Effects of Epinephrine and Phenylephrine on QT Interval Dispersion in Congenital Long QT Syndrome

Objectives. Measurement of QT interval dispersion during pharmacologic adrenergic stimulation was used to assess the effect of alpha- and beta-adrenergic stimulation on arrhythmic vulnerability in familial long QT syndrome (LQTS).Background. Nonhomogeneity in the ventricular action potential duration causes electrical instability leading to life-threatening ventricular arrhythmias and is markedly increased in LQTS. QT interval dispersion measured from the electrocardiogram (ECG) can be used as an index of nonhomogeneous ventricular repolarization.Methods. Sixteen symptomatic patients with LQTS and nine healthy control subjects were examined at baseline and during epinephrine (mainly beta-adrenergic agonist, 0.05 μg/kg body weight per min) and phenylephrine infusions (alpha-adrenergic agonist, mean 1.4 μg/kg per min). QT interval dispersion was determined from a 12-lead ECG as interlead range and coefficient of variation measured to the end (QT_end) and apex (QT_apex) of the T wave.Results. At baseline QT_enddispersion was greater in patients with LQTS compared with control subjects (mean [±SD] 68 ± 34 vs. 36 ± 7 ms, p = 0.001). QT_enddispersion was markedly increased in patients with LQTS by use of epinephrine (from 68 ± 34 to 90 ± 36 ms, p = 0.002), but remained unchanged in control subjects. Phenylephrine did not affect QT dispersion in either group (all p = NS). Atrial pacing to achieve comparable heart rates during baseline and epinephrine and phenylephrine infusions did not influence the magnitude of QT dispersion in either group. QT_apexdispersion analysis gave congruent results.Conclusions. Epinephrine but not phenylephrine increased QT dispersion, suggesting that beta-adrenergic stimulation provokes arrhythmias in patients with LQTS by aggravating nonhomogeneity of ventricular repolarization, whereas alpha-adrenergic stimulation is less important for arrhythmic vulnerability. The results also suggest that rapid pacing may not reduce vulnerability to arrhythmias in congenital LQTS.     

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     

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     

Prolonged QT interval at onset of acute myocardial infarction in predicting early phase ventricular tachycardia

The prospectively assessed time course of changes in ventricular repolarization during acute myocardial infarction (AMI) is reported in 32 patients admitted 2.0 ± 1.8 (SD) hours after AMI onset. The initial corrected QT interval (QT_c) upon hospitalization was longer (0.52 ± 0.07 seconds) in the 14 patients developing ventricular tachycardia (VT) within the first 48 hours as compared to QT_c (0.47 ± 0.03 seconds) in the eight patients with frequent ventricular premature beats (VPBs) and to QT_c (0.46 ± 0.03 seconds) in the 10 patients with infrequent VPBs (p < 0.001; analysis of variance). By the fifth day after AMI onset, the QT_c shortened significantly only in the VT group, suggesting a greater initial abnormality of repolarization in these patients. All 32 patients had coronary anglography, radionuclide ventriculography, and myocardial perfusion scintigraphy before hospital discharge. Significant discriminating factors related to early phase VT in AMI included initially longer QT and QT_c intervals, faster heart rate, higher peak serum levels of creatine kinase, acute anterior infarction, anglographically documented proximal stenosis of the left anterior descending coronary artery, and scintigraphic evidence of hypoperfusion of the interventricular septum. Prior infarction, angina pectoris, hypertension, multivessel coronary artery disease, and depressed left ventricular ejection fraction did not provide discrimination among the three different ventricular arrhythmia AMI groups. We conclude that (1) the QT interval is frequently prolonged early in AMI, (2) the initial transiently prolonged ventricular repolarization facilitates and predicts complex ventricular tachyarrhythmias within the first 48 hours of AMI, (3) jeopardized blood supply to the interventricular septum frequently coexists, and (4) therapeutic enhancement of rapid recovery of the ventricular repolarization process merits investigation for prevention of VT in AMI.     

