QT Variability Index Research Articles

Scatter in repolarization timing predicts clinical events in post–myocardial infarction patients

Increased spatial and temporal dispersion of repolarization contributes to ventricular arrhythmogenesis. Beat-to-beat fluctuations in T-wave timing are thought to represent such dispersion and may predict clinical events. The purpose of this study was to assess whether a novel noninvasive measure of beat-to-beat instability in T-wave timing would provide additive prognostic information in post-myocardial infarction patients. We studied 678 patients from 12 hospitals with 32-lead 5-minute electrocardiogram recordings 6-8 weeks after myocardial infarction. Custom software identified R wave-to-T wave intervals (RTIs) and diastolic intervals (DIs). Repolarization scatter (RTI:DI(StdErr)) was then calculated as the standard error about the RTI:DI regression line. In addition, left ventricular ejection fraction (LVEF), short-term heart rate variability (HRV) parameters, and QT variability index were measured. Patients were followed for the composite endpoint of death or life-threatening ventricular arrhythmia. After a mean follow-up of 63 months, 134 patients met the composite endpoint. An RTI:DI(StdErr) >5.50 ms was associated with a 210% increase in arrhythmias or deaths (P <.001). After adjusting for LVEF, RTI:DI(StdErr) remained an independent predictor (P <.001). RTI:DI(StdErr) was also independent of short-term HRV parameters and the QT variability index. Increased repolarization scatter, a measure of high-frequency, cycle-length-dependent repolarization instability, predicts poor outcomes in patients after myocardial infarction.

Increased QT variability in young asymptomatic patients with β‐thalassemia major

Despite recent progress in iron chelation therapy, sudden cardiac death due to malignant ventricular arrhythmias remains a vexing, clinical problem in patients with beta-thalassemia major (TM). In this study we assessed whether the major indices of QT variability, emerging tools for risk stratification of sudden cardiac death, differ in young asymptomatic patients with TM and healthy persons. Thirty patients with TM and 30 healthy control subjects underwent a 5-min electrocardiography recording to calculate the following variables: QT variance (QT(v)), QT(v) normalized for mean QT (QTVN) and QT variability index (QTVI). All subjects also underwent a two-dimensional and Doppler echocardiography study and magnetic resonance imaging (MRI) to determine cardiac and hepatic T2* values. No differences were observed in clinical and conventional echo-Doppler findings in healthy control subjects and patients with TM whereas QT(v), QTVN and QTVI values were significantly higher in patients than those in controls (QT(v), P < 0.001; QTVN, P < 0.05 and QTVI, P < 0.001) and cardiac T2* and hepatic MRI T2* values were significantly lower in patients with TM (P < 0.001). The indices of temporal QT variability correlated significantly with MRI data. Young asymptomatic patients with TM have increased cardiac repolarization variability as assessed by QT variability indices, probably due to cardiac iron deposition. These easily assessed, non-invasive markers could be used to identify increased myocardial repolarization lability early in asymptomatic patients with TM.

Acute psychosis leads to increased QT variability in patients suffering from schizophrenia

Patients with schizophrenia have been reported to experience sudden cardiac death 3 times more likely than individuals from the general population. One important factor related to an increased risk of cardiac arrhythmias and sudden death is the prolongation of the QTc interval. This study examined whether acute psychosis might influence the beat-to-beat variability of the QT interval, which reflects effectively cardiac repolarization lability. High resolution electrocardiographic recordings were performed in 25 unmedicated patients suffering from acute schizophrenia and matched controls. From these, parameters of beat-to-beat heart rate and QT variability measures such as approximate entropy and QT variability index (QTvi) were calculated. Measures were correlated with the scale for the assessment of positive symptoms (SAPS) and negative symptoms (SANS). QTvi was significantly higher in patients with schizophrenia compared to controls. While QTvi correlated with the degree of delusions and hallucinations, no correlation with electrolyte concentrations was found. Approximate entropy of heart rate was decreased indicating reduced complexity and decreased vagal tone. In conclusion, increased QT variability in patients with schizophrenia indicates abnormal cardiac repolarization lability, which can result in serious cardiac arrhythmias. The correlation of positive symptoms with QT variability might indicate high sympathetic cardiac activity in these patients, which might be associated with increased cardiovascular mortality.

