Short QT syndrome: a case report and review of literature

The short QT syndrome has been recently recognised as a genetic ion channel dysfunction. This new clinical entity is associated with an incidence of sudden cardiac death, syncope, and atrial fibrillation in otherwise healthy individuals. The distinctive ECG pattern consists of an abnormally short QT interval, a short or even absent ST segment and narrow T waves. A 30-year-old resuscitated woman with short QT syndrome is described together with an example of the classic ECG characteristics. A short-coupled variant of torsade de pointes was reveal on Holter recordings. The implantable cardioveter defibrillator seems to be the therapy of choice to prevent from sudden cardiac death. Quinidine proved to be efficient in prolonging the QT interval and rendering ventricular tachyarrhythmias non-inducible in patients with a mutation in KCNH2 (HERG). Our preliminary data suggest amiodarone combined with beta-blocker may be helpful in treating episodes of polymorphic ventricular tachycardia for patients with an unknown genotype. Because the short QT syndrome often involves young patients with an apparently normal heart, it is imperative for physicians to recognize the clinical features of the short QT syndrome in making a timely correct diagnosis.     

Two cases of short QT interval

BACKGROUND: The epidemiology of short QT interval remains unclear. We attempted to determine the incidence and clinical characteristics of short QT interval in a longitudinal cohort study. METHODS: A total of 19,153 subjects (7,525 male, 11,628 female) were enrolled in the study and all available electrocardiograms (ECGs) were investigated longitudinally from 1958 through 2003. We defined short QT interval as QTc of less than 350 ms. RESULTS: Of the 19,153 subjects, two met the criteria of short QT interval and allowed for prevalence and incidence estimates for short QT interval as 0.01% and 0.39/100,000 person-years, respectively. Both cases had neither a family history of sudden cardiac death, nor a history of drug use that might have affected for QT interval. Case 1 was a female with history of ischemic heart disease. Case 2 was a 60-year-old male who exhibited a short QT interval for the first time when he was 26 years of age. He had sick sinus syndrome as an underlying heart disease. CONCLUSIONS: Of the 19,153 subjects in this study, none were identified as having the short QT syndrome, with associated high risk of ventricular tachyarrhythmia, atrial fibrillation, and sudden death. Two subjects were identified as having QTc of less than 350 ms, and allowed prevalence and incidence estimates to be made of short QT interval. There observations were suggestive of clinical relationships between short QT interval and organic or electrophysiological heart disease.     

Clinical characteristics and treatment of short QT syndrome

Short QT syndrome is a new inherited disorder associated with familial atrial fibrillation and/or sudden death or syncope. To date, three different mutations in genes encoding cardiac ion channels (KCNH2, KCNQ1 and KCNJ2) have been identified as causing short QT syndrome. All mutations lead to a gain in function of the affected current (IK(r), IK(s )and IK(1)). The syndrome is characterized in the few patients identified so far by a shortened QT interval of less than 300-325 ms after correction for heart rate at rates below 80 beats per minute. However, no boundary or limit for the QT interval can yet be determined, as more knowledge about this disease is still restricted to a small patient population. Furthermore, the QT interval lacks adaptation to heart rate. The majority of patients exhibit shortened atrial and ventricular effective refractory periods and inducibility of ventricular fibrillation. Death already occurs in newborns, so the short QT syndrome may also account for deaths classified as sudden infant death syndrome. The therapy of choice in families with a history of sudden death or syncope seems to be the implantable cardioverter-defibrillator. Whether patients without a family history of sudden death or symptoms need a defibrillator cannot yet be answered, and requires further investigation. Pharmacologic treatment has only been investigated in patients with a mutation in KCNH2 (HERG), and it could be demonstrated that the mutant currents may be insufficiently suppressed by drugs that are targeted to block the specific current (e.g., sotalol or ibutilide) in patients with a mutation in the IK(r-)coding gene KCNH2 (HERG). Interestingly, in this specific patient population, quinidine proved to be efficient in prolonging the QT interval and normalizing the effective refractory periods. Implantable cardioverter-defibrillator therapy is associated with an increased risk of inappropriate therapies for T-wave oversensing, although this risk can be resolved by reprogramming implantable cardioverter-defibrillator detection algorithms.     

