Alteration of the QT rate dependence in anorexia nervosa

Myocardial repolarization has been evaluated in patients with anorexia nervosa (AN) with conflicting results. The authors postulated that dynamic alterations in QT interval adaptation could characterize these patients. This study compared QT dynamicity along RR intervals from 24-hour ECG data of patients with and without AN. Twenty-five patients (23 women) fulfilling the Diagnostic and Statistical Manual (DSM IV) criteria for AN were included in the study. All underwent 24-hour ECG Holter recordings, allowing QT and RR measurements, and heart rate variability (HRV) analysis in free-living conditions. A group of 25 sex- and age-matched healthy subjects served as controls. Compared with controls, AN patients presented with relative bradycardia, more particularly during night periods but neither mean QT nor corrected mean QT length (calculated using Bazett formula) over the 24 hours of monitoring differed. However, QT/RR slope was found significantly enhanced compared with normals (-2.00 +/- 0.53 vs - 1.42 +/- 0.40) (P = 0.006): QT length related to heart rate was found longer for a heart rate <55 beats/min in AN. Mean 24-hours QT length appears unaltered in AN in the absence of electrolytic disorders. However, the QT/RR relationship was enhanced reflecting the specific autonomic imbalance encountered in this population. The clinical implications of such findings need to be discussed since an equivalent enhancement of QT/RR slope has been described after myocardial infarction in patients presenting life-threatening ventricular arrhythmias.     

Influence of cardiac autonomic neuropathy on heart rate dependence of ventricular repolarization in diabetic patients

OBJECTIVE: Prolongation of the QT interval and increased QT dispersion are associated with a poor cardiac prognosis. The goal of this study was to assess the long-term influence of the autonomic nervous system on the heart rate dependence of ventricular repolarization in patients with diabetic autonomic neuropathy (DAN). RESEARCH DESIGN AND METHODS: We studied 27 subjects (mean age 51.8 years) divided into three age- and sex-matched groups: nine control subjects, nine diabetic subjects with DAN (mostly at a mild stage; DAN+), and nine diabetic subjects without DAN (DAN-). DAN was assessed on heart rate variations during standard maneuvers (Valsalva, deep-breathing, and lying-to-standing maneuvers). No subject had coronary artery disease or left ventricular dysfunction or hypertrophy, and no subject was taking any drugs known to prolong the QT interval. All subjects underwent electrocardiogram and 24-h Holter recordings for heart rate variations (time and frequency domain) and QT analysis (selective beat averaging QT/RR relation, nocturnal QT lengthening). RESULTS: Rate-corrected QT intervals (Bazett formula) did not differ significantly between the three groups. The diurnal and nocturnal levels of low frequency/high frequency, an index of sympathovagal balance, were significantly reduced in DAN+ subjects. Using the selective beat-averaging technique, a day-night modulation of the QT/RR relation was evidenced in control and DAN- subjects. This long-term modulation was significantly different in DAN+ subjects, with a reversed day-night pattern and an increased nocturnal QT rate dependence. CONCLUSIONS: In diabetic patients with mild parasympathetic denervation, QT heart rate dependence was found to be impaired, as determined by noninvasive assessment using Holter data. Analysis of ventricular repolarization could represent a sensitive index of the progression of neuropathy. The potential prognostic impact of a reversed day-night pattern with steep nocturnal QT/RR relation still remains to be defined.     

Evaluation of a subject-specific transfer-function-based nonlinear QT interval rate-correction method

The QT interval in the electrocardiogram (ECG) is a measure of total duration of depolarization and repolarization. Correction for heart rate is necessary to provide a single intrinsic physiological value that can be compared between subjects and within the same subject under different conditions. Standard formulas for the corrected QT (QTc) do not fully reproduce the complexity of the dependence in the preceding interbeat intervals (RR) and inter-subject variability. In this paper, a subject-specific, nonlinear, transfer function-based correction method is formulated to compute the QTc from Holter ECG recordings. The model includes five parameters: three describing the static QT-RR relationship and two representing memory/hysteresis effects that intervene in the calculation of effective RR values. The parameter identification procedure is designed to minimize QTc fluctuations and enforce zero correlation between QTc and effective RR. Weighted regression is used to better handle unbalanced or skewed RR distributions. The proposed optimization approach provides a general mathematical framework for further extensions of the model. Validation, robustness evaluation and comparison with existing QT correction formulas is performed on ECG signals recorded during sinus rhythm, atrial pacing, tilt-table tests, stress tests and atrial flutter (29 subjects in total). The resulting average modeling error on the QTc is 4.9 ± 1.1 ms with a sampling interval of 2 ms, which outperforms correction formulas currently used. The results demonstrate the benefits of subject-specific rate correction and hysteresis reduction.     

