The treatment of the long QT syndrome

General principles of long QT syndrome (LQTS) management are presented first. The management of pause-dependent LQTS includes the following steps: A. recognition of torsades de pointes type of ventricular tachycardia and of the ecg warning signs, B. termination of the arrhythmia and the ecg warning signs by interventions which do not shorten the QT interval and by interventions which also shorten the QT interval. The management of adrenergic-dependent LQTS includes the following steps: A. individual risk stratification, B. avoidance of deleterious sympathetic stress, C. recognition of the arrhythmia and of the ecg warning signs, D. termination of the arrhythmia, E. prevention of relapses using beta-blockers, high left cervico-thoracic sympathectomy, permanent pacemakers and automatic implantable cardioverter-defibrillators.     

Long QT 1 mutation KCNQ1A344V increases local anesthetic sensitivity of the slowly activating delayed rectifier potassium current

BACKGROUND: Anesthesia in patients with long QT syndrome (LQTS) is a matter of concern. Congenital LQTS is most frequently caused by mutations in KCNQ1 (Kv7.1), whereas drug-induced LQTS is a consequence of HERG (human ether-a-go-go-related gene) channel inhibition. The aim of this study was to investigate whether the LQT1 mutation A344V in the S6 region of KCNQ1, at a position corresponding to the local anesthetic binding site in HERG, may render drug insensitive KCNQ1 channels into a toxicologically relevant target of these pharmacologic agents. This may suggest that LQTS constitutes not only a nonspecific but also a specific pharmacogenetic risk factor for anesthesia. METHODS: The authors examined electrophysiologic and pharmacologic properties of wild-type and mutant KCNQ1 channels. The effects of bupivacaine, ropivacaine, and mepivacaine were investigated using two-electrode voltage clamp and whole cell patch clamp recordings. RESULTS: The mutation A344V induced voltage-dependent inactivation in homomeric KCNQ1 channels and shifted the voltage dependence of KCNQ1/KCNE1 channel activation by +30 mV. The mutation furthermore increased the sensitivity of KCNQ1/KCNE1 channels for bupivacaine 22-fold (KCNQ1wt/KCNE1: IC50 = 2,431 +/- 582 microM, n = 20; KCNQ1A344V/KCNE1: IC50 = 110 +/- 9 microM, n = 24). Pharmacologic effects of the mutant channels were dominant when mutant and wild-type channels were coexpressed. Simulation of cardiac action potentials with the Luo-Rudy model yielded a prolongation of the cardiac action potential duration and induction of early afterdepolarizations by the mutation A344V that were aggravated by local anesthetic intoxication. CONCLUSIONS: The results indicate that certain forms of the LQTS may constitute a specific pharmacogenetic risk factor for regional anesthesia.     

Implantable cardioverter defibrillator treatment in long QT syndrome patients: a national study on adherence to international guidelines

Objectives. Implantable cardioverter defibrillator (ICD) treatment is effective among long QT syndrome (LQTS) patients at a high risk of sudden cardiac death. Previous studies show that the international guidelines are not always followed, and that risk stratification may be based on genotype rather than individual risk profile. We analysed data from the Swedish ICD & Pacemaker Registry and medical records to examine how international guidelines were followed with regards to phenotype and genotype. Methods and results. ICD treatment was used in 150 Swedish LQTS patients from 1989–2013. The annual number of implantations increased over the study period. A total of 109 patients were included in the analysis. Most patients (91%) were symptomatic before the implantation. Seventy percent of patients who received ICD treatment met the 2006 Class I or Class IIa recommendations for LQTS treatment. Thirty-one percent of the LQT3 patients received ICD treatment despite being asymptomatic. Among LQT1 patients, 45% received ICD treatment after syncope despite beta-blockers. Conclusions. Thirty percent of Swedish LQTS patients with ICD received the treatment without a strong indication based on international guidelines. LQT3 patients were over-represented among asymptomatic patients. Many LQT1 patients received ICD despite the known effect of beta-blockers in this group.     

QT间期延长综合征与麻醉

QT间期延长综合征(long QT syndrome,LQTS)是由于离子通道变异,可引起致死性心律失常的一类疾病.围术期是LQTS的高危时期.此文总结了各种麻醉药物对QT间期的影响,以及LQTS患者围术期处理的注意事项,但尚不能确定最合理的麻醉方法,未来的研究应着重于手术期间的生理和药理对跨壁复极离散度的影响.     

