QTend Interval Research Articles

Differential diagnosis between LQT1 and LQT2 by QT/RR relationships using 24-hour Holter monitoring: A multicenter cross-sectional study.

BackgroundThe clinical course and therapeutic strategies in the congenital long QT syndrome (LQTS) are genotype‐specific. However, accurate estimation of LQTS genotype is often difficult from the standard 12‐lead ECG.ObjectivesThis study aims to evaluate the utility of QT/RR slope analysis by the 24‐hour Holter monitoring for differential diagnosis of LQTS genotype between LQT1 and LQT2.MethodsThis cross‐sectional study enrolled 54 genetically identified LQTS patients (29 LQT1 and 25 LQT2) recruited from three medical institutions. The QT‐apex (QTa) interval and the QT‐end (QTe) interval at each 15‐second were plotted against the RR intervals, and the linear regression (QTa/RR and QTe/RR slopes, respectively) was calculated from the entire 24‐hour and separately during the day or night‐time periods of the Holter recordings.ResultsThe QTe/RR and QTa/RR slopes at the entire 24‐hour were significantly steeper in LQT2 compared to those in LQT1 patients (0.262 ± 0.063 vs. 0.204 ± 0.055, p = .0007; 0.233 ± 0.052 vs. 0.181 ± 0.040, p = .0002, respectively). The QTe interval was significantly longer, and QTe/RR and QTa/RR slopes at daytime were significantly steeper in LQT2 than in LQT1 patients. The receiver operating curve analysis revealed that the QTa/RR slope of 0.211 at the entire 24‐hour Holter was the best cutoff value for differential diagnosis between LQT1 and LQT2 (sensitivity: 80.0%, specificity: 75.0%, and area under curve: 0.804 [95%CI = 0.68–0.93]).ConclusionThe continuous 24‐hour QT/RR analysis using the Holter monitoring may be useful to predict the genotype of congenital LQTS, particularly for LQT1 and LQT2.

Evaluation of Cardiac Circadian Rhythm Deconditioning Induced by 5-to-60 Days of Head-Down Bed Rest.

Head-down tilt (HDT) bed rest elicits changes in cardiac circadian rhythms, generating possible adverse health outcomes such as increased arrhythmic risk. Our aim was to study the impact of HDT duration on the circadian rhythms of heart beat (RR) and ventricular repolarization (QTend) duration intervals from 24-h Holter ECG recordings acquired in 63 subjects during six different HDT bed rest campaigns of different duration (two 5-day, two 21-day, and two 60-day). Circadian rhythms of RR and QTend intervals series were evaluated by Cosinor analysis, resulting in a value of midline (MESOR), oscillation amplitude (OA) and acrophase (φ). In addition, the QTc (with Bazett correction) was computed, and day-time, night-time, maximum and minimum RR, QTend and QTc intervals were calculated. Statistical analysis was conducted, comparing: (1) the effects at 5 (HDT5), 21 (HDT21) and 58 (HDT58) days of HDT with baseline (PRE); (2) trends in recovery period at post-HDT epochs (R) in 5-day, 21-day, and 60-day HDT separately vs. PRE; (3) differences at R + 0 due to bed rest duration; (4) changes between the last HDT acquisition and the respective R + 0 in 5-day, 21-day, and 60-day HDT. During HDT, major changes were observed at HDT5, with increased RR and QTend intervals’ MESOR, mostly related to day-time lengthening and increased minima, while the QTc shortened. Afterward, a progressive trend toward baseline values was observed with HDT progression. Additionally, the φ anticipated, and the OA was reduced during HDT, decreasing system’s ability to react to incoming stimuli. Consequently, the restoration of the orthostatic position elicited the shortening of RR and QTend intervals together with QTc prolongation, notwithstanding the period spent in HDT. However, the magnitude of post-HDT changes, as well as the difference between the last HDT day and R + 0, showed a trend to increase with increasing HDT duration, and 5/7 days were not sufficient for recovering after 60-day HDT. Additionally, the φ postponed and the OA significantly increased at R + 0 compared to PRE after 5-day and 60-day HDT, possibly increasing the arrhythmic risk. These results provide evidence that continuous monitoring of astronauts’ circadian rhythms, and further investigations on possible measures for counteracting the observed modifications, will be key for future missions including long periods of weightlessness and gravity transitions, for preserving astronauts’ health and mission success.