Beat-to-Beat repolarization variability in LQTS patients with the SCN5A sodium channel gene mutation

Current techniques evaluating beat-to-beat variability of repolarization rely on accurate determination of T wave endpoints. This study proposes a T wave endpoint-independent method to quantify repolarization variability in a standard 12-lead ECG using a wavelet transformation. Our method was used to identify repolarization variability in long QT syndrome patients (LQTS) with the SCN5A sodium channel gene mutation. Using wavelet transformations based on the second Gaussian derivative, we evaluated repolarization variability in 11 LQTS patients with the mutation, 13 noncarrier family members, and 28 unrelated healthy subjects. Time-domain repolarization variability parameters (SDRTo, SDRTm) and wavelet parameters describing temporal (beat-to-beat) variability of repolarization in time (TVT) and in amplitude (TVA) were analyzed. Reproducibility of wavelet parameters and relationship of wavelet-based variability with heart rate and preceding RR interval were investigated. The wavelet-based method quantified beat-to-beat variability of the entire repolarization segment (regardless of QT interval identification) providing insight into variability in repolarization morphology. Our method showed that SCN5A carriers have significantly increased repolarization variability in amplitude (23% +/14% vs 8 +/- 4%, P < 0.001) and in time (14 +/- 17 ms vs 3 +/-2 ms, P < 0.004) compared to noncarriers. Variability of repolarization amplitude was found to be heart rate dependent with variability decreasing with increasing heart rate. Relative error describing reproducibility of TVA and TVT was < or = 5% and < or =10%, respectively. Our method quantifies repolarization variability in amplitude and in time without the need to identify T or U wave endpoints. Wavelet-detected repolarization variability contributes to phenotypic identification of SCN5A carriers, with more pronounced beat-to-beat variability in repolarization amplitude than in time.     

Continuous positive airway pressure treatment improves the QT rate dependence adaptation of obstructive sleep apnea patients

BACKGROUND: QT rate dependence is one of the major properties of ventricular repolarization, with its circadian and autonomic modulations. The alteration of cardiac autonomic tone occurring in obstructive sleep apnea syndrome (OSAS) patients could explain the altered rate-dependent adaptation of the myocardial repolarization. Thus, we postulated that dynamic alterations in QT interval adaptation could be ameliorated in OSAS patients under continuous positive airway pressure (CPAP) treatment. To assess ventricular repolarization features in patients with OSAS, we compared QT parameters and their dynamicities along RR intervals from 24-hour ECG. METHODS: The study groups consisted of 38 consecutive OSAS patients and 38 healthy age-matched subjects. The syndrome was confirmed for OSAS patients according to standard polysomnographic criteria (apnea plus hypopnea index: 56.9 +/- 28.4/h). A second polysomnography synchronized with 24-hour ECG Holter and realized under efficient CPAP therapy confirmed the control of sleep-related breathing disorder. RESULTS: QT length related to heart rate was found significantly altered in patients with OSAS compared with controls (QTend/RR slope: -0.126 +/- 0.031 vs -0.173 +/- 0.038; P < 0.01). This flattened relationship was significantly improved with the treatment of the OSAS (-0.151 +/- 0.051; P < 0.01 vs pretreatment status). There was no significant impact of CPAP therapy on ventricular ectopic activity as well as on static repolarization parameters (QT, RT, QTc, RTc) measured separately over daytime and nighttime. CONCLUSIONS: The prognostic implications of such findings and the protective role of CPAP treatment to prevent sudden cardiac death in OSAS need to be evaluated.     

Paradoxically Shortened QT Interval after a Prolonged Pause

We analyzed Holter ECG recordings in 15 patients with episodes of prolonged RR intervals > 2.5 seconds. In 13 patients, the QT interval showed a linear prolongation when RR interval was < 1.5 seconds and became relatively flat at longer RR intervals. In the remaining two patients, the QT and RR intervals were correlated within physiological range of RR intervals. However, at longer RR intervals, the QT interval was unexpectedly shortened and constant. The paradoxically shortened QT interval observed in the present 2 cases may indicate an abnormal adaptation of repolarization time to an abrupt increase in the preceding RR intervals.     

