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.     

Evaluation of PR, RR, QT Intervals and QT Dispersion Following Stellate Ganglion Block in Chronic Shoulder–Hand Pain Patients

Abstract: Right stellate ganglion block (SGB) can increase QT interval, rate‐corrected QT interval (QTc), QT dispersion (QTD), rate‐corrected QTD (QTcD), and RR interval while left SGB can decrease these intervals in healthy volunteers. No such studies have been conducted in patients with chronic pain, hence this study was designed to investigate the effects of left and right SGB on these variables in chronic shoulder–hand pain patients. In this study, 28 patients with chronic shoulder–hand pain of at least 6 months duration were given right or left SGB depending on the shoulder affected. A 12‐lead electrocardiogram (ECG) was recorded before the block, 30 minutes and 60 minutes after the block. PR interval, RR interval, QT interval were recorded in all 12 leads while QTc, QTD, and QTcD were calculated. Right SGB was performed in 21 patients. A significant decrease (P < 0.05) in PR interval and a significant increase (P < 0.05) in RR interval, QT interval, and QTc interval were observed. QTD showed a significant increase (P < 0.05) only at 30 minutes after right SGB. Left SGB was performed in seven patients. A significant decrease (P < 0.05) in QT interval was observed throughout the study period, while QTc showed a significant decrease (P < 0.05) only at 60 minutes after the block. We conclude that right SGB induces significant increase of QT interval, RR interval, QTc interval, QTD, and a significant decrease of PR interval while left SGB produces a significant decrease in QT and QTc intervals in patients with chronic shoulder–hand pain.     

Suppression of Torsades de Pointes by Biventricular Pacing in a Patient with Long QT Syndrome

This report describes a case of a patient with long QT syndrome (LQTS) with recurrent episodes of torsades de pointes (TdP). Use of biventricular pacing (BiVP) resulted in a shorter QT interval and a shorter T‐peak‐end interval and prevented further episodes of TdP. These findings suggest that BiVP may be helpful in patients with LQTS and refractory TdP.     

Clinical Value of Electrocardiographic Parameters in Genotyped Individuals with Familial Long QT Syndrome

MOENNIG, G., et al. : Clinical Value of Electrocardiographic Parameters in Genotyped Individuals with Familial Long QT Syndrome. Rate corrected QT interval (QTc) and QT dispersion (QTd) have been suggested as markers of an increased propensity to arrhythmic events and efficacy of therapy in patients with long QT syndrome (LQTS). To evaluate whether QTc and QTd correlate to genetic status and clinical symptoms in LQTS patients and their relatives, ECGs of 116 genotyped individuals were analyzed. JTc and QTc were longest in symptomatic patients (  n = 28  ). Both QTd and JTd were significantly higher in symptomatic patients than in asymptomatic (  n = 29  ) or unaffected family members (  n = 59  ). The product of QTd/JTd and QTc/JTc was significantly different among all three groups. Both dispersion and product put additional and independent power on identification of mutation carriers when adjusted for sex and age in a logistic regression analysis. Thus, symptomatic patients with LQTS show marked inhomogenity of repolarization in the surface ECG. QT dispersion and QT product might be helpful in finding LQTS mutation carriers and might serve as additional ECG tools to identify asymptomatic LQTS patients.     

The Long QT Syndrome and Torsade De Pointes

The LQTS is a prime example of how molecular biology, ion channel, cellular, and organ physiology, coupled with clinical observations, promise to be the future paradigm for advancement of medical knowledge. Both the congenital and acquired LQTS are due to abnormalities (intrinsic and/or acquired) of the ionic currents underlying cardiac repolarization. In this review, the continually unraveling molecular biology of congenital LQTS is discussed. The various pharmacological agents associated with the acquired LQTS are listed. Although it is difficult to predict which patients are at risk for TdP, careful assessment of the risk-benefit ratio is important before prescribing drugs known to be able to cause QT prolongation. The in vivo electrophysiological mechanism of TdP in the LQTS is described using, as a paradigm, the anthopleurin-A canine model, a surrogate for LQT3. In the LQTS, prolonged repolarization is associated with increased spatial dispersion of repolarization. Prolongation of repolarization also acts as a primary step for the generation of EADs. The focal EAD induced triggered beat(s) can infringe on the underlying substrate of inhomogeneous repolarization to initiate polymorphic reentrant VT, sometimes having the characteristic twisting QHS configuration known as TdP. The review concludes by discussion of the clinical manifestations and current management of both the congenital and acquired LQTS. The initial therapy of choice for the large majority of patients with the congenital LQTS is a beta-blocking drug. This therapy seems to be effective in LQT1 and LQT2 patients, but may not be as effective in LQT3 patients. Other therapeutic options include pacemakers, cervicothoracic sympathectomy, and the implantable cardioverter defibrillator. Recent molecular genetic studies have suggested several genotype specific therapies; however, long-term efficacy data are not available.     

