Circadian Variation and Waking Hour Dynamics of the QT Interval

Background: The incidence of sudden cardiac death is maximal in the morning hours. Although ventricular arrhythmias have been implicated as a potential mechanism, and several neurohumoral factors affecting myocardial excitability have been shown to be raised in the early morning hours, it is not known if there is any circadian variation in the dynamics of ventricular repolarization when studied on a beat-to-beat basis. The objective of this study was to examine the range, diurnal variations, and circadian distribution of the variability of the QT interval in healthy subjects. Method: We developed and validated a new method for continuous measurement of QT intervals from 24-hour Holter recordings. The QT intervals measured semi-automatically were corrected by a linear regression formula derived independently for each patient from his own QT and RR values in 32 healthy males (20 ± 0.4 years). QT variability was assessed by the mean standard deviation of the average of consecutive uncorrected QT intervals (SDA-QT Index) and corrected QT intervals (SDA-QTc index) over 5-minute segments. The rate-dependent changes of the QT interval were studied as a function of the slope of the regression line between the QT and RR values. Results: The average QTc range was mean (SD) 79 (± 28) ms; the average maximal QTc interval was 481 (± 24) ms. The 95% upper confidence limit for the mean 24-hour QTc interval was 443 ms. The RR, QT, and QTc intervals were longer, while the SDA-QT and SDA-QTc indices were shorter during sleep. Hourly averages of the SDA-QT and SDA- QTc index revealed a sudden increase in QT variability in the first hour of waking (P < 0.0001 and P = 0.006). Conclusion: The dynamic behavior of the QT interval shows significant diurnal variations. The maximal QTc interval over 24 hours is longer than previously assumed. The period shortly following awakening is characterized by a peak in the variability of the QT interval. These changes may be indicative of autonomic instability during the early waking hours and correspond with the peak incidence of sudden arrhythmic death.     

Course and prognostic implications of QT interval and QT interval variability after primary coronary angioplasty in acute myocardial infarction

OBJECTIVES: The aim of this study was to determine the influence of early reperfusion on the course of QT interval and QT interval variability in patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) and its prognostic implications on major arrhythmic events during one-year follow-up. BACKGROUND: Although early coronary artery recanalization by primary angioplasty is an established therapy in AMI, a substantial number of patients is still threatened by malignant arrhythmias even after early successful reperfusion, which may be caused by an inhomogeneity of ventricular repolarization despite reperfusion. METHOD: Temporal fluctuations of ventricular repolarization were studied prospectively in 97 consecutive patients with a first AMI by measurements of QT interval and QT interval variability during and after successful PTCA (Thrombolysis in Myocardial Infarction flow grades 2 and 3). Continuous beat-to-beat QT interval measurement was performed from 24-h Holter monitoring, which was initiated at admission before PTCA. RESULTS: Reperfusion caused a significant continuous increase of mean RR interval (738 +/- 98 to 808.5 +/- 121 ms; p < 0.001) and a significant decrease of parameters of QT interval (QTc: 440 +/- 32 to 416.5 +/- 37ms; p < 0.001) and QT interval variability (QTcSD: 27.5 +/- 3 to 24.9 +/- 6 ms; p < 0.001) in the majority of patients. However, in patients with major arrhythmic events at the one-year follow-up (sudden cardiac death, ventricular fibrillation or sustained ventricular tachycardia, n = 15), parameters of QT interval remained unaltered after successful reperfusion (QTc: 447.3 +/- 41 to 432.9 +/- 45 ms, p = NS; QTcSD: 35.1 +/- 13.4 to 29.0 +/- 9.1 ms, p = NS). CONCLUSIONS: Reduction of QT interval and QT interval variability after timely reperfusion of the infarct-related artery may be a previously unreported beneficial mechanism of primary PTCA in AMI, indicating successful reperfusion.     