Autonomic modulation of the u wave during sympathomimetic stimulation and vagal inhibition in normal individuals

Prolonged repolarization time, an important contributor to the pathogenesis of ventricular arrhythmias, is usually identified by a long QT interval (QT) on the ECG but is frequently confounded by the presence of a U wave. The physiological basis and clinical relevance of the U wave is unresolved. To better understand the relationship between the T and U waves, this study examined their behavior during nonresting autonomic conditions. Twenty-five healthy subjects were evaluated during sympathomimetic infusion with isoproterenol and vagal inhibition with atropine. As heart rate (HR) increased in response to isoproterenol, the QU interval (QU) decreased by an eightfold greater extent than QT. Furthermore, a marked increase in U wave amplitude and decrease in T wave amplitude were observed with T and U wave fusion at higher HRs. During atropine, QU decreased by only a threefold greater extent than QT, T and U wave amplitudes were affected only minimally, and T-U wave fusion was not observed. These results demonstrate that sympathomimetic stimulation causes striking alterations in the timing and amplitude of U waves that differ from effects on the T wave. These effects are not observed during vagal inhibition. Thus, the U wave represents a component of cardiac repolarization that is electrocardiographically and physiologically distinct from the T wave with a unique response to sympathomimetic stimulation.     

Steady-state versus non-steady-state QT-RR relationships in 24-hour Holter recordings

The aim of the present study was to investigate the QT-RR interval relationship in ambulatory ECG recordings with special emphasis on the physiological circumstances under which the QT-RR intervals follow a linear relation. Continuous ECG recordings make it possible to automatically measure QT duration in individual subjects under various physiological circumstances. However, identification of QT prolongation in Holter recordings is hampered by the rate dependence of QT duration. Comparison of QT duration and QT interval rate dependence between different individuals implies that the nature of the QT-RR relationship is defined in ambulatory ECG. Holter recordings were performed in healthy volunteers at baseline and after administration of dofetilide, a Class III antiarrhythmic drug. After dofetilide, beat-to-beat automated QT measurements on Holter tapes were compared with manually measured QT intervals on standard ECGs matched by time. The QT-RR relationship was analyzed at baseline in individual and group data during three different periods: 24-hour, daytime, and nighttime. Data were collected under steady-state or non-steady-state conditions of cycle length and fitted with various correction formulae. Our study demonstrated an excellent agreement between manually and automated measurements. The classic Bazett correction formula did not fit the QT-RR data points in individual or group data. When heart beats were selected for a steady rhythm during the preceding minute, QT-RR intervals fit a linear relationship during the day and night periods, but not during the 24-hour period in both individual and group data. In contrast, in the absence of beat selection, data fit a more complex curvilinear relationship irrespective of the period. Our study provides the basis for comparison of QT interval durations and QT-RR relationships between individuals and between groups of subjects.     

Circadian and Sex-Dependent QT Dynamics

The dynamic QT relationship between the QT and RR intervals in normal individuals, including sex differences, has not been well examined. The aim of this Holter monitor-based study was to assess circadian and sex-related variations in QT dynamics in healthy subjects. The study population consisted of 50 healthy volunteers (mean age = 32 ± 6 years, 25 men), in whom 24-hour digital Holter monitoring and QT interactive, beat-by-beat analyses were performed. The mean lengths of QT and RR intervals were measured from the 24-hour recordings. In order to assess QT dynamics, QT/RR linear regression was performed, and the slope was calculated over 24 hour and for day and night periods, and both genders separately. In the whole population, the mean QT interval was 356.5 ± 19.2 ms and RR interval was 785.9 ± 80.7 ms. The mean value of the slope over 24 hour was 0.17 ± 0.03, though significantly steeper during the day (0.13 ± 0.03) than at night (0.09 ± 0.03, P < 0.001). The analysis of QT/RR dynamics over 24 hour revealed a significantly steeper slope in women (0.18 ± 0.03) than in men (0.16 ± 0.03, P = 0.006), as well as during daytime (0.14 ± 0.03 vs 0.12 ± 0.03, P = 0.04). Circadian variations and sex differences were observed in QT dynamics. The latter may explain the greater susceptibility of women to torsades de pointes during treatment with drugs that prolong repolarization.     

