genetic variants were identified in 36% of patients with AV block and TdP. Patients with AV block who developed TdP had significantly longer mean (± SD) corrected QT intervals (440±93 ms versus 376±40 ms, P=0.048) and T_peak to T_end (T_p-T_e) intervals (147±25 ms versus 94±25 ms, P=0.0001) than patients with AV block alone. In patients with a genetic variant, there was a significant increase in T_p-T_e intervals at baseline, in AV block and pre-TdP compared with those who were genotype negative. A personal or family history of syncope or sudden death was more likely observed in patients with a genetic variant.

CONCLUSIONS:

TdP in the setting of AV block may be a marker of an underlying genetic predisposition to reduced repolarization reserve. The T_p-T_e interval at baseline, in AV block and pre-TdP may predict a genetic mutation or polymorphism compromising repolarization reserve. Patients with TdP in the setting of AV block represent a phenotypic manifestation of latent congenital long QT syndrome.     

Interlead Difference in QT Interval Rate Adaptation During Exercise in Coronary Artery Disease Patients Susceptible to Ventricular Fibrillation

Background: Nonhomogeneity in ventricular repolarization predisposes to ventricular tachyarrhythmias. Rate adaptation of the QT interval parallels rate adaptation of the action potential, both of which reflect the repolarization phase in ventricular myocardium. The aim of this study was to examine in patients with coronary artery disease (CAD) the relation of interlead differences in QT interval rate‐adaptation to arrhythmia vulnerability. Methods: We studied 29 CAD patients with a history of ventricular fibrillation (VF) not associated with acute myocardial infarction (VF group), and their 29 individually matched CAD controls without arrhythmic events (controls). Rate adaptation of the QT intervals in the 12 leads of the electrocardiogram were determined from QT intervals measured at rest and at the end of each 3 minute load step during exercise test. The relation between heart rate (HR) and QT interval (QT/HR slope) was calculated separately in each lead by the linear regression equation. The slopes of these equations were used to characterize spatial QT interval rate adaptation. Results: The steepest QT_apex/ HR slopes in any lead were (mean ±mD SD) ?2.45 ± 0.63 in the VF group and ‐1.97 ± 0.45 in controls (P = 0.008), whereas the smallest slopes showed no difference (P = NS). The standard deviations of QT_apex/ HR slopes were 0.48 ± 0.23 in the VF group and 0.33 ± 0.12 in controls (P = 0.012). Conclusions: Rate adaptation of the QT_apex interval is locally exaggerated, resulting in nonhomogenous exercise response of the QT_apex intervals in CAD patients susceptible to life‐threatening ventricular arrhythmias. A.N.E. 2000;5(4):346–353     

Meta-analysis of Tpeak–Tend and Tpeak–Tend/QT ratio for risk stratification in congenital long QT syndrome

Background and objectives

Congenital long QT syndrome (LQTS) predisposes affected individuals to ventricular tachycardia/fibrillation (VF/VF), potentially resulting in sudden cardiac death. The T_peak–T_end interval and the T_peak–T_end/QT ratio, electrocardiographic markers of dispersion of ventricular repolarization, were proposed for risk stratification but their predictive values in LQTS have been controversial. A systematic review and meta-analysis was conducted to examine the value of T_peak–T_end intervals and T_peak–T_end/QT ratios in predicting arrhythmic and mortality outcomes in congenital LQTS.

Relation between Beat‐to‐Beat QT Interval Variability and T‐Wave Amplitude in Healthy Subjects