ECG Holter analysis to detect induced deconditioning on cardiac activity in bedridden volunteers

Abstract Introduction Prolonged bed rest (BR) is an unnatural state, often related to hospitalization, chronic diseases and ageing, inducing reduced functional capacity in multiple body systems, possibly leading to cardiovascular deconditioning. We hypothesized that measuring this decline over time could represent the first step for the formulation of appropriate countermeasures or rehabilitation programs while in the hospital. Accordingly, our aim was to assess the effects of 10-day horizontal BR on cardiac electrical activity. Methods Ten healthy male volunteers (23±5 years) were enrolled in an hospital, after ethical approval and signed consent, to participate to a 10-day strict horizontal BR campaign, preceded and followed by 2 days in the facility, respectively as acclimatization and recovery. The 12-leads 24-hours Holter ECG (1000 Hz, H12+, Mortara Instrument Inc.) was acquired 1 day before BR (PRE), the 5th (BR5) and 10th day (BR10) of bedridden immobilization. From each recording, beat-to-beat RR and QTend interval series, as well as T wave amplitude (Tamp) and upslope (Tslope) were computed. Statistical analysis was applied to test changes induced by BR (ANOVA with Tukey test, p<0.05), separately for day (7:00–23:00) and night (23:00–7:00) periods. Results Daily RR and QTend duration increased during BR, with peak changes at BR5 compared to PRE (+13.3% and +3% respectively), and were still prolonged at BR10 (+12.6% and +2.6%). During the night, while RR increased (BR5:+5.3%; BR10:+1.3%), QTend was found progressively shortened (BR5: −1.6%; BR10: −2.9%). Also, day and night Tamp (BR10: −19.5%) and Tslope (BR10 day: −17.1%; night: −7.8%) were found progressively reduced with the duration of BR. Conclusion During BR, cardiac electrical activity is affected by 10-days bedridden immobilization. Noticeably, a mismatch in RR-QTend relation was visible at night, where vagal autonomic system activity is prevailing. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Agenzia Spaziale Italiana (ASI)

Analysis of changes in cardiac circadian rhythms of RR and QT induced by a 60-day head-down bed rest with and without nutritional countermeasure.

Prolonged weightlessness exposure generates cardiovascular deconditioning, with potential implications on ECG circadian rhythms. Head-down (-6°) tilt (HDT) bed rest is a ground-based analogue model for simulating the effects of reduced motor activity and fluids redistribution occurring during spaceflight. Our aim was to evaluate the impact of 60-day HDT on the circadianity of RR and ventricular repolarization (QTend) intervals extracted from 24-h Holter ECG recordings, scheduled 9days before HDT (BDC-9), the 5th (HDT5), 21st (HDT21) and 58th (HDT58) day of HDT, the 1st (R + 0) and 8th (R + 7) day after HDT. Also, the effectiveness of a nutritional countermeasure (CM) in mitigating the HDT-related changes was tested. RR and QTend circadian rhythms were evaluated by Cosinor analysis, resulting in maximum and minimum values, MESOR (a rhythm-adjusted mean), oscillation amplitude (OA, half variation within a night-day cycle), and acrophase (φ, the time at which the fitting sinusoid's amplitude is maximal) values. RR and QTend MESOR increased at HDT5, and the OA was reduced along the HDT period, mainly due to the increase of the minima. At R + 0, QTend OA increased, particularly in the control group. The φ slightly anticipated during HDT and was delayed at R + 0. 60-Day HDT affects the characteristics of cardiac circadian rhythm by altering the physiological daily cycle of RR and QTend intervals. Scheduled day-night cycle and feeding time were maintained during the experiment, thus inferring the role of changes in the gravitational stimulus to determine these variations. The applied nutritional countermeasure did not show effectiveness in preventing such changes.

