Short QT syndrome

The short QT syndrome constitutes a new clinical entity that is associated with a high incidence of sudden cardiac death, syncope, and/or atrial fibrillation even in young patients and newborns. Patients with this congenital electrical abnormality are characterized by rate-corrected QT intervals<320 ms. Missense mutations in KCNH2 (HERG) linked to a gain-of-function of the rapidly activating delayed-rectifier current I(Kr) have been identified in the first two reported families with familial sudden cardiac death. Recently, two further gain-of-function mutations in the KCNQ1 gene encoding the alpha-subunit of the KvLQT1 (I(Ks)) channel and in the KCNJ2 gene encoding the strong inwardly rectifying channel protein Kir2.1 confirmed a genetically heterogeneous disease. The possible substrate for the development of ventricular tachyarrhythmias may be a significant transmural dispersion of the repolarisation due to a heterogeneous abbreviation of the action potential duration. The implantable cardioverter defibrillator is the therapy of choice in patients with syncope and a positive family history of sudden cardiac death. However, ICD therapy in patients with a short QT syndrome has an increased risk for inappropriate shock therapies due to possible T wave oversensing. The impact of sotalol, ibutilide, flecainide, and quinidine on QT prolongation has been evaluated, but only quinidine effectively suppressed gain-of-function in I(Kr) with prolongation of the QT interval. In patients with a mutation in HERG, it rendered ventricular tachycardias/ventricular fibrillation non-inducible and restored the QT interval/heart rate relationship towards a normal range. It may serve as an adjunct to ICD therapy or as a possible alternative treatment, especially for children and newborns.     

Kurzes QT-Syndrom

Short QT syndrome is a new genetic disorder associated with familial atrial fibrillation and/or sudden death or syncope. To date, different mutations in genes encoding for cardiac ion channels (KCNH2, KCNQ1, and KCNJ2) have been identified to cause the short QT syndrome. The mutations lead to a gain of function of the affected current (IKr, IKs, and IK1). The phenotype is characterized by a shortened QT interval<335 ms after correction for heart rate at rates<80 beats/min. Furthermore, the QT interval poorly adapts to heart rate. Patients exhibit shortened atrial and ventricular effective refractory periods and, in the majority, inducibility of ventricular fibrillation. Death occurs already in newborns. Therapy of choice seems to be the implantable cardioverter defibrillator because of the high incidence of sudden death. Pharmacological treatment has been studied and it could be demonstrated, that some mutant currents may be insufficiently suppressed by drugs targeted to block the specific current such as, e.g., sotalol or ibutilide in patients with a mutation in the IKr-coding gene KCNH2 (HERG). Quinidine proved to be efficient in prolonging the QT interval and normalizing the effective refractory periods in some patients.     

Short QT syndrome and atrial fibrillation caused by mutation in KCNH2

BACKGROUND: The short QT syndrome is a newly described clinical entity characterized by the presence of a short QT interval associated with cardiac tachyarrhythmias including sudden cardiac death at a young age in otherwise healthy individuals. A genetic basis has been identified linking the disease to mutations in KCNH2 in the familial forms and a mutation in KCNQ1 in a sporadic form of the disease. METHODS AND RESULTS: We identified a family with short QT syndrome with a high incidence of paroxysmal atrial fibrillation in their members and no known history of sudden cardiac death. QT interval ranged from 225 to 240 ms within normal heart rate ranges in the affected individuals. Programmed electrical stimulation (PES) was performed in all affected members, which revealed a remarkably short atrial and ventricular refractory period, and inducibility of atrial and ventricular fibrillation. Treatment with propafenone has maintained the individuals free of atrial fibrillation to date. Genetic analysis identified a missense mutation (C to G substitution at nucleotide 1764) which resulted in the amino acid change (N588K) in KCNH2. This mutation had been previously described in two other families with a high incidence of sudden cardiac death. CONCLUSIONS: Our study confirms that N588K is a hotspot for familial form of the short QT syndrome. The disease is clinically heterogeneous, as indicated by the fact that, in the three families with the same mutation, there is a wide range of symptoms, varying from atrial to ventricular fibrillation and sudden death. While the implantation of a defibrillator appears warranted due to the inducibility at PES, the clinical follow-up provides indication that the class Ic agent propafenone could be effective to prevent episodes of paroxysmal atrial fibrillation.     