Dynamics of T-U wave in patients with idiopathic ventricular tachycardia originating from the right ventricular outflow tract

Postextrasystolic U wave augmentation is observed in patients with long QT syndrome and those with organic heart disease. This phenomenon is considered a marker of increased risk of arrhythmia. However, the characteristics of the U wave have not been evaluated in patients with idiopathic VT originating from the right ventricular outflow tract (RVOT-VT). The present study evaluated the dynamic change in the T-U wave in patients with RVOT-VT. Holter ECGs obtained from 14 patients with RVOT-VT and 11 healthy control subjects were analyzed. The amplitude of T and U waves (Tamp and Uamp) and preceding RR intervals were measured during stable sinus rhythm (rate dependent change) and in the postextrasystolic sinus complex (pause dependent change). Uamp correlated negatively and significantly with the preceding RR interval in 13 (93%) RVOT-VT patients but in only 2 (18%) control subjects. The average value of the slope of the Uamp/RR relationship was negative (-0.22 +/- 0.10 mV/s) in the RVOT-VT group, but was positive (0.04 +/- 0.07 mV/s, P < 0.001) in the control group. Pause dependent U wave augmentation was observed in 12 (86%) of 14 patients. Increased frequency of consecutive preceding premature ventricular contractions (PVCs) was associated with a larger postextrasystolic Uamp. PVC or the first ventricular beat of VT arose from near the peak of augmented U waves. The dynamic changes in the T-U wave were observed in patients with RVOT-VT. Further investigations are required to elucidate the precise role of the U wave in arrhythmogenesis in those patients.     

Autonomic Effects of Dipyridamole Stress Testing on Frequency Distribution of RR and QT Interval Variability

Transient myocardial ischemia and associated changes in the autonomic nervous system may influence heart rate and ventricular repolarization to variable degrees. This study evaluated the effect of dipyridamole (DIP) induced ischemia on the autonomic balance by spectral analysis of RR and QT intervals variability. Patients with coronary artery disease undergoing DIP stress echocardiography were studied. From high resolution ECG recordings, RR and QT interval measurements were performed by a dynamic template-matching algorithm. A time-variant analysis was used to estimate power in the LF (0.05–0,15 Hz) and in the HF (0.15–0.4 Hz) band of RR and QT interval spectra. Patients were grouped in ischemic and nonischemic subgroups based on the echocardiographic detection of wall-motion abnormalities. In patients without ischemia (n = 28), DIP caused a decrease in LF power and an increase in HF power of the RR and QT interval variability, indicating concordant changes of both intervals. In contrast, patients with inducible ischemia (n = 11) showed a decrease in HF power of the RR interval spectra and an increase of HF power of QT interval spectra. Furthermore, LF power was increased for RR but decreased for QT interval spectra. Our study suggests that DIP induced ischemia causes a loss of autonomic coupling between heart rate and ventricular repolarization for sympathetic and parasympathetic activities. This lability in ventricular repolarization may constitute an arrhythmogenic substrate during acute ischemia in patients with coronary artery disease.     

Alteration of QT Rate Dependence Reflects Cardiac Autonomic Imbalance in Patients with Obstructive Sleep Apnea Syndrome

QT rate dependence is one of the major properties of ventricular repolarization with its circadian and autonomic modulations. The authors postulated that dynamic alterations in QT interval adaptation could help characterize patients with cardiac autonomic alterations, like those with obstructive sleep apnea syndrome (OSAS). To assess ventricular repolarization features in patients with OSAS, QT parameters and their dynamicity along RR intervals were compared from 24-hour ECG data of patients with and without this syndrome, assessing cardiac autonomic nervous system equilibrium by means of time-domain and frequency-domain analyses of heart rate variability (HRV). The study group consisted of 74 consecutive patients referred to the Sleep Laboratory for clinically suspected OSAS. The syndrome was confirmed in 30 (40.5%) patients according to standard polysomnographic criteria. QT length related to heart rate (HR) was found significantly shorter for HR < 70 beats/min in patients with OSAS   (−1.32 ± 0.35)   compared with patients without OSAS   (−1.99 ± 0.40; P < 0.01)   . This flattened relationship was correlated with the severity of the sleep related disorder. Using multiple linear regression analysis, the apnea/hypopnea index and nocturnal normalized high frequencies (HFnu) were the most significant predictors of the QT/RR slope   (R = 0.61; P < 0.0001)   . OSAS is significantly associated with a flattened relationship between QT duration and RR interval at low HRs. The alteration of cardiac parasympathetic tone occuring in severe OSAS patients may explain this altered rate dependent adaptation of myocardial repolarization. (PACE 2003; 26[Pt. I]:1446–1453)     