Cardiac repolarization in recently postmenopausal women with or without hot flushes.

Menopausal hot flushes are associated with elevated activity of the sympathetic nervous system and may be related to increased risk for cardiovascular events. Sympathetic activation may trigger severe arrhythmias by modulating cardiac repolarization. The aim of this study was to evaluate the impact of hot flushes on cardiac repolarization in postmenopausal women with and without hot flushes. We assessed 150 recently postmenopausal healthy women-72 with hot flushes and 78 without hot flushes. They underwent 24-hour electrocardiographic recording, comprising a total of over 10,000,000 QT-interval measurements. The cardiac repolarization was assessed by measuring QT-intervals, heat rate dependence of QT-end intervals, and T-waves. The maximal QT-end interval was shorter in women with hot flushes compared with those without hot flushes (481 ± 64 ms vs 493 ± 50 ms; P = 0.046). There were no differences between the rate dependence of QT-end intervals and T-wave measures between the groups. During the night-time hot flush period, we detected a steeper rate-dependence of QT-end intervals and a longer maximal T-peak-T-end interval (117 ± 54 ms vs 111 ± 56 ms; P < 0.001) compared with the control period. Women with hot flushes did not have clinically significant differences in ambulatory cardiac repolarization measurements compared with asymptomatic women. However, a sudden sympathetic surge occurring during the night-time hot flush may have direct effects on cardiac repolarization.

0210 : Effect of SCN5A mutations and SCN10A, SCN5A and HEY2 frequent variants on ECG of Brugada patients during ajmaline test

Inactivating mutations in the SCN5A and frequent variants in SCN10A , SCN5A and HEY2 genes have been both associated with Brugada syndrome. The myocardial transmural electrical gradient that could explain the ‘Brugada’ ECG pattern, is considered as increased by inactivation of the sodium channel. Na channel blocker drug can likewise increase or unmask this pattern. To better assess phenotype correlation with those SCN5A mutation and frequent variants, we compare ECG parameters during Na channel blocker test according to the genetical status. ECG parameters (P, PR, QRS, QT peak and QT end intervals; J wave amplitude in V1, V2, V3) were double measured in 73 unrelated Brugada patients with a positive Na blocker challenge. Data were measured at baseline and at the end of the test. Each patient was screened for SCN5A mutation and SCN10A , SCN5A and HEY2 frequent variants by direct sequencing and genotyped using Axiom Genome-Wide CEU 1 arrays (Affymetrix). The 10 patients carrying known SCN5A mutations (14%) didn’t show any clinical differences at baseline with those without SCN5A mutation. Baseline ECGs revealed a lengthening of PR (181 ±27 vs 156 ±30 p=0.017) and QRS interval (101 ±15 vs 89 ±14 p=0.020). No other parameter was significantly different. Once ECG parameters fulfilled diagnostic criteria for Brugada pattern, ECG parameters were not significantly different in the 2 groups. A similar effect on ECG was found in patients without SCN5A mutations but carrying more than 4 frequent variants. SCN10A polymorphism (rs10428132) was associated with a progressive effect on PR (p=0.044) and QRS (p=0.030) duration according to the risk allele number. According to the genetic status, no clinical difference was found after a mean follow up of 6 years. Frequent variants associated with Brugada syndrome could present the same effect on ECG than SCN5A mutations. Lengthening of PR and QRS interval observed at baseline in those patients disappears during NA blocker test suggesting a non cumulative and a saturable effect of SCN5A in brugada syndrome’s pathophysiology.

