Methadone-induced torsades de pointes: a twist of fate

A case of methadone-induced torsades de pointes is presented to demonstrate clinical features that predispose patients to this serious cardiac arrhythmia. A patient who was receiving methadone maintenance treatment for heroin addiction presented to the hospital with dizziness and near-syncope. He was taking a relatively high dose of methadone but was not taking any concomitant cytochrome P450 inhibitor or QT-prolonging drugs. He had prolonged corrected QT interval, hypokalemia, and hypomagnesemia on admission and was later found to have severe left ventricular dysfunction. On admission to a telemetry unit, the patient experienced chest discomfort and palpitations with corresponding torsades de pointes that was terminated with correction of hypokalemia and hypomagnesemia. The corrected QT interval became shorter but remained profoundly prolonged until methadone was substituted with buprenorphine.     

Fibrillation atriale et allongement du QT sur hypomagnésémie secondaire à un traitement par inhibiteur de la pompe à protons

Proton pump inhibitors are widely prescribed but their long-term use can expose patients to adverse effects. Some of these are not very well known, including hypomagnesemia. Hypomagnesemia can be manifested by cardiac complications such as supraventricular arrhythmia or QT prolongation, increasing the risk of torsade de pointe. We present a case of atrial fibrillation triggered by severe hypomagnesemia secondary to proton pump inhibitor use and exacerbated by thiazide diuretic treatment. Conversion to sinus rhythm showed a prolonged corrected QT interval. We approach the pathophysiology and the electrophysiologic effects of hypomagnesemia.     

Torsade de Pointes Complicating the Treatment of Bleeding Esophageal Varices: Association with Neuroleptics, Vasopressin, and Electrolyte Imbalance

Torsade de pointes is an unusual life-threatening ventricular arrhythmia that has been associated with vasopressin, neuroleptic drugs, and electrolyte imbalances, including hypokaleniia and hypomagnesemia. Over a 9-month period, we observed torsade de pointes in three patients with cirrhosis and bleeding esophageal varices who did not have prior cardiac disease. All had received endoscopic sclerotherapy and continuous infusions of vasopressin and nitroglycerin. For sedation, two patients received haloperidol and one droperidol. In addition, two patients had either hypokalemia or hypomagnesemia. In all three patients, there was prolongation of the electrocardiographic QT interval and a "long-short" initiating sequence followed by ventricular tachycardia with torsade de pointes morphology. All were successfully cardioverted; there was one late death due to aspiration and septicemia. We conclude that cirrhotics with variceal hemorrhage may be at increased risk of developing this arrhythmia in the setting of treatment with vasopressin, sedation with neuroleptic drugs, and electrolyte abnormalities. We urge close monitoring of these patients for cardiac arrhythmia and recommend that neuroleptics be used cautiously, if at all.     

A case of torsade de pointes caused by hypomagnesemia

The author reports a case of a patient who had serious arrhythmia of the kind Torsade de pointes with hypomagnesemia as the only a abnormal parameter. This confirms previous reports and propose again a ion often forgotten in medical practice.     

急性心肌梗死时血清镁与心律失常关系的探讨

目的　探讨急性心肌梗死时血清镁与心律失常的关系。方法　回顾性分析１１２ 名ＡＭＩ患者于入院７２ 小时内行持续心电监护及心电图检查,并测血清镁。结果　心律失常组６１ 人中低镁血症４４ 人,心律正常组５１ 人中低镁血症１３ 人,两组有显著差别（ Ｐ＜ ０－０１） ,两组平均血镁浓度间亦有显著差异（ Ｐ＜ ０－０１） 。经补镁治疗的低血镁心律失常患者预后优于未予补镁者（ Ｐ＜ ０－０５） 。结论　ＡＭＩ并低镁血症比血镁正常者更易出现心律失常,早期监测血镁、及时补镁有利于心律失常的防治。     

Large goiter and multiple rib tumors

We report an interesting case of a 47-yr-old who had a large goiter and multiple rib tumors. The patient was initially suspected of having thyroid cancer, which had metastasized on the ribs, based on imaging studies. However, laboratory tests revealed a high level of ionized calcium and parathyroid hormone (PTH). The large goiter was diagnosed as having parathyroid tumors owing to the high level of PTH in the tissue fluid. The biopsy specimen from a rib tumor was diagnosed as containing brown tumors associated with primary hyperparathyroidism (PHP). The patient also had prolactinoma and pancreatic gastrinoma. Her daughter had both prolactinoma and PHP, and her brother and her father had PHP. Thus, the patient was diagnosed as having multiple endocrine neoplasia type 1.     