Estrogen and Progestin Use and the QT Interval in Postmenopausal Women

Objective: To determine whether menopausal hormone therapy alters the QT interval in primarily healthy postmenopausal women. Background: Despite well‐known gender differences in myocardial repolarization that include a longer heart‐rate‐corrected QT interval (QT_C) in women compared to men, the effects of menopausal hormone therapy on myocardial repolarization in women have not been well characterized. Methods: We studied 34,378 postmenopausal women participating in the dietary intervention component of the Women's Health Initiative. Cross‐sectional associations were examined to assess possible effects of estrogen + progesterone on myocardial repolarization. Women who reported that they were never treated with menopausal hormone therapy (n = 12,451) were compared to women with a past use of menopausal hormone therapy (n = 3891), currently taking unopposed estrogen therapy (n = 9987), or combined current estrogen and progesterone therapy (n = 8049). Results: Using analysis of covariance, the mean (±SEM) QT_C interval was 423.1 ± 0.2 milliseconds (ms) in those never treated with menopausal hormone therapy, 423.9 ± 0.3 ms in past menopausal hormone therapy users, 425.6 ± 0.2 ms in those currently on estrogen alone, and 424.0 ± 0.2 ms in women currently on combined estrogen–progesterone therapy. Differences in mean QT_C between those on estrogen alone and the other three groups were statistically significant. Comparisons of JT intervals, QT intervals, and linear corrected QT intervals among the groups yielded similar results. Conclusion: These results suggest that unopposed estrogen in menopausal women mildly prolongs myocardial repolarization, and the effect is reversed by progesterone. Whether these findings have clinical significance requires further study.     

Effect of balloon inflation-induced acute ischemia on QT dispersion during percutaneous transluminal coronary angioplasty

Background: QT dispersion (QTd = QT_max - QT_min) measured as interlead variability of QT interval reflects the spatial inhomogeneity of ventricular repolarization times, and increased QTd may provide a substrate for malignant ventricular arrhythmias. Ischemia is associated with regional abnormalities of conduction and repolarization. Hypothesis: This study aimed to investigate the effect of acute ischemia on QTd during successful percutaneous transluminal coronary angioplasty (PTCA). Methods: Forty-three patients (10 women, 33 men, mean age 56 years) were enrolled in the study. Electrocardiogram (ECG) recordings were taken before PTCA and during balloon inflation period. QT maximum (QT_max), QT minimum (QT_min), and QTd (QT_max - QT_min) values were calculated from the surface ECG. Results: There was no difference among QT_max values (p = 0.6). Mean QT_min during balloon inflation was lower than before PTCA (368 ± 45 vs. 380 ± 41 ms, p = 0.002). The difference between QTd values before and during balloon inflation was statistically important (65 ± 9 vs. 76 ± 10 ms, p = 0.001). This difference is caused by a decrease in QT_min during balloon inflation. Conclusion: Acute reversible myocardial ischemia induced by balloon inflation causes an increase in QTd value, and this increment is the result of a decrease in QT_min interval. Therefore, QTd may be a marker of reversible myocardial ischemia.     

Coronary Artery Disease May Alter the Spatial Dispersion of the QT Interval at Rest

Background: Increases of QT dispersion (QT_d) have been observed in patients with coronary artery-disease (CAD) under stress. In contrast to ECG, multichannel magnetocardiography (MCG) allows the assessment of the spatial distribution of QT_d, which may be altered earlier than standard QT_d. The aim of this study was the investigation of repolarization patterns in patients with CAD at rest. Methods: 12-lead ECG and 36-channel MCG were performed in 20 healthy subjects (N) (6 m; aged 54 ± 7) and 23 patients with CAD (14 m; aged 59 ± 9). QT intervals were determined for each ECG lead and MCG registration site. QT_d was calculated as QT_max-QT_min for both methods. In MCG, QT_d was also examined spatially by calculating the difference between QT_min and QT at each registration site and plotting this value relative to its position. Spatial variability was quantified using two indexes: SI, which quantifies the mean dispersion at each registration site and Sin, which normalizes SI by taking the overall spatial dispersion pattern into account. Results: In contrast to ECG, the MCG QT_d values were higher in patients with CAD (P < 0.05). These patients also displayed more QT variability between neighboring sites and an alteration in global pattern. Accordingly, the SI and Sin values differed most clearly between groups (P < 0.001). Conclusions: CAD may lead to increased heterogeneity of repolarization at rest. Spatial changes are better able to identify patients with CAD than standard QT_d based on ECG. Their visualization and quantification is possible on the basis of multichannel magnetocardiography. A.N.E. 1999;4(3):267–273     

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.     