短QT综合征的研究近况

短QT综合征是近来被认识的一种遗传综合征,以持续短QT间期、高的家族性心悸、晕厥、猝死和心房颤动发生率,缩短的有效不应期和电生理研究中诱发的心室颤动为特征。本文结合了近年来的临床研究,综述了短QT综合征的诊断标准、电生理特点、发病机制、临床表现、治疗方法以及有待于研究的问题。     

Short QT syndrome: mechanisms, diagnosis and treatment

Short QT syndrome is an inheritable primary electrical disease of the heart that was discovered in 1999. The disorder is characterized by an abnormally short QT interval (<300 ms) and a propensity to atrial fibrillation, sudden cardiac death or both. As in the case of long QT syndrome, more than one relevant genetic mutation has been identified that can lead to a short QT interval on electrocardiography; so far two have been identified. Shortening of the effective refractory period combined with increased dispersion of repolarization is the likely substrate for re-entry and life-threatening tachyarrhythmias. Thus far, 22 people have been classified as having short QT syndrome: 15 from the actual measurement of a short QT interval on electrocardiograms and 7 by history after they died from sudden cardiac death. Several cases, especially among children, have probably been overlooked, since the shortness of the QT interval becomes apparent only at heart rates less than 80 beats/min. The best form of treatment is still unknown, but prevention of atrial fibrillation has been accomplished by propafenone. Implantation of an implantable cardioverter defibrillator is recommended for prevention of sudden cardiac death.     

Short QT interval syndrome: a case report

Twelve-lead electrocardiograms revealed fine atrial fibrillation and a short QT interval (SQTI) (<300 milliseconds) with an average ventricular rate of 54/min in a 20-year-old male presented with exertional dyspnea. His echocardiographic evaluation revealed interatrial septal aneurysm and slightly dilated pulmonary artery. An electrophysiologic study revealed atrial fibrillation with a very high frequency, short ventricular effective refractory period (130 milliseconds) and ventricular fibrillation inducible with 3 short coupled extrastimuli. Signs were consistent with the rare SQTI syndrome. Although SQTI syndrome is associated with increased risk for sudden cardiac death, the patient was free of arrhythmia symptoms and denied any syncope or presyncope. Family history was also negative for sudden cardiac death and for any symptom suggestive of arrhythmia. The patient refused implantable defibrillator and was treated with anticoagulation and quinidine therapy.     

Short QT syndrome: pharmacological treatment

OBJECTIVES: The purpose of this study was to evaluate the efficacy of various antiarrhythmic drugs at prolonging the QT interval into the normal range and preventing ventricular arrhythmias in patients with short QT syndrome. BACKGROUND: Short QT syndrome is a recently described genetic disease characterized by short QT interval, high risk of sudden death, atrial fibrillation, and short refractory periods. METHODS: Six patients with short QT syndrome, five of whom had received an implantable cardioverter-defibrillator (ICD) and one child, were tested with different antiarrhythmic drugs, including flecainide, sotalol, ibutilide, and hydroquinidine, to determine whether they could prolong the QT interval into the normal range and thus prevent symptoms and arrhythmia recurrences. RESULTS: Class IC and III antiarrhythmic drugs did not produce a significant QT interval prolongation. Only hydroquinidine administration caused a QT prolongation, which increased from 263 +/- 12 ms to 362 +/- 25 ms (calculated QT from 290 +/- 13 ms to 405 +/- 26 ms). Ventricular programmed stimulation showed prolongation of ventricular effective refractory period to > or =200 ms, and ventricular fibrillation was no longer induced. CONCLUSIONS: The ability of quinidine to prolong the QT interval has the potential to be an effective therapy for short QT patients. This is particularly important because these patients are at risk of sudden death from birth, and ICD implant is not feasible in very young children.     