Objectives: Elevated beat‐to‐beat QT interval variability (QTV) has been associated with increased cardiovascular morbidity and mortality.The aim of this study was to investigate interlead differences in beat‐to‐beat QTV of 12‐lead ECG and its relationship with the T wave amplitude. Methods: Short‐term 12‐lead ECGs of 72 healthy subjects (17 f, 38 ± 14 years; 55 m, 39 ± 13 years) were studied. Beat‐to‐beat QT intervals were extracted separately for each lead using a template matching algorithm. We calculated the standard deviation of beat‐to‐beat QT intervals as a marker of QTV as well as interlead correlation coefficients. In addition, we measured the median T‐wave amplitude in each lead. Results: There was a significant difference in the standard deviation of beat‐to‐beat QT intervals between leads (minimum: lead V₃ (2.58 ± 1.36 ms), maximum: lead III (7.2 ± 6.4 ms), ANOVA: P < 0.0001). Single measure intraclass correlation coefficients of beat‐to‐beat QT intervals were 0.27 ± 0.18. Interlead correlation coefficients varied between 0.08 ± 0.33 for lead III and lead V₁ and 0.88 ± 0.09 for lead II and lead aVR. QTV was negatively correlated with the T‐wave amplitude (r =–0.62, P < 0.0001). There was no significant affect of mean heart rate, age or gender on QT variability (ANOVA: P > 0.05). Conclusions: QTV varies considerably between leads in magnitude as well as temporal patterns. QTV is increased when the T wave is small.     

Weighing the QT Intervals with the Slope or the Amplitude of the T Wave

Objective: The reproducibility of QT interval measurements is low, even for the mean QT interval based on the standard ECG. In this study we analyzed whether the reproducibility of the mean weighed QT interval was better than the simple mean QT interval. The weighing was based on the amplitude of the T wave or the slope of the steepest tangent on the terminal part of the T wave. Material and methods: 12‐lead ECGs of 130 postmyocardial infarction patients were obtained. The QT intervals were measured by the tangent‐method on two occasions by the same observer Mismatch QT intervals were defined as QT intervals that were measured at only one occasion. Sixteen ECGs were rejected. The data were split into 34 and 80 ECGs for optimization and validation of the weighing, respectively. The weighed QT dispersion was calculated as the weighed mean of the three longest minus the weighed mean of the three shortest QT intervals. Results: Weighing with the slope increased the reproducibility by 41% (P = 3 10^‐6), but weighing with the amplitude reduced it by 20% (P = 0.02). However, if measurements with errors above 75 ms were rejected, weighing with the slope or the amplitude increased the reproducibility with 26% and 20% (P = 0.02), respectively. Weighing did not change the reproducibility of the weighed QT dispersion. Conclusion: Weighing with the slope improved the reproducibility of the mean weighed QT interval. However, if measurements with errors above 75 ms were rejected, weighing with the amplitude also increased the reproducibility. Weighing did not change the reproducibility of the weighed QT dispersion. Weighing is particularly efficient at reducing the negative impact of mismatch QT intervals on the reproducibility. A.N.E. 2002;7(1):4–9     

Automated versus Manual Measurement of the QT Interval and Corrected QT Interval

Background: The International Conference on Harmonization E14 Guideline specifies detailed assessment of QT interval or corrected QT interval prolongation when developing new drugs. We recently devised new software to precisely measure the QT interval. Methods and Results: The QT intervals of all leads for a selected single heart beat were compared between automated measurement with the new software from Fukuda Denshi and manual measurement. With both automated and manual measurement, QT intervals obtained by the tangent method were shorter than those obtained by the differential threshold method, but the extent of correction was smaller. QT interval data obtained by the differential threshold method were more similar to values obtained by visual measurement than were data obtained by the tangent method, but the extent of correction was larger. Variability was related to the T‐wave amplitude and to setting the baseline and tangent in the tangent method, while skeletal muscle potential noise affected the differential threshold method. Drift, low‐amplitude recordings, and T‐wave morphology were problems for both methods. Among the 12 leads, corrections were less frequent for leads II and V₃–V₆. Conclusion: We conclude that, for a thorough assessment of the QT/QTc interval, the tangent method or the differential threshold method appears to be suitable because of smaller interreader differences and better reproducibility. Correction of data should be done by readers who are experienced in measuring the QT interval. It is also important for electrocardiograms to have little noise and for a suitable heart rate and appropriate leads to be selected. Ann Noninvasive Electrocardiol 2011;16(2):156–164     