Effects of Ischemia and Reperfusion on QT Dispersion During Coronary Angioplasty

The effects of ischemia and reperfusion on QT interval dispersion (QTD: QT_max-QT_min in the 12-lead ECG) were analyzed in 15 patients (12 males, 57 ± 13 years) undergoing coronary angiopiasty (PTCA). AH patients had single-vessel coronary artery disease (only one ≥ 85% stenosis in a major coronary artery) and normal left ventricular function. AH were in sinus rhythm with normal atrioventricular and intraventricular conduction on the surface ECG. No patient was on therapy that could affect the QT interval. The ECG was recorded (all 12 leads simultaneously) at 50 mm/s speed before the first balloon inflation, at the end of the first inflation during PTCA, and at 30" and 60" during reperfusion following the first inflation. In order to avoid ischemic preconditioning, only recordings of the first inflation were used. In each tracing QT_max and QT_min were evaluated. All values were rate corrected using a simple linear equation (QT linear corrected = QT + 0.154 [1-RR]). QTD increased significantly during both ischemia and reperfusion. QT_max was not changed by ischemia and was increased by reperfusion. QT_min was reduced by ischemia and increased by reperfusion. These results indicate that both ischemia and reperfusion alter ventricular repolarization, inducing a less homogeneous ventricular recovery pattern.     

Hyperbaric oxygen therapy decreases QT dispersion in diabetic patients

Diabetes mellitus is frequently associated with the malignant ventricular arrhythmias and sudden death. The QT dispersion is the difference between the longest and shortest QT interval calculated from the standard 12-lead electrocardiogram. The QT dispersion is suggested as an index of myocardial electrical activity. An increase in QT dispersion is associated with the malignant ventricular arrhythmias and sudden cardiac death. Diabetic patients receive hyperbaric oxygen (HBO) therapy for non-healing lower extremity ulcers. The aim of this study was to determine the effect of HBO therapy on QT dispersion in diabetic patients. Thirty diabetic patients (18 male and 12 female, 59.9 +/- 10 years), who were planning to undergo ten sessions of HBO therapy in two weeks for non-healing lower extremity ulcers, were consecutively enrolled into the study. The 12-lead resting electrocardiography recordings were taken before the first HBO therapy and after the 10th HBO-therapy session. QT intervals were measured on electrocardiogram. QT intervals were corrected for heart rate by using Bazett's formula (corrected QT [QTc] = QT/ radical R - R [seconds]). QTc dispersion was significantly decreased from 59.8 +/- 17.4 msec to 52.2 +/- 15.5 msec after ten sessions of HBO therapy (p < 0.05). However, maximum QTc, minimum QTc and mean QTc did not change significantly after HBO therapy. We have concluded that HBO therapy may reduce the risk of malignant ventricular arrhythmia and sudden cardiac death in diabetic patients when applied repetitively.     

Prediction of torsade de pointes from the QT interval: analysis of a case series of amisulpride overdoses

Electrocardiograms (ECGs) from a case series of 86 amisulpride overdose events in 66 patients were reviewed for abnormal QT intervals and torsade de pointes (TdP). Eight patients exhibited TdP. In this investigative case series, the magnitude of prolongation of the QT interval was a stronger predictor of TdP than the mere presence of a prolongation per se.     

Evidences of the gender-related differences in cardiac repolarization and the underlying mechanisms in different animal species and human

Clinical and experimental studies have shown that gender differences exist in cardiac repolarization in various animal species and human, as is evidenced by significantly longer QT, JT intervals and action potential duration in females than in males due to a reduced repolarization reserve in females. The latter is shown by the relatively greater increase in ventricular repolarization and higher incidence of torsades de pointes (TdP) in preparations from females by drugs blocking repolarizing K(+) currents. These results can be modulated by gonadectomy, suggesting that gonadal steroids are important determinants of gender difference in repolarization. In human subjects, QT and JT intervals are longer in women, whereas QT dispersion and Tp-e interval (the interval from the peak to the end of T wave) are longer in men. At slow heart rates greater prolongation in QT and increase in transmural repolarization heterogeneity (i.e. increase in Tp-e) may predispose to TdP tachycardias in women. In healthy postmenopausal women, hormone replacement therapy with estrogen alone usually produced a prolongation of QT interval, while estrogen plus progesterone had no significant effects on QT interval but reduced QT dispersion. Along with these, there are still conflicting data reported. Further work is needed before the elucidation of the basis of gender differences in ventricular repolarization.     