Dynamic QT interval analysis in uraemic patients receiving chronic haemodialysis

OBJECTIVE: To analyse the duration of the QT interval and its relationship with heart rate changes in patients with uraemia, before and during haemodialysis. METHODS: QT and RR intervals were measured automatically using a dedicated algorithm with 24-h Holter recordings in 29 patients (15 women) receiving chronic haemodialysis. QT corrected for heart rate (QTc) and the slope of QT/RR linear regression were calculated. Arterial blood pressure (ABP) was measured before and during haemodialysis. Plasma concentrations of K+, Mg2+ and Ca2+ were assessed before and after haemodialysis. RESULTS: ABP decreased significantly from baseline (102.7 +/- 11.0 mmHg) during the first (100.6 +/- 8.8 mmHg, P < 0.05), second (95.6 +/- 10.6 mmHg, P < 0.05), and third (94.9 +/- 10.3 mmHg, P < 0.05) hours of haemodialysis. QTc was longer during haemodialysis than during a 4-h period of no dialysis (447 +/- 28 ms compared with 429 +/- 22 ms, P < 0.001), and increased progressively during haemodialysis, with the greatest value during the last hour of haemodialysis (454 +/- 32 ms compared with 426 +/- 22 ms, P < 0.001). QT/RR slopes and correlation coefficients were lower during haemodialysis than during the period of no dialysis (0.13 +/- 0.08 compared with 0.20 +/- 0.07, P < 0.001 and 0.48 +/- 0.30 compared with 0.81 +/- 0.20, respectively; P < 0.001), suggesting a reduced ability to adapt the QT interval in response to changes in heart rate. The effects of haemodialysis on QT interval and the QT/RR relationship were greater in women than in men. QTc variations during dialysis were not correlated with changes in ABP, but were inversely related to changes in Ca2+ concentration (r2 = 0.35; P = 0.001). CONCLUSIONS: In patients with uraemia, the haemodialysis session induces a progressive increase in QT interval and modifies its relationship with heart rate. These effects may predispose some individuals to ventricular arrhythmias at the end of and immediately after the haemodialysis session.     

Regulation of QT indices mediated by autonomic nervous function in patients with type 2 diabetes

Both the QT interval and QT dispersion in diabetic patients have been reported to increase with the progression of cardiac autonomic neuropathy and to have a prognostic value. We assessed the cardiac autonomic influences on QT indices using the measurements of baroreflex sensitivity, heart rate variability, and cardiac (123)I-metaiodobenzylguanidine scintigraphic findings in patients with type 2 diabetes mellitus. Forty-two consecutive patients with type 2 diabetes (mean+/-SD: 54+/-10 years, 22 women and 20 men) were studied. Baroreflex sensitivity negatively correlated with the maximum and minimum QTc intervals as well as QT/QTc dispersion. However, the high-frequency power and the ratio of low-frequency power to high-frequency power of heart rate variability did not correlate with any QT indices. The percent washout rate of (123)I-metaiodobenzylguanidine positively correlated with QT/QTc dispersion, but not with maximum and minimum QTc intervals. Our findings suggest that cardiac vagal dysfunction is related to QT interval prolongation while both sympathetic and vagal dysfunctions are related to increased QT dispersion in type 2 diabetic patients. Baroreflex sensitivity and percent washout rate of (123)I-metaiodobenzylguanidine may be useful parameters indicating the abnormalities of the cardiac ventricular repolarization in this population.     

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.     

