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CARDIOLOGY CASEBOOK |
A 50-year-old woman with a history of essential hypertension and depression was admitted to a telemetry unit because of 2 episodes of syncope within a 48-hour period. There were no other symptoms. Her blood pressure was 130/78 mm Hg, and findings on chest radiographs were normal. The serum potassium level was 3.3 mmol/L. The patient was being treated with clarithromycin for an upper respiratory tract infection. Her other medications were hydrochlorothiazide, fluoxetine, and a potassium supplement. A rhythm trace was recorded (Figure 1
).
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?). reveals which of the following?
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1. a. sinus with paroxysmal ventricular tachycardia
b. torsades de pointes
d. prefibrillatory ventricular arrhythmia
The arrhythmia is a form of paroxysmal ventricular tachycardia, which because of its characteristic electrocardiographic morphology is referred to as torsades de pointes (twisting of the points). The ventricular complexes continuously change their configuration and electrical axis as if they are twisting around an isoelectric line. The widened QRS deflections change cyclically every 5 to 20 beats from an upright to an inverted direction. The T waves are more rounded and opposite in direction to the QRS. The paroxysms are usually recurrent, may be brief or prolonged, and may progress to ventricular fibrillation. The majority, however, end spontaneously with a fusion beat or with a ventricular premature beat similar to the one that initiated the tachycardia. A distinctive electrocardiographic feature of acquired torsades de pointes is the long-short R-R cycle that precedes the onset of the undulating waveforms in Figure 1.1
2. a. left atrial enlargement
b. prolonged QT interval with TU fusion
c. right axis deviation
d. left inferior posterior hemiblock
A diagnosis of left atrial enlargement is based on the following features: (a) wide and notched P waves in lead I with an interval between peaks greater than 0.04 seconds; (b) the terminal portion of the p wave in lead II is negative and to the left, representing left atrial activation; and (c) prominent terminal negativity of the p wave in lead V1. The mean QRS axis in the frontal plane is right axis +120 degrees and is likely a result of a left posterior fascicular block (block of the posteroinferior division of the left bundle branch). When the posteroinferior division of the left bundle is blocked, the ventricle is activated through the anterosuperior division of the left bundle, the impulse emerges from the unblocked anterosuperior division proceeding initially to the left and superior and then to the right and inferior, which shifts the axis to the right. A lateral wall myocardial infarction or right ventricular hypertrophy may also result in a right axis. The absence of prominent R waves in the initial left precordial leads tends to rule out right ventricular hypertrophy, and the absence of q waves in leads I and aVL rules out lateral wall infarction. The r waves in leads I and aVL are consistent with left posterior hemiblock.
The QT interval is measured from the onset of the QRS complex to the end of the following T wave. Indirectly, it is a measure of the duration of ventricular repolarization. It is rate dependent, with the interval being longer with slower R-R cycles and shorter with faster heart rates. The Bazett formula is used to calculate the "true" value or corrected QT interval (QTc) in the electrocardiogram and minimizes errors.
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The upper limit of a corrected QT interval is generally 0.44 seconds. The QT interval for men is usually 0.46 seconds, and 0.47 seconds for women is borderline normal.1–3 Leads V3 and V4 are the most reliable leads when measuring QT intervals.2 In some cases, a prolonged QT interval may actually be the QU interval. A prominent and abnormal U wave may fuse with a T wave. The QTc measures 0.62 seconds, which is abnormally long even for a heart rate of 50/min.
Prolonged QT or QU intervals are associated with life-threatening ventricular arrhythmias that cause syncope, seizures, or even sudden death. Although often self-terminating, these arrhythmias may range from frequent ventricular premature beats to multiform ventricular tachycardias (eg, torsades de pointes) and can deteriorate to ventricular flutter and fibrillation. Potassium ions are primary mediators of myocardial repolarization. The potassium currents responsible for repolarization are 2 subtypes of the delayed rectifier current, IKr (rapid) and the IKs (slow). Most drugs that prolong the QT interval block the delayed rectifier current IKr and delay phase 3, the rapid repolarization of the action potential. Additionally, repolarization delays may distort T waves and/or produce prominent U waves.2,4
3. f. any of the above
Abnormal low serum levels of potassium, calcium, or magnesium affect the repolarization phase of the electrocardiogram and prolong QT intervals. An increased incidence of complex ventricular arrhythmias can occur in hypokalemia and less frequently with hypocalcemia or hypomagnesemia. The electrocardiographic changes in hypokalemia that correlate with the serum levels are QT prolongation and TU fusion; the U wave increases in amplitude and fuses with the terminal portion of the T wave. In hypocalcemia, the prolongation of the ST segment parallels the serum level of calcium.
The QT interval is prolonged with an increased susceptibility to ventricular arrhythmias in central nervous system disease, particularly subarachnoid hemorrhage and acute cerebral trauma. Prolonged QT intervals can result from stimulation of the sympathetic nervous system. Adam-Stokes episodes may result in giant inverted or upright T waves with a prolonged repolarization phase. This electrocardiographic abnormality has been considered as being a result of an increase in sympathetic stimulation that occurs with anoxia and the syncopal attacks (L. L., unpublished data, 2007). In the absence of electrolyte abnormalities, or drug therapy, a prolonged QT interval is rare in chronic atherosclerotic heart disease. Prolonged QT intervals and torsades de pointes occur in some cases of myocarditis.