Is hypomagnesemia arrhythmogenic?

An understanding of the role of magnesium in cardiac conduction is complicated by the multiplicity of intracellular events coordinated by the magnesium ion. Several reports have cited magnesium deficiency as the cause of a variety of ventricular and supraventricular arrhythmias. On further inspection, the circumstances of each report strongly suggest the coexistence of significant potassium depletion; isolated hypomagnesemia as a cause of arrhythmia is not reported. This discussion brings together new data from basic science with that of clinical research to refute the suggestion that isolated hypomagnesemia is arrhythmogenic. However, there is sufficient evidence to indicate that hypomagnesemia will significantly exacerbate the proarrhythmic effect of hypokalemia, particularly if occurring in the presence of digoxin toxicity. Potassium and magnesium depletion are commonly concomitant, and simultaneous repletion of both ions in the presence of hypokalemia-induced arrhythmia would be both logical and effective. The beneficial effects of intravenous magnesium in the acute control of ventricular tachyarrhythmia are concluded to occur as a result of a separate antiarrhythmic action, quite independent of underlying magnesium balance.     

Torsade de pointes: the long-short initiating sequence and other clinical features: observations in 32 patients

The clinical setting, precipitating factors, electrocardiographic features and response to treatment of 32 patients with torsade de pointes were reviewed. Thirty-one patients had underlying cardiac disease and 30 patients had a previous underlying cardiac arrhythmia. Antiarrhythmic medications, often in association with electrolyte abnormalities (such as hypokalemia and hypomagnesemia) were the most common precipitating factors. In 22 of 26 patients, the serum drug levels of the antiarrhythmic agents were found to be within the therapeutic range. However, before the administration of agents known to prolong the QT interval, 20 of the 32 patients had, either alone or in combination, baseline prolongation of the QT interval, hypokalemia or hypomagnesemia. All patients had QTc interval prolongation (mean 0.59 second) immediately before the development of torsade de pointes. Marked lability of T wave morphology was frequently noted. Cardiac pacing was the only consistently effective mode of therapy. A characteristic long-short ventricular cycle length as the initiating sequence was found in 41 of 44 episodes of torsade de pointes. Reported data support the high frequency of this electrocardiographic feature of torsade de pointes in which its onset could be analyzed. It is suggested that this electrocardiographic characteristic will aid in both establishing the diagnosis of torsade de pointes and distinguishing it from other polymorphic forms of ventricular tachycardia.     

Primary hyperparathyroidism as the leading symptom in a patient with a Y791F RET mutation.

Primary hyperparathyroidism (PHP; serum calcium 2.75 mmol/L, PTH 226 pg/ml) had been the first clinical manifestation of MEN-2A in a female patient (aged 55 years) with a mutation (Y791F, TAT-->TTT) in exon 13 of the RET proto-oncogene. The patient has a pentagastrin-induced rise in serum calcitonin (up to 57 pg/ml) considered normal for noncarriers but abnormal in family members of MEN-2 patients. This is the first case of MEN-2 due to this specific mutation with primary hyperparathyroidism as the first manifestation of the disease. In addition, the patient harbored, within the Menin gene, a polymorphism (D418D) reportedly associated with sporadic primary hyperparathyroidism. This case report indicates that molecular biological tests in MEN- 2 may only suggest a certain phenotype but cannot predict it with certainty. It may also suggest that genetic screening for MEN-2 may be advisable in patients with primary hyperparathyroidism and a borderline-high pentagastrin stimulation test, even in the absence of a positive family history.     

