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.     

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.     

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.     

急性冠状动脉综合征患者的QT间期变异性与室性心律失常的相关性分析探讨

目的现已明确急性冠状动脉综合征（acute coronary syndrome，ACS）患者发生猝死与恶性室性心律失常密切相关，本文旨在探讨ACS患者QT间期变异性与发生室性心律失常的相关性。方法采用动态心电图分析54例ACS室性心律失常患者24h QT间期变异性。结果ACS室性心律失常患者24h QT间期变异性明显减低。结论ACS室性心律失常患者24h QT间期变异性较正常人明显减低，其发生心律失常的可能性将明显增加。     

心电图Tp-e/QT比值在预测心源性猝死及恶性心律失常中的意义

目的:探讨心电图T波峰末间期(Tp-e)比QT间期(Tp-e/QT)预测心源性猝死及恶性心律失常的意义。方法:收集我院2004年3月-2009年3月发生心源性猝死及恶性心律失常28例患者的完整资料,对其发生心源性猝死前同步12导联心电图Tp-e间期、QT间期及Tp-e/QT比值进行测量并统计分析。结果:猝死前60.71%患者心电图Tp-e/QT0.22,21.42%患者比值0.15,分布有一定规律性。结论:心电图Tp-e/QT对预测心源性猝死有一定价值。     

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.     

Fatal QT interval

A 21-year-old woman, without medical history, was admitted after cardiac arrest. Cardiopulmonary resuscitation and use of semiautomatic defibrillator quickly restored sinus rhythm. Clinical examination was normal with no cardiac murmur or abnormal heart sound. Electrocardiogram revealed sinus rhythm with short QT interval. Serum electrolytes and arterial blood gazes were normal. One hour after admission, lethal ventricular fibrillation occurred. Factors that shorten QT interval including increase in heart rate, hyperthermia, increased calcium, or potassium plasma levels and acidosis were excluded. Short-QT syndrome has been recently recognized as a genetic ion channel dysfunction leading to an abbreviation of action potential and a potential substrate for arrhythmias. This syndrome is characterized by a short QT interval (typically <320 milliseconds), associated with a high incidence of sudden death, syncope, or atrial fibrillation in individuals with an apparently normal heart. Implementation of an internal cardiac defibrillator remains the only effective preventive treatment.     

Electrocardiographic evaluation of cardiovascular status

The electrocardiogram (ECG) is indispensable for the diagnosis and management of patients with a wide variety of cardiac and noncardiac diseases. The purpose of this paper is focused on recent research that used ECG, specifically the long-QT interval and microvolt T wave alternans, for the evaluation of life-threatening ventricular arrhythmias. Although remaining to be validated, QT prolongation along with other emerging electrocardiographic indices such as T wave morphology, T peak-to-T end time, or beat-to-beat QT variability may be sensitive indicators of malignant polymorphic ventricular tachyarrhythmia, torsade de pointes. Microvolt T wave alternans may provide important information in identifying a low-risk group with left ventricular dysfunction who is unlikely to benefit from unnecessary prophylactic implantable cardioverter defibrillator therapy. These ECG markers have the potential to aid in the safe administration of individualized medications, avoidance of sudden cardiac death, and provision of a noninvasive strategy to identify patients who are most and least likely to benefit from expensive prophylactic implantable cardioverter defibrillator placement.     

Prolongation of the QT interval in palliative care patients

Prolonged QT interval on the electrocardiogram (ECG) is associated with an increased risk of cardiac arrhythmia and sudden death. Many drugs used in palliative medicine increase the QT interval and several have had their licenses withdrawn or severely restricted. The relative importance of prolonged QT interval will increase for palliative medicine physicians when dealing with patients with longer prognoses and especially cardiac disease. Given these safety concerns, the aim of this study was to determine the prevalence of a prolonged QT interval in palliative care patients who were not in the terminal stage and were referred to a specialist service. Of 300 patients, 47 (16%) had prolonged QTc but only two had QT >500ms. The presence of coexistent cardiac disease or high levels of serum alkaline phosphatase appear to be the clinical features most robustly associated with a prolonged QTc. Although prolonged QTc is relatively common in patients referred to a specialist palliative care service, severely prolonged QT is rare.     

Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome

Long QT syndrome (LQTS) is a heritable disease associated with ECG QT interval prolongation, ventricular tachycardia, and sudden cardiac death in young patients. Among genotyped individuals, mutations in genes encoding repolarizing K+ channels (LQT1:KCNQ1; LQT2:KCNH2) are present in approximately 90% of affected individuals. Expression of pore mutants of the human genes KCNQ1 (KvLQT1-Y315S) and KCNH2 (HERG-G628S) in the rabbit heart produced transgenic rabbits with a long QT phenotype. Prolongations of QT intervals and action potential durations were due to the elimination of IKs and IKr currents in cardiomyocytes. LQT2 rabbits showed a high incidence of spontaneous sudden cardiac death (>50% at 1 year) due to polymorphic ventricular tachycardia. Optical mapping revealed increased spatial dispersion of repolarization underlying the arrhythmias. Both transgenes caused downregulation of the remaining complementary IKr and IKs without affecting the steady state levels of the native polypeptides. Thus, the elimination of 1 repolarizing current was associated with downregulation of the reciprocal repolarizing current rather than with the compensatory upregulation observed previously in LQTS mouse models. This suggests that mutant KvLQT1 and HERG interacted with the reciprocal wild-type alpha subunits of rabbit ERG and KvLQT1, respectively. These results have implications for understanding the nature and heterogeneity of cardiac arrhythmias and sudden cardiac death.     

Continuous positive airway pressure treatment improves the QT rate dependence adaptation of obstructive sleep apnea patients

BACKGROUND: QT rate dependence is one of the major properties of ventricular repolarization, with its circadian and autonomic modulations. The alteration of cardiac autonomic tone occurring in obstructive sleep apnea syndrome (OSAS) patients could explain the altered rate-dependent adaptation of the myocardial repolarization. Thus, we postulated that dynamic alterations in QT interval adaptation could be ameliorated in OSAS patients under continuous positive airway pressure (CPAP) treatment. To assess ventricular repolarization features in patients with OSAS, we compared QT parameters and their dynamicities along RR intervals from 24-hour ECG. METHODS: The study groups consisted of 38 consecutive OSAS patients and 38 healthy age-matched subjects. The syndrome was confirmed for OSAS patients according to standard polysomnographic criteria (apnea plus hypopnea index: 56.9 +/- 28.4/h). A second polysomnography synchronized with 24-hour ECG Holter and realized under efficient CPAP therapy confirmed the control of sleep-related breathing disorder. RESULTS: QT length related to heart rate was found significantly altered in patients with OSAS compared with controls (QTend/RR slope: -0.126 +/- 0.031 vs -0.173 +/- 0.038; P < 0.01). This flattened relationship was significantly improved with the treatment of the OSAS (-0.151 +/- 0.051; P < 0.01 vs pretreatment status). There was no significant impact of CPAP therapy on ventricular ectopic activity as well as on static repolarization parameters (QT, RT, QTc, RTc) measured separately over daytime and nighttime. CONCLUSIONS: The prognostic implications of such findings and the protective role of CPAP treatment to prevent sudden cardiac death in OSAS need to be evaluated.     

Abnormalities of the electrocardiogram during hypoglycaemia: the cause of the dead in bed syndrome?

