Dynamic Relationship Between the Q-aT Interval and Heart Rate in Patients with Long QT Syndrome During 24-Hour Holter ECG Monitoring

The purpose of this study was to investigate the dynamic relationship between heart rate and the Q-aT interval (the interval from the Q wave to the T wave apex) in patients with long QT syndrome. The QT to heart rate relation is useful for evaluating abnormalities of the ventricular repolarization, but its clinical application to the long QT syndrome requires accurate computer aided measurement of the QT interval and the sampling of a large number of beats. Therefore, the Q-aT interval was used on the basis of some reports that the heart rate dependency of the QT interval was concentrated in the Q-aT interval. Recent advances in the computer technology have allowed analysis of the relationship between the Q-aT and RR intervals on Holter ECG recordings. However, in addition to a prolonged QT interval, most patients with long QT syndrome have bizarre and variable T waves and the influence of this T wave morphology on the Q-aT to heart rate relation has not been clarified. We investigated the dynamic relationship between the Q-aT interval and heart rate in 10 patients with long QT syndrome and 11 control subjects using our original computer algorithm for the analysis of 24-hour Holter ECG recordings. The patients showed morphological T wave changes associated with heart rate changes during Holter recordings and these affected the Q-aT interval. The patients showed the following characteristics in the relationship between the major T wave peak and the RR interval: (1) a modestly decreased correlation between Q-aT and RR than in the control subjects (a median r value of 0.87 vs 0.93; P = 0.001); and (2) a steeper Q-aT/RR slope than in controls (a median slope of 0.24 vs 0.16; P < 0.05). Abnormal and variable T wave morphology in the long QT patients was closely related to a modestly decreased correlation between Q-aT and RR than in the control subjects. The steep Q-aT/RR slope might reflect unstable repolarization of the ventricle, which could act as a substrate for ventricular tachyarrhythmias.     

Neonatal Long QT Syndrome Type 3 Predicted by Positive Lidocaine Challenge

A female infant presented with bradycardia and an electrocardiogram demonstrating 2:1 atrioventricular depolarization, a prolonged QT interval, and T wave alternans. After propranolol therapy was initiated, a lidocaine challenge was performed with progressive shortening of the QT interval. This positive lidocaine challenge prompted clinical suspicion of long QT syndrome type 3 (LQT3) and early initiation of mexiletine therapy. Subsequent genetic testing confirmed the infant's diagnosis of LQT3. (PACE 2010; 33:377–379)     

Digital Holter measurement of QT prolongation in ziprasidone overdose

Objective. QT prolongation is an important complication in drug overdose, particularly with some antidepressants and antipsychotics. There are problems with the accurate measurement of the QT interval and determining for what QT interval patients should be monitored, because of the risk of torsades des pointes (TdP). We report a case of ziprasidone overdose with QT prolongation, demonstrating different methods of measuring the QT interval. Case report. A 47-year-old female presented after taking 1.2 g of ziprasidone and 250 mg of diazepam. She was taking propranolol and venlafaxine therapeutically. She developed bradycardia and QT prolongation (540 msec). She was transferred to a telemetry bed and observed for 48 h until her QT interval returned to normal (460 msec). QT intervals were extracted from (1) 12-lead digital Holter recordings (gold standard); (2) automated measurements on standard electrocardiograms (ECGs); and (3) manual measurements on standard ECGs, and compared on a QT versus time plot. An abnormal QT was determined based on the QT nomogram. Manual QT measurements showed a clear temporal association between ziprasidone overdose and a long QT, consistent with accurate QT measurements using continuous 12-lead Holter recordings with automatic QT measurements. However, standard automated measurements did not indicate an abnormal QT. Conclusions. Manual measurement of the QT interval appeared to be similar to the more accurate measurement of the QT by automated digital Holter recordings and better than standard automated measurements. Manual QT measurements would be more appropriate in clinical assessment of patients.     

Long QT syndrome

The long QT syndrome (LQTS) is characterized by prolongation of the QT interval, causing torsade de pointes and sudden cardiac death. This syndrome can be divided into idiopathic (congenital) and acquired forms. The idiopathic form is a familial disorder that can be associated with sensorineural deafness (Jervell and Lange--Nielsen syndrome, autosomal recessive) or normal hearing (Romano--Ward syndrome, autosomal dominant). The acquired form has a long QT interval caused by various drugs such as quinidine sotalol and dofetilide, also by noncardiovascular drugs such as antihistamine, antibiotics, antipsychotics and others. Also, the QT interval is prolonged by electrolyte abnormalities such as hypokalemia and hypomagnesemia, central nervous system lesions, significant bradyarrhythmias, cardiac ganglionitis, mitral valve prolapse and probucol. DNA variants appearing to predispose to drug-associated acquired long QT syndrome have been reported in congenital long QT.     

