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Torsade de pointes associated with elevated N-acetylprocainamide levels
Volume
109
Number
2
Brief Communications
successfully treated by low thoracic duct ligation and establishment of a pericardial window.3 To prevent repeated accumulation of a pericardial effusion and the completion of constrictive pericarditis, surgical treatment is preferable to drug therapy when the diagnosis of chylopericardium is established.
375
I. Procainamide (PA) and N-acetylprocainamide (NAPA) levels during torsade de pointes
Table
Date
PA level hglml~
NAPA led (dml)
7113 7114
33.0 2.1
32.4 39.0
QT, fsec) 0.64 0.66
REFERENCES
1. Dunn RP: Primary chylopericardium: A review of the literature and an illustrated case. AM HEART J 89:369, 1975. 2. Charinilas Y, Levo Y, Weiss A, Glaser J, Levy MJ: Isolated idiopathic chylopericardium. J Thorac Cardiovasc Surg 73:719, 1977. 3. Logue PB: Etiology, recognition and management of pericardial disease. ed 5, New York, 1982, McGraw-Hill Book Company, Inc, p 1385.
Torsade elevated
de pointes associated N-acetylprocainamide
with levels
Henry G. Stratmann, M.D., Kenneth E. Walter, M.D., and Harold L. Kennedy, M.D., M.P.H. St. Louis, MO
N-acetylprocainamide (NAPA), the major metabolite of procainamide, has been shown to have separate antiarrhythmic and sideeffects from procainamide.l Torsade de pointes, a type of polymorphous ventricular tachycardia characterized by “twisting” of ventricular complexes around the isoelectric line and usually associatedwith QT prolongation,2hasbeen reported to occur with administration of procainamide.3However, only recently has it been associatedwith NAPA.* Becauseprocainamide is such a widely used antiarrhythmic agent, this association has important clinical implications. The following caseconfirms this associationof torsade de pointes with NAPA. A 57-year-old black man wasadmitted to the St. Louis Veterans Administration Medical Center on June 21, 1982,with a diagnosisof biventricular heart failure. There were no symptomsor history suggestiveof coronary artery diseaseor cardiac arrhythmias. He wastaking no medications. The admission ECG showed sinus rhythm, right bundle branch block, and a QT interval of 0.46 second. Two-dimensional echocardiography showedmarked fourchamber enlargement and severe diffuse left ventricular hypokinesis. He improved on treatment with digoxin, furosemide,and hydralazine. On June 25, however, he had a cardiopulmonary arrest, with a slow idioventricular rhythm but no ventricular tachycardia. He wasintubated and stabilized but required mechanical ventilation. A
subsequentdiagnosisof sepsiswas made basedon blood cultures positive for Clostridium perfringens. On June 30 he had transient recurrent episodes of paroxysmal supraventricular tachycardia with rates of 160 to 180bpm unresponsiveto intravenous verapamil. Treatment with 500 mg intravenous procainamide did prevent further episodes,and he was maintained on a 2 mg/min continuous infusion of this drug with continued good control of the arrhythmia until July 9 when, after a recurrence, the infusion rate was increasedto 4 mg/min. Procainamide was discontinued on July 12 when the QT, which had been0.44 secondon July 8, wasnoted to be 0.64 second.Hours later, however, the patient developed torsadede pointes (Fig. l), which respondedto DC cardioversion. The procainamide and NAPA levels drawn just before this arrhythmia developedwere 33.0pg/ml and 32.4 rg/ml, respectively (Table I). The serum creatinine was 2.0 mg/dl and the serum potassium was 4.6 mEq/L. No further treatment was instituted. On July 14, 34 hours after procainamide was discontinued, the QT was 0.66 second and a second episode of torsade de pointes occurred (Fig. 2), again responding to DC cardioversion. Procainamide and NAPA levels drawn at that time were 2.1 pg/ml and 39.0 pg/ml, respectively, with a serum creatinine of 2.6 mg/dl and serum potassium of 4.2 mEq/L. Thereafter the patient had no further episodesof this arrhythmia and the QT normalized over the next several days. Torsade de pointes, first identified by Dessertennein 19665in a patient with complete heart block, has subsequently been associatedwith hypokalemia, left ventricular dysfunction, and certain antiarrhythmic drugs, especially quinidine, disopyramide, and procainamide.2These agentscan produce a dose-relatedor idiosyncratic delay of ventricular repolarization manifested by prolongation of the QT interval, and several authors have recently stressedthe strong clinical association and therapeutic implications of QT prolongation with torsade de pointes.6.7NAPA, which also produces QT prolongation, would also seemlikely to produce this arrhythmia; our case, and that of Olshansky et al.,4 indicate that it does. While
the patient’s
Moreover, From the Division of Cardiology, John Cochran Veterans Administration Hospital and St. Louis University Medical Center. Reprint requests: Henry G. Stratmann, M.D., Division of Cardiology, John Cochran VA Hospital, 916 N. Grand, St. Louis, MO 63106.