Increased QT interval variability index in acute alcohol withdrawal

Objective Acute alcohol withdrawal is associated with increased cardiovascular mortality, most likely due to cardiac arrhythmias. As the QT interval reflects the most critical phase for the generation of reentry and thus for arrhythmia, we examined QT variability in patients suffering from acute alcohol withdrawal. Methods High resolution electrocardiographic recordings were performed in 18 male unmedicated patients suffering from acute alcohol withdrawal, 18 matched controls and 15 abstained alcoholics. From these, parameters of beat-to-beat heart rate and QT variability such as approximate entropy and QT variability index (QTvi) were calculated. Measures were correlated with the severity of withdrawal symptoms and with serum electrolyte concentrations. Results Heart rate and QTvi were significantly increased in acute alcohol withdrawal. Abstained alcoholics did not significantly differ from controls. While QTvi correlated with the severity of alcohol withdrawal symptoms, the mean QT interval duration showed an inverse relationship with serum potassium concentrations. Conclusion Our data indicate increased QT variability and thus increased repolarization lability in acute alcohol withdrawal. This might add to the elevated risk for serious cardiac arrhythmias. In part, these changes might be related to increased cardiac sympathetic activity or low potassium, thus suggesting the latter as possible targets for adjuvant pharmacological therapy during withdrawal.

QT variability strongly predicts sudden cardiac death in asymptomatic subjects with mild or moderate left ventricular systolic dysfunction: a prospective study

The most widely accepted marker for stratifying the risk of sudden cardiac death (SCD) in post myocardial infarction patients is a depressed left ventricular function. Left ventricular ejection fractions (EF) of 35% or less increase the risk of sudden death but values between 35 and 40% raise concern. The underlying pathophysiological mechanism is sustained ventricular tachycardia or fibrillation, both associated with increased cardiac repolarization variability. We assessed whether the indices of QT variability from a short-term electrocardiographic (ECG) recording predict sudden death. A total of 396 subjects with chronic heart failure (CHF) due to post-ischaemic cardiomyopathy, with an EF between 35 and 40% and in NYHA class I, underwent a 5 min ECG recording to calculate the following variables: QT variance (QT(v)), QT normalized for the square of the mean QT (QTVN), and QT variability index (QTVI). Corrected QT (QT(c)) was calculated from a 12-lead ECG recording. All participants were followed for 5 years. A multivariable survival model indicated that a QTVI greater than or equal to the 80th percentile indicated a high risk of SCD [hazards ratio (HR) 4.6, 95% confidence interval (CI) 1.5-13.4, P = 0.006] and, though to a lesser extent, a high risk of total mortality (HR 2.4, 95% CI 1.2-4.9, P = 0.017). The model including QTVI as a continuous variable confirmed a similar high risk for SCD (HR 2.9, 95% CI 1.3-6.5, P = 0.01) and for total mortality (HR 2.6, 95% CI 1.3-5.2, P = 0.008). Although asymptomatic patients with CHF who have a slightly depressed EF are at low risk of sudden death, the category is extraordinarily numerous. The QTVI could be helpful in stratifying the risk of sudden death in this otherwise undertreated population.

Correlation Between Beat‐to‐Beat QT Interval Variability and Impaired Left Ventricular Function in Patients with Previous Myocardial Infarction

Beat-to-beat QT interval variability (QTV) is associated with sudden cardiac death and New York Heat Association functional class severity. We sought to evaluate the relationship between QTV and left ventricular (LV) function in patients with previous myocardial infarction (MI). Fifty-nine patients with previous anterior MI were enrolled. LV ejection fraction (EF), LV end-systolic volume index (LVESVI), and LV end-diastolic volume index (LVEDVI) were measured by LV contrast angiography. QT interval was measured by automated analysis of 512-beat records of 12-lead electrocardiogram. The mean interval, standard deviation and variance in RR and QT intervals, and the QT variability index (QTVI) were calculated for each patient using two leads that corresponded with and without the infarction site. High-frequency power, low-frequency power, total-frequency power, and the ratio of low-frequency to high-frequency power in RR and QT intervals were calculated. While measured indices of RR intervals and indices of QT intervals, which did not correspond with the infarction site, did not correlate with differences in LV function, measured indices of QT intervals, which corresponded with the infarction site, did correlate with differences in LV function. However, there were no correlations between the ratio of low-frequency to high-frequency power in QT intervals and EF or LVEDVI. Correlations between QTVI and LV function were observed, particularly between QTVI and LVESVI (r = 0.712, P < 0.0001). In patients with previous anterior MI, there was variability in temporal dispersion of QT interval and a strong correlation between QTV corresponded with the infarcted site and LV function.