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.     

Long QT Syndrome Unmasked in an Adult Subject Presenting with Excited Delirium

Background

Excited delirium is increasingly recognized as a risk factor for sudden death, though the specific pathophysiology of these deaths is typically unclear.

Objectives

We describe a survivor of excited delirium that displayed a transient severe prolongation of the QT interval, suggesting unmasking of long QT syndrome as a possible mechanism of sudden death.

Case Report

A 30-year-old man was arrested by police for violent assaultive behavior. Officers at the scene noted confusion, nonsensical speech, sweating, and bizarre agitated behavior; he was transported to the Emergency Department for medical evaluation of possible excited delirium. His initial electrocardiogram revealed a markedly prolonged corrected QT interval of over 600 ms. Intravenous hydration and sodium bicarbonate were administered, with normalization of the QT; he was admitted and recovered uneventfully.

Conclusions

We discuss the possible association between long QT syndrome and unexplained sudden deaths seen with excited delirium. Sodium bicarbonate may be considered when long QT syndrome is identified during or after agitated delirium, though its routine use cannot be recommended based on a case report.     

Sudden arrhythmia death syndrome: importance of the long QT syndrome

In approximately 5 percent of sudden cardiac deaths, no demonstrable anatomic abnormality is found. Some cases are caused by sudden arrhythmia death syndrome. A prolonged QT interval is a common thread among the various entities associated with sudden arrhythmia death syndrome. A number of drugs are known to cause QT prolongation (e.g., terfenadine), as are hypokalemia, hypomagnesemia, myocarditis, and endocrine and nutritional disorders. Recently, attention has focused on a group of inherited gene mutations in cardiac ion channels that cause long QT syndrome and carry an increased risk for sudden death. Some of the highest rates of inherited long QT syndrome occur in Southeast Asian and Pacific Rim countries. The median age of persons who die of long QT syndrome is 32 years; men are predominately affected. In addition to a prolonged QT interval, which occurs in some but not all persons with long QT syndrome, another characteristic electrocardiographic abnormality is the so-called Brugada sign (an upward deflection of the terminal portion of the QRS complex). Most cardiac events are precipitated by vigorous exercise or emotional stress, but they also can occur during sleep. Torsades de pointes and ventricular fibrillation are the usual fatal arrhythmias. Long QT syndrome should be suspected in patients with recurrent syncope during exertion and those with family histories of sudden, unexpected death. Unfortunately, not all persons with long QT syndrome have premonitory symptoms or identifiable electrocardiographic abnormalities, and they may first present with sudden death. Beta blockers, potassium supplements, and implantable defibrillators have been used for treatment of long QT syndrome. Identifying the specific gene mutation in a given patient with long QT syndrome can help guide prophylactic therapy.     

Indapamide induced syncope in a patient with long QT syndrome

A 60-year-old woman who had been successfully treated with atenolol and cardiac pacing for hypertension and long QT syndrome developed recurrent episodes of palpitations and syncope. Several days prior to these episodes, indapamide 2.5 mg/day was taken for better control of hypertension. The episodes were associated with prolongation of QT interval and mild hypokalemia (3.1 MEQ/L). Indapamide was immediately stopped, but the QT remained prolonged 2 days later, although the potassium level was normalized. This case suggests that indapamide can cause potassium independent prolongation of the QT interval, resulting in arrhythmia induced syncope.     

Is Flecainide Dangerous in Long QT‐3 Patients?

Mutations of the cardiac sodium channel gene, SCN5A, are present in both long-QT and Brugada syndromes. Flecainide is used as a provocative test to unmask the electrocardiogram (ECG) phenotype of the Brugada syndrome, as well as long-term treatment for long QT-3 syndrome, since it shortens the QT interval. We report a case where oral flecainide induced syncope with a Brugada ECG pattern in a patient with known long QT-3 syndrome.     