left ventricular
dysfunction
may have
contributed to the production of torsade de pointes, hypokalemia and bradyarrhythmias were notably absent. occurrence
of the
arrhythmia
only
during
marked QT prolongation (0.64 to 0.66 second)associated with high levels of NAPA
(Table
I), and its abatement
as
drug levels decreasedand the QT normalized, are analogous to other reports of drug-induced torsade de
February.
376
Brief
Communications
American
Heart
1985 Journal
Fig. 1. Modified lead V, rhythm strips show (uboue) a prolonged QT, interval of 0.64 secondfollowed shortly thereafter by (below) onset of episodeof torsade de pointes. Both the procainamide level and the NAPA level were markedly elevated.
Fig. 2. Thirty-four hours after procainamidewasdiscontinued, the QT, wasstill prolonged at 0.66 second and torsade de pointes recurred. The procainamide level wasnow low but the NAPA level waseven more markedly elevated.
pointes.z.8During the first episodeof torsade de pointes, both procainamide and NAPA levelswere elevated (Table I) and may have acted in concert to produce QT prolongation and its subsequentdevelopment. However, during the secondepisode,marked QT prolongation wasstill present when the procainamide level was low and that of NAPA was high, thus implicating the latter drug as the cause. These findings are similar to those of the patient reported by Olshanskyet a1.,4who developedthe arrhythmia with a QT of 0.64 secondand procainamide and NAPA levels of 4.1 pg/ml and 32.8 bg/ml, respectively. High NAPA levels alone, however, may not be adequate to produce torsade de pointes, asindicated by the study of Kluger et al.,‘” who reported patients with levels of NAPA up to 66 fig/ml without drug-induced arrhythmia. Rather, in a manner similar to that of other antiarrhythmic agents associated with torsade de pointes, the presenceof marked (greater than 0.56 second)QT prolongation seemsto be the most reliable measureof susceptibility.