Drug-induced torsades de pointes was commonly seen with quinidine or procainamide therapy for atrial arrhythmias. Amiodarone is more commonly used and may cause prolongation of the QT interval; however, it rarely induces torsades de pointes. Although amiodarone increases repolarization across myocardial cells, it reduces transmural dispersion, which lessens the occurrence of torsades de pointes.4 Drugs may be restricted or removed from use because they are implicated in torsades de pointes.2,5 Antiarrhythmics such as dofetilide, ibutilide, and sotalolol progressively prolong the QT interval as the serum levels increase.2,6 Hypokalemia, often a result of diuretic use, may be implicated in arrhythmia genesis. Women are at greater risk than men for drug-induced torsades de pointes.2,4,7
Medications are categorized as either inducing torsades de pointes in a dose-dependent manner or causing torsades de pointes at any dose because of potassium channel blockade. Additionally, there are drugs that are metabolized by cytochrome P450 3A4 (CYP3A4). The CYP3A4 system may interfere with the metabolism of medications that prolong the QT interval. To safely monitor drug effects, healthcare professionals should be cognizant of medications that inhibit this system (see Table). In this case, an upper respiratory infection was treated with clarithromycin, a macrolide antibiotic (eg, erythromycin) that has been associated with episodes of sudden death due to torsades de pointes.2
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Dose-dependent prolongation of the QT interval occurs with the use of psychotropic drugs, especially the phenothiazines and tricyclic antidepressants. These agents, especially thioridazine, are considered risk factors for torsades de pointes developing, and more so when combined with other agents that may induce torsades de pointes. Other examples of commonly prescribed medications are the antimalarials, systemic antifungals (ie, fluconazole, ketoconazole), and pentamidine, the antifungal and antiprotozoal drug used in the treatment of parasitic infections and Pneumocystis carinii pneumonia.
Methadone and some herbal supplements prolong the QTc and increase the risk for torsades de pointes. Although it may not be possible to remember all of these drugs, it is nevertheless important to know the possibility and probability of interactions. A University of Arizona database lists all drugs stratified by risk that are associated with QT prolongation. This site can be accessed at www.torsades.org or www.qtdrugs.org.2
Several hereditary or congenital QT or QU prolongation syndromes are associated with ventricular arrhythmias, syncope, and sudden death. These syndromes are exemplified by Jervel and Lange-Nielsen syndrome, which is characterized by deafness, and by Romano-Ward syndrome, in which hearing is normal.1 The electrocardiogram may show normal QT intervals; with exercise, the QT becomes prolonged and abnormal. Changes in height and polarity of the T wave warn of the risk of impending serious ventricular arrhythmias.
4. c. intravenous magnesium
d. electrical pacing
e. intravenous isoproterenol hydrochloride
Initial treatment of torsades de pointes (American Heart Association standards) is a 1- to 2-g bolus of magnesium sulfate diluted in 5% dextrose (in water) to be given over 5 to 60 minutes.8 Defibrillation may be necessary but does not always terminate the arrhythmia. The cause should be promptly treated and the offending medication discontinued. More than one drug may be involved. The serum potassium should be kept in the upper limits of normal (>4.5 mmol/L).2
Electrical overdrive with temporary pacing may be indicated to shorten repolarization time. Isoproterenol infusion is helpful while waiting for a temporary pacemaker; however, it is contraindicated in ischemic heart disease or in the congenital long QT syndrome.2 In the congenital syndromes of QT prolongation, the goal of therapy is to prevent arrhythmia and syncope. The β-adrenergic agents are drugs of choice and may be combined with class IB antiarrhythmic drugs. A permanent pacemaker is indicated in symptomatic bradycardia and when prolonged R-R intervals predispose to torsades de pointes. Surgical removal of the left stellate and upper thoracic ganglia has been successful in obstinate cases. In selected patients, implantation of a cardioverter-defibrillator may be indicated.1
Summary
Prolonged QT or QU intervals may be caused by a variety of conditions, including drugs, electrolyte imbalance, and acquired and congenital diseases. The electrocardiographic description is referred to as torsades de pointes, a French terminology for a life-threatening polymorphic ventricular arrhythmia. Prompt defibrillation plus intravenous magnesium sulfate is indicated. Potassium should be kept at high normal levels, and drugs that prolong the QT interval should be discontinued.
ACKNOWLEDGMENTS
Supported in part from a grant from the Applebaum Foundation, in loving memory of Joseph Applebaum.
Reprint requests: Louis Lemberg, MD, University of Miami Miller School of Medicine, Division of Cardiology (D-39), PO Box 016960, Miami, FL 33101.
DeSilvey DL, Moss AJ. Primidone in the treatment of the long QT syndrome: QT shortening and ventricular arrhythmia suppression. Ann Intern Med. 1980;93(1):53–54.[Medline]
Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with sprolongation of the Q-T interval. Am Heart J. 1957;54(1):59–68.[Medline]
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