Review and Management of the Dental Patient With Long QT Syndrome (LQTS)

Long QT syndrome (LQTS) is a unique cardiovascular condition, with both congenital and acquired forms that afflict patients. These patients show a lengthening of the repolarization phase of the cardiac cycle, which can be best visualized on an electrocardiogram (ECG). The ECG changes can include QT interval (the time between the start of the Q wave and the end of the T wave, as seen on an ECG) and T wave abnormalities, as well as progression to torsades de pointes and ventricular fibrillation. The ECG changes are most commonly elicited by physical activity, emotional stress, and certain medications. This condition represents a challenge for the oral and maxillofacial surgeon. Patients with LQTS must receive proper medical management and a controlled and anxiety-free surgical environment. The purpose of this article was to present a review of LQTS and provide recommendations for effective surgical management. Additionally, a case report of a patient with LQTS, treated by one of the authors, has been included.     

Long QT 1 Mutation KCNQ1A344V Increases Local Anesthetic Sensitivity of the Slowly Activating Delayed Rectifier Potassium Current

Background: Anesthesia in patients with long QT syndrome (LQTS) is a matter of concern. Congenital LQTS is most frequently caused by mutations in KCNQ1 (Kv7.1), whereas drug-induced LQTS is a consequence of HERG (human ether-a-go-go-related gene) channel inhibition. The aim of this study was to investigate whether the LQT1 mutation A344V in the S6 region of KCNQ1, at a position corresponding to the local anesthetic binding site in HERG, may render drug insensitive KCNQ1 channels into a toxicologically relevant target of these pharmacologic agents. This may suggest that LQTS constitutes not only a nonspecific but also a specific pharmacogenetic risk factor for anesthesia.

Methods: The authors examined electrophysiologic and pharmacologic properties of wild-type and mutant KCNQ1 channels. The effects of bupivacaine, ropivacaine, and mepivacaine were investigated using two-electrode voltage clamp and whole cell patch clamp recordings.

Results: The mutation A344V induced voltage-dependent inactivation in homomeric KCNQ1 channels and shifted the voltage dependence of KCNQ1/KCNE1 channel activation by +30 mV. The mutation furthermore increased the sensitivity of KCNQ1/KCNE1 channels for bupivacaine 22-fold (KCNQ1wt/KCNE1: IC50 = 2,431 +/- 582 [mu]m, n = 20; KCNQ1A344V/KCNE1: IC50 = 110 +/- 9 [mu]m, n = 24). Pharmacologic effects of the mutant channels were dominant when mutant and wild-type channels were coexpressed. Simulation of cardiac action potentials with the Luo-Rudy model yielded a prolongation of the cardiac action potential duration and induction of early afterdepolarizations by the mutation A344V that were aggravated by local anesthetic intoxication.     

Trauma associated with cardiac dysrhythmias: results from a large matched case-control study

BACKGROUND: Various cardiac dysrhythmias such as supraventricular and ventricular premature beats, supraventricular and ventricular paroxysmal tachycardia, atrial and ventricular fibrillation and atrial flutter have been reported in case series, as complications of blunt cardiac and thoracic trauma. The objective of this research was to determine whether thoracic or blunt cardiac injury is associated with cardiac dysrhythmia in a large multistate hospitalized population. METHODS: Cases and matched (by age) controls were identified based on hospital discharge information that was collected from 986 acute general hospitals across 33 states in 2001. Both the exposure (thoracic trauma and blunt cardiac injury) and the outcome (cardiac dysrhythmias) were identified based on ICD-9-CM discharge diagnoses. Unadjusted and conditional adjusted (for gender, race, length of stay, and primary source of payment) multivariate logistic regression analyses were performed. RESULTS: After adjusting for potential confounders, patients 50 years and younger diagnosed with blunt cardiac injury had a fourfold (95% confidence interval, 1.40-11.60) increase in the risk of cardiac dysrhythmia. Independent of potential confounding factors, discharge for blunt cardiac injury among patients 51 to 70 years old was associated with a twofold (95% confidence interval, 1.36-3.82) increased risk for cardiac dysrhythmia. CONCLUSION: Blunt cardiac injury was found to be a significant risk factor for cardiac dysrhythmia. Longitudinal studies are needed to better establish the association between trauma and cardiac dysrhythmias.     