We have previously demonstrated that experimental hypoglycaemia in adults with type 1 diabetes causes an abnormal electrocardiogram (ECG), with increases in QT interval and dispersion. These abnormalities in cardiac repolarisation indicate a risk of ventricular tachycardia and sudden death in other conditions, including ischemic heart disease and congenital long QT syndrome. We have hypothesised that they could contribute to the dead in bed syndrome--the recently described sudden unexpected death in young people with type 1 diabetes--which occurs around three times more frequently than in those without diabetes. It is clearly impossible to explore the causes of a rare and fatal complication by direct observation. We have therefore explored the pathophysiology in a series of experimental studies involving non-diabetic subjects and surrogate endpoints. These have demonstrated that abnormal cardiac repolarisation occurs consistently during insulin-induced hypoglycaemia and that either potassium infusion or beta-blockade prevents increased QT dispersion but only partially prevents QT lengthening. The sympathoadrenal discharge induced by hypoglycaemia alters cardiac repolarisation by both direct and indirect (by reducing extracellular potassium) mechanisms. Other factors that might contribute to the clinical risk of cardiac arrhythmias during nocturnal hypoglycaemia include autonomic neuropathy. This is associated with prolonged QT interval in the non-hypoglycaemic state and has been proposed as a cause of sudden death in those affected. We have examined cardiac repolarisation during clamped hypoglycaemia in patients with type 1 diabetes, with and without autonomic neuropathy. Our data demonstrate lengthening of QTc (QT interval corrected for heart rate) during hypoglycaemia in all groups with no significant differences between the groups, suggesting that autonomic dysfunction does not contribute to hypoglycaemia-induced QTc lengthening in type 1 diabetes. Our hypothesis would be strengthened by demonstrating similar changes during clinical hypoglycaemia. We have recently completed studies in prepubescent children and adults that show modest but significant changes in QTc during nocturnal hypoglycaemia in both populations. We have also demonstrated that pre-treatment with beta-blocking agents prevents abnormal cardiac repolarisation during experimental hypoglycaemia. This has identified a possible treatment if we can identify patients at high risk. Further work is necessary to determine whether we can reliably identify patients who could be at special risk during hypoglycaemia and who might benefit from protection with agents such as beta-blockers. Sudden death in young people with diabetes is, thankfully, rare. However its consequences are so devastating that an excess risk of 3 to 4 times the non-diabetic population seems sufficient to warrant further investigation of the mechanisms that may cause it.     

Dilated Cardiomyopathy with Short QT Interval: Is It a New Clinical Entity?

Short QT syndrome is a rare autosomal dominant channelopathy of structurally normal hearts characterized by atrial fibrillation, ventricular arrhythmias, and sudden cardiac death. We report a case having short QT, dilated ventricles, and severe ventricular dysfunction, an unreported association so far.     

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 ).     

QT dispersion in essential hypertension

Increased QT dispersion is associated with sudden cardiac deathin congestive heart failure, hypertrophic cardiomyopathy, andfollowing acute myocardial infarction. Patients with hypertension,in particular those with left ventricular hypertrophy, are alsoat greater risk of sudden cardiac death. We examined whetherQT dispersion, which is easily obtained from a routine ECG,correlates with echo LVH. Sixty-nine untreated patients withessential hypertension had QT dispersion measured from a surface12-lead electrocardiogram, and twodimensional echocardiographyperformed to measure interventricular septal thickness, posteriorwall thickness, and left ventricular internal diameter. Officeblood pressure was recorded, and in 56 patients, 24 h ambulatoryblood pressure monitoring was also done. Multivariate analysisdemonstrated significant relationships between QT dispersionand office systolic blood pressure, and left ventricular massindex. Similar findings were obtained when QT dispersion wascorrected for heart rate (QTc dispersion). After patients withelectrocardiographic left ventricular hypertrophy (n = 5) wereexcluded from the analysis, the above relationships persisted.Increased QT dispersion is thus found in those essential hypertensivesat greatest risk of sudden death. Since this relationship persistseven in the absence of electrocardiographic left ventricularhypertrophy, measurement of QT dispersion might be a simple,non-invasive screening procedure to identify those hypertensivesat greatest risk of sudden death.     