Levofloxacin induced polymorphic ventricular tachycardia with normal QT interval

Polymorphic ventricular tachycardia (PVT) is a form of ventricular tachycardia characterized by QRS complexes that seem to change direction during the tachycardia. If associated with a prolonged QT interval, it is called torsades de pointes. In the absence of a congenital long QT syndrome, torsades is seen with certain drugs such as antiarrhythmic agents (Class IA, IC, III), psychotropic medications, antidepressants, antihistamines, and electrolyte disturbances. We report the first case of polymorphic ventricular tachycardia with normal QT interval associated with the oral use of levofloxacin in the absence of other etiologies known to cause these arrhythmias.     

Medikamentös induzierte Verlängerung des QT-Intervalls

Prolongation of the ventricular repolarisation manifests itself as a prolongation of the QT intervall on the surface ECG and represents a major risk for a special form of ventricular tachycardia called "torsades de pointes". Torsades de pointes are often self limited and are associated with palpitations, dizziness or syncope. Degeneration into ventricular fibrillation and sudden cardiac death can occur. In addition to the various forms of the congenital long QT syndrome many drugs, such as antiarrhythmic drugs class IA and III, antibiotics, antihistamines, antidepressants, and methadone are known to prolong the QT interval. Most of these drugs block a specific potassium channel substantially involved in the ventricular repolarisation. In addition, drug interaction or disturbances of drug metabolism may play a major role in the acquired form of the long QT syndrome. The individual risk and the potential of a pharmacologic substance to prolong the QT interval are not predictable. Certain risk factors identify patients at higher risk for drug-induced prolongation of the QT interval. Correctable factors include electrolyte disorders (e.g. hypokalemia) and concomitant administration of different QT prolonging drugs. External defibrillation is the therapy of choice in the hemodynamic unstable patient presenting torsades de pointes. In hemodynamic more stable patients application of intravenous magnesium can terminate torsades de pointes (membrane stabilizing properties). Temporary external or transvenous pacing at high heart rate might terminate incessant torsades de pointes by decreasing QT interval. Repeated ECG controls during therapy with QT prolonging drugs are mandatory, especially when drug doses are changed, additional drugs are prescribed, or in case of vomiting and diarrhea. QT prolongation in individual medical therapy is not always predictable. Therefore, updated lists of drugs with the potential of QT prolongation are available on the Internet (e.g. www.qtdrugs.org ).     

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.     

Torsades de pointes in congenital long QT syndrome following low-dose orphenadrine

We report the case of a woman, affected by congenital long QT syndrome (LQTS), who experienced three syncopal episodes shortly after the assumption of a low dose of orphenadrine. The ECG revealed a QT interval of 600 ms, and the corrected QT interval (QTc) was 537 ms. No structural cardiac disease was demonstrated by echocardiography. Orphenadrine treatment was discontinued. During the first 12 h of monitoring, three short-lasting, asymptomatic episodes of torsades de pointes occurred. No other sustained ventricular arrhythmia was revealed at Holter monitoring in the following days. During the ensuing 6 months, the patient remained asymptomatic, and the QTc did not change. Orphenadrine is an analogue of diphenhydramine, an antihistaminic drug that produces sodium channel blockade similar to that caused by quinidine and other Class Ia antiarrhythmic drugs. Our case rises the suspicion that orphenadrine could cause life-threatening arrhythmias in LQTS even at a low dose, and independently from concomitant assumption of potentially QT-prolonging drugs.     

Idiopathic polymorphic ventricular tachycardia with normal QT interval in a structurally normal heart

Polymorphic ventricular tachycardia (PVT) is a life-threatening arrhythmia that is typically related to long QT syndrome, organic heart disease, electrolyte abnormalities, cardiotoxic drugs, or adrenergic stimulation. A review of the literature reveals that PVT with normal QT interval and without underlying cause is quite rare. We report a case of idiopathic spontaneous PVT with structurally normal heart and without electrolyte abnormalities, drug reactions, or evidence of catecholamine induced arrhythmia. We also review the literature on the electrocardiographic characteristics and management of idiopathic PVT.     