Analysis of the QT interval and its variability in healthy adults during rest and exercise

The aim of the present study was to quantify the variability of electrocardiographic QT and RR intervals during rest and dynamic physical exercise, and to interpret these variabilities in terms of relative autonomic modulation of the atrial and ventricular myocardium. We also sought to characterize the relationships between QT, heart rate-corrected QT (QTc) and RR intervals, and to consider their associations with differential autonomic regulation. Nine males and eight females of similar age (22.8 ± 4.7 years), mass (75.5 ± 13.0 kg) and aerobic fitness (43.6 ± 7.7 ml kg−1 min−1) (mean ± SD) undertook progressive bicycle exercise. A three-lead Holter ECG was recorded continuously during pre-exercise, exercise and recovery, and mean values of RR, QT, QTc, QT variability index (QTVI) and mean-normalized QT variance (QTVN) were determined. At the onset of exercise QTVI increased rapidly compared with rest and remained significantly elevated throughout exercise and recovery. There were significant differences between QTaVI and QTeVI (QT measured from Q wave onset to T wave apex (QTa) and T wave end (QTe), respectively) throughout the experimental protocol. QTVI was significantly reduced in males compared with females prior to exercise but was similar thereafter. We suggest that physical exercise perturbs the resting QT–RR relationship owing to the onset of differential parasympathetic modulation of the atrial and ventricular myocardium. QTVI can be used to quantify the relative autonomic influence on the atrial and ventricular myocardium during rest and exercise, and might be related to HR-dependent and HR-independent influences on the QT interval.

Age and QT variability index during free breathing, controlled breathing and tilt in patients with chronic heart failure and healthy control subjects

The QT variability index (QTVI) indicates temporal dispersion in myocardial repolarization, and a high QTVI is associated with a propensity for sudden death from malignant ventricular arrhythmias in subjects at high risk. In this study, the authors assessed the effects of free breathing, controlled breathing, and sympathetic stress (tilt) on the QTVI in patients with chronic heart failure (CHF) and healthy control subjects. The authors also examined the influence of age on the same variables. To obtain normative data, they calculated 95% confidence intervals for healthy subjects grouped according to age. Under all experimental conditions, the QTVI was larger in the CHF group overall and in the age subsets than in controls. In patients and controls, the QTVI increased significantly during tilt, although no differences were found between the QTVI measured during free and controlled breathing. In healthy controls, the following variables correlated significantly with the QTVI: age and baseline heart rate (P < 0.001). In patients with CHF, aging had no influence on the QTVI. Age, sympathetic stress, and CHF all tend to increase the QTVI and could potentially induce sudden death. Further studies should assess the usefulness of the QTVI as a marker predicting sudden cardiac death under the various conditions of risk.

Increased pulse-wave velocity in patients with anxiety: implications for autonomic dysfunction

Decreased vagal function is associated with vascular dysfunction. In this study, we compared vascular indices and correlated heart rate and QT variability measures with vascular indices in patients with anxiety disorders and normal controls. We compared age- and sex-matched controls ( n=23) and patients with anxiety ( n=25) using the Vascular Profiler (VP-1000; Colin Medical Instruments, Japan), approved by the US Food and Drug Administration. Using this machine, we obtained ankle and brachial blood pressure (BP) in both arms (brachial), both legs (ankle), and carotid artery, and lead I electrocardiogram (ECG) and phonocardiogram. Using these signals, pulse-wave velocity (PWV), and arterial stiffness index % and preejection period can be calculated. We also obtained ECG sampled at 1000 Hz in lead II configuration in supine posture to obtain beat-to-beat interbeat interval (R-R) and QT interval variability for 256 s. Patients with anxiety had significantly higher carotid mean arterial pressure (MAP) %, brachial-ankle PWV (BAPWV), arterial stiffness index %, MAP, and diastolic BP of the extremities compared to controls. We found significant negative correlations ( r values from .4 to .65; P<.05 to .007) between R-R interval high-frequency (0.15–0.5 Hz) power (which is an indicator of cardiac vagal function), and increased BAPWV and systolic BP of the extremities only in patients. We were unable to find such correlations in controls. We also found significant positive correlations between QT variability index (a probable indicator of cardiac sympathetic function) and MAP of the extremities and BAPWV only in the patient group. These findings suggest an important association between decreased vagal and increased sympathetic function, and decreased arterial compliance and possible atherosclerotic changes and increased BP in patients with anxiety.