Short QT Syndrome

Short QT syndrome (SQTS) is an inheritable primary electrical disease of the heart, discovered in 1999. It is characterized by an abnormally short QT interval (<300 ms) and a propensity to atrial fibrillation and sudden cardiac death (SCD). Like in the case of long QT syndrome there is more than one genetic mutation that can lead to a short QT interval in the ECG and so far two have been identified. Shortening of the effective refractory period combined with increased dispersion of repolarization is the likely substrate for reentry and life threatening tachyarrhythmias. Only 22 people have been classified as having SQTS: 15 from the actual measurement of a short QT interval in their ECG and 7 by history, all having died from SCD. It is very likely that several cases, especially among children, have been overlooked, since the shortness of the QT interval only becomes apparent at heart rates <80 beats/min. The best form of treatment is still not known, but prevention of atrial fibrillation has been accomplished by propafenone, and an implantable cardioverter defibrillator is recommended for prevention of SCD.     

心脏离子通道病引起的晕厥

心脏离子通道病是近10年来被人们逐渐认识的一类原发性心电疾病,其病因是编码心肌细胞上各主要离子通道亚单位的基因突变导致相应通道功能异常。已明确的病种有长QT综合征、B rugada综合征、特发性心室颤动、儿茶酚胺敏感的多形性室性心动过速、短QT综合征、孤立性心房颤动、病窦综合征、心脏传导阻滞等,这些疾病可引起晕厥甚至猝死。本文综述了这类疾病的分子致病机制、诊断标准、临床表现及治疗。     

Arrhythmogenic hereditary syndromes: Brugada Syndrome, long QT syndrome, short QT syndrome and CPVT

In approximately 10-20% of all sudden deaths no structural cardiac abnormalities can be identified. Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome and catecholaminergic polymorphic ventricular tachyarrhythmias. Each of these cardiac channelopathies is charaterized by unique genetic and clinical features. The resting ECG and the ECG under exercise are pivotal for the diagnosis of ion channel diseases. Molecular genetic screening can reveal underlying mutations in a variable degree among the cardiac ion channel diseases in up to 70% (LQTS) and may identify individuals with incomplete penetration of the disease. In patients with primary electrical diseases specific clinical triggers for arrhythmic events such as syncope or sudden cardiac death have been identified including exercise, strenuous activity, auditory stimuli or increased vagal tone. The significance of programmed ventricular stimulation is at present unclear concerning risk stratification in patients with Brugada syndrome and short QT syndrome and of no significance in long QT syndrome and catecholaminergic polymorphic ventricular tachycardias. The success of medical therapy remains modest for prevention of sudden cardiac death and may necessitate the insertion of an implantable cardioverter. However, side effects with inappropriate therapies in this patient group with often young and active individuals have to be encountered. More insights into the arrhythmogenesis is critical for future development of effective medical treatment strategies.     

短QT综合征诊断与治疗

摘要：短QT综合征(SQTS)是以QT间期缩短为特征、与心源性猝死(SCD)相关、常伴有家族性心房颤动和(或)心室颤动,而心脏结构正常的离子通道疾病。目前已知7个致病基因,包括KCNH2、KCNQ1、KCNJ2、CACNAIC、CACNB2B、CACNA2D1及SCN5A基因,分别编码于钾通道、钙通道和钠通道亚单位。复极离散度增加和不应期的缩短被认为是SQTS心律失常的分子机制。SCD的一级和二级预防均推荐植入心脏复律除颤器。奎尼丁是有效的治疗药物。      

Lack of prognostic value of syncope in patients with Wolff-Parkinson-White syndrome

Syncope in patients with Wolff-Parkinson-White syndrome may be considered a premonitory event heralding the future development of sudden death. Therefore, the clinical and electrophysiologic data of 101 patients with Wolff-Parkinson-White syndrome referred for invasive evaluation of known arrhythmias were reviewed to assess the incidence and clinical relevance of syncope. Thirty-six patients reported the occurrence of one or more syncopal episodes (group 1) and 65 patients had no syncope (group 2). These two groups did not differ significantly with regard to age, gender, incidence and characteristics of arrhythmia, clinical history, frequency of arrhythmic events and presence of associated cardiac disease. There were 10 patients in group 1 and 12 in group 2 who had ventricular fibrillation. There were no statistical differences between the two groups with respect to the effective refractory period of the right atrium, atrioventricular node, accessory pathway and right ventricle. Furthermore, no differences between the two groups were noted with respect to cycle length of circus movement tachycardia, mean heart rate during atrial fibrillation, and minimum RR interval during atrial fibrillation. In addition, the accessory pathway location was not significantly different between group 1 and group 2. The occurrence of syncope could not be predicted from any electrophysiologic finding and this symptom had a low sensitivity and specificity for recognition of dangerous rapid heart rates. Furthermore, the prognostic value of syncope was less accurate and predictive than the shortest RR interval during atrial fibrillation and the anterograde effective refractory period of the accessory pathway for aborted sudden death occurrence.(ABSTRACT TRUNCATED AT 250 WORDS)     