QT interval in cardiac amyloidosis

The aim of the study was to investigate whether cardiac amyloidosis is associated with QT interval abnormalities and ventricular arrhythmias. A controlled study of 30 patients was undertaken at a university cardiology department in a large referral hospital. Thirty patients (18 men, 12 women, mean age 56 ± 12 years) with systemic amyloidosis verified by biopsy and strong indications of cardiac amyloidosis comprised the study group, with 30 healthy age- and sex-matched individuals serving as controls. Complete M-mode and two-dimensional echocardiographic study was undertaken and QT interval and QT_c were calculated. All patients and controls underwent 24-h Holter monitoring for arrhythmias. Left ventricular (LV) wall thickening was found in all patients with cardiac amyloidosis. The LV mass in the patients with cardiac amyloidosis was significantly greater than that of the control group, as was the ratio LVmass/body surface area (p < 0.001). There was no significant difference in the max QT interval or in QT_c dispersion between the two groups, although the max QT_c was greater in the patients with cardiac amyloidosis. Patients with cardiac amyloidosis did not have a higher incidence of arrhythmias than the controls. Although patients with thickened cardiac walls due to cardiac amyloidosis have a prolonged QT_c in comparison with controls, they do not show an increase in interlead QT_c dispersion which might suggest the possibility of regional disturbances of the uniformity of repolarization. Patients with cardiac amyloidosis do not have a higher incidence of arrhythmias than controls.     

Modulation of ventricular repolarization in patients with transient left ventricular apical ballooning: a case control study

Objective: Even though diffuse T wave inversion and prolongation of the QT interval in the surface electrocardiogram (ECG) have been consistently reported in patients with transient stress‐induced left ventricular apical ballooning (AB), ventricular repolarization has not yet been systematically investigated in this clinical entity. Background: AB, an emerging syndrome that mimics acute ST‐segment elevation myocardial infarction (MI), is characterized by reversible left ventricular wall motion abnormalities in the absence of obstructive coronary heart disease and significant QT interval prolongation. Methods: We prospectively enrolled 22 consecutive patients (21 women, median age 65 years) with transient left ventricular AB. A total of 22 age‐, gender‐, body‐mass‐index‐, and left‐ventricular‐function‐matched patients with acute anterior ST‐segment elevation MI undergoing successful direct percutaneous coronary intervention for a proximal occlusion of the LAD, as well as 22 healthy volunteers served as control groups. Beat‐to‐beat QT interval and QT interval dynamicity were determined from 24‐hour Holter ECGs, recorded on the third day after hospital admission. Results: There were no significant differences in baseline clinical characteristics, except higher peak enzyme release in MI patients. Compared with MI patients, AB patients exhibited significantly prolonged mean QT intervals and rate‐corrected QT intervals (QT: 418 ± 37 vs 384 ± 33 msec, P < 0.01; QTc_Bazett: 446 ± 40 vs 424 ± 35 msec, P < 0.05; QTc_Fridericia: 437 ± 35 vs 412 ± 31 msec, P < 0.05). Mean RR intervals tended to be higher in AB patients, without reaching statistical significance (877 ± 96 vs 831 ± 102 msec, P = NS). The linear regression slope of QT intervals plotted against RR intervals was significantly flatter in AB patients at both day‐ and nighttime (QT/RR slope_day: 0.18 ± 0.04 vs 0.22 ± 0.06, P < 0.01; QT/RR slope_night: 0.12 ± 0.03 vs 0.17 ± 0.05, P < 0.01). Conclusion: The present study is the first to demonstrate significant differences of QT interval modulation in patients with transient left ventricular AB and acute ST‐segment elevation MI. Even though transient AB is associated with a significant QT interval prolongation, rate adaptation of ventricular repolarization (i.e., QT dynamicity) is not significantly altered, suggesting a differential effect of autonomic nervous activity on the ventricular myocardium in transient AB and in acute MI.     