Identification of NAPA as a causeof torsade de pointes has important clinical implications. Patients receiving procainamide are thus at risk for developing this potentially fatal arrhythmia, not only from the procainamide itself but also from the NAPA produced by its metabolism. Since procainamide is used so commonly and widespread availability of methods to determine NAPA levels hasoccurred only recently, it is possiblethat somecasesof QT prolongation and even torsadede pointes attributed to procainamidewere due at least in part to NAPA. This risk from NAPA may be especially important in patients who are “fast acetylators” (i.e., who produce higher levels of NAPA relative to procainamide) and in patients with renal impairment. In patients with normal renal function the half-lives of procainamide and NAPA are 3 to 4 hours and 7 hours, respectively, but that of NAPA may be prolonged to 21 hours when the glomerular filtration rate is reduced to 35 ml/min. I0 In our patient, renal impairment (serum creatinine of 2.0 to 2.6 mg/dl) undoubtedly
Volume
109
Number
2
Brief
contributed to his high NAPA levels. This difference in half-lives between the two drugs means that patients may have QT prolongation and be at risk of developing torsade de pointes from elevated NAPA levels long after procainamide has been discontinued clinically and its serum levels have decreased to normal or low values. In such patients, additional nonspecific therapy may include DC cardioversion of acute episodes of the arrhythmia and prophylaxis with isoproterenol infusion or overdrive ventricular pacing as drug levels fall.*,* REFERENCES
Roden DM, Reele SB, Higgins SB, Wilkinson GR, Smith RF, Oates JA, Woosley RL: Antiarrhythmic efficacy, pharmacokinetics and safety of N-acetylprocainamide in human subjects: Comparison with procainamide. Am J Cardiol 46:463, 1980. JJ: “Les torsade de pointes”: An 2. Smith WM, Gallagher unusual ventricular arrhythmia. Ann Intern Med 93:578, 1980. 3I Strasberg B, Sclarovsky S, Erdberg A, Duffy CE, Lam W, Swiryn S, Agmon J, Rosen KM: Procainamide-induced polymorphous ventricular tachycardia. Am J Cardiol 47:3109, 1981. 4. Olshansky B, Martins J, Hunt S: N-acetyl procainamide causing torsades de pointes. Am J Cardiol 50:1439, 1982. 5. Dessertenne F: La tachycardie ventriculaire h deux foyers opposes variables. Arch Ma1 Coeur 59:263, 1966. 6. Soffer J, Dreifus L, Michelson E: Polymorphous ventricular tachycardia associated with normal and long Q-T intervals. Am d Cardiol 49:2021, 1982. I. Kluger J, Leech S, Reidenberg MM, Lloyd V, Drayer DE: Long-term antiarrhythmic therapy with acetylprocainamide. Am J Cardiol 46:1124, 1981. 8. Winkle RA, Jaillon P, Kates RE, Peters F: Clinical pharmacology and antiarrhythmic efficacy of N-acetylprocainamide. Am J Cardiol 47:123, 1981. J, Klein SW: Procainamide dosage schedule, 9. Koch-Weser plasma concentrations and clinical effects. JAMA 215:1454, 1.
1971. 10.
Kluger J, Drayer D, Reidenberg M, Ellis G, Lloyd V, Tyberg T, Hayes J: The clinical pharmacology and antiarrhythmic efficacy of acetylprocainamide in patients with arrhythmias. Am J Cardiol 45:1250, 1980.
Unusual ventricular depolarizations associated with torsade de pointes* Joseph J. Sarmiento, M.D., Peder M. Shea, M.D., and Ary L. Goldberger, M.D. San Diego, Calif.
From the Division of Cardiology, Department of Internal Medicine and the Clinical Investigation Department, Naval Hospital; the Veterans Administration Medical Center; and the University of California at San Diego. This study was sponsored and supported Clinical Investigation Program, Project Reprint Hospital,
requests: LCDR J. J. Sarmiento, Box 3511, Oakland, CA 94627.
by the Naval No. 78-16-1139. MC,
USNR,
Medical
Command,
Oakknoll
Naval
*The opinions or assertions expressed herein are those of the authors and are not to be construed as official or as necessarily reflecting the views of the Department of the Navy or the naval service at large.