短QT综合征的研究进展

短QT综合征是近年发现的一种遗传性心脏电生理疾病。目前已有5种与之相关的基因变异被确定:KCNH2(HERG)、KCNQ1、KCNJ2及CACNB2b和CACNA1C。临床表现主要有心房颤动、晕厥反复发作,甚至出现心脏性猝死,但也可无任何症状。     

A Primer on Arrhythmias in Patients with Hypertrophic Cardiomyopathy

Patients with hypertrophic cardiomyopathy are at risk of atrial and ventricular arrhythmias, yet treatment options for these patients are made almost solely by extrapolation from patients with other diseases. Heart block may be seen spontaneously but is especially prevalent following septal reduction strategies. Atrial fibrillation is the most common arrhythmia in patients with hypertrophic cardiomyopathy. The onset of atrial fibrillation often represents a turning point clinically for patients, marked by substantial functional deterioration and morbidity. Sudden cardiac death is the most common cause of death in the young patient, but still contributes to mortality in older patients. Major risk factors for sudden cardiac death include resuscitated sudden cardiac death, marked hypertrophy, syncope, and family history of sudden cardiac death due to hypertrophic cardiomyopathy. Minor risk factors for sudden cardiac death include nonsustained ventricular tachycardia, and hypotensive response to exercise. Emerging possible risk factors include atrial fibrillation, myocardial ischemia, left ventricular outflow tract obstruction, genetic mutations, left ventricular apical aneurysms, myocardial fibrosis, and end stage disease.     

Brief Review of the Recently Described Short QT Syndrome and Other Cardiac Channelopathies

There are many diseases related to ion‐channel disorders, so‐called “channelopathies.” Hereditary short QT syndrome is a clinical‐electrocardiographic entity with autosomal‐dominant mode of transmission and it is the most recently described channelopathy. The syndrome may affect infants, children, or young adults with strong positive family background of sudden cardiac death. Short QT syndrome is characterized by short QT and heart‐rate‐corrected QTc intervals. It is frequently associated with tall‐, peaked‐, and narrow‐based T waves that are reminiscent of the typical “desert tent” T waves of hyperkalemia. There is a high tendency for paroxysmal atrial fibrillation due to the heterogeneous abbreviation of action potential duration and refractoriness of atrial myocytes. The arrhythmia can also be induced by programmed electrical stimulation. The safest treatment suggested is an implantable cardioverter defibrillator, though the possibilities of inappropriate shocks have caused some concern, especially in teenagers. The ability of quinidine to prolong the QT interval has the potential to be an effective therapy for patients with short QT syndrome. This is particularly important in developing countries, where the implantable cardioverter‐defibrillator therapy is not always available. Since these patients are at risk of sudden cardiac death from birth, and implantable cardioverter‐defibrillator implantation has a lot of limitations in very young children, the utility of quinidine has to be evaluated further. Clinicians need to be aware of this deadly electrocardiographic (ECG) pattern as it portends a high risk of sudden cardiac death in otherwise healthy subjects with structurally normal hearts.     