Assessment of Cardiac Autonomic Regulation and Ventricular Repolarization after Off-Pump Coronary Artery Bypass Grafting

Altered autonomic regulation precipitates cardiac arrhythmias and increases the risk of sudden cardiac death. This risk is further increased by changes in ventricular repolarization. Autonomic regulation is deranged in patients after myocardial on-pump revascularization. We aimed to clarify how off-pump coronary artery bypass grafting (CABG) affects postoperative cardiac autonomic regulation and ventricular repolarization within 4 weeks after CABG. Forty-two patients (mean age, 61.9 +/- 9.3 years; mean EURO score 2.6 +/- 1.9) were electively admitted for off-pump CABG. The electrocardiographic and respiratory waveform recordings were performed in the afternoon in the supine position for 10 minutes. Autonomic modulation was assessed using heart rate variability analysis. Power spectra were computed from 5-minute stable RR intervals using Fourier Transform analysis. Total power of spectra was defined in the range of 0.01 to 0.40 Hz, high-frequency power within 0.15 to 0.40 Hz, and low-frequency power within 0.04 to 0.15 Hz. Normalized power was defined as a ratio of power in each band/total power. The high- and low-frequency power as well as their normalized values indicated cardiac vagal and sympathetic modulation, respectively. Ventricular repolarization was assessed using QT interval, QT interval variability, and QT-RR interdependence analysis. QT intervals were determined from the beginning of the 5-minute segments. QT interval variability was evaluated by a T-wave template-matching algorithm. Pearson correlation between length of RR and QT interval was applied to study QT-RR characteristics. The results were tested for significance using the Fisher exact test, nonpaired t test, and analysis of variance; a P <.05 was considered significant. The frequency of arrhythmic events and heart rate increased from the fourth to the seventh postoperative day and returned to preoperative levels 4 weeks after CABG. Heart rate variability measures indicating autonomic modulation remained depressed even 4 weeks after the procedure. QT variability index increased from -1.2 +/- 0.5 to -0.8 +/- 0.4 on the fourth day after the operation (P <.05) and returned to -1.0 +/- 0.5 4 weeks after CABG (P = not significant). QT-RR correlation decreased from 0.41 to 0.23 (P <.05) and remained significantly impaired as long as 4 weeks after CABG. Observed faster heart rates until 1 week after off-pump CABG imply excessive adrenergic activation, which is comparable to on-pump CABG procedure rates. The results indicate profound autonomic derangement and loss of rate-dependent regulation after off-pump CABG even 4 weeks after operation. Restituted repolarization as assessed by QT variability index 4 weeks postoperatively corresponded with decreased frequency of rhythm disturbances 4 weeks after CABG. The loss of coupling between QT and RR intervals shows increased electrical instability postoperatively, which may serve as an additional promoter for postoperative arrhythmias, especially at higher heart rates.

Circadian Variation of Beat‐to‐Beat QT Interval Variability in Patients with Prior Myocardial Infarction and the Effect of β‐Blocker Therapy

Recent studies have demonstrated that increased QT interval variability (QTV) is associated with a greater susceptibility to ventricular arrhythmias and that patients with prior myocardial infarction (MI) were prone to ventricular arrhythmias during the daytime. The goal of the present study was to investigate the circadian variation of the QTV and to determine whether beta-blocker therapy improves the temporal fluctuation of the ventricular repolarization in patients with MI. The study population consisted of 15 MI patients who had not received beta-blocker therapy, 11 MI patients who had received beta-blocker therapy, and 12 healthy subjects. Twenty-four hour Holter monitoring was obtained, and the RR and QT intervals were calculated automatically from 512 consecutive sinus beats for every 2 hours. In the daytime, the QT-SD was significantly greater in the MI group than in the healthy subjects (P<0.01), but there was no difference in the QT-SD when comparing the beta-blocker group to the control group. Moreover, the QT variability index and the QT variance normalized for the mean QT were similar pattern with QT-SD. The heart rate variability did not significantly differ when compared between the three study groups. These data indicate that the QTV increases during the daytime in patients with MI and that this circadian effect is prevented by beta-blocker therapy. Thus, beta-blocker therapy may reverse the maladaptation of the ventricular repolarization to the change in the heart rate and may thereby reduce the ventricular arrhythmias and decrease the mortality in patients with MI.