The role of acute hyperinsulinemia in the development of cardiac arrhythmias

Patients with perturbed metabolic control are more prone to develop cardiac rhythm disturbances. The main purpose of the present preclinical study was to investigate the possible role of euglycemic hyperinsulinemia in development of cardiac arrhythmias. Euglycemic hyperinsulinemia was induced in conscious rabbits equipped with a right ventricular pacemaker electrode catheter by hyperinsulinemic euglycemic glucose clamp (HEGC) applying two different rates of insulin infusion (5 and 10mIU/kg/min) and variable rate of glucose infusion to maintain euglycemia (5.5 ± 0.5mmol/l). The effect of hyperinsulinemia on cardiac electrophysiological parameters was continuously monitored by means of 12-lead surface ECG recording. Arrhythmia incidence was determined by means of programmed electrical stimulation (PES). The possible role of adrenergic activation was investigated by determination of plasma catecholamine levels and intravenous administration of a beta adrenergic blocking agent, metoprolol. All of the measurements were performed during the steady-state period of HEGC and subsequent to metoprolol administration. Both 5 and 10mIU/kg/min insulin infusion prolonged significantly QTend, QTc, and Tpeak-Tend intervals. The incidence of ventricular arrhythmias generated by PES was increased significantly by euglycemic hyperinsulinemia and exhibited linear relationship to plasma levels of insulin. No alteration on plasma catecholamine levels could be observed; however, metoprolol treatment restored the prolonged QTend, QTc, and Tpeak-Tend intervals and significantly reduced the hyperinsulinemia-induced increase of arrhythmia incidence. Euglycemic hyperinsulinemia can exert proarrhythmic effect presumably due to the enhancement of transmural dispersion of repolarization. Metoprolol treatment may be of benefit in hyperinsulinemia associated with increased incidence of cardiac arrhythmias.

Heritability of Tpeak-Tend Interval and T-Wave Amplitude

Background— Tpeak-Tend interval (TpTe) and T-wave amplitude (Tamp) carry diagnostic and prognostic information regarding cardiac morbidity and mortality. Heart rate and QT interval are known to be heritable traits. The heritability of T-wave morphology parameters such as TpTe and Tamp is unknown. TpTe and Tamp were evaluated in a large sample of twins. Methods and Results— Twins from the GEMINAKAR study (611 pairs, 246 monozygotic, 365 dizygotic; mean age, 38±11 years; 49% men) who had an ECG performed during 1997 to 2000 were included. Tamp was measured in leads V1 and V5. Duration variables (RR interval, QTpeak and QTend interval) were measured and averaged over 3 consecutive beats in lead V5. TpTe was calculated as the QTend- and QTpeak-interval difference. Heritability was assessed using structural equation models adjusting for age, sex, and body mass index. All models were reducible to a model of additive genetics and unique environment. All variables had considerable genetic components. Adjusted heritability estimates were as follows: TpTe, 46%; Tamp lead V1, 34%; Tamp lead V5, 47%; RR interval, 55%; QT interval, 67%; and Bazett-corrected QT interval, 42%. Conclusions— RR interval, QT interval, Tamp, and TpTe interval are heritable ECG parameters.

Epinephrine Bolus Test in Detecting Long QT Syndrome Mutation Carriers with Indeterminable Electrocardiographic Phenotype

In long QT syndrome (LQTS), prolonged and heterogeneous ventricular repolarization predisposes to serious arrhythmias. We examined how QT intervals are modified by epinephrine bolus in mutation carriers of three major LQTS subtypes with indefinite QT interval. Genotyped, asymptomatic subjects with LQTS type 1 (LQT1; n = 10; four different KCNQ1 mutations), type 2 (LQT2; n = 10; three different HERG mutations), and type 3 (LQT3; n = 10; four different SCN5A mutations), and healthy volunteers (n = 15) were examined. Electrocardiogram was recorded with body surface potential mapping system. After an epinephrine 0.04 μg/kg bolus QT end, QT apex, and T-wave peak-to-end (Tpe) intervals were determined automatically as average of 12 precordial leads. Standard deviation (SD) of the 12 channels was calculated. Heart rate increased 26 ± 10 bpm with epinephrine bolus, and similarly in all groups. QT end interval lengthened, and QT apex interval shortened in LQTS and normals, leading to lengthening of Tpe interval. However, the lengthening in Tpe was larger in LQTS than in normals (mean 32 vs 18 ms; P < 0.05) and SD of QT apex increased more in LQTS than in normals (mean 23 vs 7 ms; P < 0.01). The increase in Tpe was most pronounced in LQT2, and in SD of QT apex in LQT1 and LQT2. Abrupt adrenergic stimulation with a moderate dose of exogenous epinephrine affects ventricular repolarization in genotype-specific fashion facilitating distinction from normals. This delicate modification may help in diagnosing electrocardiographically silent mutation carriers when screening LQTS family members.