Clinical investigation on the patients with tachyarrhythmic syncope with special reference to comparative study between long QT syndrome and ventricular tachycardia without long QT interval

The long QT syndrome (LQTS) is one of the important diseases that may lead to sudden death mainly in childhood, however etiology and pathogenesis are still poorly understood. The group studied consisted of 6 patients with a history of ventricular tachyarrhythmic syncope, 3 with long QT syndrome (LQTS) and 3 without long QT interval, and of 4 patients with ventricular tachycardia without syncopal episode. Their ages ranged from 5 years to 17 years. Histopathology of endomyocardial biopsy was nonspecific and mild in two cases but in one patient with LQTS, who had several episodes of syncope and refractory ventricular arrhythmia, remarkable subendocardial fibrosis, interstitial fibrosis and hypertrophy of myocytes were demonstrated. As far as ventricular tachycardia without long QT interval was concerned, in the patients with VT with syncope, histopathological abnormalities were more remarkable than in those without syncope. Electrophysiological findings in the patients with LQTS showed no characteristic findings, but only mild abnormalities with functional atrioventricular conduction disturbance on programmed atrial pacing. No inducible VT was demonstrated. Although electrophysiologic study and endomyocardial biopsy are of limited value, such studies are considered to be worthwhile for treating ventricular arrhythmias, and making a prognosis of the patients with tachyarrhythmic syncope and LQTS.     

心动过速终止后短暂心室复极异常和严重室性心律失常

目的 观察长时间心动过速终止后对心室复极和恶性室性心律失常发生的影响.方法 3例长时间心动过速(9 d～6个月)患者,两例为长时间发作室性心动过速(室速),其中1例为无休止性左心室特发性室速并诱发心动过速性心肌病;另1例为主动脉瓣换瓣术后5年发生束支折返性室速;第3例为持续性心房扑动伴心功能不良并因三度房室阻滞于10年前植入单腔起搏器.结果 3例患者在心动过速时并无晕厥和恶性室性心律失常发生,而在心动过速间隙或射频导管消融终止后均出现qr间期延长和恶性心律失常,其中1例持续心房扑动合并心力衰竭的患者最后死于多脏器功能衰竭;另两例室速射频导管消融治疗后1周QT间期逐渐恢复正常,分别随访20和39个月无室速和晕厥发作.结论 长时间心动过速后可导致短时间心室复极异常及恶性室性心律失常,应加强防范,防止发生心脏性猝死.     

Prolonged QT and cardiac arrest after heart transplantation: inherited or acquired?

The long QT syndrome is an inherited arrhythmogenic disease characterized by prolongation of QT interval, syncope, and sudden cardiac death because of ventricular tachycardia, mainly in the form of Torsades de Pointes. We present an unusual case of prolonged QT interval and cardiac arrest caused by Torsades de Pointes in the early phase after orthotopic heart transplant.     

The surdo-cardiac syndrome and therapeutic observations

First recognized in 1957, the surdo-cardiac syndrome includes congenital deafness, prolonged QT interval, and a high incidence of syncope and sudden death. Haemodynamic studies in two patients were normal except for an abnormal wave during left ventricular diastole probably related to abnormal left ventricular relaxation. The syncopal attacks are based on cardiac arrhythmias: both ventricular fibrillation and asystole may occur. Abnormal adrenergic stimulation of the heart is probably responsible. Propranolol appears to be effective in preventing the syncopal attacks. Artificial pacemaking provoked ventricular fibrillation in one patient and seems contraindicated.     

Prognostic significance of syncope in patients with Wolff-Parkinson-White syndrome

The prognostic value of syncope in symptomatic patients with Wolff-Parkinson-White syndrome (WPW) is unknown. Therefore, in order to evaluate the sensibility, specificity, positive and negative predictive value of syncope and compare those values with the one obtained for the shortest RR interval (less than or equal to 250 msec) as well as for the anterograde refractory period of the accessory pathway (less than 270 msec), we reviewed the clinical and electrophysiological data of 158 symptomatic patients with WPW. Fourty-eight patients (30%) reported at least one episode of syncope, and 24 out of 158 patients experienced an aborted sudden death, probably due to rapid conduction via the accessory pathway during atrial fibrillation. Syncope has poor sensibility but high specificity in recognizing an aborted sudden death. However, the syncope demonstrated it had a lower prognostic value when compared with other electrophysiological parameters in correctly identifying patients with a history of ventricular tachycardia and/or fibrillation. In conclusion, the data of this study propose the symptom "syncope" as a frequent event in the history of symptomatic patients with WPW referred to electrophysiological study. Generally its presence does not correctly identify patients who experienced an aborted sudden death. Furthermore, its prognostic value is significantly lower than a shorter RR interval (less than or equal to 250 msec) during atrial fibrillation and an anterograde effective refractory period less than 270 msec.