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Hepatoma presenting as a right atrial mass
906
Brief Communications
American
October 1987 Noaft Journal
pericarditis as the first manifestation of AIDS in the course of a disseminated tuberculosis. Even with the serious immunosuppressed state of these patients, the standard treatment is usually successful and at this moment (11 months from the begining of the treatment) there is no evidence of tuberculosis in our patient. We have recently described 12 patients with tuberculosis and infection by human immunodeficiency virus; among them only two patients showed a typical pattern of a reactivation disease; the remaining patients showed an atypical pattern.6 Cardiac manifestations in AIDS are very unu5ud and limited to nonbacterial thrombotic endocarditis, focal metastatic involvement by Kaposi’s sarcoma, or congestive cardiomyopathy probably of viral origin.6 Cardiologists should be aware that AIDS may start with cardiac involvement within the context of a systemic disease. REFERENCES
1.
2.
3.
4.
5.
6.
Duncanson FP, Hewlett D, Maayan S, Estapan H, Perla EN, Wormser GP. et al. Tuberculosis and the acauired immunodeficiency syndrome in non-Haitian intravenous abusers. Presented at the International Conference on Acquired Immunodeficiency Syndrome (AIDS), Atlanta, Ga., April 1985. Stoneburner RL, Kristal A. Increasing tuberculosis incidence and its relationship to acquired immunodeficiency syndrome in New York City. Presented at the Interantional Conference on Acquired Immunodeficiency Syndrome (AIDS), Atlanta, Ga., April 1985. Pitchenick AE, Rubinson HA. The radiographic appearance of tuberculosis in patients with the acquired immunodeficiency syndrome (AIDS) and pre-AIDS. Am Rev Respir Dis 1985;131:393-6. Centers for Disease Control, US Department of Health and Human Services, Atlanta, Ga. Classification system for human T-lymphotropic virus type III/lymphadenopathyassociated virus infections. Ann Intern Med 1986;105:234-7. Navarro V, Navarro R, Juan G, Nieto A, Minguez J, Lloret T. Tuberculosis en pacientes adictos a drogas por via parenteral (ADVP) con infection por HTLV-III. Arch Bronconeumol i986,22155. Cohen IS, Anderson DW, Virmani R, Reen BM, Macher AM, Sennesh J, Di Lorenzo P, Redfield RR. Congestive cardiomyopathy in association with the acquired immunodeficiency syndrome. N Engl J Med 1986;315:628-30.
Hepatoma mass
presenting
as a right atrigl
Daniel L. Miller, M.D., Nevin M. Katz, M.D., and Randolph S. Pallas, M.D. Washington, D.C. A large right atria1 masswas diagnosedby echocardiography in a young man. At surgery the masswasfound to be a From the Departments of Medicine and Surgery, Georgetown University Hospital. Reprint requests: N&n M. Katz, M.D., Department of Surgery, Georgetown University Hospital, 3800 Reservoir Rd. NW, Washington, DC 20007.
Fig. 1. Two-dimensional echocardiographic apical fourchamber view demonstrates the large tumor (T) within the right atrium.
direct
extension
of a hepatocellular
carcinoma.
We are
reporting this casebecauseprecisepreoperative diagnosis was difficult, and to our knowledge, only one other surgical casehas been described.’ A 36year-old white man with a history of psoriasis developed fever, malaise, proximal muscle weakness, abdominal distension, and lower extremity edema. On admissionto the hospital he was in respiratory distress, heart rate was 120 bpm, and pulsesparadoxus of 25 mm Hg was present. Jugular venous distension was absent. Heart sounds were muffled. There was marked ascites with hepatomegaly and pretibial edema to midcalf. ECG revealed right atrial enlargement with sinus tachycardia. Liver function test results were abnormal: direct bilirubin 2.0 mg/dl, total bilirubin 5.3 mg/dl, alkaline phosphatase 393Ill/L (normal <88), SGOT 52 IU/L (normal <42), and SGPT 89 IU/L (normal <60). Serum cy-fetoprotein was normal. An abdominal computerized tomographic scan with contrast material was negative for tumor. A twodimensional echocardiogram showed a 5 by 6 cm right atrial massoccupying a major portion of the right atrium (Fig. 1). Intermittent obstruction of the tricuspid valve and inferior vena caval orifice was seen. At operation through a median sternotomy there was marked thickening along the medial aspect of the right atrioinferior vena caval junction. The patient was cooled on cardiopulmonary bypass to 18’ C with venous drainage via the right atria1 appendageand right femoral vein. On
Volum* Number
114 4, Part 1
Brief
Communications
907
Fig. 2. The right atrium mass represented extension of a hepatocellular carcinoma through the diaphragm almost completely obstructing the inferior vena cava (WC) orifice and the orifice of the tricuspid valve. The intrathoracic portion of the tumor was excised and the right atriocaval wall was reoonstructured with a 4 by 6 cm oval patch of Gore-Tex. (WC = superior vena cava.)