Communications
377
Torsade de pointes (TdP), first described in 1966 by Dessertenne,’is a major precursor of sudden death. This type of ventricular tachycardia (VT) is of particular significancebecauseantiarrhythmic drugs, such as quinidine, are major predisposing causes.*Thus, predictive signsof TdP are of paramount clinical importance. We present two patients with TdP who showedwide, bizzare ventricular depolarizations having markedly prolonged repolarization times. Retrospective review of additional published casessuggeststhat such unusual ventricular beats may be of possiblevalue in identifying patients at risk for this arrhythmia. Case No. 1. A 53-year-old woman with a CarpentierEdwards prosthetic mitral valve was admitted to an outlying hospital becauseof recurrent syncope. Repeated episodesof VT on quinidine and procainamide led to her transfer to the Naval Hospital, San Diego. The admitting ECG demonstrated atria1 fibrillation, rare ventricular extrasystoles, a QT interval varying between 0.58 and 0.67 second, left ventricular hypertrophy, and nonspecific repolarization abnormalities. Her medications included digoxin, 0.25 mg orally once a day; procainamide hydrochloride sustained releasetablets (Procan SR), 500 mg orally every 6 hours; furosemide, 80 mg orally once a day; and 40 mEq potassium chloride orally once a day. The procainamide level was 2 pg/ml and the N-acetylprocainamide level was 4 pg/ml. She spontaneouslyconverted to normal sinus rhythm on the secondhospital day. On the fourth hospital day, the patient sustained a grand ma1 seizure with VT noted on the ECG monitor (retrospectively diagnosedas TdP). The patient was resuscitated and begunon a lidocaine drip. The digoxin level was4.0 rig/ml. Digoxin wasdiscontinued, lidocaine was gradually discontinued, and procainamide was increasedto 750 mg orally every 6 hours. On the thirteenth hospital day, the patient again developedTdP. Procainamidewasdiscontinued and the arrhythmia did not recur. Review of the records showedthat marked QT prolongation had beenpresent on admission to the Naval Hospital and that TdP was present during the patient’s seizure. Similarily, review of the record from the referring hospital revealed that the QT interval had been persistently prolonged throughout her course and that bizzare premature ventricular contractions (PVCs) with markedly prolonged repolarization times (0.68 second)shortly precededher first bout of TdP (Fig. 1). Case No. 2. A 76-year-old man, with a history of an inferior wall myocardial infarction in 1974, was admitted to our Intermediate Coronary Care Unit with dyspnea on exertion, fatigue, and rapid atria1 fibrillation (132 bpm). Digitalization slowedthe ventricular responseto 85 bpm. Oral quinidine sulfate wasaddedon the fifth hospital day, 300 mg every 6 hours. On the sixth hospital day, he converted to normal sinus rhythm and 12 hours later developed TdP (Fig. 2, A), which degenerated into ventricular fibrillation. He was successfullydefibrillated and quinidine was discontinued. The QT interval, ineasured on the morning of the patient’s cardiac arrest, was not markedly prolonged (0.42 second) nor was it prolonged
109
Number
2
Brief Communications
successfully treated by low thoracic duct ligation and establishment of a pericardial window.3 To prevent repeated accumulation of a pericardial effusion and the completion of constrictive pericarditis, surgical treatment is preferable to drug therapy when the diagnosis of chylopericardium is established.
375
I. Procainamide (PA) and N-acetylprocainamide (NAPA) levels during torsade de pointes
Table
Date
PA level hglml~
NAPA led (dml)
7113 7114
33.0 2.1
32.4 39.0
QT, fsec) 0.64 0.66
REFERENCES
1. Dunn RP: Primary chylopericardium: A review of the literature and an illustrated case. AM HEART J 89:369, 1975. 2. Charinilas Y, Levo Y, Weiss A, Glaser J, Levy MJ: Isolated idiopathic chylopericardium. J Thorac Cardiovasc Surg 73:719, 1977. 3. Logue PB: Etiology, recognition and management of pericardial disease. ed 5, New York, 1982, McGraw-Hill Book Company, Inc, p 1385.