Comparison of QT/RR Relationship Using Two Algorithms of QT Interval Analysis for Identification of High Risk Patients for Life-Threatening Ventricular Arrhythmias

Objective: The purpose of this study was to evaluate the dynamic relationship between QT and RR intervals considering either the QTe interval (i.e., time between the onset of QRS and the end of the T wave) or the QTa interval (i.e., time between the onset of QRS and the apex of the T wave) from 30-second modules. Method: The Holter recordings in three groups of adult subjects (30 patients with malignant ventricular tachyarrhythmias [VT/VF patients], 40 patients with coronary artery disease [CAD], and 44 normal subjects) were analyzed using the ELATEC System. Results: In normal subjects the correlation coefficient between QTa and RR (QTa/RR) was significantly higher (0.87 ± 0.12) than those between QTe and RR (QTe/RR) (0.79 ± 0.17). In the other groups there was no significant difference between QTa/RR and QTe/RR: QTa/RR (CAD: 0.71 ± 0.3; VT/VF: 0.73 ± 0.19); and QTe/RR (CAD: 0.63 ± 0.33; VT/VF: 0.69 ± 0.21). The slope of QTe/ RR over 24 hours was significantly larger in VT/VF patients (0.23 ± 0.11) than in the other groups (control: 0.18 ± 0.08; CAD: 0.17 ± 0.1). Measuring the QTa/RR relation there was no difference between the three groups (VT/VF: 0.19 ± 0.09; CAD: 0.15 ± 0.09; normal: 0.19 ± 0.06). Conclusion: QTe/RR as well as QTa/RR analyses are methods of detecting a deranged rate dependence of QT intervals in high risk patients. An increased QTe/RR slope indicates a higher risk of life-threatening ventricular arrhythmias. Because there was no difference in QTa/RR we conclude that the end of the T wave gives important information about disorders in repolarization.     

QT interval prolongation in type 2 (non-insulin-dependent) diabetic patients with cardiac autonomic neuropathy

Summary QT interval alterations were measured in 41 non-insulin-dependent (type 2) diabetic patients and 14 age- and sex-matched control subjects. Cardiac autonomic neuropathy (CAN) was assessed by noninvasive tests (deep breathing, Valsalva maneuver and lying-to-standing) and diabetics were divided into three groups according to the results of these tests: diabetics with definitive (n=14), early (n=13) and without (n=14) CAN. The corrected values of QT intervals (QT_c) at rest were significantly longer in diabetics with definitive (447±5 ms; p<0.001), early (426±5 ms; p<0.05) and without (424±5 ms; p<0.05) CAN than in controls (407±5 ms). Moreover, QT_c intervals at rest were significantly (p<0.01) longer in diabetics with definitive CAN than in diabetics with early and without CAN. QT_c intervals at maximum tachycardia, induced by Valsalva maneuver, were considerably longer in diabetics with definitive CAN (451±6 ms) than in controls (407±6 ms; p<0.001) and in diabetics with early (434±6 ms; p<0.05) or without (422±6 ms; p<0.01) CAN. Furthermore, QT_c intervals at maximum tachycardia were significantly (p<0.01) longer in diabetics with early CAN than in controls. QT_c intervals at maximum bradycardia after Valsalva maneuver were significantly longer in diabetics with definitive (446±5 ms; p<0.001), early (434±5 ms; p<0.001) and without (424±5 ms; p<0.01) CAN than in controls (403±5 ms). Moreover, QT_c intervals at maximum bradycardia were considerably (p<0.01) longer in diabetics with definitive than without CAN. At least one abnormal (>440 ms) QT_c period was found in 19 out of 27 patients with early or definitive CAN, but 4 of 14 diabetics without any signs of CAN and none of the controls exibited abnormal QT_c period. It was concluded that QT_c interval prolongation due to imbalance of autonomic nervous tone could be observed in type 2 diabetic patients with CAN, suggesting a possible role in sudden cardiac death.     

Spectral Analysis of RR and R-T Variabilities in Patients with Coronary Artery Disease

Background: As the duration of the Q-T interval is dependent upon the length of the preceding cardiac cycle, changes in QT interval duration mainly reflect, in normal subjects, the physiological beat-by-beat variability of the sinus node. However, little information is available on short-term Q-T variability in patients with an abnormal neural modulation of the sinus node. Methods: We analyzed, with autoregressive techniques, RR and R-T_apex, and R-T_end variabilities in 12 patients after myocardial infarction, in 13 patients before and after percutaneous transluminal coronary angioplasty (PTCA), and in 10 age-matched controls. Results: No significant differences in mean value and variance of RR, R-T^apex, and R-T_end interval among the three groups of subjects were observed. Spectral analysis of RR variability was characterized by signs of sympathetic activation with a predominance of low frequency (LF) component in patients after myocardial infarction (69 ± 5 nu) and before PICA (74 ± 5 nu) in comparison to controls (50 ± 4 nu). Instead, spectral energy was equally distributed within LF and HF (high frequency) components of RT_apex and R-T_end variabilities in the three groups of subjects. Conclusions: These data indicate that the predominance of LFRR in normalized units, indicating an increase of sympathetic modulation of sinus node activity in patients with coronary artery disease, are not accompanied by a parallel predominance of the LF component of R-T_apex and R-T_end variabilities. This difference reflects, in our opinion, a minor dependency of duration of ventricular repolarization from the preceding cardiac cycle in patients with coronary artery disease.     

