What accounts for the high mortality of anorexia nervosa?

The exact medical complications, leading to the well-known high risk of death in patients with anorexia nervosa (AN), remain elusive. Such deaths are often abrupt with no satisfactory explanation. Suspected causes include cardiac QTc prolongation and, in turn, torsade de pointes (TdP). Psychotropic medications often prescribed to these patients are linked to QTc prolongation. AN is also presumed to cause heart failure due to malnutrition with increased susceptibility to QTc prolongation, and TdP, resulting in sudden cardiac death. Recent literature, however, is conflicting, and the likely cause of death may involve other cardiac abnormalities, such as low heart rate, abnormal heart rate variability, or increased QT dispersion. With an ongoing gap in research explaining the high mortality rate in AN, a compelling need to define the exact proximate causes of death in these patients remains. Because low serum potassium is the most common trigger for TdP, we postulate the early signal of sudden cardiac death, especially in patients with AN who purge, is hypokalemia. We also speculate that hypoglycemia could be a major factor in the sudden death of patients with AN as well as bradycardia or sinus arrest. A path forward to elucidate potential causes is offered.

Prolonged ST segment and T-wave alternans with torsade de pointes secondary to hypocalcemia due to hypoparathyroidism: A case report.

Hypoparathyroidism predisposes patients to hypocalcemia. Patients with hypoparathyroidism are thus at risk of electrocardiographic abnormalities, including T-wave alternans. T-wave alternans is poorly understood and lacks uniform diagnostic criteria. Its presence suggests myocardial electrical instability, and it has become an important sign for identifying patients at high risk of malignant arrhythmias and sudden cardiac death. We report a rare case of T-wave alternans with torsade de pointes due to hypocalcemia. The etiology of T-wave alternans may easily be overlooked. It should thus be thoroughly investigated to avoid misdiagnosis and poor outcomes.

QTc Prolongation and Risk of Torsades de Pointes in Hospitalized Pediatric Oncology Patients.

OBJECTIVE: To evaluate the prevalence of torsades de pointes and to identify risk factors associated with QTc prolongation of ≥500 milliseconds in hospitalized pediatric oncology patients. A QTc prolongation of ≥500 milliseconds is associated with higher mortality in hospitalized adults but has not been demonstrated in pediatrics. STUDY DESIGN: A single-center, retrospective review of all hospitalized oncology patients ≤21 years of age was performed from 2014 to 2016. Patients with long/short QT syndrome or a QRS interval of ≥120 ms were excluded. Rapid response events were reviewed to determine the prevalence of torsades. In patients with ECGs for review, data were compared between patients with a QTc of <500 and ≥500 ms via logistic regression. RESULTS: There were 1934 hospitalized patients included. Rapid response events occurred in 90 patients (4.7%) with 2 torsades events (0.1%). There were 1412 electrocardiograms performed in 287 unique patients (10.6 ± 6.3 years of age; 43% female). The mean QTc was 448 ± 31 ms; 25 patients (8.7%) had ≥1 ECG with a QTc of ≥500 ms. The prevalence of torsades was greater in patients with a QTc of ≥500 ms (8% vs 0%; P<.01). In multivariate analysis, factors associated with a QTc of ≥500 ms included female sex, (OR 2.95) and ≥2 QT-prolonging medications (OR, 2.95). CONCLUSIONS: The prevalence of torsades in hospitalized pediatric oncology patients was low (0.1%), although the risk was significantly greater in patients with a QTc of ≥500 ms. Routine monitoring of electrocardiograms and electrolytes is essential in patients with risk factors predisposing to QTc prolongation.

Management of anaphylaxis and allergies in patients with long QT syndrome: A review of the current evidence.

OBJECTIVE: To develop a treatment algorithm for patients with long QT syndrome (LQTS) in case they need antiallergic medications for allergic reactions, including asthma and anaphylaxis. DATA SOURCES: A literature review was performed to assess safety and to develop antiallergic treatment strategies for patients with LQTS. STUDY SELECTIONS: LQTS is a heterogeneous group of myocardial repolarization disorders characterized by prolongation of the QT interval that potentially results in life-threatening torsades de pointes tachycardia. Data on pharmacologic treatment in case of anaphylaxis in LQTS are sparse. For this narrative review, all currently available articles on the use of antiallergic drugs for allergic reactions, anaphylaxis, and asthma in patients with LQTS were used. RESULTS: Local allergic symptoms can be safely treated primarily with fexofenadine, levocetirizine, desloratadine, or cetirizine and, if needed, a short course of corticosteroids. In case of systemic symptoms, epinephrine should be administered. It may be less effective in patients with LQTS treated with ß-blockers, necessitating the use of glucagon as add-on treatment. In case of lower airway obstruction, ipratropium bromide should be used, but if not effective, inhaled ß2-adrenergic agents may be used. Continuous cardiac monitoring is indicated with the use of epinephrine and inhaled ß2-adrenergic agents. The use of the latter also warrants intense monitoring of serum potassium levels. Clemastine and dimetindene should be avoided in patients with LQTS. CONCLUSION: Patients with LQTS have a higher risk of life-threatening complications during the treatment of their allergic reactions because of the underlying disease and concomitant treatment with ß-blockers. Treatment algorithms will certainly decrease these complications.