The Prognostic Accuracy of Different QT Interval Measures

Background: The QT intervals accuracy for predicting arrhvthmic death varies between studies, possibly due to differences in the selection of the lead used for measurement of the QT interval. The purpose of this study was to analyze the prognostic accuracy of all known ways to select the lead. Methods and Results: Three institutions that used different methods for measuring QT intervals provided their QT databases. They included more than 3500 twelve‐lead surface ECGs. The data represented low‐ and high‐risk patients of the normal population (survivors vs dead from cardiovascular causes), acute myocardial infarction (survivors versus death from all causes) and remote myocardial infarction (with vs without a history of ventricular arrhythmia). The prognostic accuracy was defined as the area under the Receiver Operator Curve (ROC‐area). The most accurate standard leads were I and aVL and the least accurate was AVR. The most accurate precordial lead was V₄. The prognostic accuracy of the longest QT interval was higher than for any standard lead. The prognostic accuracv of the mean of the three longest QT intervals was equal to or slightly lower than for the longest QT interval. Conclusions: The highest prognostic accuracy is obtained with the longest QT interval. The accuracies of the lead selection methods are so different that it can explain a substantial part of the differences between otherwise similar studies in the literature. We recommend the use of the mean value of the three longest QT intervals. A.N.E. 2002;7(1):10–16     

Circadian Pattern of QT/RR Adaptation in Patients with and Without Sudden Cardiac Death after Myocardial Infarction

Background: Abnormalities in the adaptation of the QT interval to changes in the RR interval may facilitate the development of ventricular arrhythmias. Methods: This study sought to evaluate the dynamic relation between the QT and RR intervals in patients after acute myocardial infarction. The study population consisted of 14 patients after myocardial infarction (age 60 ± 7 years, 12 men) who died suddenly (SCD victims) within 1 year after the myocardial infarction and 14 pair-matched age, sex, left ventricular ejection fraction, infarct site, thrombolytic therapy) patients who remained event-free after myocardial infarction (Ml survivors) for at least 3 years. Fourteen normal subjects were studied as controls (age 55 ± 9 years, 11 men). QT and RR intervals were measured on a beat-to-beat basis automatically with a visual control from 24-hour ambulatory ECGs using Reynolds Pathfinder 700. Mean hourly values of the QT/RR slope (QT =α+βRR) and corrected QT interval at 1000 ms of RR interval (QT_1s) were derived for each subject using an inhouse program (QT_1s=α+1000β). The dynamics of the QT/RR slope and QT_1s were assessed on the basis of hourly mean values. The circadian rhythm of ventricular repolarization (QT_1s and QT/RR slope) was examined by harmonic regression analysis. Results: There was a trend towards a significant difference in 24-hour mean value of QT_1s between study groups (408 ± 26 ms vs 381 ± 43 ms and 386 ± 22 ms, P = 0.06), and a significant difference was found between SCD victims and normal subjects (408 ± 26 vs 386 ± 22 ms, P = 0.02). The QT_1s differed significantly between study groups (P = 0.038) only during the day time (09:00–19:00 hour), when QT_1s was significantly longer in SCD victims than in normal subjects (409 ± 33 vs 380 ± 27 ms, P = 0.02) and tended to be longer than in Ml survivors (409 ± 33 vs 379 ± 42 ms, P = 0.08). The 24-hour mean value of QT/RR slope was significantly different between study groups (P = 0.04), with a significantly steeper slope in SCD victims than in normal subjects (0.15 ± 0.07 vs 0.09 ± 0.02, P = 0.008). During day time, the QT/RR slope differed significantly between study groups (P = 0.04), while the difference was less marked at night (P = 0.08). The slope was significantly steeper in SCD victims than in normal subjects during both day and night (P < 0.05). A marked circadian variation of QT_1s was observed in normal subjects, which was blunted in Ml survivors and SCD victims. Conclusions: Abnormal repolarization behaviors, characterized by longer QT_1s and impaired adaptation of QT to variations in RR intervals, were found in SCD victims. Hence, lethal ventricular tachyarrhythmias might be provoked by the altered repolarization dynamics in patients after myocardial infarction. A.N.E. 1999;4(3):286–294     

Common candidate gene variants are associated with QT interval duration in the general population