Torsade elevated
de pointes associated N-acetylprocainamide
with levels
Henry G. Stratmann, M.D., Kenneth E. Walter, M.D., and Harold L. Kennedy, M.D., M.P.H. St. Louis, MO
N-acetylprocainamide (NAPA), the major metabolite of procainamide, has been shown to have separate antiarrhythmic and sideeffects from procainamide.l Torsade de pointes, a type of polymorphous ventricular tachycardia characterized by “twisting” of ventricular complexes around the isoelectric line and usually associatedwith QT prolongation,2hasbeen reported to occur with administration of procainamide.3However, only recently has it been associatedwith NAPA.* Becauseprocainamide is such a widely used antiarrhythmic agent, this association has important clinical implications. The following caseconfirms this associationof torsade de pointes with NAPA. A 57-year-old black man wasadmitted to the St. Louis Veterans Administration Medical Center on June 21, 1982,with a diagnosisof biventricular heart failure. There were no symptomsor history suggestiveof coronary artery diseaseor cardiac arrhythmias. He wastaking no medications. The admission ECG showed sinus rhythm, right bundle branch block, and a QT interval of 0.46 second. Two-dimensional echocardiography showedmarked fourchamber enlargement and severe diffuse left ventricular hypokinesis. He improved on treatment with digoxin, furosemide,and hydralazine. On June 25, however, he had a cardiopulmonary arrest, with a slow idioventricular rhythm but no ventricular tachycardia. He wasintubated and stabilized but required mechanical ventilation. A
subsequentdiagnosisof sepsiswas made basedon blood cultures positive for Clostridium perfringens. On June 30 he had transient recurrent episodes of paroxysmal supraventricular tachycardia with rates of 160 to 180bpm unresponsiveto intravenous verapamil. Treatment with 500 mg intravenous procainamide did prevent further episodes,and he was maintained on a 2 mg/min continuous infusion of this drug with continued good control of the arrhythmia until July 9 when, after a recurrence, the infusion rate was increasedto 4 mg/min. Procainamide was discontinued on July 12 when the QT, which had been0.44 secondon July 8, wasnoted to be 0.64 second.Hours later, however, the patient developed torsadede pointes (Fig. l), which respondedto DC cardioversion. The procainamide and NAPA levels drawn just before this arrhythmia developedwere 33.0pg/ml and 32.4 rg/ml, respectively (Table I). The serum creatinine was 2.0 mg/dl and the serum potassium was 4.6 mEq/L. No further treatment was instituted. On July 14, 34 hours after procainamide was discontinued, the QT was 0.66 second and a second episode of torsade de pointes occurred (Fig. 2), again responding to DC cardioversion. Procainamide and NAPA levels drawn at that time were 2.1 pg/ml and 39.0 pg/ml, respectively, with a serum creatinine of 2.6 mg/dl and serum potassium of 4.2 mEq/L. Thereafter the patient had no further episodesof this arrhythmia and the QT normalized over the next several days. Torsade de pointes, first identified by Dessertennein 19665in a patient with complete heart block, has subsequently been associatedwith hypokalemia, left ventricular dysfunction, and certain antiarrhythmic drugs, especially quinidine, disopyramide, and procainamide.2These agentscan produce a dose-relatedor idiosyncratic delay of ventricular repolarization manifested by prolongation of the QT interval, and several authors have recently stressedthe strong clinical association and therapeutic implications of QT prolongation with torsade de pointes.6.7NAPA, which also produces QT prolongation, would also seemlikely to produce this arrhythmia; our case, and that of Olshansky et al.,4 indicate that it does. While
the patient’s
Moreover, From the Division of Cardiology, John Cochran Veterans Administration Hospital and St. Louis University Medical Center. Reprint requests: Henry G. Stratmann, M.D., Division of Cardiology, John Cochran VA Hospital, 916 N. Grand, St. Louis, MO 63106.
left ventricular
dysfunction
may have
contributed to the production of torsade de pointes, hypokalemia and bradyarrhythmias were notably absent. occurrence
of the
arrhythmia
only
during
marked QT prolongation (0.64 to 0.66 second)associated with high levels of NAPA
(Table
I), and its abatement
as
drug levels decreasedand the QT normalized, are analogous to other reports of drug-induced torsade de
February.
376
Brief
Communications
American
Heart
1985 Journal
Fig. 1. Modified lead V, rhythm strips show (uboue) a prolonged QT, interval of 0.64 secondfollowed shortly thereafter by (below) onset of episodeof torsade de pointes. Both the procainamide level and the NAPA level were markedly elevated.