173 Study of the circadien variation of the QT dynamics in myocardial infarction

The relation between the QT interval and heart rate is linear. The QT interval/RR interval relationship is generally described as QT dynamics. the linear QT/RR slope is influenced by the autonomic nervous system. In healthy individuals, the slope exhibits circadian variations: it is steeper during the day than during the night. The aim of this study is to evaluate the circadian variation of the QT interval and the QT/RR slope in patients experiencing myocardial infarction. This prospective study included 90 patients having myocardial infarction. They underwent 21 days after the acute phase, 24 hours ambulatory ECG (Holter) recording. The following parameters were studied : the QT end interval (QTe), the QT apex interval (QTa) and the slopes of QTe/RR and QTa/RR during diurnal and nocturnal periods. There was no significant difference regarding the QTe and the QTa intervals during the day and night. The mean diurnal slope and nocturnal slopes of QTe/RR were similar (0,147 ± 0,073 vs 0,131 ± 0,062, p = NS). The mean diurnal slope and nocturnal slopes of QTa/RR were also comparable (0,123 ± 0,067 vs 0,119 ± 0,065, p = NS). The lack of circadian variation of the QT interval and the linear QT/RR slope in myocardial infarction patients reflects an imbalance in the autonomic nervous system. These results suggest an increase in the nocturnal sympathic tone and may be associated with a higher risk of arrhythmia in this population. Further studies are needed to evaluate the role of the QT/RR slope in risk stratification after myocardial infarction.

Comparison of QT peak and QT end interval responses to autonomic adaptation in asymptomatic LQT1 mutation carriers

BackgroundLQT1 subtype of long QT syndrome is characterized by defective IKs, which is intrinsically stronger in the epicardium than in the midmyocardial region. Electrocardiographic QT peak and QT end intervals may reflect complete repolarization of epicardium and midmyocardial region of the ventricular wall, respectively. Repolarization abnormalities in LQT1 carriers may therefore be more easily detected in the QT peak intervals.MethodsAsymptomatic KCNQ1 mutation carriers (LQT1, n = 9) and unaffected healthy controls (n = 8) were studied during Valsalva manoeuvre, mental stress, handgrip and supine exercise. Global QT peak and QT end intervals derived from 25 simultaneous electrocardiographic leads were measured beat to beat with an automated method.ResultsIn unaffected subjects, the percentage shortening of QT peak was greater than that of QT end during mental stress and during the recovery phases of Valsalva and supine exercise. In LQT1 carriers, the percentage shortening of the intervals was similar. At the beginning of Valsalva strain under abrupt endogenous sympathetic activation, QT peak shortened in LQT1 but not in control patients yielding increased electrocardiographic transmural dispersion of repolarization in LQT1.ConclusionsIn asymptomatic KCNQ1 mutation carriers, repolarization abnormalities are more evident in the QT peak than in the QT end interval during adrenergic adaptation, possibly related to transmural differences in the degree of IKs block.

212 Study of the effect of mode of pacing on ventricular repolarization in heart failure patients

Background Cardiac resynchronization therapy (CRT) is a well established treatment in selected patients with heart failure. The non physiological ventricular activation sequence has been implicated in the occurrence of sudden death after CRT. There is conflicting date concerning the effect of different pacing modes on ventricular repolarization in heart failure patients. Purpose Assessing the effects of biventicular (Bi V), left ventricular (LV) epicardial pacing and right ventricular endocardial pacing (RV) on QT intervals (QT end, QT apex, JT) and transmural dispersion of repolarization (TDR) in patients with heart failure having CRT. Methods 20 patients (15 men and 5 women, age = 63.4 ± 11 years) with NYHA III-IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony received CRT. We measured QT end intervals, JT intervals and TDR according to recommended methods on a 12 lead ECG recorded at baseline and after implant. After implant, ECG was recorded with temporary right ventricular pacing, temporary left ventricular pacing and then the final pacing mode : simultaneous biventricular pacing. Results There was no significant difference between QT end interval, JT interval and TDR at baseline and after implant with different pacing modes. Conclusion In our study, we noticed no effect of pacing modes on repolarization in patients with heart failure. The high incidence of sudden death observed in CRT may be explained by competitvity of modes of death rather than induced abnormal repolarization.