The preclinical assessment of the risk for QT interval prolongation

Some drugs have been reported to induce severe ventricular arrhythmias, including torsades de pointes, and have been responsible in some cases for sudden death of patients. Although the mechanisms of these arrhythmias are not well understood, they are often, but not always, associated with QT interval prolongation. Regulatory authorities (CPMP in Europe) have recently pointed out the necessity to assess most carefully the potential, especially of non-cardiovascular drugs, for QT interval prolongation. Different methodological approaches are presented in this paper and experimental protocols are suggested; limitations and advantages of the presently available in vitro and in vivo models are discussed. It appears that both in vitro and in vivo approaches are complementary. In particular it is pointed out that only the in vitro models using isolated cardiac tissues (Purkinje fibres or papillary muscles) enable assessment of the drug properties under low cardiac rhythm conditions. This model allows us to mimic pathological situations of long QT interval (such as acquired or congenital long QT syndrome) in which most of the major clinical problems are encountered. Finally, a strategy for the preclinical assessment of the potential of a molecule for QT interval prolongation is presented.     

Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes

Macrolide antibiotics are known to have a different proarrhythmic potential in the presence of comparable QT prolongation in the surface ECG. Because the extent of QT prolongation has been used as a surrogate marker for cardiotoxicity, we aimed to study the different electrophysiological effects of the macrolide antibiotics erythromycin, clarithromycin, and azithromycin in a previously developed experimental model of proarrhythmia. In 37 Langendorff-perfused rabbit hearts, erythromycin (150-300 microM, n = 13) clarithromycin (150-300 microM, n = 13), and azithromycin (150-300 microM, n = 11) led to similar increases in QT interval and monophasic action potential (MAP) duration. In bradycardic (atrioventricular-blocked) hearts, eight simultaneously recorded epi- and endocardial MAPs demonstrated increased dispersion of repolarization in the presence of all three antibiotics. Erythromycin and clarithromycin led to early afterdepolarizations (EADs) and torsade de pointes (TdP) after lowering of potassium concentration. In the presence of azithromycin, no EAD or TdP occurred. Erythromycin and clarithromycin changed the MAP configuration to a triangular pattern, whereas azithromycin caused a rectangular pattern of MAP prolongation. In 13 additional hearts, 150 microM azithromycin was administered after previous treatment with 300 microM erythromycin and suppressed TdP provoked by erythromycin. In conclusion, macrolide antibiotics lead to similar prolongation of repolarization but show a different proarrhythmic potential (erythromycin > clarithromycin > azithromycin). In the presence of azithromycin, neither EAD nor TdP occur. This effect may be related to a rectangular pattern of action potential prolongation, whereas erythromycin and clarithromycin cause triangular action potential prolongation and induce TdP.     

Electrical alternans in long QT syndrome resembling a Brugada syndrome pattern

Isolated T wave alternans (repolarization alternans) is frequently associated with long QT syndrome. However, electrical alternans involving the P wave, QRS complex, ST segment (depolarization alternans), and the T wave is a rare finding. This report describes a 62-year-old woman with long QT syndrome and an electrical alternans occurring after previous syncope. Alternating QRS complexes showed a prolonged PR interval, a Brugada syndrome resembling pattern of the QRS complexes (elevation and downslope of the ST segments), and a T wave alternans. A genetic basis for the long QT syndrome has been ruled out by sequencing of all coding areas of the LQT genes. Potential mechanisms for the electrical alternans are discussed.     

Extreme QT prolongation during therapeutic hypothermia after cardiac arrest due to long QT syndrome

During therapeutic hypothermia, QT interval is prolonged. In patients with congenital long QT syndrome (LQTs), a longer QT interval was associated with significantly increased risk of cardiac arrest (CA). Therefore, therapeutic hypothermia may have proarrhythmic effects in survivors of CA due to congenital LQTs. A 27-year-old man was resuscitated from CA due to congenital LQTs type 3 and Brugada syndrome. Torsade de pointes (TdP) recurred spontaneously on admission (body temperature, 36.9°C). During mild hypothermia therapy, QTc increased from 499 (36.9°C) to 667 milliseconds (33.8°C), although TdP was not induced. A 13-year-old boy with congenital LQTs type 1 underwent therapeutic hypothermia after resuscitation. Short-acting β-blocker was administered intravenously during this treatment. The QTc increased from 534 (36.4°C) to 626 milliseconds (34.3°C). However, TdP did not recur during mild hypothermia therapy. In both patients, electrolyte abnormalities were checked frequently and corrected immediately. QT prolongation remained a couple of days after completion of rewarming. The withdrawal of sedative drugs and extubation were not pursued before QT shortening reached to a plateau. Both patients were fully recovered from neurologic damage. During therapeutic hypothermia, QT interval was extremely prolonged, although TdP did not recur in 2 patients with congenital LQTs. Therapeutic hypothermia may be beneficial for comatose survivors of CA due to LQTs.