Reproducibility of methods for assessing baroreflex sensitivity and temporal QT variability in end-stage renal disease and healthy subjects

Spontaneous baroreflex sensitivity (BRS), the reflex heart rate modulation in response to blood pressure changes (predominantly an index of cardiac vagal activity) and temporal QT variability (an index of myocardial repolarization) have been demonstrated to convey important prognostic information. The information about reproducibility of BRS and temporal QT variability is limited and there is lack of information regarding patients with cardiovascular diseases. We investigated reproducibility of spontaneous BRS using the sequence technique and temporal QT variability index (QTVI) in terms of intra-, interexaminer and within-subject variability in end-stage renal disease patients (ESRD, n=17, age 55+/-14 years) and healthy subjects (HS, n=29, age 32+/-12 years, P<0.01). ECG and blood pressure (Portapres) were recorded on two separate days and BRS and QTVI were evaluated by two independent examiners. The mean heart rate was similar in ESRD patients in comparison to healthy controls, whereas the mean arterial pressure was 13 % higher in ESRD patients (P<0.01). Spontaneous BRS was 62% lower (P<0.01) and QTVI was 41% higher in ESRD patients (P<0.01) compared to healthy subjects, respectively. Coefficient of variation (CV) of within-subject reproducibility of BRS and QTVI measurements was moderate (BRS: 33 % for ESRD, 27% for HS; QTVI: 40% for ESRD, 18% for HS). The 95% limit of within-subject reproducibility of BRS measurements was 3.8 ms/mm Hg for ESRD patients and 8.1 ms/mm Hg for healthy subjects; whereas the 95% limit of reproducibility of within-subject reproducibility of QTVI measurements was 0.73 for ESRD patients and 0.55 for healthy subjects. Concordance correlation coefficients of within-subject variability of BRS and QTVI were between 0.74 and 0.83 in both groups. CV of intra- and inter-examiner reproducibility of BRS and QTVI measurements in both groups ranged between 1 and 11%. In conclusion, the intra- and inter-examiner reproducibility/agreement of BRS and QTVI were high, whereas the within-subject reproducibility of these two methods was moderate, in both ESRD patients and healthy subjects. Thus, small differences in BRS and QTVI in longitudinal/interventional studies should be interpreted with caution.

Elevated temporal QT variability index in patients with chronic renal failure.

Patients with CRF (chronic renal failure) are at increased risk of cardiovascular diseases, and 60% of cardiovascular mortality in CRF is attributed to sudden death. Various abnormalities in myocardial repolarization are associated with the risk of ventricular arrhythmia. The aim of this study was to evaluate an index of temporal myocardial repolarization lability, the temporal QTVI (QT variability index), in patients with CRF. ECGs were recorded in 153 patients with CRF on haemodialysis (n=67), continuous ambulatory peritoneal dialysis (n=43) or conservative treatment (n=43) during 30 min of rest. QTVI was calculated as the logarithm of the ratio between the variances of the normalized QT and RR intervals. Age-matched healthy subjects (n=39) were examined for comparison. QTVI was increased by 47% in CRF patients compared with healthy subjects (-0.82+/-0.56 compared with -1.54+/-0.27 respectively; P<0.01). QTVI did not differ among patients on dialysis or conservative treatment, whereas QTVI was elevated further in patients with diabetes compared with non-diabetic CRF patients (-0.56+/-0.54 compared with -0.94+/-0.52 respectively; P<0.01). In a multiple linear regression analysis, diabetes and a history of coronary artery disease were the only independent predictors of QTVI in the CRF population. The present study demonstrates that elevated QTVI in patients with CRF is associated with diabetes and coronary disease. The present findings are important given that repolarization instability may predispose to ventricular arrhythmia and sudden death, events that occur frequently in CRF patients.