Dofetilide (Tikosyn): a new drug to control atrial fibrillation

Dofetilide, a new class III antiarrhythmic agent, selectively blocks a specific cardiac potassium channel, IKr, increasing the effective refractory period of the myocyte and thereby terminating reentrant arrhythmias. Given orally, it appears to effectively convert atrial fibrillation and atrial flutter to sinus rhythm and maintain sinus rhythm after conversion in appropriately selected patients. This paper reviews the pharmacology of dofetilide, the evidence of its effectiveness, and the appropriate precautions in using it. KEY POINTS: Dofetilide is generally well tolerated but like other class III drugs can cause torsades de pointes. The risk is dose-dependent and can be minimized by adjusting the dosage according to creatinine clearance and QT interval, by excluding patients with known risk factors for long QT syndrome and torsades de pointes, and by starting treatment in an inpatient monitored setting for the first 3 days. Unlike other antiarrhythmic agents, oral dofetilide did not increase the mortality rate in clinical studies in postmyocardial infarction patients or those with congestive heart failure at high risk for sudden cardiac death. Concomitant use of drugs that increase the plasma level of dofetilide is contraindicated; these include cimetidine, ketoconazole, trimethoprim-sulfamethoxazole, and verapamil.     

Dofetilide: a new class III antiarrhythmic agent

Dofetilide is a relatively new class III antiarrhythmic agent that selectively blocks the rapid component of the cardiac ion channel delayed rectifier current. This results in an increase in the action potential duration and effective refractory period of the myocyte, thereby terminating reentrant tachyarrhythmias and preventing their re-induction. Oral dofetilide is effective in the conversion of atrial fibrillation and flutter to sinus rhythm and in the maintenance of sinus rhythm after conversion. It is generally well tolerated but like other antiarrhythmic agents in its class, torsades de pointes may be induced as a consequence of therapy. This risk is minimized by dosage adjustment according to creatinine clearance and QT(c) interval, by selecting patients without known risk factors for torsades and by initiating treatment in a monitored hospital setting for the first 3 days. Unlike other antiarrhythmic agents, oral dofetilide did not increase mortality in patients with a recent myocardial infarction or congestive heart failure, hence its importance as an alternative medication for the pharmacological conversion of atrial fibrillation and flutter, and maintenance of sinus rhythm after conversion in patients at high risk of sudden death.     

Epicardial scar in a patient with no apparent heart disease

A 35-year-old man, who had an episode of aborted sudden cardiac death due to ventricular fibrillation, suffered from multiple storms of ventricular tachycardia (VT). Conventional cardiac examinations did not reveal any structural heart diseases, and he had been treated by an implantable cardioverter defibrillator since 2007. At the latest admission, epicardial but not endocardial voltage mapping revealed a small area of low voltage at the left ventricular (LV) postero-lateral wall where a delayed potential was recorded during sinus rhythm. Excellent pacemapping with a prolonged stimulus to QRS interval was obtained from the area, and a mid-diastolic potential was recorded during the VT. Radiofrequency application terminated the VT and any VT became noninducible after the ablation. In some patients diagnosed as LV-VT with no apparent heart disease, arrhythmogenic substrate may exist on the epicardial surface of the ventricle.     

Antiplatelet treatment for secondary prevention of acute ischemic stroke and transient ischemic attacks: mechanisms,choices and possible emerging patterns of use