Beat‐to‐Beat QT Interval Variability Is Primarily Affected by the Autonomic Nervous System

Beat-to-beat QT interval variability is associated with life-threatening arrhythmias and sudden death, however, its precious mechanism and the autonomic modulation on it remains unclear. The purpose of this study was to determine the effect of drugs that modulate the autonomic nervous system on beat-to-beat QT interval. RR and QT intervals were determined for 512 consecutive beats during fixed atrial pacing with and without propranolol and automatic blockade (propranolol plus atropine) in 11 patients without structural heart disease. Studied parameters included: RR, QTpeak (QRS onset to the peak of T wave), QTend (QRS onset to the end of T wave) interval, standard deviation (SD) of the RR, QTpeak, and QTend (RR-SD, QTpeak-SD, and QTend-SD), coefficients of variation (RR- CV, QTpeak-CV, and QTend-CV) from time domain analysis, total power (TP; RR-TP, QTpeak-TP, and QTend-TP), and power spectral density of the low-frequency band (LF; RR-LF, QTpeak-LF, and QTend-LF) and the high-frequency band (HF; RR-HF, QTpeak-HF and QTend-HF). Administration of propranolol and infusion of atropine resulted in the reduction of SD, CV, TP, and HF of the QTend interval when compared to controlled atrial pacing (3.7 +/- 0.6 and 3.5 +/- 0.5 vs 4.8 +/- 1.4 ms, 0.9 +/- 0.1 and 0.9 +/- 0.1 vs 1.2 +/- 0.3%, 7.0 +/- 2.2 and 7.0 +/- 2.2 vs 13.4 +/- 8.1 ms(2), 4.2 +/- 1.4 and 4.2 +/- 1.2 vs 8.4 +/- 4.9 ms(2), respectively). Administration of propranolol and atropine did not affect RR interval or QTpeak interval indices during controlled atrial pacing. Beat-to-beat QT interval variability is affected by drugs that modulate the autonomic nervous system.

Mutation Site Dependent Variability of Cardiac Events in Japanese LQT2 Form of Congenital Long-QT Syndrome

In the LQT2 form of long QT syndrome (LQTS), mutation sites are reported to correlate with clinical phenotypes in Caucasians, but the relationship in Asian patients remains unknown. The present study was designed to determine whether the location of KCNH2 mutations would influence the arrhythmic risk in LQT2 patients. In 118 genetically-confirmed LQT2 patients (69 families, 62 KCNH2 mutations), the ECG parameters, Schwartz scores, and the incidence of cardiac events, defined as syncope, aborted cardiac arrest, and sudden cardiac death, were evaluated. To examine the effect of mutation sites, the participants were divided accordingly: pore (n=56) and non-pore (n=62) groups. The corrected QTend interval was significantly greater in the pore than in the non-pore group (QTc; 522+/-63 ms vs 490+/-49 ms, p=0.002). In this study, the clinical course of each of the probands did not differ according to the mutation sites, whereas non-probands carrying the pore site mutation experienced their first cardiac events at significantly younger age than those with the non-pore site mutation (log-rank, p=0.0005). In a Japanese LQT2 cohort, family members with the pore site mutation were at higher arrhythmic risk than those with the non-pore site mutation.