Heart rate–corrected QT interval in men increases during winter months

BACKGROUND: Sudden cardiac death increases during winter months in both men and women. The heart rate-corrected QT (QTc) interval exhibits circadian variation. However, little is known about QTc interval variation with month of year. OBJECTIVE: We sought to determine whether the QTc interval varies with month of year. METHODS: We retrospectively analyzed a database of 24,370 electrocardiograms (ECGs) to determine seasonal variation in QTc intervals. The analysis data set included 7,976 baseline ECGs, one each for 3,700 men and 4,276 women. ECGs selected for analysis were normal, recorded in regions north of the equator, and taken on subjects >or=18 years old. The QT correction for heart rate (HR) was performed using QTc = QT*(HR/60)(0.4). The monthly mean QTc intervals were compared, for men and women separately, using a one-way analysis of variance with the Bonferroni correction for multiple comparisons. RESULTS: Subject ages ranged from 18 to 95 years. The monthly mean QTc intervals were consistently greater for women than for men by 5.2 +/- 2.3 ms. After correction for multiple comparisons, the difference between the greatest and least monthly mean QTc interval was 6.1 +/- 1.5 ms (P <.01) for men and 3.5 ms (nonsignificant) for women. The maximum monthly mean QTc interval of 413 +/- 18 ms (n = 560; P <.05) occurred in October for men and of 417 +/- 16 ms (n = 350) in March for women, but it was not significant. CONCLUSIONS: Significant seasonal variation in QTc interval exists among male subjects >or=18 years of age with normal baseline ECGs, with the QTc interval being longest in October. No significant variation was seen for women.     

Continuous QT Interval Measurements from 24-Hour Electrocardiography and Risk after Myocardial Infarction

Objectives: The aim of this study was to examine the clinical value of QT analysis from Holter recordings in patients after myocardial infarction (Ml). Background: Prolongation and dispersion of QT intervals in the 12-lead standard ECG have been proposed as indicators of risk for arrhythmic events. However, the value of QT and T wave measurements from Holter recordings has yet to be established. Methods: Intervals from Q to the peak and to the end of T were determined every 30 seconds from 24-hour Holter recordings and corrected for cycle length (QTc). The duration of late repolarization was calculated as QT end minus QT peak. 24-hour QT variability was determined as the standard error of estimate from the linear regression analysis of QT and RR intervals. In a case control design, 51 post-MI patients suffering from subsequent cardiac death within 1 year were compared to 51 post-MI patients with an uncomplicated follow-up. Results: QTc intervals as well as 24-hour QT variability did not differ between post-MI patients with favorable and unfavorable clinical outcome. However, there was a prolonged interval from the peak to the end of the T wave in cardiac death victims (mean ± SE: 110 ± 4 ms) as compared to controls (95 ± 3ms, P < 0.001). Conclusions: Prolongation of the late repolarization phase seems to be associated with an increased risk of cardiac death after Ml. Standard QT measurements from ambulatory ECG recordings have no predictive value in post-MI patients.     

QT离散度昼夜的变化与心率变异性的联系

目的 探讨QT离散度的昼夜改变与心率变异性的关系。方法 测量计算20例正常人24小时动态心电图的QT、QTc、QT与QTc离散度及心率变异参数。结果 发现QT、QTd、QTcd、RR间期、RMSSD、HF、LH/HF存在昼夜的明显差异。QTd、QTcd与RR间期、RMSSD、HF呈现明显的负性相关，与LF/HF呈明显的正性相关。结论 QT离散度的增加与交感神经活动的增加和迷走神经活动的减弱密切相关。     

Corrected QT variability in serial electrocardiograms in long QT syndrome: the importance of the maximum corrected QT for risk stratification.

OBJECTIVES: We evaluated the incremental prognostic information provided by multiple corrected QT (QTc) measurements on serial electrocardiograms (ECGs) in patients with the inherited long QT syndrome (LQTS). BACKGROUND: A baseline QTc of > or =500 ms has been shown to be associated with increased risk of cardiac events among LQTS patients. However, the value of QTc measurements on follow-up ECGs in risk assessment has not been determined. METHODS: The risk of a first LQTS-related cardiac event during adolescence was assessed in 375 patients enrolled in the International LQTS Registry for whom serial follow-up ECGs were recorded before age 10. RESULTS: The mean +/- SD difference between the minimum and maximum QTc values on serial ECGs recorded in study patients was 47 +/- 40 ms. The maximum QTc interval recorded before age 10 was the strongest predictor of cardiac events during adolescence (adjusted hazard ratio [HR] = 2.74; p < 0.001). Other follow-up QTc measures, including the baseline, the mean, and the most recent QTc interval recorded before age 10, were less significant risk factors. After adjusting for the maximum QTc value during follow-up, no significant association remained between the baseline QTc value and the risk of subsequent cardiac events (HR = 1.04; p = 0.91). CONCLUSIONS: In LQTS patients, there is a considerable variability in QTc measures in serial follow-up ECGs. The maximum QTc interval provides incremental prognostic information beyond the baseline measurement. We suggest that risk stratification in LQTS patients should include follow-up ECG data.     