Fig. 2. Thirty-four hours after procainamidewasdiscontinued, the QT, wasstill prolonged at 0.66 second and torsade de pointes recurred. The procainamide level wasnow low but the NAPA level waseven more markedly elevated.
pointes.z.8During the first episodeof torsade de pointes, both procainamide and NAPA levelswere elevated (Table I) and may have acted in concert to produce QT prolongation and its subsequentdevelopment. However, during the secondepisode,marked QT prolongation wasstill present when the procainamide level was low and that of NAPA was high, thus implicating the latter drug as the cause. These findings are similar to those of the patient reported by Olshanskyet a1.,4who developedthe arrhythmia with a QT of 0.64 secondand procainamide and NAPA levels of 4.1 pg/ml and 32.8 bg/ml, respectively. High NAPA levels alone, however, may not be adequate to produce torsade de pointes, asindicated by the study of Kluger et al.,‘” who reported patients with levels of NAPA up to 66 fig/ml without drug-induced arrhythmia. Rather, in a manner similar to that of other antiarrhythmic agents associated with torsade de pointes, the presenceof marked (greater than 0.56 second)QT prolongation seemsto be the most reliable measureof susceptibility.
Identification of NAPA as a causeof torsade de pointes has important clinical implications. Patients receiving procainamide are thus at risk for developing this potentially fatal arrhythmia, not only from the procainamide itself but also from the NAPA produced by its metabolism. Since procainamide is used so commonly and widespread availability of methods to determine NAPA levels hasoccurred only recently, it is possiblethat somecasesof QT prolongation and even torsadede pointes attributed to procainamidewere due at least in part to NAPA. This risk from NAPA may be especially important in patients who are “fast acetylators” (i.e., who produce higher levels of NAPA relative to procainamide) and in patients with renal impairment. In patients with normal renal function the half-lives of procainamide and NAPA are 3 to 4 hours and 7 hours, respectively, but that of NAPA may be prolonged to 21 hours when the glomerular filtration rate is reduced to 35 ml/min. I0 In our patient, renal impairment (serum creatinine of 2.0 to 2.6 mg/dl) undoubtedly
Volume
109
Number
2
Brief
contributed to his high NAPA levels. This difference in half-lives between the two drugs means that patients may have QT prolongation and be at risk of developing torsade de pointes from elevated NAPA levels long after procainamide has been discontinued clinically and its serum levels have decreased to normal or low values. In such patients, additional nonspecific therapy may include DC cardioversion of acute episodes of the arrhythmia and prophylaxis with isoproterenol infusion or overdrive ventricular pacing as drug levels fall.*,* REFERENCES
Roden DM, Reele SB, Higgins SB, Wilkinson GR, Smith RF, Oates JA, Woosley RL: Antiarrhythmic efficacy, pharmacokinetics and safety of N-acetylprocainamide in human subjects: Comparison with procainamide. Am J Cardiol 46:463, 1980. JJ: “Les torsade de pointes”: An 2. Smith WM, Gallagher unusual ventricular arrhythmia. Ann Intern Med 93:578, 1980. 3I Strasberg B, Sclarovsky S, Erdberg A, Duffy CE, Lam W, Swiryn S, Agmon J, Rosen KM: Procainamide-induced polymorphous ventricular tachycardia. Am J Cardiol 47:3109, 1981. 4. Olshansky B, Martins J, Hunt S: N-acetyl procainamide causing torsades de pointes. Am J Cardiol 50:1439, 1982. 5. Dessertenne F: La tachycardie ventriculaire h deux foyers opposes variables. Arch Ma1 Coeur 59:263, 1966. 6. Soffer J, Dreifus L, Michelson E: Polymorphous ventricular tachycardia associated with normal and long Q-T intervals. Am d Cardiol 49:2021, 1982. I. Kluger J, Leech S, Reidenberg MM, Lloyd V, Drayer DE: Long-term antiarrhythmic therapy with acetylprocainamide. Am J Cardiol 46:1124, 1981. 8. Winkle RA, Jaillon P, Kates RE, Peters F: Clinical pharmacology and antiarrhythmic efficacy of N-acetylprocainamide. Am J Cardiol 47:123, 1981. J, Klein SW: Procainamide dosage schedule, 9. Koch-Weser plasma concentrations and clinical effects. JAMA 215:1454, 1.
1971. 10.