Cardiac arrhythmias in the intensive care unit

Cardiac arrhythmias are a common problem encountered in the intensive care unit (ICU) and represent a major source of morbidity. Arrhythmias are most likely to occur in patients with structural heart disease. The inciting factor for an arrhythmia in a given patient may be an insult such as hypoxia, infection, cardiac ischemia, catecholamine excess (endogenous or exogenous), or an electrolyte abnormality. Management includes correction of these imbalances as well as medical therapy directed at the arrhythmia itself. The physiological impact of arrhythmias depends on ventricular response rate and duration, and the impact of a given arrhythmia in a given situation depends on the patient's cardiac physiology and function. Similarly, urgency and type of treatment are determined by the physiological impact of the arrhythmia as well as by underlying cardiac status. The purpose of this review is to provide an update regarding current concepts of diagnosis and acute management of arrhythmias in the ICU. A systematic approach to diagnosis and evaluation will be presented, followed by consideration of specific arrhythmias.     

Drug Therapy For Torsade de Pointes

Torsade de Pointes. Torsade de pointes is an uncommon and unique type of ventricular tachycardia. It differs from other forms of ventricular tachycardia by its morphological features, underlying mechanism, and modes of therapy. Recognizing torsade de pointes is of major clinical importance, as standard antiarrhythmic regimens might not only be ineffective in abolishing this life-threatening arrhythmia but may aggravate it. Torsade de pointes is most commonly precipitated by QT prolonging drugs, mainly type IA antiarrhythmic therapy such as quinidine and disopyramide, and other antiarrhythmic agents are reported to cause torsade de pointes as well. Predisposing factors known to increase the likelihood of developing torsade de pointes are: electrolyte imbalance (hypokalemia, hypomagnesemia, or both) and slow heart rate induced either by sinus bradycardia or heart block. Treatment of torsade de pointes is aimed at shortening the QT interval. By acceleration of the heart rate, the QT interval is shortened, thus preventing the recurrence of the arrhythmia. Treatment of torsade de pointes includes: isoproterenol infusion, cardiac pacing, and intravenous atropine. Intravenous magnesium sulfate, a relatively new mode of therapy for torsade de pointes, was proven to be extremely effective and is now regarded as the treatment of choice for this arrhythmia.( Cardiovasc Electrophysiol, Vol. 4, pp. 206–210, April 1993 )     

After more than 300 defibrillation shocks,patient still alive 12 years later refractory torsade de pointes due to polypharmacy and persistent vomiting

Acquired torsade de pointes ventricular tachycardia (TdP) is a rare but serious life-threatening arrhythmia caused by an array of cardiac and non-cardiac drugs. It is often refractory to pharmacological therapy and may result in death or require frequent defibrillations. In our case study a young female patient with no underlying heart disease developed very frequent sustained TdP requiring frequent defibrillations without which she would have certainly died. The ventricular arrhythmia in this patient was of multifactorial origin – cisapride, drug–drug interaction and persistent vomiting resulting in electrolyte disturbance and malnutrition. The patient survived after more than 300 defibrillation shocks over a period of 5 days and she is still alive 12 years later.     

Primary hyperparathyroidism in a patient with systemic lupus erythematosus

Primary hyperparathyroidism (PHP) is a metabolic illness that results from autonomous secretion of parathyroid hormone and is one of the most common causes of hypercalcemia. We present the case of a 47-year-old female with a previous diagnosis of systemic lupus erythematosus (SLE) in whom clinical (diffuse bone pain, emotional lability, jaw tumor) and laboratory features (calcium= 13.5 mg/dL, phosphate= 1.8 mg/dL, alkaline phosphatase= 3028 U/L, PTH intact= 1472 pg/dL) prompted the diagnosis of PHP secondary to parathyroid adenoma as demonstrated by the anatomopathology. After treatment with calcitonin spray 400 UI per day, IV pamidronate 90 mg/week, and subtotal parathyroidectomy, the patient status improved with normal laboratory tests. This is the second report to describe the coexistence of these two disorders in a single patient. Although the pathophysiology of the association of PHP and SLE is not known, the recognition of this association has a practical implication since the therapeutical strategy is completely different.     