Ankyrin-B syndrome: a case of sinus node dysfunction, atrial fibrillation and prolonged QT in a young adult.

Ankyrin-B protein is involved in regulating expression and localisation of cardiac ion channels and transporters. Mutations of the ANK2 gene in the rare condition Ankyrin-B syndrome result in loss of function of the ankyrin-B protein which in turn leads to abnormal regulation of intracellular sodium and calcium and a predisposition to cardiac arrhythmia including torsades de pointes. We describe a rare case of this condition characterised by sinus node dysfunction, atrial fibrillation and prolonged QT syndrome in a young patient with a family history of sudden death. The management of Ankyrin-B syndrome may include avoidance of QT prolonging medications, insertion of a permanent pacemaker for sinus node dysfunction, or a cardioverter defibrillator for those at high-risk of sudden death from torsades de pointes.

Prolonged QT: A rare cause of cardiac arrest.

A prolonged QT interval can be caused by medications, electrolyte abnormalities, or long QT syndrome, a genetic mutation that prolongs the action potential. Torsades de pointes is a potentially fatal polymorphic VT most often associated with prolonged QT interval. This article focuses on recognizing and treating drug-induced torsades de pointes.

Cardiac arrest and electrical storm due to recurrent torsades de pointes caused by concomitant clarithromycin, cotrimoxazole and amiodarone treatment.

Torsades de pointes (TdP) is a rapid, polymorphic and usually self-terminating ventricular tachycardia associated with the long QT syndrome. Many drugs may cause prolongation of QT interval and be the trigger for TdP occurrence. We present the case of 52-year-old male who was treated with clarithromycin due to bilateral atypical pneumonia. However, on the fourth day of hospitalization he deteriorated, developed pulmonary edema and short cardiac arrest. After successful resuscitation, unfortunately amiodarone and co-trimoxazole were given causing the arrhythmic storm which required many defibrillations. The case highlights the importance of careful QT measurement, appropriate TdP treatment and difficulties resulting from the patient's disagreement for invasive treatment. We think, that knowledge of drug-induced long QT syndrome and its consequences should be widely spread not only in cardiologists, but also in others doctors.

Incidences, risk factors, and clinical correlates of severe QT prolongation after the use of quetiapine or haloperidol.

BACKGROUND: Case reports suggest that quetiapine or haloperidol use is associated with severe QT prolongation (SQTP) and torsades de pointes. OBJECTIVE: The purpose of this study was to examine the incidences, risk factors, and outcomes of SQTP in quetiapine and haloperidol users. METHODS: This study accessed electronic medical records from a multicenter health-care hospital system in Taiwan and included patients who received quetiapine or haloperidol therapy and had both baseline and follow-up electrocardiograms. SQTP was defined as a posttreatment corrected QT (QTc) interval exceeding 500 ms or an increase in QTc interval of >60 ms compared with the baseline value. We analyzed the risk factors and outcomes of SQTP using multivariate logistic regression. RESULTS: Mean increases in QTc interval were +8.3 ± 51.8 and +8.9 ± 44.0 ms after the administration of quetiapine (n = 8832) and haloperidol (n = 2341). Among these users, 1149 (13.0%) and 333 (14.2%) developed SQTP, respectively. Common risk factors for SQTP included old age, heart failure, hypokalemia, amiodarone use, and baseline QTc interval. SQTP in quetiapine users was significantly associated with ventricular arrhythmias (odds ratio 2.84; 95% confidence interval 1.95-4.13) and sudden cardiac death (odds ratio 2.29; 95% confidence interval 1.44-3.66). CONCLUSION: More than 10% of patients receiving quetiapine or haloperidol therapy developed SQTP, and many of them were exposed to risk factors for SQTP. SQTP in quetiapine users was significantly associated with increased risks of ventricular arrhythmias and sudden cardiac death. Clinicians should be vigilant for ventricular arrhythmias in quetiapine users who have risk factors for SQTP.

Novel rare variants in congenital cardiac arrhythmia genes are frequent in drug-induced torsades de pointes.