Objectives. QT interval prolongation is associated with increased risk of sudden cardiac death at the population level. As 30–40% of the QT‐interval variability is heritable, we tested the association of common LQTS and NOS1AP gene variants with QT interval in a Finnish population‐based sample. Methods. We genotyped 12 common LQTS and NOS1AP genetic variants in Health 2000, an epidemiological sample of 5043 Finnish individuals, using Sequenom MALDI‐TOF mass spectrometry. ECG parameters were measured from digital 12‐lead ECGs and QT intervals were adjusted for age, gender and heart rate with a nomogram (Nc) method derived from the present study population. Results. The KCNE1 D85N minor allele (frequency 1.4%) was associated with a 10.5 ms (SE 1.6) or 0.57 SD prolongation of the adjusted QT_Nc interval (P = 3.6 × 10^?11) in gender‐pooled analysis. In agreement with previous studies, we replicated the association with QT_Nc interval with minor alleles of KCNH2 intronic SNP rs3807375 [1.6 ms (SE 0.4) or 0.08 SD, P = 4.7 × 10^?5], KCNH2 K897T [?2.6 ms (SE 0.5) or ?0.14 SD, P = 2.1 × 10^?7] and NOSA1P variants including rs2880058 [4.0 ms (SE 0.4) or 0.22 SD, P = 3.2 × 10^?24] under additive models. Conclusions. We demonstrate that each additional copy of the KCNE1 D85N minor allele is associated with a considerable 10.5 ms prolongation of the age‐, gender‐ and heart rate‐adjusted QT interval and could thus modulate repolarization‐related arrhythmia susceptibility at the population level. In addition, we robustly confirm the previous findings that three independent KCNH2 and NOSA1P variants are associated with adjusted QT interval.     

Comparison of the Four Formulas of Adjusting QT Interval for the Heart Rate in the Middle‐Aged Healthy Turkish Men

Objective: The aim of this study was to evaluate the QT intervals at different rest heart rates in healthy middle‐aged Turkish men and to compare the known four QT adjusting methods for heart rate. Methods and Results: The QT intervals were measured in electrocardiograms of 210 healthy men (mean age = 35–60 years). A curve relating QT intervals and heart rates from 45 to 135 beats/min was constructed for study population. Based on the formula of Bazett, Fridericia, and Framingham, adjusted QT intervals in these range of heart rates were separately estimated. An adjusting nomogram for different heart rates was created using a reference value, which was the measured QT interval at heart rate of 60 beats/min (QT_No= QT + correcting number). These four QT correction methods were compared with each other. The reference value of QT interval at heart rate of 60 beats/min was 382 ms. The relationship between QT and RR interval was linear (r = 0.66, P < 0.001). Nomogram method corrected QT interval most accurately for all the heart rates compared with other three adjusting methods. At heart rates of 60–100 beats/min, the equation of linear regression was QT = 237 + 0.158 × RR (P < 0.001). Bazett's formula gave the poorest results at all the heart rates. The formulas of Fridericia and Framingham were superior to Bazett's formula; however, they overestimated QT interval at heart rate of 60–110 beats/min (P < 0.01). At lower rates (<60 beats/min), all methods except nomogram method, underestimated QT interval (P = 0.03). Conclusion: Among four QT correction formulas, the nomogram method provides the most accurately adjusted values of QT interval for all the heart rates in healthy men. Bazett's formula fails to adjust the QT interval for all the heart rates.     

Reproducibility of Minimum,Maximum and Median QT Intervals in the 12‐Lead Resting ECG