Problems of heart rate correction in assessment of drug-induced QT interval prolongation

INTRODUCTION: Estimation of QT interval prolongation belongs to safety assessment of every drug. Among unresolved issues, heart rate correction of the QT interval may be problematic. This article proposes a strategy for heart rate correction in drug safety studies and demonstrates the strategy using a study of ebastine, a nonsedating antihistamine. METHODS AND RESULTS: Four-way cross-over Phase I study investigated 32 subjects on placebo, ebastine 60 mg once a day, 100 mg once a day, and terfenadine 180 mg twice a day. Repeated ECGs were obtained before each arm and after 7 days of treatment. The changes in heart rate-corrected QTc interval were investigated using (A) 20 published heart rate correction formulas, (B) a correction formula optimized by QT/RR regression modeling in all baseline data, and (C) individual corrections optimized for each subject by drug-free QT/RR regression modeling. (A) Previously published correction formulas found QTc interval increases on terfenadine. The results with ebastine were inconsistent. For instance, Bazett's and Lecocq's correction found significant QTc increase and decrease on ebastine, respectively. The results were related (absolute value(r) > 0.95) to the success of each formula (independence of drug-free QTc and RR intervals). (B) The pooled drug-free QT/RR regression found an optimized correction QTc = QT/RR(0.314). QTc interval changes on placebo, ebastine 60 mg, ebastine 100 mg, and terfenadine were -1.95 +/- 6.87 msec (P = 0.18), -3.91 +/- 9.38 msec (P = 0.053), 0.75 +/- 8.23 msec (P = 0.66), and 12.95 +/- 14.64 msec (P = 0.00025), respectively. (C) Individual QT/RR regressions were significantly different between subjects and found optimized corrections QTc = QT/RR(alpha) with alpha = 0.161 to 0.417. Individualized QTc interval changes on placebo, ebastine 60 mg, ebastine 100 mg, and terfenadine were -2.76 +/- 5.51 msec (P = 0.022), -3.15 +/- 9.17 msec (P = 0.11), -2.61 +/- 9.55 msec (P = 0.19), and 12.43 +/- 15.25 msec (P = 0.00057, respectively. Drug-unrelated QTc changes up to 4.70 +/- 8.92 msec reflected measurement variability. CONCLUSION: Use of published heart rate correction formulas in the assessment of drug-induced QTc prolongation is inappropriate, especially when the drug might induce heart rate changes. Correction formulas optimized for pooled drug-free data are inferior to the formulas individualized for each subject. Measurement imprecision and natural variability can lead to mean QTc interval changes of 4 to 5 msec in the absence of drug treatment.     

Assessment of QT dispersion in symptomatic patients with congenital long QT syndromes.