Rate-corrected QT interval: Techniques and limitations

The duration of the QT interval on the surface electrocardiogram represents the time required for all ventricular depolarization and repolarization processes to occur. Among the many physiologic and pathologic factors that contribute to the QT interval, heart rate plays a major role. Several approaches have been used to correct the QT interval, all of which take into account the heart rate at which the interval is measured. The simplest and most common approach to correcting the QT interval is to divide its value by the square root of the preceding RR interval expressed in seconds, i.e., by using Bazett's formula. This calculation provides a corrected QT (QT_c) interval that represents the QT interval normalized for a heart rate of 60 beats/min. However, several studies have shown that Bazett's correction formula is not optimal. Fridericia's cube-root formula has been shown to perform better in correcting the QT interval for heart rate. Other formulas require the measurement of several QT-RR pairs at various heart rates to obtain a reliable QT_c interval and are therefore not easily usable. Any correction formula is likely to introduce an error in assessing the QT_c interval. Although the importance of this error should not be minimized, the corrected QT interval remains useful in assessing the effects of drugs on the duration of repolarization. For this purpose, Fridericia's cube-root formula is preferable to Bazett's square-root formula. However, correcting the QT interval for heart rate may conceal important information, such as the kinetics of QT-interval adaptation to a change in heart rate. The most reliable method for assessing the QT interval during drug administration is to avoid QT correction and to measure QT intervals at fixed heart rates.     

Recovery of Heart Rate Variability and Ventricular Repolarization Indices Following Exercise

Background: There is a heightened risk of sudden cardiac death related to exercise and the postexercise recovery period, but the precise mechanism is unknown. We have demonstrated that sympathoexcitation persists for ≥45 minutes after exercise in normals and subjects with coronary artery disease (CAD). The purpose of this study is to determine whether this persistent sympathoexcitation is associated with persistent heart rate variability (HRV) and ventricular repolarization changes in the postexercise recovery period. Methods and Results: Twenty control subjects (age 50.7 ± 1.4 years), 68 subjects (age 58.2 ± 1.5 years) with CAD and preserved left ventricular ejection fraction (LVEF), and 18 subjects (age 57.6 ± 2.4 years) with CAD and depressed LVEF underwent a 16‐minute submaximal bicycle exercise protocol with continuous ECG monitoring. QT and RR intervals were measured in recovery to calculate the time dependent corrected QT intervals (QTc), the QT–RR relationship, and HRV. QTc was dependent on the choice of rate correction formula. There were no differences in QT–RR slopes among the three groups in early recovery. HRV recovered quickly in controls, more slowly in those with CAD‐preserved LVEF, and to a lesser extent in those with CAD‐depressed LVEF. Conclusion: Despite persistent sympathoexcitation for the 45‐minute recovery period, ventricular repolarization changes do not persist for that long and HRV changes differ by group. Additional understanding of the dynamic changes in cardiac parameters after exercise is needed to explore the mechanism of increased sudden cardiac death risk at this time.     

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     

Changes in ventricular repolarization during percutaneous transluminal coronary angioplasty in humans assessed by QT interval, QT dispersion and T vector loop morphology