Difference in QT Interval Measurement on Ambulatory ECG Compared with Standard ECG

Measurement of the QT interval on standard ECG has diagnostic importance in the congenital long QT syndrome, in pharmacological therapy of arrhythmias, as well as in ischemic heart disease. It has been suggested that QT prolongation on ambulatory ECG (Holter) may have similar importance. To assess agreement between methods, QT interval measurement on standard ECG was compared to that on Holter. Simultaneously obtained ECG and Holter tracings (25 mm/s) of the same complexes in leads V₁ and V₅ were studied in 14 patients (age range 4–36 years). ECG pairs (n = 100, 49 V₁ and 51 V₅) were compared over a range of QT interval from 300–620 ms, as determined with the use of calipers by two observers blinded to pairing relationship. Correlation between methods was high for both observers (observer 1: r[V₁] = 0.872, r[V₅] = 0.973; observer 2: r[V₁] = 0.972, r[V₅] = 0.988), and interobserver variability was small (> 85% of measurements within 20 ms). As compared to ECG, Holter underestimated QT interval in V₁ mean difference (QT [Holter]—QT [ECG]) observer 1 (-23 ms, P < 0.001), observer 2 (-7 ms, P < 0.05), and overestimated QT in V5, mean difference observer 1 (+ 13 ms, P < 0.001), observer 2 (+13 ms, P < 0.001). However, individual variation between methods was wide, as expressed by the difference between individual measurements (95% confidence interval [V₁]: observer 1 [-99 to +53 ms] observer 2 [-47 to +33 ms]; [V₅]: observer 1 [-33 to +59 ms] observer 2 [-17 to +43 ms]). Furthermore, when using the QTA (interval from onset of Q wave to apex of T wave) similar variability was observed. In the assessment of QT interval, potential sources of error of this magnitude could limit the clinical utility of ambulatory monitoring in detecting prolongation of the QT interval for diagnostic purposes.     

Comparison of Formulae for Heart Rate Correction of QT Interval in Exercise Electrocardiograms

The study investigated the differences in five different formulae for heart rate correction of the QT interval in serial electrocardiograms recorded in healthy subjects subjected to graded exercise. Twenty-one healthy subjects (aged 37+/-10 years, 15 male) were subjected to graded physical exercise on a braked bicycle ergometer until the heart rate reached 120 beats/min. Digital electrocardiograms (ECG) were recorded on baseline and every 30 seconds during the exercise. In each ECG, heart rate and QT interval were measured automatically (QT Guard package, Marquette Medical Systems, Milwaukee, WI, USA). Bazett, Fridericia, Hodges, Framingham, and nomogram formulae were used to obtain QTc interval values for each ECG. For each formula, the slope of the regression line between RR and QTc values was obtained in each subject. The mean values of the slopes were tested by a one-sample t-test and the comparison of the baseline and peak exercise QTc values was performed using paired t-test. Bazett, Hodges, and nomogram formulae led to significant prolongation of QTc intervals with exercise, while the Framingham formula led to significant shortening of QTc intervals with exercise. The differences obtained with the Fridericia formula were not statistically significant. The study shows that the practical meaning of QT, interval measurements depends on the correction formula used. In studies investigating repolarization changes (e.g., due to a new drug), the use of an ad-hoc selected heart rate correction formula is highly inappropriate because it may bias the results in either direction.     