Short QT syndrome is a new inherited disorder associated with familial atrial fibrillation and/or sudden death or syncope. To date, three different mutations in genes encoding cardiac ion channels (KCNH2, KCNQ1 and KCNJ2) have been identified as causing short QT syndrome. All mutations lead to a gain in function of the affected current (IK_r, IK_s and IK₁). The syndrome is characterized in the few patients identified so far by a shortened QT interval of less than 300–325 ms after correction for heart rate at rates below 80 beats per minute. However, no boundary or limit for the QT interval can yet be determined, as more knowledge about this disease is still restricted to a small patient population. Furthermore, the QT interval lacks adaptation to heart rate. The majority of patients exhibit shortened atrial and ventricular effective refractory periods and inducibility of ventricular fibrillation. Death already occurs in newborns, so the short QT syndrome may also account for deaths classified as sudden infant death syndrome. The therapy of choice in families with a history of sudden death or syncope seems to be the implantable cardioverter-defibrillator. Whether patients without a family history of sudden death or symptoms need a defibrillator cannot yet be answered, and requires further investigation. Pharmacologic treatment has only been investigated in patients with a mutation in KCNH2 (HERG), and it could be demonstrated that the mutant currents may be insufficiently suppressed by drugs that are targeted to block the specific current (e.g., sotalol or ibutilide) in patients with a mutation in the IK_r-coding gene KCNH2 (HERG). Interestingly, in this specific patient population, quinidine proved to be efficient in prolonging the QT interval and normalizing the effective refractory periods. Implantable cardioverter-defibrillator therapy is associated with an increased risk of inappropriate therapies for T-wave oversensing, although this risk can be resolved by reprogramming implantable cardioverter-defibrillator detection algorithms.     

Atrial fibrillation and recurrent ventricular fibrillation during hypokalemia in Brugada syndrome

A 41-year-old man with Brugada syndrome (BS) and no previous episodes of aborted sudden death or syncope referred to local emergency room for an episode of symptomatic atrial fibrillation. Blood chemistry results showed hypokalemia (2.9 mEq/L). The other parameters were within the normal range. After few minutes, an episode of ventricular fibrillation treated with biphasic DC shock 150 J occurred. In successive 2 hours, the patient experienced recurrent episodes of ventricular tachycardia and fibrillation. Each biphasic DC shock 150 J was effective to restore sinus rhythm. No further episodes occurred after normalization of serum levels of potassium. Before discharge, an implantable cardioverter defibrillator was inserted to prevent sudden cardiac death. Hypokalemia increases the risk of arrhythmic events in BS.     

Marked QT prolongation and torsades de pointes secondary to acute ischemia in an elderly man taking dofetilide for atrial fibrillation: a cautionary tale

Dofetilide has been shown to be effective and safe in maintaining sinus rhythm in patients with persistent atrial fibrillation and congestive heart failure. Because of serious side effects of an increase in the QT interval causing torsades de pointes, dofetilide must be initiated with close monitoring of the QT interval in an inpatient setting. However, little has been reported about conditions surrounding the change in QT interval after the steady state is achieved that may have implications in the safety and efficacy of the drug. We report marked QT prolongation and torsades de pointes in a setting of flash pulmonary edema resulting from acute myocardial ischemia in a patient who was being treated with dofetilide for atrial fibrillation. Our case reminds the clinicians that the adverse and proarrhythmic effects of dofetilide can occur due to changes in the arrhythmic substrate during acute severe ischemia.     

Beat-To-Beat Behavior of QT Interval During Conducted Supraventricular Rhythm in the Normal Heart

To assess beat-to-beat behavior of QT interval under different conditions, high resolution recordings and computerized beat-to-beat analysis of the electrocardiogram were performed at rest, during recovery after short exercise, and during atrial pacing. Beat-to-beat variations of QT interval during sinus rhythm at rest and after short exercise were measured in ten healthy men. In an additional three patients with supraventricular tachycardia, beat-to-beat QT changes were studied after abrupt sustained acceleration and deceleration of heart rate by atrial pacing. Beat-to-beat changes in RH interval at rest are followed by minimal changes of the QT interval. The measured proportional change of the QT interval compared with the change in HR interval (Δ QT/A BR) was 0.02. This value represents 10% of the value expected for QT changes from Bazett's formula. Following short exercise QT interval did not change for 15 seconds and reached a maximal value 30 seconds later as compared to the RR interval (192 vs 115 sees, P < 0.001). The steady state of the QT interval during sustained atrial pacing was achieved after 132, 135, and 133 seconds for pacing intervals of 600, 500, and 600 msec, respectively. Our data indicate a relatively slow adaptation of the QT interval to changes in heart rate.     