Marked prolongation of the QT interval and polymorphic ventricular tachycardia following medication (drug-induced long QT syndrome, diLQTS) is a severe adverse drug reaction (ADR) that phenocopies congenital long QT syndrome (cLQTS) and is one of the leading causes for drug withdrawal and relabeling. We evaluated the frequency of rare non-synonymous variants in genes contributing to the maintenance of heart rhythm in cases of diLQTS using targeted capture coupled to next-generation sequencing. Eleven of 31 diLQTS subjects (36%) carried a novel missense mutation in genes with known congenital arrhythmia associations or with a known cLQTS mutation. In the 26 Caucasian subjects, 23% carried a highly conserved rare variant predicted to be deleterious to protein function in these genes compared with only 2-4% in public databases (P<0.003). We conclude that the rare variation in genes responsible for congenital arrhythmia syndromes is frequent in diLQTS. Our findings demonstrate that diLQTS is a pharmacogenomic syndrome predisposed by rare genetic variants.

Degenerating regenerating torsades de pointes.

Ventricular fibrillation (VF) commonly ends in death. Isolated case reports describe the uncommon occurrence of spontaneous termination of VF. Torsades de pointes (TdP), a peculiar form of polymorphic ventricular tachycardia associated with a prolonged QT interval on the surface electrocardiogram, most often spontaneously terminates and then returns to the underlying rhythm. Here, we present an unusual case of TdP degenerating into VF, reorganizing into TdP, and then spontaneously terminating. Our case suggests that the mechanisms underlying the maintenance of TdP and VF are not dissimilar. The precipitants to this event and the likely mechanisms operative are discussed.

Suppression of Torsades de Pointes by biventricular pacing in a patient with long QT syndrome.

This report describes a case of a patient with long QT syndrome (LQTS) with recurrent episodes of torsades de pointes (TdP). Use of biventricular pacing (BiVP) resulted in a shorter QT interval and a shorter T-peak-end interval and prevented further episodes of TdP. These findings suggest that BiVP may be helpful in patients with LQTS and refractory TdP.

Licorice-induced severe hypokalemia with recurrent torsade de pointes.

A 38-year-old obese woman presented with recurrent polymorphic ventricular tachycardia secondary to persistent hypokalemia necessitating more than 40 DC shocks. All endocrine investigations for hypokalemia were negative with impression of "mysterious hypokalemia." On repeated inquiry, a hidden history of licorice use was elicited causing persistent hypokalemia. The case highlights a life threatening complication of licorice use. In addition, it reiterates the importance of repeated history taking in a patient with undiagnosed hypokalemia and torsade de pointes which avoided a device therapy.

Torsade de pointes. A rare cause of syncope in severe aortic stenosis.

The evaluation of syncope in severe aortic stenosis usually requires intense work-up. Mechanical obstruction should not always be implicated as the underlying cause of syncope. Syncope at rest may be rarely associated with ventricular arrhythmias. We present a patient with severe aortic stenosis who experienced syncopal events due to torsade de pointes.

Double jeopardy.

Torsades de pointes ("twisting of points") (TdP) is a broad complex tachyarrhythmia which was first described in 1966 by Francois Dessertenne and usually results from prolongation of the QT interval.(1) A wide variety of drugs have been shown to prolong the QT interval in susceptible individuals.(2) We present the case of a former intravenous heroin user presenting with several episodes of TdP which were caused by QT prolongation due to methadone treatment and exacerbated by hepatitis B/C infection. Despite aggressive medical treatment and withdrawal of methadone, he had recurrent episodes of TdP which required continuous temporary cardiac pacing for six days. He was found to have moderate LV dysfunction on his echocardiogram and unobstructed coronary arteries on coronary angiography. He underwent implantation of a defibrillator due to concerns about further episodes of ventricular arrhythmias which could recur even in the absence of further methadone use.

Life-Threatening Cardiac Arrhythmias in a Case of Undetected Myxedema Coma: Importance of Early Detection and Medication Adherence.

BACKGROUND Myxedema coma is a rare, life-threatening condition caused by a severe form of hypothyroidism. The dangerously low levels of circulating thyroid hormone can lead to progressive mental status changes and numerous organ dysfunctions, including serious cardiac abnormalities. CASE REPORT We present a case of a 59-year-old woman who presented with altered mental status and fall who was originally thought to have a cerebrovascular accident but was later diagnosed with myxedema coma, after multiple cardiac arrests. It was discovered that the patient had not been taking any of her medications for the last several weeks, after her primary care provider retired from practice. Initial laboratory evaluation was significant for a TSH level of 159.419 mIU/L and an undetectable free T4 level. Complications of the myxedema coma resulted in QTC interval prolongation, causing torsades de pointes and sustained polymorphic ventricular tachycardia, requiring cardioversion. CONCLUSIONS This case demonstrates the importance of early detection and treatment of myxedema coma, as it can cause life-threatening cardiac arrhythmias. It also emphasizes the need to ensure proper medication adherence in patients with chronic medical conditions, as non-compliance can result in dire consequences.