Reproducibility of Computerized Measurements of QT Interval from Multiple Leads at Rest and During Exercise

Accurate measurement of the QT interval is important for diagnosing long QT syndrome (LQTS), and in research on determinants of ventricular repolarization time. We tested automatic analysis of QT intervals from multiple ECG leads on chest. Eleven healthy volunteers and 10 genotyped LQTS patients were tested at rest and during exercise with a bicycle ergometer twice 1-31 months apart. Electrocardiograms were recorded with the body surface potential mapping system, and 12 precordial channels were selected for analysis. Averaged QT peak and QT end intervals were determined with an automated algorithm, and the difference QT end minus QT peak (Tp-e) was calculated. Repeatability was assessed by coefficient of variation (CV) between measurements. Within one test at rest the QT end intervals were highly repeatable with CV 0.6%. In repeated tests CV was 4.4% for QT end interval and 3.5% when the QT interval was corrected for heart rate. In exercise test at specified heart rates, mean CV was 3.0% for QT end and 2.9% for QT peak interval. The CV of Tp-e interval was 10.2% at rest, and 9.3% in exercise test. Reproducibility was comparable between healthy subjects and LQTS patients. The BSPM system with automated analysis produced accurate and highly repeatable QT interval measurements. Reproducibility was adequate also over prolonged time periods both at rest and in exercise stress test. The method can be applied in studying duration of ventricular repolarization time in different physiologic and pharmacologic interventions.

Ventricular Repolarization and Heart Rate Responses During Cardiovascular Autonomic Function Testing in LQT1 Subtype of Long QT Syndrome

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. 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. 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. 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.

Short QT syndrome: Should we push the frontier forward?

15-year-old boy was resuscitated from ventricular fibrilation (VF). The cardiac arrest occurred while he was at ome resting. The patient had no family history of sudden eath or syncope, and he had never complained of any ardiac symptoms. Initial and all subsequent successive ECGs display short T intervals with tall symmetric T waves on precordial eads (mean QT 283 16 ms, range 245–310 ms; Figure 1). orrected QT intervals using the Bazett formula, calculated hen heart rate was 85 bpm, were 340 20 ms (range 15–375 ms). QTpeak–QTend interval was 80 ms. QT disersion was evaluated at 30 ms on 12-lead ECG. Calcium nd potassium blood levels were consistently in the normal ange. Except for the first echocardiogram, which displayed nitial pericardial effusion after resuscitation maneuvers and ransient septal thickening, no other argument in favor of a yocarditis was found. Coronary angiograms, further reeated echocardiograms, and cardiac magnetic resonance maging were unremarkable. Repeated 24 hour-ECG recordings displayed permanent inus rhythm with poor adaptation of QT intervals to the eart rate, as shown by the lack of lengthening of repolarzation after pauses. Infrequent isolated monomorphic venricular ectopies were documented. QT shortening contined with isoproterenol infusion or during exercise testing shortest QT 200 ms) with documentation of short-coupled 200 ms) isolated ectopic ventricular beats with left bundle ranch block, left-axis deviation with isoproterenol (30 g/ in). There was a linear relationship between QT interval nd heart rate during exercise testing (curve slope 0.7 ms/ pm, R 0.9). Drug challenge (1 mg/kg intravenous jmaline in 5 minutes) administered to reveal a Brugada

Effects of sympathetic stimulation on various repolarization indices in the congenital long QT syndrome.

Sympathetic stimulation or catecholamines modulate ventricular repolarization and provoke ventricular tachyarrhythmias in a variety of heart diseases and conditions. Among those, the congenital form of long QT syndrome (LQTS) has long been known to be a Rosetta stone for sympathetic-related ventricular tachyarrhythmias. Recent experimental studies employing arterially-perfused ventricular wedge preparations as well as some clinical studies have greatly advanced our knowledge of the cellular mechanism of the T wave and the various repolarization indices in the ECG, as well as the effect of sympathetic stimulation on these repolarization indices under normal and long QT conditions. Differences in the time course of repolarization of the three predominant cell types, the epicardial, midmyocardial (M), and endocardial cells, across the ventricular wall give rise to voltage gradients responsible for the inscription of normal T waves as well as the manifestation of abnormal T waves in the congenital LQTS. The data from the wedge experiments suggest that the repolarization time of the longest M cell action potential determines the Q-Tend interval, while that of the epicardial action potential determines the Q-Tpeak interval. Therefore, Tpeak-end interval in the ECG may provide an index of transmural dispersion of repolarization (TDR). In this review article, sympathetic stimulation with isoproterenol or epinephrine infusion is demonstrated to modulate differentially these repolarization indices in the ECG as well as the action potentials of the three cells between the LQT1, LQT2, and LQT3 syndromes both experimentally and clinically, explaining the differences in the sensitivity of genotypes of congenital LQTS to sympathetic stimulation.