Kluger J, Drayer D, Reidenberg M, Ellis G, Lloyd V, Tyberg T, Hayes J: The clinical pharmacology and antiarrhythmic efficacy of acetylprocainamide in patients with arrhythmias. Am J Cardiol 45:1250, 1980.
Unusual ventricular depolarizations associated with torsade de pointes* Joseph J. Sarmiento, M.D., Peder M. Shea, M.D., and Ary L. Goldberger, M.D. San Diego, Calif.
From the Division of Cardiology, Department of Internal Medicine and the Clinical Investigation Department, Naval Hospital; the Veterans Administration Medical Center; and the University of California at San Diego. This study was sponsored and supported Clinical Investigation Program, Project Reprint Hospital,
requests: LCDR J. J. Sarmiento, Box 3511, Oakland, CA 94627.
by the Naval No. 78-16-1139. MC,
USNR,
Medical
Command,
Oakknoll
Naval
*The opinions or assertions expressed herein are those of the authors and are not to be construed as official or as necessarily reflecting the views of the Department of the Navy or the naval service at large.
Communications
377
Torsade de pointes (TdP), first described in 1966 by Dessertenne,’is a major precursor of sudden death. This type of ventricular tachycardia (VT) is of particular significancebecauseantiarrhythmic drugs, such as quinidine, are major predisposing causes.*Thus, predictive signsof TdP are of paramount clinical importance. We present two patients with TdP who showedwide, bizzare ventricular depolarizations having markedly prolonged repolarization times. Retrospective review of additional published casessuggeststhat such unusual ventricular beats may be of possiblevalue in identifying patients at risk for this arrhythmia. Case No. 1. A 53-year-old woman with a CarpentierEdwards prosthetic mitral valve was admitted to an outlying hospital becauseof recurrent syncope. Repeated episodesof VT on quinidine and procainamide led to her transfer to the Naval Hospital, San Diego. The admitting ECG demonstrated atria1 fibrillation, rare ventricular extrasystoles, a QT interval varying between 0.58 and 0.67 second, left ventricular hypertrophy, and nonspecific repolarization abnormalities. Her medications included digoxin, 0.25 mg orally once a day; procainamide hydrochloride sustained releasetablets (Procan SR), 500 mg orally every 6 hours; furosemide, 80 mg orally once a day; and 40 mEq potassium chloride orally once a day. The procainamide level was 2 pg/ml and the N-acetylprocainamide level was 4 pg/ml. She spontaneouslyconverted to normal sinus rhythm on the secondhospital day. On the fourth hospital day, the patient sustained a grand ma1 seizure with VT noted on the ECG monitor (retrospectively diagnosedas TdP). The patient was resuscitated and begunon a lidocaine drip. The digoxin level was4.0 rig/ml. Digoxin wasdiscontinued, lidocaine was gradually discontinued, and procainamide was increasedto 750 mg orally every 6 hours. On the thirteenth hospital day, the patient again developedTdP. Procainamidewasdiscontinued and the arrhythmia did not recur. Review of the records showedthat marked QT prolongation had beenpresent on admission to the Naval Hospital and that TdP was present during the patient’s seizure. Similarily, review of the record from the referring hospital revealed that the QT interval had been persistently prolonged throughout her course and that bizzare premature ventricular contractions (PVCs) with markedly prolonged repolarization times (0.68 second)shortly precededher first bout of TdP (Fig. 1). Case No. 2. A 76-year-old man, with a history of an inferior wall myocardial infarction in 1974, was admitted to our Intermediate Coronary Care Unit with dyspnea on exertion, fatigue, and rapid atria1 fibrillation (132 bpm). Digitalization slowedthe ventricular responseto 85 bpm. Oral quinidine sulfate wasaddedon the fifth hospital day, 300 mg every 6 hours. On the sixth hospital day, he converted to normal sinus rhythm and 12 hours later developed TdP (Fig. 2, A), which degenerated into ventricular fibrillation. He was successfullydefibrillated and quinidine was discontinued. The QT interval, ineasured on the morning of the patient’s cardiac arrest, was not markedly prolonged (0.42 second) nor was it prolonged