It has been suggested that QT dispersion recorded on the surface electrocardiogram may be a predictor of arrhythmic events in patients with congenital QT prolongation. To evaluate this, 9 patients (6 female, mean age 17.6 years) with congenital long QT syndromes, all of whom had syncope and documented torsades de pointes, were studied. Patients were studied off treatment and during therapy with beta-blocking agents. Three patients were also studied after left stellate ganglionectomy. An age-matched control group was also studied. Good quality 12-lead electrocardiograms were recorded from all patients. For each lead, QT and RR intervals were measured, and QTc value was calculated. QT and QTc dispersions were calculated for each patient. Patients had a significantly longer mean QT interval compared with that of the control group (450 +/- 100 vs 359 +/- 63 ms; p = 0.015) at similar mean RR intervals (736 +/- 231 vs 783 +/- 289 ms), with a longer mean QTc value (0.53 +/- 0.08 vs 0.41 +/- 0.02 s1/2; p = 0.004). Patients also had longer QT and QTc dispersions compared with those of the control group (110 +/- 45 vs 43 +/- 12 ms [p = 0.004], and 0.108 +/- 0.03 vs 0.05 +/- 0.02 s1/2 [p = 0.002], respectively). QT and QTc dispersions on and off beta-blocking agents were not significantly different. Comparing patients with frequent and those with infrequent symptoms, there was no difference in QT or QTc dispersion either off treatment or during therapy with beta-blocking agents.(ABSTRACT TRUNCATED AT 250 WORDS)     

QT interval prolongation and sudden cardiac death in diabetic autonomic neuropathy

Alterations in cardiac sympathetic innervation may result in QT interval prolongation and predispose to sudden arrhythmias and death. Sudden cardiac death occurs in diabetic patients who have autonomic neuropathy, but the cause is uncertain. In 30 patients with insulin-dependent diabetes mellitus who had no evidence of ischemic heart disease, cardiac autonomic neuropathy, determined by clinical tests, was found in 17. The corrected QT interval (QTc), measured using Bazett's formula at rest and peak exercise, was prolonged (greater than 440 msec) in 12 of these patients at rest and in 15 at peak exercise. Prolonged QTc intervals were found only in patients who had definite cardiac autonomic neuropathy. As a group, the QTc interval (mean +/- SD) in the diabetic patients with cardiac autonomic neuropathy was prolonged compared to that in patients without cardiac autonomic neuropathy at rest (447 +/- 28 vs. 405 +/- 9 ms; P less than 0.0001) and peak exercise (468 +/- 23 vs. 402 +/- 23 ms; P less than 0.0001). There was a direct linear relationship between the extent of cardiac autonomic neuropathy and the QTc interval (r = 0.71; P less than 0.001). One of the patients with cardiac autonomic neuropathy and prolonged QTc intervals had a nonuniform loss of adrenergic neurons in his heart demonstrated by meta-iodobenzyl-guanidine scintigraphy, indicating sympathetic imbalance; he subsequently died unexpectedly. These data suggest that diabetic cardiac autonomic neuropathy may result in sympathetic imbalance and QTc interval prolongation, predisposing these patients to sudden arrhythmias and death.     

Beat-to-beat variability of QT intervals is increased in patients with drug-induced long-QT syndrome: a case control pilot study.

AIMS: Torsades de pointes arrhythmias (TdP) occur by definition in the setting of prolonged QT intervals. Animal models of drug induced Long-QT syndrome (dLQTS) have shown higher predictive value for proarrhythmia with beat-to-beat variability of repolarization duration (BVR) when compared with QT intervals. Here, we evaluate variability of QT intervals in patients with a history of drug-induced long QT syndrome (dLQTS) and TdP in absence of a mutation in any of the major LQTS genes. METHODS AND RESULTS: Twenty patients with documented TdP under drugs with QT-prolonging potential were compared with 20 matched control individuals. An observer blinded to diagnosis manually measured lead-II, RR, and QT intervals from 30 consecutive beats. BVR was determined from Poincaré plots of QT intervals as short-term variability (STV(QT) = Sigma|QT(n)(+1) - QT(n)|/[30 x radical2]). QRS interval and cycle length was comparable between study groups and controls. No difference was found in QTc between dLQTS and controls (428 +/- 25 vs. 421 +/- 34 ms, P = 0.26), whereas STV(QT) was significantly higher in dLQTS when compared with controls (8.1 +/- 3.7 vs. 3.6 +/- 1.3 ms, P = 0.001). Proarrhythmic predictive power of STV(QT) was superior to that of the QTc interval (AUC: 0.89 vs. 0.57, 95% CI: 0.79-0.99 vs. 0.39-0.75). CONCLUSION: In the absence of QTc prolongation, baseline STV(QT) characterized patients with documented drug-induced proarrhythmia. STV(QT) could prove to be a useful non-invasive, easily obtainable parameter aiding the identification of the patient at risk for potentially life threatening arrhythmia in the context of drugs with QT prolonging potential.     