Spinal anesthesia for Cesarean section in a parturient with long QT syndrome

PURPOSE: To report the first use of spinal anesthesia for Cesarean section (CS) in a parturient with a long QT syndrome (LQTS) and an automatic implantable cardiac defibrillator (AICD). Although both general and epidural anesthesia have been described for CS in patients with LQTS, there are no previous case reports on the use of spinal anesthesia. The clinical features, diagnosis, treatment and anesthetic management of LQTS are discussed. CLINICAL FEATURES: A 31-yr-old woman, gravida 2 para 1 known to have LQTS and an AICD, presented in labour at 35 weeks gestation, three weeks before her scheduled CS. Her previous delivery by CS under spinal anesthesia at our institution was uneventful. On this occasion, we elected to administer spinal anesthesia because she was asymptomatic (no arrhythmia or cardiac arrest) for the last few years, was hemodynamically stable, and had received uneventful spinal anesthesia before. CONCLUSION: Spinal anesthesia was used safely for CS in this parturient with LQTS.     

床旁心脏临时起搏对获得性长QT间期综合征伴尖端扭转型室性心动过速的干预研究

目的评价床旁心脏临时起搏对获得性长QT间期综合征（LQTS）伴尖端扭转型室性心动过速（TdP）患者的治疗作用。方法分析12例获得性LQTS伴TdP患者的临床资料、心电图、动态心电图和临床治疗情况,对常规治疗不能控制TdP发作的患者紧急行床旁心脏临时起搏。结果12例患者在常规治疗的基础上均成功完成床旁经股静脉心脏临时起搏,平均操作时间（10．5±2．4）min。与起搏前比较,起搏后QT间期和QTc间期均缩短[（0．42±0．03）S比（0．52±0．06）S,（0．43±0．04）s比（0．53．4±0．05）s],差异均有统计学意义（P〈0．05）;起搏前TdP发作（4．6．±1．2）次,d,起搏后TdP发作消失,平均起搏时间（3．8±1.4）d,停止起搏后QT间期和QTc间期分别为（0．41±0．02）S和（0．42±0．05）s,与起搏前比较,差异有统计学意义（P〈0．05）。出院后随访1年无TdP发作,QT间期和QTc间期分别为（0．41±0．06）8和（0．42±0．05）s。结论获得性LQTS患者伴TdP是一种危急的情况,常规治疗不能控制发作时,紧急床旁心脏临时起搏是一种安全有效的方法。     

Drug‐induced long QT syndrome and fatal arrhythmias in the intensive care unit

Long QT syndrome (LQTS) is a genetic or acquired condition characterised by a prolonged QT interval on the surface electrocardiogram (ECG) and is associated with a high risk of sudden cardiac death because of polymorph ventricular tachyarrhythmia called Torsade de Pointes arrhythmia. Drug‐induced LQTS can occur as a side effect of commonly used cardiac and non‐cardiac drugs in predisposed patients, often with baseline QT prolongation lengthened by medication and/or electrolyte disturbances. Hospitalised patients often have several risk factors for proarrhythmic response, such as advanced age and structural heart disease. Patients in the intensive care unit (ICU) are particularly prone to develop drug induced LQTS because they receive several different intravenous medications. Additionally, they might have impaired drug elimination because of reduced kidney and/or liver function, and also drug‐drug‐interactions. The clinical symptoms and signs of LQTS range from asymptomatic patients to sudden death because of malignant arrhythmias, and it is therefore important to recognise the clinical characteristics and typical ECG changes. Treatment of acquired LQTS is mainly awareness, identification and discontinuation of QT prolonging drugs, in addition to eventually supplement of magnesium and potassium. Overdrive cardiac pacing is highly effective in preventing recurrences, and antiarrhythmic drugs should be avoided. Recent data suggest that QT prolongation is quite common in ICU patients and adversely affects patient mortality. Thus, high‐risk patients should be sufficiently monitored, and the use of medications known to cause drug‐induced LQTS might have to be restricted.     

Anesthesia for patients with congenital long QT syndrome

Long QT syndrome is a malfunction of cardiac ion channels resulting in impaired ventricular repolarization that can lead to a characteristic polymorphic ventricular tachycardia known as torsades de pointes. Stressors, by increasing sympathetic tone, and drugs can provoke torsade de pointes, leading to syncope, seizures, or sudden cardiac death in these patients. Beta blockade, implantation of cardioverter defibrillators, and left cardiac sympathetic denervation are used in the treatment of these patients. However, these treatment modalities do not guarantee the prevention of sudden cardiac death. Certain drugs, including anesthetic agents, are known to contribute to QT prolongation. After reviewing the literature the authors give recommendations for the anesthetic management of these patients in the perioperative period.     