Total gastrectomy for severe proton pump inhibitor-induced hypomagnesemia in a MEN1/Zollinger Ellison syndrome patient

We report here the first case of life-threatening hypomagnesemia in a Zollinger-Ellison syndrome patient with multiple endocrine neoplasia type 1 (MEN1) syndrome. The severe symptomatic hypomagnesemia proved to be due to proton pump inhibitors (PPIs), but withdrawal of PPIs led to early severe peptic complications despite a substitution by histamine H2-receptor antagonist therapy. Simultaneous management of life-threatening hypomagnesemia, severe gastric acid hypersecretion and MEN1-associated gastrinomas was complex. A total gastrectomy was performed in order to definitely preclude the use of PPIs in this frail patient who was not eligible for curative pancreatoduodenal resection.     

Arrhythmias following cardiac surgery: relation to serum digoxin levels.

Arrhythmias were analyzed in 50 patients undergoing cardiac surgery: 27 with valve surgery, 15 with coronary artery bypass (CAB), 5 with CAB and valve surgery, and 3 with miscellaneous procedures. The role of electrolyte abnormalities, pericarditis, serum osmolarity, digoxin level, and the type of surgery performed was evaluated. Thirty-seven out of 50 patients (74 per cent) had a postoperative arrhythmia, and a total of 78 different arrhythmias were noted. Twenty-six out of 27 patients with valve surgery had an arrhythmia vs. six out of 15 patients with CAB (p less than 0.001). Atrial fibrillation was the most common arrhythmia in all groups. Although postoperative hypocalcemia, hypomagnesemia, pericarditis, and wide shifts in osmolarity were common, they did not correlate with arrhythmias. Seventeen patients developed postoperative arrhythmias compatible with digitalis toxicity, including junctional rhythm, atrioventricular dissociation, or atrial tachycardia with block. However, the range of serum digoxin levels in these patients was zero to 2.80 ng. per milliliter. This suggests increased sensitivity to digitalis glycosides or the effects of surgical trauma as the etiology of arrhythmia in many patients. The distinction between digitalis-induced arrhythmia and spontaneously occurring arrhythmia cannot be made with certainty in most postoperative patients. Therapy should reflect an awareness of the potential for postoperative digitoxicity.     

Hypocalcemic Heart Failure in Thalassemic Patients

Hypocalcemic cardiomyopathy in primary or secondary hypoparathyroidism is usually refractory to conventional treatment of cardiac failure. We report the case of a thalassemic patient with severe cardiac failure that might have been attributed to several factors, such as hemosiderosis, hypomagnesemia, and hypocalcemia, refractory to conventional cardiac therapy. Cardiac echocardiography showed impaired biventricular performance, and laboratory analyses revealed hypoparathyroidism due to hemosiderosis. When concomitant treatment of heart failure and calcium supplementation was initiated, correction of hypocalcemia resulted in clinical and laboratory improvement, providing strong evidence in support of our hypothesis about hypocalcemic myocardiopathy.     

The prognostic significance of serial exercise testing after myocardial infarction.

Serial treadmill exercise testing (mean 5.5 tests/patient) was used to evaluate the prognosis of 200 males (mean age 53 years) without clinical heart failure or unstable angina pectoris 3 weeks after acute myocardial infarction (MI). Exercise-induced ischemic ST-segment depression greater than or equal to 0.2 mV 3 weeks after MI was significantly more prevalent in patients with subsequent cardiac arrest (100%) or coronary artery bypass graft surgery (64%) than in patients without subsequent events within 2 years of infarction (35%) (p less than 0.05). Exercise-induced ventricular arrhythmia on multiple tests 5-52 weeks after MI was more prevalent in patients with recurrent myocardial infarction (90%) than in patients without subsequent events (47%) (p less than 0.001). By contrast, exercise-induced ventricular arrhythmia on a single test at 3 weeks was a less powerful predictor of subsequent cardiac events. Exercise-induced ischemia 3 weeks after MI predicted early fatal events, while ventricular arrhythmia on serial testing predicted later nonfatal events.     