Management of atrial arrhythmias secondary to severe congenital heart disease with the Atrioverter

An atrial defibrillator was implanted in a patient with congenitally corrected transposition of the great arteries, associated cardiac abnormalities, and persistent atrial arrhythmias. During a 15-month follow-up, 14 of 20 spontaneous episodes of his arrhythmias were successfully treated with the device. Two of these episodes were converted to sinus rhythm during ambulatory use of the device. Successful use of the device required implantation of a third defibrillation lead in the persistent left-sided superior caval vein and rigid control of congestive heart failure. An atrial defibrillator may be a valid treatment option in patients with congenital heart disease crippled by atrial fibrillation.     

Asymptomatic ventricular fibrillation in continuous flow left-ventricular assist device

Left ventricular assist devices (LVADs) have increased survival for heart failure patients. Individuals with LVADs are a growing patient population with frequent complications and Emergency Department (ED) visits. A 50-year-old female presented to the ED due to a low flow alarm on her LVAD. Upon arrival in the ED she was noted to be in ventricular fibrillation. She was defibrillated with restoration to normal sinus rhythm and was started on amiodarone. An implantable cardiac defibrillator was placed during hospital admission. Amiodarone was continued as an outpatient. Patients with continuous flow LVADs can be in dysrhythmias including ventricular tachycardia and ventricular fibrillation and remain relatively asymptomatic. We present a rare case of a patient with an LVAD and ventricular fibrillation who was completely asymptomatic in the ED.     

The Prognostic Value of Right Atrium Monophasic Action Potential after Conversion of Atrial Fibrillation

Abstract. After conversion of atrial fibrillation right atrium monophasic action potentials have been recorded in 45 patients, using a bedside suction technique. In 30 patients who reached sinus rhythm after DC shock, a good correlation was, found between the duration of monophasic action potential and the sinus rhythm stability during a follow-up period of six months. In 8 patients still in sinus rhythm after six months and in 15 patients who reached sinus rhythm spontaneously, the duration of monophasic action potential was in the normal range. In 22 patients who relapsed into atrial fibrillation during the follow-up period, the maintenance of sinus rhythm was closely related with the duration of the monophasic action potential, which was shorter than in stable sinus rhythm. The duration of monophasic action potential after conversion of atrial fibrillation has a prognostic value for the maintenance of sinus rhythm, and when its duration is short a conservative treatment instead of repeated DC shocks may be considered.     

Nibentan in arresting acute atrial fibrillation: risk or benefit?

AIM: To study efficacy and safety of using a domestic anti-arrhythmic drug nibentan for arresting acute atrial fibrillation. MATERIAL AND METHODS: A total of 210 patients received nibentan in a dose 0.125 mg/kg dissolved in 20.0 ml of 0.9% sodium chloride solution by intravenous slow jet 3-min injection. In no response, the injection was repeated 20 min later. Nibentan injection was accompanied with continuous ECG monitoring, measurements of QT interval, arterial pressure. The criterion of efficacy was atrial fibrillation conversion into the sinus rhythm within 24 hours after injection of a total nibentan dose. RESULTS: Nibentan in a dose 0.125 mg/kg demonstrated high efficacy (91.9%) and sufficient safety (incidence of polymorphic ventricular tachycardia 2.4%) including patients taking other antiarrhythmic drugs. A basic marker of an electrophysiological effect of nibentan on the myocardium is a dynamic change in the interval QT which may serve a predictor of sinus rhythm reestablishment (in QT > or =480 ms) and of a risk to develop proarrhythmogenic complications (in QT > or =640 ms).     

伊布利特治疗预激综合征合并房颤患者的临床疗效观察

[目的]探讨伊布利特治疗预激综合征合并房颤的临床疗效.[方法]回顾性分析2017年2月至2019年6月本院收治的7例预激综合征合并房颤患者,所有患者均给予富马酸依布利特注射液治疗,所有患者在用药后均行预激旁道和(或)房颤射频消融术治疗.观察记录所有患者用药后窦性心律转复情况及手术情况.[结果]7例患者静脉注射伊布利特后...     