exploration via a right atriotomy it was found that a large tumor massoccupied more than half of the interior of the right atrium (Fig. 2). The masswas densely adherent to the medial wall of the right atrium at its junction with the inferior vena cava. External to this the diaphragm was intimately adherent to this area. The tumor masswas excised by mobilizing a collar of atriocaval junction. Dissection was carried through the diaphragm and the column of tumor wasdivided by electrocautery. An inferior vena caval thrombus, separatefrom the tumor column, was removed by balloon catheter. Under a secondperiod of circulatory arrest the right atrioinferior vena caval junction was reconstructed with a Gore-Tex patch (W.L. Gore & Associates,Inc., Elkton, Md.) After surgery a good hemodynamic state was present and there was normal pulmonary and renal function, no evidence of neurologic deficit, and a gradual resolution of lower body edema. Anticoagulation was employed. Arteriography demonstrated extensive tumor involvement of the liver and venography showed residual thrombus in the infrarenal vena cava. The patient is now 6 months postoperative, moderately active, and undergoing a combined program of radiotherapy and immunotherapy.
Hepatocellular carcinoma represents 1% to 2.5 % of all malignanciesin the United States2 Right atrial metastases occur in 1% to 4% of patients with hepatoma.3 Steffens’ reported the first echocardiographicdiagnosisof metastatic hepatocellular carcinoma to the heart. To the best of our knowledge, only four cases of metastatic hepatocellular carcinoma to the right atrium have been diagnosedby echocardiography antemortem.5*6In our case two-dimensional echocardiographyprovided the diagnosis of a right atria1 massleading to surgical exploration. The computerized tomographic scan of the abdomen in our patient was performed to rule out an extracardiac source for the right atria1 masssuch asrenal cell carcinoma. The computerized tomographic scandid not detect the hepatoma despite its extensive involvement. Hepatomasmay be isodensewith normal hepatic parenchyma, thus alluding detection by computerized tomographic scan unless hepatic contour is altered. This is especially true in well-differentiated hepatocellular carcinoma as in our patient. Dynamic computerized tomography has made it possible to identify isodensetumors whose recognition was difficult on conventional computerized tomographic scans7 Arteriography is the best method of detecting
90%
Brief
Communications
American
small tumors, particularly by the technique of infusion hepatic angiography.8The reported caseof surgical excision of a right atria1 metastatic hepatoma was diagnosed by arteriography.’ With regard to our surgical approach, femoral vein cannulation avoided direct contact of the drainage cannula with the tumor and permitted exploration of the orifice of the inferior vena cava. Circulatory arrest with profound hypothermia was employed for part of the resection and reconstruction because subtotal occlusion of the caval orifice precluded adequate visualization. Ralloon catheter occlusion of the atriocaval junction during the latter part of the procedure shortened the period of circulatory arrest. Gore-Tex was usedfor patch reconstruction. Similar techniques have been usedfor resection of hypernephroma with involvement of the inferior vena cava.g It was anticipated that the Gore-Tex patch material would provide a barrier to recurrent extension of the tumor and, if hepatic resection were feasible, provide a well-defined margin for the superior resection. REFERENCES
1. Ehrlich DA, Widmann JJ, Berger RL, Abelmann WH. Intracavitary cardiac extension of hepatoma. Ann Thorac Surg 19’75;19:206-11. 2. Alpert E. Primary tumors of the liver: etiologic and diagnostic features. View Dig Dis 1982;14:9-11. 3. Tokuda K. Pathomorphological study on hepatocellular carcinoma. Kurume Med J 1978:41:1044-51. 4. St&ens TG. Echocardiographic diagnosis of a right ventricular metastatic tumor. Arch Intern Med 1980;140:122-4. 5. Chua SO, Chiang CW, Lee YS, Lin SH, Liaw YF. Moving right atria1 mass associated with hepatoma. Chest 1986; 8914%50. 6. Chia BL, Choo MH, Tan L, Tan A, Oon CJ, Chiw PH. Two-dimensional echocardiographic abnormalities of the right atria1 metastatic tumors in hepatoma. Chest 1985;87: 399-401. 7. Kunstlinger F, Federle MP, Marlos W. Computed tomography of hepatocellular carcinoma. AJR 1980;134:431-7. 8. Takashima T, Matsui 0, Suzuki M, Ida M. Infusion hepatic angiography in the detection of small hepatoce!lular carcinomas. Radiology 1980;137:321-5. 9. Katz NM, Spence JJ, Wallace RB. Reconstruction of the inferior vena cava with a polytetrafluoroethylene tube graft after resection for hypemephroma of the right kidney. J Thorac Cardiovasc Surg 1984;87:791-7.