Coeliac axis thrombosis and acute hepatic failure in a patient with dilated cardiomyopathy.

We present the case of a female patient in her 40s who presented with jaundice, orthopnoea, paroxysmal nocturnal dyspnoea and bilateral pedal oedema. After extensive investigations, she was diagnosed with hepatic dysfunction, dilated cardiomyopathy (DCM) and coeliac axis thrombosis. Her case was further complicated with episodes of torsades de pointes due to metabolic disturbance, with consequent sudden cardiac arrest. In this case report, we explore the clinical features, pathophysiology and treatment of acute hepatic failure and coeliac axis thrombosis, secondary to DCM and alcoholic liver disease.

OTc prolongation and torsade de pointes ventricular tachycardia in a small dose voriconazole therapy.

Torsade de pointes (TdP) is a life-threatening arrhythmia that can result from long QT syndrome. Drug-induced QT prolongation is a potentially dangerous adverse effect of some drug combinations. A 34-year-old woman with history of nephrotic syndrome and rheumatic mitral valve disease was admitted to our Hospital because of high fever. The patient continued to be febrile until antifungal treatment was switched to voriconazole. The electrocardiogram demonstrated sinus tachycardia and a prolonged QTc interval of 580 ms. Patient was resuscitated with electrical cardioversion and had an emergent temporary pacemaker placed. We recommend careful monitoring for QTc prolongation and arrhythmia in patients who are receiving voriconazole, particularly those who have significant electrolyte disturbances.

Torsade de pointes in Kearns-Sayre syndrome.

A 47-year-old woman with Kearns-Sayre syndrome (KSS) and an implanted pacemaker for complete heart block was admitted to the intensive care unit following a cardiac arrest due to ventricular tachycardia (torsade de pointes) in the setting of QT prolongation. Complete heart blocks and ventricular tachycardia are implicated as mechanisms of sudden deaths in KSS; such patients may require pacemaker implantation and implantation of an automatic implantable cardioverter-defibrillator.

Prolonged QT Interval in Cirrhosis: Twisting Time?

Approximately 30% to 70% of patients with cirrhosis have QT interval prolongation. In patients without cirrhosis, QT prolongation is associated with an increased risk of ventricular arrhythmias, such as torsade de pointes (TdP). In cirrhotic patients, there is likely a significant association between the corrected QT (QTc) interval and the severity of liver disease, and possibly with increased mortality. We present a stepwise overview of the pathophysiology and management of acquired long QT syndrome in cirrhosis. The QT interval is mainly determined by ventricular repolarization. To compare the QT interval in time it should be corrected for heart rate (QTc), preferably by the Fridericia method. A QTc interval >450 ms in males and >470 ms in females is considered prolonged. The pathophysiological mechanism remains incompletely understood, but may include metabolic, autonomic or hormonal imbalances, cirrhotic heart failure and/or genetic predisposition. Additional external risk factors for QTc prolongation include medication (IKr blockade and altered cytochrome P450 activity), bradycardia, electrolyte abnormalities, underlying cardiomyopathy and acute illness. In patients with cirrhosis, multiple hits and cardiac-hepatic interactions are often required to sufficiently erode the repolarization reserve before long QT syndrome and TdP can occur. While some risk factors are unavoidable, overall risk can be mitigated by electrocardiogram monitoring and avoiding drug interactions and electrolyte and acidbase disturbances. In cirrhotic patients with prolonged QTc interval, a joint effort by cardiologists and hepatologists may be useful and significantly improve the clinical course and outcome.

The genetics of drug-induced QT prolongation: evaluating the evidence for pharmacodynamic variants.

Drug-induced long QT syndrome (diLQTS) is an adverse effect of many commonly prescribed drugs, and it can increase the risk for lethal ventricular arrhythmias. Genetic variants in pharmacodynamic genes have been associated with diLQTS, but the strength of the evidence for each of those variants has not yet been evaluated. Therefore, the purpose of this review was to evaluate the strength of the evidence for pharmacodynamic genetic variants associated with diLQTS using a novel, semiquantitative scoring system modified from the approach used for congenital LQTS. KCNE1-D85N and KCNE2-T8A had definitive and strong evidence for diLQTS, respectively. The high level of evidence for these variants supports current consideration as risk factors for patients that will be prescribed a QT-prolonging drug.