QT prolongation modifies dynamic restitution and hysteresis of the beat-to-beat QT-TQ interval relationship during normal sinus rhythm under varying states of repolarization

The analysis of cardiac electrical restitution (the relationship between an action potential duration and its preceding diastolic interval) has been used to predict arrhythmia liability. However, the procedure to measure restitution is invasive and disrupts normal physiological autonomic balance. Dynamic analysis of sequential beat-to-beat ECG data was used to study restitution under normal sinus rhythm and to quantify changes in temporal hysteresis with heart rate acceleration/deceleration during QT prolongation. Congenital long QT (LQT) 1 and LQT2 syndromes during sympathetic stimulation were modeled because of their association with increased risk of ventricular arrhythmia. Temporal heterogeneity and hysteresis of restitution were examined in the conscious dog under varying conditions of delayed repolarization using either the selective inhibitors of the slowly activating delayed rectifier potassium current (R)-2-(4-trifluoromethyl)-N-[2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]acetamide (L-768,673); the rapidly activating delayed rectifier potassium current (1-[2-(6-methyl-2-pyridyl)ethyl]-4-methyl-sulfonylaminobenzoyl)-piperidine (E-4031); or a combination of both at rest and during heart rate acceleration with sympathetic stimulation using isoproterenol challenges. Impaired repolarization with the combination of E-4031 and L-768,673 increased heterogeneity of restitution at rest 55 to 91%, increased hysteresis during heart rate acceleration after isoproterenol challenge by approximately 40 to 60%, and dramatically reduced the minimum TQ interval by 72% to only 28 ms. Impaired repolarization alters restitution during normal sinus rhythm and increases hysteresis/heterogeneity during heart rate acceleration following sympathetic stimulation. Thus, dynamic beat-to-beat measurements of restitution could lead to clinically applicable ECG obtained biomarkers for assessment of changes associated with arrhythmogenic risk.     

Intravenous amiodarone bolus for treatment of atrial fibrillation in patients with advanced congestive heart failure or cardiogenic shock

BACKGROUND: The clinical course of patients with advanced organic heart disease is often complicated by the occurrence of atrial fibrillation. Slowing the ventricular rate and, if possible, restoration of normal sinus rhythm is crucial but difficult in the state of decreased ventricular function. METHODS: We included 78 consecutive patients with atrial fibrillation and heart rate above 135 beats min(-1) in an observational, uncontrolled study in the coronary care unit of a tertiary care center. Thirty-nine patients suffered from advanced congestive heart failure, 26 patients had pulmonary edema, and 13 patients were in cardiogenic shock. All patients were treated with 450 mg amiodarone given as a single intravenous bolus through a peripheral venous access without further infusion. Ventricular heart rate and cardiac rhythm were measured within 30 minutes after drug administration. Cardiac rhythm was monitored for 24 hours. The site of venous access was examined 30 minutes after drug administration and every 6 hours until the needle was removed after a maximum of 48 hours. RESULTS: Twenty-five patients (32%) converted to normal sinus rhythm within 30 minutes. Another 15 (19%) reverted into sinus rhythm during the following 24 hours. Within 30 minutes after amiodarone administration, ventricular heart rate decreased significantly from 152 +/- 12 to 88 +/- 17 (p < 0.0001) beats min(-1) in patients who converted to sinus rhythm and from 157 +/- 14 to 98 +/- 16 beats min(-1) in patients who did not. The degree of reduction in heart rate was similar among patients presenting with exacerbated congestive heart failure, pulmonary edema, or cardiogenic shock. Systolic blood pressure decreased in two patients, from 115 to 80 mmHg and from 130 to 100 mmHg, but was reversible after 10 and 90 minutes respectively without specific intervention. No proarrhythmia or clinical relevant bradycardia was observed, and no inflammation detected at the site of venous access. CONCLUSIONS: Amiodarone, given as a single intravenous bolus through a peripheral vein rapidly reduced ventricular rate and was well tolerated in patients with atrial fibrillation, even in the presence of congestive heart failure and cardiogenic shock.     