Background: Heterogeneity in the recovery of ventricular refractory periods is an important factor in the development of ventricular arrhythmia. The QT dispersion (QTD) is increasingly used to measure this heterogeneity but its clinical value is limited due to methodological problems. QTD is defined as the maximum minus the minimum QT intervals that are suspected to be the least reproducible of the QT measurements. Objective: To analyze the reproducibility of the minimum, maximum and median QT intervals. Material: One database consisted of 356 subjects: 169 with diabetes and 187 nondiabetic control persons. The other database consisted of 110 subjects with remote myocardial infarction: 55 with no history of arrhythmia, and 55 with a recent history of ventricular tachycardia or fibrillation. Methods: 12‐lead surface ECGs were recorded with an amplification of 10 millimeters per millivolt at a paper speed of 50 mm/s. QT was measured manually by the tangent‐method. The reproducibility was calculated from measurements of QT in successive beats. Results: The standard deviation (SD) of QTs reproducibility was 9 ms for the arrhythmia data and 8 ms for the diabetes data. The reproducibility of QT_max and QT_min were on average 30% and 15% worse than for QT_median. The SD of QT_max was significantly higher than for QT_median in both database (P < 0.001), whereas SD of QT_min was only significantly higher than for QT_median for the diabetes data (P < 0.001). Conclusions: The reproducibility of QT_min and in particular QTmax was significantly lower than for QT_median. This indicates that the QT dispersion is based on the least reproducible of the QT measurements. A.N.E. 2000;5(4):354–357     

The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens

Aims. To evaluate the prognostic value of the QT interval and QT intervaldispersion in total and in cardiovascular mortality, as wellas in cardiac morbidity, in a general population. Methods and results. The QT interval was measured in all leads from a standard 12-leadECG in a random sample of 1658 women and 1797 men aged 30–60years. QT interval dispersion was calculated from the maximaldifference between QT intervals in any two leads. All causemortality over 13 years, and cardiovascular mortality as wellas cardiac morbidity over 11 years, were the main outcome parameters.Subjects with a prolonged QT interval (430ms or more) or prolongedQT interval dispersion (80ms or more) were at higher risk ofcardiovascular death and cardiac morbidity than subjects whoseQT interval was less than 360ms, or whose QT interval dispersionwas less than 30ms. Cardiovascular death relative risk ratios,adjusted for age, gender, myocardial infarct, angina pectoris,diabetes mellitus, arterial hypertension, smoking habits, serumcholesterol level, and heart rate were 2·9 for the QTinterval (95% confidence interval 1·1–7·8)and 4·4 for QT interval dispersion (95% confidence interval1·0–19·1). Fatal and non-fatal cardiac morbidityrelative risk ratios were similar, at 2·7 (95% confidenceinterval 1·4–5·5) for the QT interval and2·2 (95% confidence interval 1·1–4·0)for QT interval dispersion. Conclusion. Prolongation of the QT interval and QT interval dispersion independentlyaffected the prognosis of cardiovascular mortality and cardiacfatal and non-fatal morbidity in a general population over 11years.     

The Effect of Left Ventricular Function on QT Dispersion in Postmyocardial Infarction Patients with Previous Ventricular Tachyarrhythmias

Objectives: To determine if the presence of left ventricular dysfunction increases the QT and QT_c dispersion in postmyocardial infarction patients with ventricular tachyarrhythmias and to determine if left ventricular infarct location is associated with differences in QT and QT_c dispersion. Methods: The data was gathered from a retrospective electrophysiology (EP) database. All postinfarction patients (n = 87) with a past medical history of left ventricular myocardial infarction and ventricular tachyarrhythmia at baseline without bundle branch block or other intraventricular conduction abnormality were included. Patients were separated into those with an LVEF < 40% or < 40%. For secondary analysis, patients were separated into groups based on the location of the infarction. The QT and R‐R intervals were determined from each lead of a 12‐lead electrocardiogram (ECG) taken during the baseline EP study. The shortest QT and QT_c intervals were subtracted from the longest intervals on the 12‐lead ECG to give the QT and QT_c dispersions. Results: The QT and QT_c interval dispersions were significantly greater among patients with an LVEF < 40% than among those with an LVEF < 40% (57.3 ± 28.2 vs 47.4 ± 17.7, P = 0.05; 64.5 ± 32.1 vs 48.8 ± 18.2. P = 0.005, respectively). No differences in QT or QT_c dispersion were noted between patients with anterior or inferior myocardial infarctions. Conclusions: A higher QT dispersion can be predicted in patients with left ventricular dysfunction, but the location of the myocardial infarction does not predict the QT dispersion.     