Ambulatory Assessment of the QT Interval in Patients with Hypertrophic Cardiomyopathy: Risk Stratification and Effect of Low Dose Amiodarone

This study aims to assess the dynamics of the QT interval in patients with hypertrophic cardiomyopathy (HCM). Three consecutive QT intervals and the preceding RR intervals were measured on 24-hour ambulatory electrocardiograms at 30-minute intervals in ten high risk patients with HCM (sudden cardiac death [SCD] and/or documented ventricular fibrillation), aged 29 ± 17 years, compared with ten age and sex matched low risk patients with HCM (no syncope, no adverse family history, and no ventricular tachycardia on Holter monitoring), and ten normal subjects. Another ten patients who were on amiodarone therapy (200-mg daily) were also studied. Patients witb intraventricular conduction defects were excluded. There were 4,424 pairs of QT intervals and their preceding RR intervals were measured in this study. A nonsignificant prolongation in the QT interval and a significant prolongation in QT_c values (Bazett's and Fridericia's formulas) were demonstrated in patients with HCM compared with normals. There were no significant differences in the QT and QT_c between high and low risk patients. The slope of regression line for the QT against RR interval was significantly different between normals and HCM (0.1583 ± 0.040 vs 0.2017 ± 0.043. P < 0.05), but not between high and low risk patients. Amiodarone significantly prolonged the QT and QT_c without significantly altering the slope of the regression line (0.2017 ± 0.043 vs 0.2099 ± 0.037, NS). Our findings support the observations that there is a prolonged QT interval in patients with HCM and that there is no significant use dependent effect of amiodarone on ventricular repolarization. In conclusion, ambulatory assessment of the QT interval provides an alternative method for the assessment of ventricular repolarization and for the assessment of use dependent effects of anti arrhythmic drugs on ventricular repolarization during normal daily activities. However, this method does not help in the identification of patients at high risk of SCD in HCM.     

QT Interval Variability and Adaptation to Heart Rate Changes in Patients with Long QT Syndrome

Background: Increased QT variability (QTV) has been reported in conditions associated with ventricular arrhythmias. Data on QTV in patients with congenital long QT syndrome (LQTS) are limited.
Methods: Ambulatory electrocardiogram recordings were analyzed in 23 genotyped LQTS patients and in 16 healthy subjects (C). Short-term QTV was compared between C and LQTS. The dependence of QT duration on heart rate was evaluated with three different linear models, based either on the RR interval preceding the QT interval (RR₀), the RR interval preceding RR₀ (RR_-1), or the average RR interval in the 60-second period before QT interval (mRR).
Results: Short-term QTV was significantly higher in LQTS than in C subjects (14.94 ± 9.33 vs 7.31 ± 1.29 ms; P < 0.001). It was also higher in the non-LQT1 than in LQT1 patients (23.00 ± 9.05 vs 8.74 ± 1.56 ms; P < 0.001) and correlated positively with QTc in LQTS (r = 0.623, P < 0.002). In the C subjects, the linear model based on mRR predicted QT duration significantly better than models based on RR₀ and RR_-1. It also provided better fit than any nonlinear model based on RR₀. This was also true for LQT1 patients. For non-LQT1 patients, all models provided poor prediction of QT interval.
Conclusions: QTV is elevated in LQTS patients and is correlated with QTc in LQTS. Significant differences with respect to QTV exist among different genotypes. QT interval duration is strongly affected by noninstantaneous heart rate in both C and LQT1 subjects. These findings could improve formulas for QT interval correction and provide insight on cellular mechanisms of QT adaptation.     

Ventricular repolarization and heart rate responses during cardiovascular autonomic function testing in LQT1 subtype of long QT syndrome

Background: In the most prevalent LQT1 form of inherited long QT syndrome symptoms often occur during abrupt physical or emotional stress. Sympathetic stimulation aggravates repolarization abnormalities in experimental LQT1 models. We hypothesized that autonomic function tests might reveal the abnormal repolarization in asymptomatic LQT1 patients.
Methods: We measured heart rates (HRs) and QT intervals in nine asymptomatic carriers of a C-terminal KCNQ1 mutation and 8 unaffected healthy subjects using an approach of global QT values derived from 28 simultaneous electrocardiographic leads on beat-to-beat base during Valsalva maneuver, mental stress, sustained handgrip, and light supine exercise.
Results: LQT1 patients exhibited impaired shortening of both QTpeak and QTend intervals during autonomic interventions but exaggerated lengthening of the intervals—a QT overshoot—during the recovery phases. The number of tests with a QT overshoot was 2.4 ± 1.7 in LQT1 patients and 0.8 ± 0.7 in unaffected subjects (P = 0.02). Valsalva strain prolonged T wave peak to T wave end interval (TPE) in LQT1 but not in unaffected patients. LQT1 patients showed diminished HR acceleration in response to adrenergic challenge whereas HR responses to vagal stimuli were similar in both groups.
Conclusions: Standard cardiovascular autonomic provocations induce a QT interval overshoot during recovery in asymptomatic KCNQ1 mutation carriers. Valsalva maneuver causes an exaggerated fluctuation of QT and TPE intervals partly explaining the occurrence of cardiac events during abrupt bursts of autonomic activity in LQT1 patients.     