Insights Into the Pathogenesis of Sudden Cardiac Death From Analysis of Circadian Fluctuations of Potential Triggering Factors

Sudden cardiac death continues to be a poorly understood event in terms of its underlying pathophysiological mechanisms. The observation of a circadian variability in the incidence of this catastrophic event with a prominent peak in the early morning hours provides an opporfunity to study triggering factors that may play a causative role in the genesis of sudden cardiac death. As reviewed in this article, there is convincing evidence that transient disturbances in autonomic tone and the resulting consequences may predispose the heart to increased electrical vulnerability. This evidence is based for instance on circadian fluctuations of spontaneous ventricular ectopic activity and transient ischemia, which may serve as trigger factors for the genesis of sustained ventricular tachyarrhythmias. Analysis of heart rate variability provides further evidence of reduced vagal and elevated sympathetic tone during the morning hours particularly in patients with compromised left ventricuiar function. Diurnal variations in ventricular repolarization as indicated by QT interval changes in the surface ECG also support the concept of triggering factors in the genesis of sudden cardiac death. Therapeutic measures aiming at a reduction in sympathetic input to the heart have been successful in preventing ventricular fibrillation and thus indicate the importance of unbalanced sympathetic tone in patients prone to sudden cardiac death.     

The electrocardiogram in the patient with syncope

Syncope is a common and challenging presentation for the emergency physician. Various investigators have developed clinical risk score and clinical decision rules which are designed to identify the population at highest risk for adverse events. In each of these clinical decision tools, the electrocardiogram (ECG) is one of the key clinical variables used to evaluate the patient. Certain electrocardiographic presentations in the patient with syncope will not only provide a reason for the loss of consciousness but also guide early therapy and disposition in this individual. Bradycardia, atrioventricular block, intraventricular conduction abnormality, and tachydysrhythmia in the appropriate clinical setting provide an answer to the clinician for the syncopal event. Morphologic findings suggesting the range of cardiovascular malady are also encountered; these entities are far ranging, including the various ST-segment and T-wave abnormalities of acute coronary syndrome, ventricular preexcitation as seen in the Wolff-Parkinson-White syndrome, Brugada syndrome with the associated tendency for sudden death, prolonged QT interval common in the diverse long QT interval presentations, and right ventricular hypertrophy suggestive of hypertrophic cardiomyopathy. This review discusses the ECG in the patient with syncope. The general use of the 12-lead ECG in this patient population is discussed. Furthermore, specific electrocardiographic presentations seen in the patient with syncope are also reviewed.     

Sudden cardiac death and obesity

For individuals and the society as a whole, the increased risk of sudden cardiac death in obese patients is becoming a major challenge, especially since obesity prevalence has been increasing steadily around the globe. Traditional risk factors and obesity often coexist. Hypertension, diabetes, obstructive sleep apnea and metabolic syndrome are well-known risk factors for CV disease and are often present in the obese patient. Although the bulk of evidence is circumstantial, sudden cardiac death and obesity share common traditional CV risk factors. Structural, functional and metabolic factors modulate and influence the risk of sudden cardiac death in the obese population. Other risk factors such as left ventricular hypertrophy, increased number of premature ventricular complexes, altered QT interval and reduced heart rate variability are all documented in both obese and sudden cardiac death populations. The present review focuses on out-of-hospital sudden cardiac death and potential mechanisms leading to sudden cardiac death in this population.     

Holter‐monitored sudden cardiac arrest after atrioventricular junction ablation

We present a case of sudden cardiac arrest 7 hours after radiofrequency ablation of the atrioventricular junction for symptomatic permanent atrial fibrillation unresponsive to medical therapy. The Holter monitoring revealed a progressive increasing of QT interval after the procedure, highlighting the repolarization instability after acute changes in heart rates associated with modification of ventricular activation, leading to occurrence of short coupling interval ventricular extra beats and finally to a “torsade de pointes.” This illustration underlines the need to program a relatively rapid ventricular rate first weeks after junction ablation, especially in case of rapid ventricular rate prior to the procedure, as well as the role of continuous ECG and QT interval monitoring during hospital stay.     

Congenital long QT syndrome: considerations for primary care physicians

Congenital long QT syndrome is an inherited disorder of cardiac repolarization that predisposes to syncope and to sudden death from polymorphic ventricular tachycardia. The disorder should be suspected when the electrocardiogram shows characteristic QT abnormalities, or when there is a family history of long QT syndrome or of an event that raises suspicion of long QT syndrome, such as sudden death, syncope, or ill-defined "seizure" disorder. We can now classify some types of congenital long QT syndrome according to their genetic mutations and their triggers, such as exercise, rest, or startle.