Left ventricular hypertrophy increases transepicardial dispersion of repolarisation in hypertensive patients: a differential effect on QTpeak and QTend dispersion.

Ventricular arrhythmias in left ventricular hypertrophy (LVH) are related to regional electrical heterogeneity. The significance of noninvasive electrocardiographic indices of electrical heterogeneity in LVH has not been established. The aim of the study was to investigate changes in the Tpeak-Tend interval (an index of transmural dispersion of repolarisation) in addition to other traditional electrocardiographic indices of electrical dispersion in patients with hypertensive LVH. Consecutive patients were screened for the presence of hypertensive echocardiographic LVH and compared with a control group. LVH was identified as left ventricular mass > 134 g m-2 in men and > 110 g m-2 in women. Twelve-lead ECGs were analysed in respect of various indices of electrical dispersion. Left ventricular mass was greater in the LVH than in the control group (174 +/- 39 vs. 101 +/- 18 g m-2, P < 0.0001). The Tpeak-Tend interval was not affected by LVH. The main effect of LVH was an increase in QTpeak dispersion (40 +/- 13 vs. 53 +/- 21 ms, P < 0.05), which resulted from an increase in the maximum QTpeak interval (337 +/- 24 vs. 358 +/- 30 ms, P < 0.04), without any change in the minimum QTpeak interval. There was a significant correlation between the left ventricular mass index and QTpeak dispersion (r = 0.40; P < 0.01). In contrast, LVH did not exert any effect on QTend dispersion (65 +/- 21 vs. 65 +/- 16 ms, ns), because LVH increased both the maximum QTend interval (430 +/- 30 vs. 449 +/- 28 ms, P < 0.05) and the minimum QTend interval (365 +/- 29 vs. 384 +/- 27 ms, P < 0.04). Hypertensive LVH exerts a differential effect on QTpeak and QTend interval dispersion. The most likely explanation is that these changes reflect a nonuniform prolongation of action potential duration across the epicardium, leading to an increase in transepicardial dispersion of repolarisation.

Repolarization abnormalities detected by magnetocardiography in patients with dilated cardiomyopathy and ventricular arrhythmias.

Abnormal repolarization is one of the acknowledged mechanisms leading to malignant ventricular arrhythmias. We used a novel magnetocardiographic technique to investigate the role of inhomogeneous repolarization in patients with nonischemic dilated cardiomyopathy prone to sustained ventricular arrhythmias. Forty-nine dilated cardiomyopathy patients were studied, 18 with a history of sustained ventricular tachycardia (n = 6) or ventricular fibrillation (n = 12) and 31 with no ventricular arrhythmias. The magnetocardiogram was registered and QT apex and QT end intervals were determined by a computer algorithm. Inhomogeneity of repolarization was characterized with indices describing QT apex and QT end dispersion, and T wave end duration. In addition, time-domain late fields of the QRS complex in magnetocardiography and QT dispersion in 12-lead ECG were determined. T wave end was longer in the arrhythmia group in patients with sinus rhythm (87 +/- 15 msec vs 73 +/- 12 msec; P = 0.005) and in those not having bundle branch block. Magnetocardiographic late fields of the QRS complex were not different between groups. QT apex and end dispersion on magnetocardiography or 12-lead ECG showed no difference. Prolongation of the end part of the T wave revealed by magnetocardiography is related to malignant ventricular arrhythmias in dilated cardiomyopathy. The results suggest that abnormal repolarization rather than delayed conduction underlies the arrhythmias in this disease.