Epinephrine-induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome

OBJECTIVE: To determine the effect of epinephrine on the QT interval in patients with genotyped long QT syndrome (LQTS). PATIENTS AND METHODS: Between May 1999 and April 2001, 37 patients (24 females) with genotyped LQTS (19 LQT1, 15 LQT2, 3 LQT3, mean age, 27 years; range, 10-53 years) from 21 different kindreds and 27 (16 females) controls (mean age, 31 years; range, 13-45 years) were studied at baseline and during gradually increasing doses of intravenous epinephrine infusion (0.05, 0.1, 0.2, and 0.3 microg x k(-1) x min(-1)). The 12-lead electrocardiogram was monitored continuously, and heart rate, QT, and corrected QT interval (QTc) were measured during each study stage. RESULTS: There was no significant difference in resting heart rate or chronotropic response to epinephrine between LQTS patients and controls. The mean +/- SD baseline QTc was greater in LQTS patients (500+/-68 ms) than in controls (436+/-19 ms, P<.001). However, 9 (47%) of 19 KVLQT1-genotyped LQT1 patients had a nondiagnostic resting QTc (<460 milliseconds), whereas 11 (41%) of 27 controls had a resting QTc higher than 440 milliseconds. During epinephrine infusion, every LQT1 patient manifested prolongation of the QT interval (paradoxical response), whereas healthy controls and patients with either LQT2 or LQT3 tended to have shortened QT intervals (P<.001). The maximum mean +/- SD change in QT (AQT [epinephrine QT minus baseline QT]) was -5+/-47 ms (controls), +94+/-31 ms (LQT1), and -87+/-67 ms (LQT2 and LQT3 patients). Of 27 controls, 6 had lengthening of their QT intervals (AQT >30 milliseconds) during high-dose epinephrine. Low-dose epinephrine (0.05 microg x kg(-1) x min(-1)) completely discriminated LQT1 patients (AQT, +82+/-34 ms) from controls (AQT, -7+/-13 ms; P<.001). Epinephrine-triggered nonsustained ventricular tachycardia occurred in 2 patients with LQTS and in 1 control. CONCLUSIONS: Epinephrine-induced prolongation of the QT interval appears pathognomonic for LQT1. Low-dose epinephrine infusion distinguishes controls from patients with concealed LQT1 manifesting an equivocal QTc at rest. Thus, epinephrine provocation may help unmask some patients with concealed LQTS and strategically direct molecular genetic testing.     

Genotype-specific clinical manifestation in long QT syndrome

The congenital form of long QT syndrome (LQTS) is characterized by QT prolongation in the electrocardiogram (ECG) and a polymorphic ventricular tachycardia, Torsade de Pointes (TdP) mainly as a result of an increased sympathetic tone during exercise or mental stress. Recent genetic studies have so far identified seven forms of congenital LQTS caused by mutations in genes of the potassium and sodium channels or membrane adapter located on chromosomes 3, 4, 7, 11, 17 and 21. It is of particular importance to examine the genotype-phenotype correlation, especially in the LQT1, LQT2 and LQT3 forms of LQTS, which make up more than 90% of genotyped patients with LQTS, because it would enable us to manage and treat genotyped patients more effectively.     

QT dispersion is not increased in familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autoimmune disease inherited as an autosomal recessive trait and is characterized by recurrent attacks of fever and sterile polyserositis. This study examined electrocardiographic ventricular repolarization parameters (QT interval and QT dispersion) in 38 FMF patients and 35 healthy controls. The QT interval was measured manually from the onset of QRS to the end of the T wave (return to the TP baseline). QT dispersion was defined as the difference between the maximum and minimum QT values, and corrected QT was calculated according to the Bazett formula. There were no significant differences between FMF patients and healthy control subjects in any parameter of ventricular repolarization; hence QT dispersion was not affected by FMF. Electrocardiographic assessment of QT interval and QT dispersion are, therefore, of little value for the evaluation of cardiac impairment and risk of arrhythmia in FMF patients.     