Evaluation of drug-induced QT interval modifications in dynamic electrocardiography: the case of bepridil

Summary— Drug-induced modifications of QT interval are usually assessed through formulae defining the corrected QT interval “QTc”. They are all based on the assumption that the correction is adequate, and that drug-induced heart rate variations and rate-dependent QT changes are proportional. Holler ECG allows to study the repolarization in selected RR cycles while controlling environmental rate-related and circadian influences. Repolarization duration was evaluated in 15 normal individuals and 13 patients with stable coronary artery disease and no heart failure who did not differ in terms of 24-hour heart rate, age and sex. The effects of a 3-month treatment with bepridil were assessed in the latter. Using the conventional evaluation through the corrected QT (Bazett formula), no difference was found between the two groups at baseline, and bepridil induced a non-significant 5% prolongation of QTc. At Holler recordings, the QTa (Q-T apex) duration was linearly correlated with the heart rate over 24 hours. To specifically study day-tonight variations and to exclude the rate-dependent and short-term autonomic influences. QTa was studied in populations of averaged QRS-T selected according to i) the last RR cycle length and ii) an identical mean RR interval during the preceding minute. Both RR values were fixed at 800 ms to obtain the “QTa-800” measured directly or extrapolated from linearly correlated, other RR values. Using this technique, the two groups differed at baseline in terms of dynamicity of QTa: the QTa/RR regression line slope was steeper in normals, and the strongly significant day-to-night difference of QTa-800 (P < 0.001) observed in them was absent in coronary patients. Bepridil, wliich did not significantly modify the 24-hour heart rate, lengthened the QTa-800 by 4–5%: although no more marked than with the QTc, this increase became significant at daytime (P = 0.04) and at night (P = 0.01) because of the inter-individual consistency of the modifications. These results suggest that the approach of QT evaluation in strictly comparable conditions of environmental rate and time allowed by the Hotter technique is better adapted than the conventional QTc method to assess limited drug-induced changes.     

Circadian variation of beat-to-beat QT interval variability in patients with prior myocardial infarction and the effect of beta-blocker therapy

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

New Insight into Repolarization Abnormalities in Patients with Congenital Long QT Syndrome: the Increased Transmural Dispersion of Repoiarization

There is evidence from experimental studies that the time interval from the peak to the end of T-wave reflects the transmural dispersion in repolarization (electrical gradient) between myocardial "layers" (epicardial, M-cells, endocardial). Since Congenital Long QT Syndrome (LQTS) is considered to be classical disease or repolarisation abnormalities, we performed the present study to assess the transmtiral dispersion of repolarization in LQTS patients. The study group consisted of 17 patients: 7 LQTS pts and 10 pts from the control group. In each patient the 24-hour ECG recording was performed on magnetic tape. The interval from the peak to the end of the T-wave (TpTo) was automatically measured by Holter system during every hour as a measure of transmural dispersion of repolarisation. Thereafter the mean TpTo from 24-hours was calculated. In addition the spatial QT dispersion was measured from 12 lead ECG and 3 channel Holter tape as a difference between the shortest and the longest QT interval between leads. The values were compared between groups using the Anova test.
TpTo was 79,6±9,6 ms (72–92 ms) in LQTS group and 62,4±7,5 ms (51–70) in the control group (p< 0.001). In LQTS group TpTo was significantly longer at night hours 72,5±2 when compared to day hours 87,4±8 (p<0.01). The spatial QT dispersion was significantly higher in LQTS patients when compared to control, both in 12-lead standard and Holter ECG.
Congenital long QT syndrome is associated with increase in both transmural and spatial dispersion of repolarization. The extent of prolongation of the terminal portion of QT in patients with congenital long QT syndrome is greater at night sleep hours compared to daily activity.