Direct Current Application: Easy Induction of Ventricular Fibrillation for the Determination of the Defibrillation Threshold in Patients with Implantable Cardioverter Defibrillators

For the determination of the defibrillation threshold, the induction of ventricular fibrillation is mandatory. However, in severely damaged hearts it is sometimes difficult to induce ventricular fibrillation by rapid stimulation or alternating current. Only rapid nonclinical ventricular tachycardias may result, and their cardioversion threshold may be different from the defibrillation threshold. Therefore, it was the purpose of this study to test the potential of direct current (DC) application to rapidly induce ventricular fibrillation in patients with an implanted cardioverter defibrillator. The defibrillation threshold had to be determined in 13 patients (9 with coronary heart disease, 4 with dilative cardiomyopathy, ejection fraction 35%) during and 2 weeks after the implantation of a cardioverter defibrillator. DC was applied 37 times by a commercially available 9-V DC battery via a bipolar catheter for about 3 seconds. Ventricular fibrillation was induced 23 times (62%) and rapid nonclinical ventricular tachycardias were induced six times (16%). In one patient clinical ventricular tachycardia was observed. In seven instances (19%) sinus rhythm remained. In 12 of the 13 patients, ventricular fibrillation could be induced by DC. Thus, the induction of ventricular fibrillation by DC application may serve as an additional tool to induce ventricular fibrillation, determining the defibrillation threshold in implantable cardioverter defibrillator patients.     

Hemodynamic effects after conversion of arrhythmias

Systemic and coronary hemodynamic parameters were determined during an arrhythmia and immediately after a direct current transthoracic shock given in an attempt to convert the arrhythmia to a sinus mechanism. No anesthesia or drugs were administered between the two studies. 16 patients with atrial fibrillation converted to sinus rhythm and five did not. In two patients with atrial flutter and one with supraventricular tachycardia, the arrhythmia was corrected. The arrhythmia persisted in a single patient with ventricular tachycardia. Utilizing each patient as his own control, we compared statistically various hemodynamic parameters before and after the shock. In addition, the group of patients whose atrial fibrillation terminated was compared to the group treated in the same manner but in which the atrial fibrillation persisted. Pressures in the right side of the heart decreased in both groups so that the changes appeared to be caused by factors associated with the transthoracic direct current shock or the catheterization procedure. The differences between those with atrial fibrillation who converted to sinus rhythm as compared to those who did not were a decrease in heart rate, an increase in stroke volume, and an increase in cardiac efficiency. There was no immediate effect on the cardiac output or coronary blood flow.     

Defibrillation threshold and cardiac responses using an external biphasic defibrillator with pediatric and adult adhesive patches in pediatric-sized piglets

Before recommendations for using an automatic external defibrillator on pediatric patients can be made, a protocol for the energy of a biphasic waveform energy dosing needs to be determined that will allow ventricular defibrillation of 8 year olds while causing only a minimal amount of cardiac damage to infants. Pediatric- and adult-sized electrode patches were alternately applied to 10 isoflurane-anesthetized piglets weighing 3.8-20.1 kg to approximate the body weights of newborns to children < 8 years old. The defibrillation threshold (DFT) was determined for biphasic truncated exponential waveform shocks. Additional shocks, varying from the DFT to 360 Joules (J), were delivered during sinus rhythm or following 30 s of ventricular fibrillation (VF). The DFT was 2.4+/-0.81 and 2.1+/-0.65 J/kg for pediatric and adult patches, respectively (P = N.S.). The change in left ventricular (LV) dP/dt from baseline as a function of shock strength was significantly different at 1 and 10 s after shocks of increasing energy that were delivered in sinus rhythm, and 1, 10, 20, and 30 s after defibrillation shocks. There was no significant difference in LV dP/dt with increasing shock energy at 60 s with either patch size. The time to return of sinus rhythm, ST-segment deviation, and cardiac output were also not significantly different from baseline 60 s following shocks of up to 360 J delivered during sinus rhythm or VF with either patch. The same amount of energy delivered with a biphasic external defibrillator successfully defibrillated VF whether adult or pediatric patches were used. Cardiac rhythm and hemodynamic variables were unaltered at 60 s after shocks delivered at energies of up to 360 J. These data suggest that there is a substantial safety margin above a DFT strength shock for this biphasic waveform in piglets.