Beat‐to‐Beat QT Dynamics in Healthy Subjects

Background: Measures of QT dynamics express repolarization abnormalities that carry prognostic information, but the reproducibility of beat‐to‐beat QT dynamics has never been established. The QT interval is prolonged at night, but how the circadian rhythm and heart rate influence the dynamic QT measurements is still unsettled. The aims of the present study were: (1) to describe the reproducibility of beat‐to‐beat QT dynamics with respect to intrasubject, between‐subject, and between‐observer variability and (2) to describe the normal range, circadian variation, and heart rate dependence of QT dynamics. Methods: Ambulatory Holter recordings were performed three times on 20 healthy volunteers and were analyzed by two experienced cardiologists. Slope and intercept of the QT/RR regression, the variability of QT and R‐R intervals expressed as the standard deviation, and the relation between QT and RR variability expressed as a variability ratio were measured among other QT dynamics. Results: The reproducibility of all QT dynamics was good. All QT dynamics showed circadian variation when calculated on an hourly basis. The day/night variation in slope could be explained by the differences in heart rate, whereas the day/night variation in intercept was heart rate independent. Conclusion: The present study shows that reliable automatic QT measurements could be performed, encouraging further evaluation of the clinical value of QT dynamics in risk stratification of cardiac patients.     

Beat-to-beat QT dynamics in paroxysmal atrial fibrillation

BACKGROUND: QT dynamics parameters are used only in sinus rhythm. However, because many patients with paroxysmal atrial fibrillation undergo antiarrhythmic treatment that changes QT, developing methods for measuring QT dynamics during atrial fibrillation is important. OBJECTIVES: The purpose of this study was to evaluate whether QT dynamics in atrial fibrillation can be measured more reliably if additional RR intervals are included in the QT calculation. METHODS: QT and RR intervals were measured in 15 patients with atrial fibrillation and sinus rhythm on the same 24-hour Holter recording. Full QT adaptation is not instantaneous but lags behind over several beats. To correct for this lag, we adapted a weighted average method using five successive RR intervals. Linear regression was performed on (QT, RR) and (QT, RR(modified)) pairs. Variability ratio (standard deviation of all QT intervals/standard deviation of all RR intervals) and modified variability ratio (standard deviation of all QT intervals/modified standard deviation of all RR intervals) were calculated. RESULTS: QT-RR slope was reduced in atrial fibrillation compared with sinus rhythm (0.076 +/- 0.009 vs 0.113 +/- 0.0013, P = .0005). When correcting for lag, using the QT-RR(modified) slope, the slope in atrial fibrillation became similar to the slope in sinus rhythm (0.126 +/- 0.013 vs 0.126 +/- 0.013, P = .9547). The variability ratio was reduced in atrial fibrillation compared with sinus rhythm (0.175 +/- 0.017 vs 0.240 +/- 0.031, P = .009), but when correcting for the lag, the modified variability ratio was similar in atrial fibrillation and sinus rhythm (0.262 +/- 0.029 vs 0.267 +/- 0.038, P = .80). CONCLUSION: The results of this study demonstrate that QT dynamics can be measured reliably in atrial fibrillation using 24-hour Holter recordings.     