Abstract. Nowinski K, Jensen S, Lundahl G, Bergfeldt L (Karolinska Hospital, Stockholm, Norrlands University Hospital, Umeå and Ortivus AB, Täby, Sweden). Changes in ventricular repolarization during percutaneous transluminal coronary angioplasty in humans assessed by QT interval, QT dispersion and T vector loop morphology. J Intern Med 2000; 248 : 126–136. Objectives. Based on clinical, epidemiological, and experimental data, transient cardiac ischaemia is one of the major triggering factors of malignant ventricular arrhythmia. According to animal studies, increased dispersion of repolarization is of pathophysiological relevance in this context. Therefore we explored the impact of myocardial ischaemia during single vessel coronary angioplasty on the change in ventricular repolarization, measured by QT and JT intervals and their dispersion in the 12‐lead electrocardiogram. We also assessed a novel method, the 3‐dimensional T vector loop, to find out whether it was sensitive to changes in ventricular repolarization during ischaemia, and whether there was any correlation with changes in the dispersion of the QT and/or JT intervals. Design. This study was prospective with consecutive patients. Only patients in sinus rhythm and without bundle branch block were included. Setting. All coronary angioplasties were performed at Norrlands University Hospital, Umeå. The analysis of the material was performed at the Karolinska Hospital, Stockholm. Subjects. Twenty‐nine consecutive patients went through 30 elective one‐vessel percutaneous transluminal coronary angioplasty (PTCA) procedures. PTCA was performed in 10 stenoses of the left anterior descending, 10 of the left circumflex, and 10 of the right coronary artery. Interventions. A 12‐lead electrocardiogram was recorded continuously as part of routine monitoring of the patient during PTCA and the T vector loop was calculated from the simultaneously recorded. X, Y, Z leads. Main outcome measures. Repolarization was assessed by the QRS, QT and JT intervals as well as by the T vector loop parameters (Tarea, Tavplan, and Teigenv) before and at the end of the first occlusion during PTCA. Results. PTCA, with an average occlusion time of 171 ± 60 s (mean ± SD), induced ischaemia on the 12‐lead electrocardiogram in 73% of cases. The overall response for the 30 procedures was a significantly increased dispersion of ventricular repolarization, both corrected and uncorrected for heart rate. QT dispersion increased by, on average, 19% from 74 ± 35 to 88 ± 36 ms, QT_c dispersion by 27% from 71 ± 39 to 90 ± 42 ms, and JTc dispersion by 19% from 78 ± 32 to 94 ± 43 ms (P < 0.05). The T vector loop became more circular and bulgy during occlusion (all three parameters changed by between 33% and 59%). There was a significant correlation between changes in one of the T vector loop parameters (Teigenv), and changes in JT and QT dispersion in the left anterior descending group. Conclusions. Transient ischaemia during PTCA induced significant changes in ventricular repolarization, especially during occlusion of the left anterior descending artery and resulted in a significant increase in both QT and QT_c dispersion. The degree of QT dispersion was such that several patients were at risk of ventricular arrhythmia, if a proper triggering extrasystole had occurred. In addition, and as an original observation, the 3‐dimensional T vector loop morphology seemed even more sensitive to coronary occlusion than QT dispersion.     

Surface Electrocardiography and Histologic Rejection Following Orthotopic Heart Transplantation*

Background: Intraventricular conduction delay and QT interval dispersion may be related to electrical instability and the risk of ventricular arrhythmogenesis. The interlead variability of the QT interval on a surface 12‐lead electrocardiogram (ECG) has been associated with an increased likelihood of sudden death in patients with long QT syndromes, in patients recovering from myocardial infarction, and dilated cardiomyopathy. We sought to determine the incidence of increased QT_c dispersion (QT_c‐d) relative to biopsy grade of severity of rejection. Methods: Records of patients having undergone orthotopic heart transplantation (OHT) were reviewed focusing specifically on surface ECGs performed in temporal proximity to endomyocardial biopsy. Results: Seventy‐five patients were evaluated on 1573 occasions, to include 999 surface ECGs, and 847 endomyocardial biopsies. There were 269 interpretable surface ECGs and endomyocardial biopsies performed within 1.1 ± 4.6 days. There were no identifiable trends in atrioventricular or intraventricular conduction abnormalities (to include right bundle branch block) when comparing those with and without significant rejection on endomyocardial biopsy. The mean QT_c‐d of those with none (n = 34), mild (n = 194), moderate (n = 39), and severe (n = 2) rejection was 49 ± 29, 49 ± 35, 57 ± 38, 81 ± 7 ms, respectively (P = 0.28 by ANOVA of means). When comparing those with significant rejection so as to change management there was a trend toward increased dispersion (no to mild rejection, 49 ± 34 ms vs moderate to severe rejection, 59 ± 37 ms, P = 0.09). Conclusions: In this study investigating noninvasive ventricular depolarization/repolarization and correlation to histologic manifestation of rejection, there was suggestion, but no statistical significance, of QT_c‐d and severity of rejection. QT_c‐d should not be considered a sensitive marker for OHT rejection.     