Manifestation of Long QT syndrome with normal QTc interval under anesthesia: a case report

Patients with congenital Long QT are known to have normal QT interval in symptom-free period and in the early years of life. Precipitating factors like surgical stress, interactions with anesthetic agents prolonging QT interval, and electrolyte imbalances can manifest with life threatening arrhythmias in congenital or acquired Long QT syndrome. We report a case of concealed LQTS manifesting under anesthesia and its subsequent perioperative course.     

Anesthesia for videoscopic left cardiac sympathetic denervation in children with congenital long QT syndrome and catecholaminergic polymorphic ventricular tachycardia – a case series

Objective: To describe our experience in the anesthetic management of pediatric patients who have undergone left cardiac sympathetic denervation (LCSD) for congenital long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Background: Long QT syndrome and CPVT predispose patients to ventricular arrhythmias and sudden death. One treatment option for these patients is LCSD. When these patients present for LCSD or other surgical procedures, anesthetic management is challenging, as many medications may exacerbate QT prolongation. Methods: Retrospective review of the electronic medical records of 22 pediatric patients who underwent LCSD between November 2005 and December 2008. Results: Six patients (27%) received midazolam as a premedication. Eleven patients (50%) underwent inhalation induction with sevoflurane. Eighty‐six percentage received either sevoflurane or isoflurane for maintenance of anesthesia, while the remaining 14% received a propofol infusion. Nine patients (41%) received esmolol infusions intraoperatively, while one patient (4.5%) received a labetalol infusion. Three patients (14%) received lidocaine infusions. No significant cardiac or other events occurred in any of these patients in the perioperative period. Conclusions: Important anesthetic considerations in this population include avoidance of sympathetic stimulation, correction of any abnormal electrolytes, and the immediate availability of a defibrillator and magnesium sulfate to treat arrhythmias. Anxious patients may benefit from premedication to reduce sympathetic tone. We have safely used both volatile agents and propofol for induction and maintenance of anesthesia. In our experience, intraoperative infusions of β‐blockers and lidocaine seem to be helpful in reducing arrhythmogenic potential, especially in patients with profound QT prolongation.     

Anesthesia for cesarean section in a patient with Holt-Oram syndrome

Holt-Oram syndrome is a rare genetic disorder affecting the heart and upper limbs (atriodigital dysplasia). The manifestations of the limb defects may vary in severity from subtle carpal bone defects and triphalangeal thumb to digit aplasia and upper extremity phocomelia. Cardiac abnormalities include atrial and/or ventricular septal defects, anomalies in pulmonary venous return and various dysrhythmias. We present the anesthetic management of a parturient with this syndrome who underwent elective cesarean section and tubal ligation, conducted under combined spinal-epidural anesthesia with a low dose of intrathecal bupivacaine. Our goal was to avoid an excessively high sympathetic block or excessive sympathetic stimulation accompanied by potential deleterious effects on cardiac rhythm. Cardiac monitoring was continued in the postoperative period for 6 h because of the possibility of dysrhythmia.     

Total intravenous anesthesia for repositioning an implantable defibrillator in a patient with long QT syndrome

We report the case of a 27-year-old woman with congenital long QT syndrome (LQTS) who was scheduled for surgery to reposition an implantable defibrillator. Given the risk of sudden death due to fatal ventricular arrhythmia, the woman required implantation of a defibrillator with pacemaker capability. Combined anesthesia-analgesia was used in order to minimize the risk of ventricular arrhythmia caused by increased serum concentrations of catecholamines. When cardioversion, defibrillation and anti-tachycardia functions had been deactivated, anesthesia was induced with propofol, fentanyl and rocuronium. Anesthesia was maintained with an infusion of propofol and remifentanil. We describe the pathophysiology and treatment of LQTS and discuss anesthetic management for repositioning a defibrillator in a patient with congenital LQTS.     

The effects of propofol and sevoflurane on the QT interval and transmural dispersion of repolarization in children

Prolongation of the QT interval is associated with torsades de pointes (TdP), especially in children or young adults with long QT syndromes. Susceptibility to TdP arises from increased transmural dispersion of repolarization (TDR) across the myocardial wall. Several anesthetic drugs prolong the QT interval, but their effect on TDR is unknown. TDR can be measured on the electrocardiograph (ECG) as the time interval between the peak and end of the T wave (Tp-e). We investigated the effects of propofol and sevoflurane on the corrected QT (QTc) and Tp-e intervals in 50 unpremedicated ASA physical status I-II children, aged 1-16 yr, who were randomized to receive propofol (group P) or sevoflurane (group S). Twelve-lead ECGs were recorded preoperatively and intraoperatively. Sevoflurane significantly prolonged the preoperative QTc; propofol did not. Neither anesthetic had any significant effect on the preoperative Tp-e. Sevoflurane increases the duration of myocardial repolarization in children to a larger extent than does propofol, but as the dispersion of repolarization appears unaffected, the risk of TdP is likely to be minimal with either anesthetic.     