Ethanol septal ablation for refractory ventricular tachycardia

It is not uncommon for patients with severe ischemic or nonischemic cardiomyopathy to have recurrent ventricular arrhythmias. Many of these arrhythmias remain asymptomatic and can be controlled with beta-blockers or amiodarone. However, for a subset of these patients, the arrhythmia is persistent and requires antitachycardic pacing, internal defibrillation, or radiofrequency ablation therapy. We present a patient with end-stage nonischemic cardiomyopathy and recurrent ventricular tachycardia (VT) who was listed for cardiac transplantation. His VT was not responsive to medical management, and standard endocardial or epicardial VT radiofrequency ablation (VTRFA) procedures. Therefore, this patient underwent successful ethanol septal ablation (ESA) to obliterate the source of arrhythmia. Five days after the ablation procedure, he underwent cardiac transplantation. Therefore, this case presents a rare opportunity to review the use of ESA for refractory VT and an excellent opportunity to review the acute pathologic and histologic changes induced by ESA.     

Antibiotic‐induced Cardiac Arrhythmias

This review aims to clarify the underlying risk of arrhythmia associated with the use of macrolides and fluoroquinolones antibiotics. Torsades de pointes (TdP) is a rare potential side effect of fluoroquinolones and macrolide antibiotics. However, the widespread use of these antibiotics compounds the problem. These antibiotics prolong the phase 3 of the action potential and cause early after depolarization and dispersion of repolarization that precipitate TdP. The potency of these drugs, as potassium channel blockers, is very low, and differences between them are minimal. Underlying impaired cardiac repolarization is a prerequisite for arrhythmia induction. Impaired cardiac repolarization can be congenital in the young or acquired in adults. The most important risk factors are a prolonged baseline QTc interval or a combination with class III antiarrhythmic drugs. Modifiable risk factors, including hypokalemia, hypomagnesemia, drug interactions, and bradycardia, should be corrected. In the absence of a major risk factor, the incidence of TdP is very low. The use of these drugs in the appropriate settings of infection should not be altered because of the rare risk of TdP, except among cases with high‐risk factors.     

Prevalence of supraventricular tachycardia and tachyarrhythmias in resuscitated cardiac arrest

Supraventricular arrhythmias are considered to be benign when the ventricular rate is slowed and treated by anticoagulants. The aim of this study was to determine the possible influence of these arrhythmias in resuscitated cardiac arrest. Between 1980 and 2002, 151 patients were admitted after a cardiac arrest. Supraventricular arrhythrmias were identified as a possible cause of the cardiac arrest in 21 patients. They underwent echocardiography, exercise stress test, Holter ECG monitoring , coronary angiography and electrophysiological investigation. After these investigations, three patients had a malignant form of the Wolff-Parkinson-White syndrome, two were asymptomatic and, in the third patient, ventricular fibrillation was induced by treatment with diltiazem. In 8 patients, a rapid supraventricular arrhythmia was considered to be the cause of cardiac arrest by cardiogenic shock; 2 patients had hypertrophic cardiomyopathy, 5 had severe dilated cardiomyopathy which regressed in one patient. In ten patients, cardiac arrest due to ventricular tachycardia or fibrillation was provoked by a rapid (> 220 beats/min) supraventricular arrhythmia; two patients had no apparent underlying cardiac pathology. In the others, myocardial ischaemia or acute cardiac failure were considered to be the cause of the cardiac arrest. The authors conclude that rapid supraventricular arrhythmias may cause cardiac arrest either by cardiogenic shock or degenerescence to ventricular tachycardia or fibrillation. Usually, this event occurs in patients with severe cardiac disease but it may occur in subjects without cardiac disease or by an arrhythmia-induced cardiomyopathy.