Dynamicity of Early and Late Phases of Repolarization in Patients with Remote Anterior Myocardial Infarction: The Interlead Differences

Background: Repolarization dynamicity (QT/RR) is supposed to be a prognostic marker in post‐MI patients. However, data on the relationships between early and late phases of QT and RR intervals (QT peak/RR and T peak–T end/RR) are insufficient, and which ECG lead should be used for the analysis is unclear. We analyzed repolarization dynamicity in patients after anterior MI with and without VT/VF history using two leads of Holter recordings‐ modified V₅ and V₃. The daytime and nighttime periods were also analyzed. Methods: Cohort of 88 patients after anterior MI (>6 months) consisted of 43 patients without VT/VF (33 males; 59 ± 12 years; LVEF: 41 ± 7%; NoVT/VF), and 45 patients with VT/VF history‐ ICD implanted as secondary prevention (40 males; 64 ± 10 years; LVEF: 32 ± 8%; VT/VF). QT/RR, QT peak/RR and T peak–T end/RR were calculated from 24‐hour ECG for the entire recording, daytime and nighttime periods, from V₅ and V₃ leads, respectively. Results: VT/VF patients had lower LVEF (P = 0.001). There were no differences in age and gender. VT/VF group had steeper QT/RR, QT peak/RR, and T peak–T end/RR in V₅: 0.233 ± 0.04 versus 0.150 ± 0.05, P = 0.0001, 0.181 ± 0.04 versus 0.120 ± 0.04, P = 0.0001, 0.052 ± 0.02 versus 0.030 ± 0.02, P = 0.0001, and in V₃: 0.201 ± 0.04 versus 0.149 ± 0.05, P = 0.0001, 0.159 ± 0.03 versus 0.118 ± 0.04, P = 0.0001, and 0.042 ± 0.02 versus 0.031 ± 0.02, P = 0.004; respectively. VT/VF patients had higher indices in V₅ than in V₃ lead (P = 0.001). QT/RR and QT peak/RR were steeper at daytime period in both leads. It was not found for T peak–T end/RR. Conclusions : Patients with VT/VF history are characterized by steeper relationships between repolarization duration and RR intervals. These findings are more evident in modified V₅ lead.     

Tpeak-Tend Interval as an Index of Global Dispersion of Ventricular Repolarization: Evaluations Using Monophasic Action Potential Mapping of the Epi- and Endocardium in Swine

The ECG interval from the peak to the end of the T wave (T_peak-T_end) has been used as an index of transmural dispersion of ventricular repolarization (DVR). The correlation between the T_peak-T_end interval and the global DVR, however, has not been well-evaluated. Methods: Monophasic action potentials (MAPs) were recorded from 51 ± 10 epicardial and 64 ± 9 endocardial sites in the left ventricles of 10 pigs, and from 41 ± 4 epicardial and 53 ± 2 endocardial sites in the right ventricles of 2 of the 10 pigs using the CARTO mapping system. The end of repolarization times over the epi- and endocardium were measured, and the end of repolarization dispersions over the epicardium (DVR-epi), over the endocardium (DVR-endo) and over both (DVR-total) were calculated. The QT_peak, QT_end and T_peak-T_end intervals as well as the QT_peak and QT_end dispersions were obtained from the simultaneously recorded 12-lead ECG. Results: The maximal T_peak-T_end intervals (57 ± 7 ms) were consistent with the DVR-total (58 ± 11 ms, p > 0.05), and significantly correlated with the DVR-total (r = 0.64, p < 0.05). However, the mean T_peak-T_end intervals (44 ± 5 ms), and T_peak-T_end intervals from lead II (41 ± 6 ms) and V₅ (43 ± 5 ms) were all significantly smaller than and poorly correlated with the DVR-total, as were the QT_peak and QT_end dispersions (15 ± 2 ms vs. 21 ± 4 ms). Conclusion: The maximal T_peak-T_end interval may be used as a noninvasive estimate for the global DVR, but not the QT_peak and QT_end dispersions, nor the mean T_peak-T_end interval and that from a single lead.