QT dynamics in risk stratification after myocardial infarction

OBJECTIVES: The purpose of this study was to compare measures of repolarization dynamics (QT dynamics) with other Holter risk predictors, left ventricular systolic function, and demographic characteristics to establish whether QT dynamics add independent information on risk stratification after myocardial infarction (MI). A novel QT dynamics parameter, the QT/RR variability ratio (VR), was introduced in this study. BACKGROUND: Abnormal repolarization contributes to arrhythmogenesis, and quantification of QT dynamics may have prognostic value after MI. METHODS: A 24-hour Holter recording was performed in 481 consecutive MI patients. Recordings from 311 patients were included in the analysis. QT/RR slope and intercept, mean and standard deviation of all QT, QTc, and RR intervals, and VR (defined as the ratio between the standard deviation of all QT intervals and the standard deviation of all RR interval) were calculated. Ventricular premature beats and ventricular tachycardia were counted. RESULTS: During 3-year follow-up, 70 deaths from all causes occurred. All parameters except mean of all QT intervals and standard deviation of all QTc intervals univariately predicted all-cause mortality. In multivariate Cox analysis, only VR per 0.1 (hazard ratio [HR]: 1.9 [1.5-2.4]), left ventricular ejection fraction per 5% (HR: 1.2 [1.1-1.3]), ventricular premature beats per 10 beats/hour (HR: 1.03 [1.002-1.06]), and age per 10 years (HR: 1.6 [1.3-2.0]) independently predicted all-cause mortality. CONCLUSIONS: Measures of QT dynamics univariately predicted total mortality. VR, left ventricular ejection fraction, ventricular premature beats, and age made up the optimal Cox model for risk stratification after MI. VR seems to be a promising risk factor for identifying sudden arrhythmic death.     

Coronary artery bypass grafting is associated with a significant worsening of QT dynamicity and heart rate variability

BACKGROUND: Imbalance in autonomic nervous system and impaired myocardial repolarization has been shown to increase the risk for arrhythmias in patients with coronary artery disease. This study evaluated the effects of coronary artery bypass grafting (CABG) on heart rate variability and QT interval dynamicity in subjects with coronary artery disease undergoing elective CABG surgery. METHODS: The study group consisted of 68 consecutive patients (mean age +/-SD: 61 +/- 9 years) with coronary artery disease who underwent elective CABG. Twenty-four-hour Holter monitoring was performed 2-5 days before cardiac surgery and was repeated 10 days after CABG. ELATEC holter software was used to calculate heart rate variability and QT dynamicity parameters. All subjects had a complete history, laboratory examination and transthoracic echocardiography. RESULTS: All patients had beta-blocking agent medication pre- and postoperatively. Standard deviation of all NN intervals for a selected time period, square root of the mean of the sum of the squares of differences between adjacent RR intervals, the proportion of differences in successive NN intervals greater than 50 ms, normalized low-frequency power, and normalized high-frequency power were significantly decreased after CABG surgery, whereas low-frequency/high-frequency ratio was significantly increased after CABG. QT/RR slopes over 24 h were significantly increased after CABG surgery for QT end and QT apex (QTapex/RR: 0.16 +/- 0.13 vs. 0.28 +/- 0.19, p < 0.001; QTend/RR: 0.18 +/- 0.13 vs. 0.36 +/- 0.23, p < 0.001). CONCLUSION: This prospective study showed for the first time that CABG was associated with a significant worsening of heart rate variability and QT dynamicity parameters in the postoperative period.     

The association between the length of the QT interval and mortality in the Cardiovascular Health Study