临终患者伴发QT间期缩短的心电图分析

目的:探讨临终患者伴发QT间期缩短的心电图特征和临床意义。方法:常规测量10例临终患者的QT间期实测值(QT),通过QT间期换算公式计算QT间期预测值(QTp)、校正后QT间期值(QTc)以及QT/QTp比值。结果:10例临终患者心电图除出现各型传导阻滞、心室停搏等心电异常外,均伴随QT间期缩短(QTc<0.32～0.34s、QT/QTp<0.88)。结论:继发性QT间期缩短可能是出现于临终患者的一种罕见心电图表现,在一定程度上反映了心脏电活动衰竭,其预后不良,应引起临床高度重视。     

The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group

Summary The prevalence of QT interval prolongation is higher in people with diabetes and its complications. Sudden death has been reported as a common cause of death in insulin-dependent diabetic patients affected by autonomic neuropathy. It has been postulated that QT prolongation predisposes to cardiac arrhythmias and sudden death. In this analysis the prevalence of QT interval prolongation and its relation with diabetic complications were evaluated in the EURODIAB IDDM Complications Study (3250 insulin-dependent diabetic patients attending 31 centres in 16 European countries). Five consecutive RR and QT intervals were measured with a ruler on the V5 lead of the resting ECG tracing and the QT interval corrected for the previous cardiac cycle length was calculated according to the Bazett's formula. The prevalence of an abnormally prolonged corrected QT was 16 % in the whole population, 11 % in males and 21 % in females (p < 0.001). The mean corrected QT was 0.412 s in males and 0.422 s in females (p < 0.001). Corrected QT duration was independently associated with age, HbA_{1 c} and blood pressure. Corrected QT was also correlated with ischaemic heart disease and nephropathy but this relation appeared to be stronger in males than in females. Male patients with neuropathy or impaired heart rate variability or both showed a higher mean adjusted corrected QT compared with male patients without this complication. The relation between corrected QT prolongation and autonomic neuropathy was not observed among females. In conclusion we have shown that corrected QT in insulin-dependent diabetic female patients is longer than in male patients, even in the absence of diabetic complications known to increase the risk of corrected QT prolongation. [Diabetologia (1999) 42: 68–75] Received: 17 April 1998 and in final revised form: 2 September 1998     

“Normal” response of the QT interval and QT dispersion following intravenous injection of the sodium channel blocker disopyramide: Methodological aspects

Summary Measurement of the QT dispersion (the maximal interlead difference) on the surface electrocardiogram has been suggested for assessing the risk for ventricular arrhythmias and for examining drug effects and their proarrhythmic potential. The acute response of QT dispersion was assessed in 10 healthy subjects receiving disopyramide, which is known to delay repolarization and to prolong global measures thereof. The QRS, JT, and QT intervals and their dispersion were assessed at spontaneous rhythm and at atrial pacing at baseline and after an intravenous injection of disopyramide 2 mg/kg over 5 minutes. The short-term (within 30 minutes) and long-term (2 weeks) variabilities of the QT interval and the QT dispersion, expressed as the coefficient of variation, were also analyzed. At spontaneous rhythm the groupaverage QT interval was between 369 and 375 msec, and the QT dispersion was between 33 and 37 msec; both were relatively stable over time. All subjects responded homogeneously to disopyramide with a significant QT prolongation (p<0.001), but no consistent response of the QT dispersion was observed. This discrepancy reflects the significant difference in time-dependent variability with a coefficient of variation of spontaneous, paced, and heart rate-corrected QT dispersion between 25% and 42%, 8–42 times greater than the corresponding values of 1–4% for the QT intervals. Theindividual response of the QT dispersion to drug challenge should therefore be interpreted with caution. Furthermore and as a consequence, QT dispersion is less sensitive for assessing drug effects on ventricular depolarization and repolarization than the QT interval.     