CIRCADIAN CHANGES IN THE QT VARIABILITY INDEX IN THE BEAGLE DOG

1. QT variability is a non-invasive marker of cardiac repolarization lability and a higher QT variability is associated with sudden death. No data exist as to the circadian fluctuations in QT variability and the QT variability index (QTvi) in the canine. The purpose of the present investigation was to explore QT interval variability over 24 h in the healthy dog. 2. Continuous lead II electrocardiogram and blood pressure data were collected for 24 h from three beagles instrumented with radiotelemetry devices. The mean heart rate (HR), detrended HR variance, mean QT interval and detrended QT variance were calculated from the instantaneous HR and QT time series of 1024 points (256 s), as described previously, and a normalized QTvi was derived. 3. The dog has a diurnal pattern of QTvi similar to healthy humans. Both dogs and humans exhibit a significantly higher QTvi during active waking hours, with more negative values during deep sleep. 4. These findings suggest QTvi may serve as an additional non-invasive tool to assess ventricular repolarization lability in dogs in relation to any conditions or drugs that are known to be associated with increased cardiac mortality.

Temporal repolarization lability differences among genotyped patients with the long QT syndrome

The investigators sought to test whether certain long QT syndrome (LQTS) mutations are associated with increased repolarization lability and whether repolarization lability (quantified by the QT variability index [QTVI]) is increased in patients with LQTS compared with controls. In 32 genotyped patients with LQTS type 1 (LQT1), 32 genotyped patients with LQTS type 2 (LQT2), and 32 controls, the QTVI was increased in patients with LQT2 (-0.973 +/- 0.394, p = 0.01 vs controls) and in patients with LQT1 with mutations other than KCNQ1-FIN (-0.942 +/- 0.264, p = 0.04 vs controls) but was similar between the KCNQ1-FIN group and controls.

Sildenafil citrate does not alter ventricular repolarization properties: novel evidence from dynamic QT analysis.

Sildenafil citrate may have direct cardiac electrophysiological effects, and is possibly responsible for some cardiac events. The aim of our study was to investigate the effects of sildenafil citrate on QT dynamicity properties with a new QT analysis program showing even small changes in ventricular repolarization. Twenty-four-hour Holter electrocardiographic recordings were used to obtain the data in the predrug phase (1-hour rest position before drug administration), and in the postdrug phase (1-hour rest position, which began 60 minutes after 50 mg oral sildenafil citrate administration). With the special QT analysis program (Verda, Reynolds Medical Ltd., UK); mean values of RR, QT, QTo (corrected QT), J (the exponent of correction formula) and S (QT/RR plots slope) parameters together with QT variability indexes (QTVI) were calculated for study phases. Mean +/- SEM values for RR and QT were higher in postdrug phase than in predrug phase (RR: 845 +/- 42 ms vs 816 +/- 46 ms, P < 0.05; QT: 371 +/- 8 ms vs 361 +/- 9 ms, P < 0.05). However, sildenafil did not induce any significant change in mean +/- SEM values for QT(o), J, and S in postdrug phase compared with predrug phase (408 +/- 10 ms vs 406 +/- 8 ms, 0.474 +/- 0.030 vs 0.433 +/- 0.025, 0221 +/- 0.020 vs 0.198 +/- 0.017, respectively; P > 0.05). QTVIs were also not different in each phase (predrug: -0.874 +/- 0.071 vs postdrug: -0.997 +/- 0.067, P = 0.109). Fifty milligrams sildenafil does not affect QT dynamicity properties. The cardiac events associated with sildenafil could not be explained with ventricular arrhythmias.

Effects of hyperventilation on heart rate and QT variability in panic disorder pre- and post-treatment

Panic disorder is associated with an elevated risk of cardiovascular disease and sudden death. Individuals with panic disorder have been shown to have reduced variability in heart rate and increased variability in the QT interval on electrocardiogram (ECG), patterns predictive of sudden cardiac death in certain forms of cardiomyopathy. Given that panic disorder patients often hyperventilate during a panic attack, we assessed the effects of voluntary hyperventilation on the ECG utilizing linear analyses of heart rate and QT interval variability. Sixteen symptomatic, medication-free patients underwent hyperventilation challenge. A small subgroup of eight subjects underwent re-challenge after treatment. Pre-treatment, hyperventilation resulted in a decrease in a measure of heart rate variability and an increase in the QT variability index (QTVI; QT variance normalized for mean QT, divided by heart rate variance normalized for mean heart rate). In a remitted state, the QTVI was reduced both during rest and during hyperventilation compared with the respective pre-treatment levels. These findings suggest a possible mechanism explaining increased rates of cardiovascular morbidity and mortality in panic disorder. Moreover, the reduction in QTVI observed post-treatment raises the question of whether treatment might have cardioprotective effects, at least in panic disorder patients who have particular types of co-morbid cardiac disease. Yet these results must be interpreted cautiously; they are preliminary, exploratory and observed in a very small sample without a healthy comparison group.