PURPOSE: A long QT interval is a risk factor for arrhythmic events and sudden death. Whether moderate QT prolongation is associated with clinical events in community-dwelling elderly patients is uncertain. METHODS: We measured the QT interval in a population-based sample of 5888 men and women at least 65 years of age who were participants in the Cardiovascular Health Study. The association between Bazett's rate-corrected QT (QTc, in ms) and mortality during the subsequent 10 years was evaluated. We stratified participants by the presence or absence of coronary heart disease status at baseline, and adjusted for coronary heart disease risk factors. RESULTS: The rates of all-cause and coronary heart disease mortality were greater in participants with longer QTc intervals. Among participants without known coronary heart disease, those whose QTc interval was >450 ms were at increased risk of all-cause mortality (relative risk [RR] = 1.34; 95% confidence interval [CI]: 1.07 to 1.67) and coronary heart disease mortality (RR = 1.6; 95% CI: 1.0 to 2.5) when compared with participants whose QTc interval was <410 ms. The associations were stronger among those with known coronary heart disease (RR for all-cause mortality = 2.3; 95% CI: 1.6 to 3.3; and RR for coronary heart disease mortality = 2.0; 95% CI: 1.1 to 3.7). CONCLUSIONS: The QT interval from the standard electrocardiograms is of value for identification of elderly persons at increased risk of coronary heart disease and total mortality. A QTc interval >450 ms should prompt clinical evaluation and possible interventions to reduce the risk of coronary events.     

QT dispersion and late potentials during doxorubicin therapy for non-Hodgkin's lymphoma

OBJECTIVES: To investigate effects of doxorubicin therapy on cardiac electrophysiology, with special emphasis on QT dispersion and late potentials, in lymphoma patients. DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Twenty-eight adult non-Hodgkin's lymphoma patients who received doxorubicin to a cumulative dose of 400-500 mg m-2. MAIN OUTCOME MEASURES: Standard 12-lead electrocardiogram (ECG) and signal-averaged ECG (SAECG) recordings were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m-2. RESULTS: Heart rate-corrected QT interval (QTc) increased from 402 +/- 4 to 416 +/- 5 ms (P = 0.002) during the study period. QT dispersion (variability in QT interval duration amongst the different leads of the standard 12-lead ECG) increased from 24.1 +/- 2.5 to 35.0 +/- 2.8 ms (P = 0.041) and QTc dispersion increased from 26.5 +/- 2.5 to 39.0 +/- 3.5 ms (P = 0.039). Five patients (18%) developed QT dispersion exceeding 50 ms. In addition, two patients (7%) developed late potentials during doxorubicin therapy. The changes in QTc duration, QT dispersion and late potentials occurred independently of the impairment of left ventricular function. CONCLUSIONS: Prolongation of QTc, increased QT dispersion and development of late potentials are indicative of doxorubicin-induced abnormal ventricular depolarization and repolarization. QT dispersion and late potentials are both known to be associated with increased risk of serious ventricular dysrhythmias and sudden death in various cardiac diseases. Thus, follow-up of these parameters might also be useful in assessing the risk of late cardiovascular events in cancer patients treated with anthracyclines.     

QT interval and repolarization time in patients with intraventricular conduction delay

A prolonged QT interval is an important prognostic indicator for cardiac arrhythmias and sudden death. The conventional QT interval measurement, however, includes in its measure the cardiac depolarization (QRS) as well as the cardiac repolarization (JT) intervals. To evaluate the relative contribution of the depolarization and the repolarization time prolongation to the prolonged QT interval in patients with intraventricular conduction delay (IVCD), the QRS, QT, and JT intervals were measured in 72 subjects with various types of IVCD. The observed intervals in IVCD subjects were compared to similar intervals in 33 healthy individuals in whom there was no evidence for intraventricular conduction abnormalities. The QTc (QT interval corrected for heart rate) in subjects with IVCD were 445 +/- 6.8 msec (mean +/- SEM) in those with LAD, 470 +/- 9.1 msec with RBBB, and 489 +/- 6.9 msec with LBBB. All of these intervals were significantly prolonged compared to 430 +/- 4.3 msec in the control group. The prolongation of QTc interval in each category of IVCD subjects was entirely secondary to a prolonged depolarization time, as the repolarization intervals were not significantly different from those observed in the control group (F = 0.5, p = NS). These observations may provide an explanation for the differential prognosis for subjects with prolonged QT interval with prolonged repolarization time as compared to those with prolonged QT interval with prolonged depolarization time.