Cardiac Arrest During Laparoscopic Roux-en-Y Gastric Bypass in a Bariatric Patient with Drug-Associated Long QT Syndrome

Obese patients often may demonstrate an acquired prolonged QTc interval due to alteration in cardiac physiology, electrolyte disturbances, and/or medication use. Intraoperatively, bariatric surgery may further contribute additional cardiac stressors to obese patients with long QT syndrome (LQTS). We present a case report of an obese woman with LQTS who underwent laparoscopic Roux-en-Y gastric bypass surgery and sustained an intraoperative cardiac arrest. We discuss identification, prevention, and treatment strategies for LQTS in the bariatric surgery patient.     

Sevoflurane-associated torsade de pointes in a patient with congenital long QT syndrome genotype 2

Although patients with congenital long QT syndrome (c-LQTS) are considered to be at high risk for anesthesia, few reports describe c-LQTS genotype-specific considerations for anesthesia. We describe a case of torsade de pointes (TdP) caused by sevoflurane in a patient with c-LQTS genotype 2 (LQT2). A 39-year-old woman diagnosed with c-LQTS was scheduled for an elective therapeutic abortion. Immediately after starting the operation, the patient developed TdP. Since pulseless ventricular tachycardia was sustained despite intravenous injection of lidocaine, defibrillation was performed. Analysis of the electrocardiogram revealed that the corrected QT interval before anesthesia was 530 ms and 2.0% sevoflurane markedly prolonged the corrected QT interval to 693 ms. Postoperative studies revealed a mutation in the KCNH2 gene. Anesthesiologists should note that patients with LQT2 could be more susceptible to volatile anesthetics than are those with other major genotypes. Genotype-specific management of anesthesia may reduce the risk of developing TdP during the perioperative period.     

Long QT interval syndrome with increased QT dispersion

This case report describes the anaesthetic management of a patient with sporadic-type long QT interval syndrome (LQTS), and increased QT dispersion, who presented for removal of an ovarian cyst. Beta adrenergic blockade and adequate depth of anaesthesia for successful management is emphasized. The Successful use of epidural administration of lignocaine and opioids in addition to general anaesthesia is described.     

The effects of droperidol and ondansetron on dispersion of myocardial repolarization in children

Objectives: To compare the effects of droperidol and ondansetron on electrocardiographic indices of myocardial repolarization in children. Aim: To refine understanding of the torsadogenic risk to children exposed to anti‐emetic prophylaxis in the perioperative period. Background: QT interval prolongation is associated with torsades des pointes (TdP), but is a poor predictor of drug torsadogenicity. Susceptibility to TdP arises from increased transmural dispersion of repolarization (TDR) across the myocardial wall, rather than QT interval prolongation per se. TDR can be measured on the electrocardiogram as the time interval between the peak and end of the T wave (Tp‐e). Tp‐e may therefore provide a readily available, noninvasive assay of drug torsadogenicity. The perioperative period is one of high risk for TdP in children with or at risk of long QT syndromes. Droperidol and ondansetron are two drugs commonly administered perioperatively, for prophylaxis of nausea and vomiting, which can prolong the QT interval. This study investigated their effects on myocardial repolarization. Methods: One hundred and eight ASA1‐2 children undergoing elective day‐case surgery were randomized to receive droperidol, ondansetron, both or neither. Pre‐ and post‐administration 12‐lead electrocardiogram (ECGs) were recorded. QT and Tp‐e intervals were measured and compared within and between groups, for the primary endpoint of a 25 ms change in Tp‐e. Results: Eighty children completed the study. There were no demographic or baseline ECG differences between groups. QT intervals lengthened by 10–17 ms after allocated treatments, with no between‐group differences. Values remained within normal limits for all groups. Tp‐e intervals increased by 0–7 ms, with no between‐group differences. There were no instances of dysrhythmia. Conclusions: Droperidol and ondansetron, in therapeutic anti‐emetic doses, produce equivalent, clinically insignificant QT prolongation and negligible Tp‐e prolongation, suggesting that neither is torsadogenic in healthy children at these doses.