Genotype-specific clinical manifestation in long QT syndrome

The congenital form of long QT syndrome (LQTS) is characterized by QT prolongation in the electrocardiogram (ECG) and a polymorphic ventricular tachycardia, Torsade de Pointes (TdP) mainly as a result of an increased sympathetic tone during exercise or mental stress. Recent genetic studies have so far identified seven forms of congenital LQTS caused by mutations in genes of the potassium and sodium channels or membrane adapter located on chromosomes 3, 4, 7, 11, 17 and 21. It is of particular importance to examine the genotype–phenotype correlation, especially in the LQT1, LQT2 and LQT3 forms of LQTS, which make up more than 90% of genotyped patients with LQTS, because it would enable us to manage and treat genotyped patients more effectively.     

QT Duration and Dispersion in Patients with Anomalous Origins of Coronary Arteries

Background: Coronary artery anomalies have been reported to show various symptoms ranging from chest pain and dyspnea to cardio-respiratory arrest and sudden death. In this study, we attempted to assess the changes in QT interval duration and dispersion in anomalous origins of coronary arteries (AOCA).
Methods: Nineteen AOCA patients (mean age: 52 ± 11 years) and 30 healthy control subjects (mean age: 50 ± 12 years) were included in the study. Minimum and maximum corrected QT intervals, and corrected QT dispersion were calculated. The two groups were compared in terms of QT dispersion and QT duration.
Results: There was no difference between the two groups in terms of baseline demographic characteristics. Maximum corrected QT intervals (QTc max), minimum corrected QT intervals (QTc min), and corrected QT dispersion were higher in AOCA patients than controls (452 ± 38 vs 411 ± 25 ms [P = 0.0001], 402 ± 31 vs 383 ± 28 ms [P = 0.048], and 51 ± 30 vs 28 ± 12 ms [P = 0.001], respectively).
Conclusion: In the patients with anomalous origins of coronary arteries, QT dispersion that is an indicator of sudden cardiac death and arrhythmias frequency increased. QTc max, QTc min, and corrected QT dispersion are higher in patients with anomalous origin of the coronary artery than in control subjects.     

Magnetocardiographic QT Interval Dispersion in Postmyocardial Infarction Patients with Sustained Ventricular Tachycardia: Validation of Automated QT Measurements

T dispersion is a measure of heterogeneity in ventricular repolarization. Increased ECG QT dispersion is associated with life-threatening ventricular arrhythmias. We studied if magnetocardiographic (MCG) measures of QT dispersion can separate postmyocardial infarction patients with and without susceptibility to sustained VT. Manual dispersion measurements were compared to a newly adapted automatic QT interval analysis method. Ten patients with a history of sustained VT (VT group) and eight patients without ventricular arrhythmias (Controls) were studied after a remote myocardial infarction. Single-channel MCGs were recorded from 42 locations over the frontal chest area and the signals were averaged. QT dispersion was defined as maximum — minimum or standard deviation of measured QT intervals. VT group showed significantly more QT and JT dispersion than Controls. QT_apex dispersions were 127 ± 26 versus 83 ± 21 ms (P = 0.004) and QT_end dispersions 130 ± 37 versus 82 ± 37 ms (P = 0.013), respectively. Automatic method gave comparable values. Their relative differences were 9% for QT_apex and 27% for QT_end dispersion on average. In conclusion, increased MCG QT interval dispersion seems to be associated with a susceptibility to VT in postmyocardial infarction patients. MCG mapping with automated QT interval analysis may provide a user independent method to detect nonhomogeneity in ventricular repolarization.     

Temporary disturbances of the QT interval precede the onset of ventricular tachyarrhythmias in patients with structural heart diseases

An increase in sinus rate prior to ventricular tachyarrhythmias has been demonstrated in previous studies. There is no clear data available concerning changes in ventricular de- and repolarization prior to ventricular tachyarrhythmias, especially in patients with structural heart disease. Therefore, the aim of this study was to analyze the QT and QTc interval (Bazett's formula immediately before the onset of ventricular tachyarrhythmias in stored electrograms of patients with ICDs. The study analyzed 228 spontaneous ventricular tachyarrhythmia episodes in 52 patients (mean age 64 +/- 10 years, 49 men, 3 women) and compared them with 146 electrograms of baseline rhythm recorded during regular ICD follow-up. Mean ventricular cycle length (CL), QT interval, and QTc were measured before the onset of ventricular tachyarrhythmia and during baseline rhythm. Prior to ventricular tachyarrhythmias onset, CL was significantly shorter than during baseline rhythm (714 +/- 139 vs 828 +/- 149 ms, P < 0.0001). By contrast, the QT interval (430 +/- 67 ms) and QTc interval (518 +/- 67 ms) were significantly prolonged before the onset of ventricular tachyarrhythmias as compared to baseline rhythm (QT 406 +/- 67 ms, QTc 450 +/- 61 ms; P < 0.0001). CL, QT, and QTc changes were independent of concomitant treatment with antiarrhythmic drugs. Ventricular tachyarrhythmias are preceded by a significant prolongation of the QT and QTc intervals. This phenomenon may represent a greater than normal disparity of repolarization recovery times possibly facilitating the development of ventricular tachyarrhythmias.     