QT interval change with age in an overtly healthy older population

Background: Prolonged QT interval on the surface electrocardiogram (ECG) is known to be associated with arrhythmias, coronary heart disease, and sudden cardiac death. Increased QT dispersion has also been related to arrhythymias which are more frequent in the elderly. Hypothesis: This study investigated the relationship between aging, QT interval, and QT dispersion. Methods: Normal resting ECGs were recorded from 96 healthy subjects (73 women, age range 40-102 years). No subject had symptoms or signs of heart disease and none was on medication affecting cardiac function. All had normal heart size on chest x-ray and normal electrolytes. Using a digitizing board, the RR and QT intervals were measured on each lead of each ECG, excluding only the leads in which the T wave was not visible. Mean RR, mean QT interval, and heart rate-adjusted QTc interval (standard Bazet's formula) were obtained from these measurements. Further, QT dispersion was calculated for each ECG as (1) the difference between the maximum and minimium QT interval, and (2) as the coefficient of variance of QT interval of all measurable leads. Results: A significant correlation between aging and prolonged QTc was noted in the total population (r = 0.43, p <0.05), as well as in men (r = 0.4, p <0.05) and women (r = 0.23, p<0.05) separately. There was no association between QT dispersion and increasing age regardless of the method of calculation (r= -0.04, r= -0.08 respectively, both NS). Conclusion: The rate-adjusted QT interval is prolonged with increasing age and may contribute to the increased risk of ventricular arrhythmias and cardiac mortality in elderly patients.     

Magnetocardiographic QT dispersion during cardiovascular autonomic function tests

QT dispersion is considered to reflect nonhomogeneity of ventricular repolarization. The autonomic nervous system modulates QT interval duration, but the effect may not be spatially homogenous. Magnetocardiography (MCG) registers the weak magnetik fields generated by myocardial electric currents with high localizing accuracy. We studied the effect of rapid cardiovascular autonomic nervous adjustment on QT dispersion in MCG. Ten healthy male volunteers were monitored during deep breathing, the Valsalva maneuver, sustained handgrip, hyperventilation, the cold pressor test and mental stress. 67 MCG channels and 12 ECG leads were recorded simultaneously. A computer algorithm was used for QT interval measurements. QT dispersion was defined as maximum – minimum or standard deviation of the QT_peak and QT_end intervals. In MCG the QT_end dispersion increased during deep inspiration compared with deep expiration (96±19 ms v 73±27 ms, p=0.05). Magnetic QT dispersion tended to increase during the bradycardia phase of the Valsalva maneuver, but the change was obvious only for QT_end (55±26 ms v 76±29 ms, p<0.05) Other tests had no significant effect on QT dispersion, not even the cold pressor test, although it causes strong sympathetic activation. Magnetic and electric QT_peak and QT_end intervals correlated closely (r=0.93 and 0.91), whereas the QT dispersion measures showed no correlation. In conclusion, magnetic QT dispersion is not modified by rapid changes in autonomic tone, but maneuvers involving deep respiratory efforts and changes in ventricular loading affect QT dispersion measurements. Received: 4 April 2000 Returned for revision: 2 May 2000 Revision received: 20 June 2000 Accepted: 10 July 2000     

Acute electrophysiologic effects of an HT2-serotonin antagonist,ketanserin, in humans

Summary The acute electrophysiologic effects of an intravenous bolus of ketanserin, a 5HT₂ serotonin blocker, were studied in ten patients (four females, six males) during invasive electrophysiology. Following baseline electrophysiologic measurements during sinus rhythm and fixed-rate atrial pacing at 600 ms, a bolus of 0.2 mg/kg ketanserin was given over a 3-minute period. After 30 minutes all measurements were repeated. Systemic blood pressure was measured at regular intervals throughout. During sinus rhythm, there was no significant change in the basic cycle length or in the PA, AH, HV, QRS, QT, and QTc intervals. During atrial pacing there was a nonsignificant increase in the QT interval, from 342±13 ms to 366±16 ms, and a significant increase in the QTc interval, from 422±27 ms to 449±29 ms (p<0.05). There was no reduction in blood pressure. Thus ketanserin produced a significant prolongation of the QTc interval, in the absence of hypokalemia, in humans.