QT variability

We hypothesized that temporal lability in ventricular repolarization is a marker for, and is mechanistically related to, increased risk of malignant ventricular arrhythmias. To assess repolarization lability in the surface electrocardiogram, we developed an automated algorithm, based on template matching, to measure beat-to-beat changes in QT interval. We calculate a QT variability index (QTVI) to quantify the relative magnitude of QT interval changes compared to heart rate variability. We found that QTVI is a reproducible measure. It is elevated in patients with ischemic and nonischemic dilated cardiomyopathy compared with age-matched controls ( P < .00001). We have also shown that QTVI is elevated in patients with malignant β-myosin heavy-chain mutations associated with hypertrophic cardiomyopathy. In a study of patients undergoing electrophysiologic testing, QTVI identified patients with cardiac arrest better than electrophysiologic test result and better than other risk stratifiers included in the analysis. QT variability is a marker of electrical disease in the ventricle and may be associated with enhanced risk of life-threatening arrhythmias.

Nonlinear measures of QT interval series: novel indices of cardiac repolarization lability: MEDqthr and LLEqthr

In this study, we investigated nonlinear measures of chaos of QT interval time series in 28 normal control subjects, 36 patients with panic disorder and 18 patients with major depression in supine and standing postures. We obtained the minimum embedding dimension (MED) and the largest Lyapunov exponent (LLE) of instantaneous heart rate (HR) and QT interval series. MED quantifies the system's complexity and LLE predictability. There was a significantly lower MED and a significantly increased LLE of QT interval time series in patients. Most importantly, nonlinear indices of QT/HR time series, MEDqthr (MED of QT/HR) and LLEqthr (LLE of QT/HR), were highly significantly different between controls and both patient groups in either posture. Results remained the same even after adjusting for age. The increased LLE of QT interval time series in patients with anxiety and depression is in line with our previous findings of higher QTvi (QT variability index, a log ratio of QT variability corrected for mean QT squared divided by heart rate variability corrected for mean heart rate squared) in these patients, using linear techniques. Increased LLEqthr (LLE of QT/HR) may be a more sensitive tool to study cardiac repolarization and a valuable addition to the time domain measures such as QTvi. This is especially important in light of the finding that LLEqthr correlated poorly and nonsignificantly with QTvi. These findings suggest an increase in relative cardiac sympathetic activity and a decrease in certain aspects of cardiac vagal function in patients with anxiety as well as depression. The lack of correlation between QTvi and LLEqthr suggests that this nonlinear index is a valuable addition to the linear measures. These findings may also help to explain the higher incidence of cardiovascular mortality in patients with anxiety and depressive disorders.

Combination of QT variability and signal-averaged electrocardiography in association with ventricular tachycardia in postinfarction patients

The authors investigate incidence of ventricular tachycardia/ventricular fibrillation (VT/VF) in relationship with combination of noninvasive arrhythmia risk markers as left ventricular ejection fraction (LVEF), late potentials (LP), and QT variability index (QTVI) and compare the utility of their combination in association with sustained ventricular arrhythmias in patients after myocardial infarction (MI). Fifty-four patients with old MI, among them 27 with documented spontaneous sustained VT/VF entered the study. All of them underwent evaluation for arrhythmias and noninvasive risk stratificaton. Logistic regression analysis demonstrated that the highest association with ventricular tachyarrhythmia had combination of LP and increased QTVI (13.8, P<.0002), followed then by combination of LVEF and LP (12.2, P<.0005), LP alone (P<.001), QTVI (P<.002) and LVEF (P<.003) alone and age (P<.01). After stepwise regression analysis showed that the model including association of LP and QTVI, age and EF is the best one for delineating patients having the risk of ventricular tachyarrhythmia development. In conclusion, patients with combination of positive LP and increased QTVI after MI have high likelihood for development of serious sustained arrhythmia.