Alteration of the QT/RR Relationship in Patients with Idiopathic Ventricular Tachycardia

It has been shown that alterations in QT/RR relationship may be associated with arrhythmogenesis in several clinical settings. In the present study the QT/RR relationship was studied in 20 patients with idiopathic ventricular tachycardia (12 men and 8 women, aged 41±14 years) compared to 20 normal subjects (9 men and 11 women, aged 39 ± 13 years). All the patients were off any antiarrhythmic drugs and had no evidence of intraventricular conduction defects. The QT intervals and their preceding RR intervals were measured on electrocardiogram strips from 24-hour Holter tapes at hourly intervals. The differences in the maximum, minimum, and mean of either the QT interval or its corrected values between patients with idiopathic ventricular tachycardia and normal subjects were not statistically significant. There was a significant correlation between the QT and RR intervals in normal subjects (γ= 0.73 ± 0.12, P < 0.05) and in patients with idiopathic ventricular tachycardia (γ= 0.80 ± 0.10, P < 0.05). However, the linear regression line of the QT interval against the RR interval were significantly (P < 0.001) altered in patients with idiopathic ventricular tachycardia (QT = 0.24 + 0.18 RR) compared to normal subjects (QT = 0.27 ± 0.12 RR). We conclude that although there is no significant change in the QT interval and its corrected values, the QT/RR relationship is significantly altered in patients with idiopathic ventricular tachycardia as compared to normal subjects. This may be of importance in the pathogenesis of idiopathic ventricular tachycardia in these patients.     

陈旧性心肌梗死患者T波峰末间期的检测及其与室性心律失常的关系

目的检测陈旧性心肌梗死患者T波峰末间期（Tpe）及T波峰末间期离散度,并探讨其与室性心律失常发生的关系。方法对31例陈旧性心肌梗死患者（分为室性心律失常亚组与无室性心律失常亚组）及40例对照组患者,测量其同步12导联动态心电图的Tpe间期和Tpe离散度（最长Tpe减最短Tpe之差）,计算校正的T波峰末间期（Tpe√RR）、心率校正的Tpe离散度（Tpe离散度√RR）,并进行比较。结果心肌梗死组的Tpe/√RR、Tpe离散度√RR均较对照组组明显延长（P〈0．01）,而心律失常亚组的Tpe／√RR、Tpe离散度／√RR亦较无心律失常亚组延长（P〈0．05）。结论心肌梗死组的Tpe间期、Tpe离散度延长有显著统计学意义,Tpe间期、Tpe离散度延长与室性心律失常的发生关系密切。     

Acquired long QT syndrome: risk assessment,prudent prescribing and monitoring,and patient education

PURPOSE: To inform nurse practitioners (NPs) about risk factors that precipitate the potentially fatal cardiac arrhythmia torsade de pointe (TdP) in patients with long QT syndrome (LQTS), and to recommend preventative strategies and prudent prescribing advice to use in clinical practice. DATA SOURCES: A review of the current literature is used to explain factors that cause prolonged repolarization during phase 2 and phase 3 of the cardiac action potential and relate these to the development of LQTS and TdP. The major risk factors reviewed are drugs, drug-drug interactions, electrolyte disturbances, and populations at risk for LQTS. CONCLUSIONS: The LQTS is an increasingly recognized cardiovascular problem. Nurse practitioners should be cognizant of the risk factors and be able to apply them in clinical practice. IMPLICATIONS FOR PRACTICE: Recognition of patients at risk for acquired LQTS is imperative in primary care practice. Currently, there are no practice guidelines that address acquired LQTS. In lieu of practice guidelines, the prudent NP uses physiology to guide treatment decisions, especially those decisions related to the use of drugs.