Increased procainamidq plasma concentrations caused by cquhidh: drug interaction
A new
Beverly Hughes, M.D., Jo Ellen Dyer, Pharm. D., and Alan B. Schwartz, M.D. Davis and Martinez, Calif. From the Department of Medicine, University of California, Davis,and the Medical Service, Veterans Administration Hospital, Martinez. Reprint requests: A. B. Schwartz, M.D., Veterans Administration Medical Center
(lllB),
150 Muir
Rd.,
Martinez,
CA 94553.
October 1987 Heart Journal
The class IA ant&rhythmic agents procainamide and quinidine have similar cardiac electrophysiologic effects but differ in their extracardiac side effects.’ Despite these similar electrophysiologic effects, patients’ responsesto one of these agentsmay not predict their responsesto the other.2 Becausetheir extracardiac effects are doserelated and specificto each agent, it hasbeensuggestedthat when either quinidine or procainamide is ineffective because extracardiac side effects limit maximal administration, combination therapy with lower tolerable dosesof each of these may avoid these adverse effects and may be more effective than either drug alone at maximal doses.3While using combination therapy of high (but submaximal)-dose procainamide and quindine to treat a patient with sustained ventricular tachycardia, we observed increased plasmaprocainamide concentrations after the administration of quinidine, a previously unreported drug interaction. Kim et als treated patients with frequent ventricular ectopy first with maximal doses of procainamide and quinidine alone and then with the combination at submaximal dosesof each drug. Plasma concentrations of procainamide were not followed. It is thus not known if the addition of quinidine resulted in increasedprocainamide levels, although in that study3further QRS and QTc prolongation resulted with the combination compared with each drug alone. A 53-year-old man with sustained ventricular tachycardia was treated with sustained-release procainamide hydrochloride (Procan SR) after an electrophysiologic study
indicated
that
his arrhythmia
was suppressed
by
high-doseintravenous procainamide with a corresponding high plasmalevel (11.9 rig/ml). Oral sustained-releaseprocainamide was progressively increased.Steady-state concentrations
(at least 4% half-lives
at each dose level) were
measured2 to 3 hours after a dose.Determinations were made at 4,6,8, and 12 gmlday. At 12 &day (3 gm every 6 hours) plasma levels similar to those that suppressed the induction of ventricular tachycardia by programmed electrical stimulation
were achieved. The initial
QTc and QRS
durations were 562 and 192msecand increasedto 688 and 240 msec,respectively, with this regimen. Becauseof the concern for drug toxicity, procainamidewasdecreasedto 8 gm/day (2 gm every 6 hours), and quinidine gluconate (Quinaglute), 324 mg every 8 hours, was added. After 4% half-lives, a similar steady-state concentration of procainamide wasdetermined. The QTc and QRS durations were 678 and 232 msec.When compared with the levels with 8 to 9 gmlday of procainamide alone, the combination with quinidine produced substantially greater levels of procaim&de and N-acetylprocainamide (Table I). The QTc and QRS intervals and 228 msec.
at 8 gmlday
of procainamide
were 648
No medications were added or discontinued during this period. The only concomitant medication was diltiazem, 30 mg every 6 hours, the dose of which remained unchanged. Hepatic and renal function were normal before and during these measurements. The baseline (before antiarrhythmic drugs) left ventricular ejection fraction
was 11% . Steady-state
concentrations
of procain-
Brief Communications
American
October 1987 Noaft Journal
pericarditis as the first manifestation of AIDS in the course of a disseminated tuberculosis. Even with the serious immunosuppressed state of these patients, the standard treatment is usually successful and at this moment (11 months from the begining of the treatment) there is no evidence of tuberculosis in our patient. We have recently described 12 patients with tuberculosis and infection by human immunodeficiency virus; among them only two patients showed a typical pattern of a reactivation disease; the remaining patients showed an atypical pattern.6 Cardiac manifestations in AIDS are very unu5ud and limited to nonbacterial thrombotic endocarditis, focal metastatic involvement by Kaposi’s sarcoma, or congestive cardiomyopathy probably of viral origin.6 Cardiologists should be aware that AIDS may start with cardiac involvement within the context of a systemic disease. REFERENCES
1.
2.
3.
4.
5.
6.
Duncanson FP, Hewlett D, Maayan S, Estapan H, Perla EN, Wormser GP. et al. Tuberculosis and the acauired immunodeficiency syndrome in non-Haitian intravenous abusers. Presented at the International Conference on Acquired Immunodeficiency Syndrome (AIDS), Atlanta, Ga., April 1985. Stoneburner RL, Kristal A. Increasing tuberculosis incidence and its relationship to acquired immunodeficiency syndrome in New York City. Presented at the Interantional Conference on Acquired Immunodeficiency Syndrome (AIDS), Atlanta, Ga., April 1985. Pitchenick AE, Rubinson HA. The radiographic appearance of tuberculosis in patients with the acquired immunodeficiency syndrome (AIDS) and pre-AIDS. Am Rev Respir Dis 1985;131:393-6. Centers for Disease Control, US Department of Health and Human Services, Atlanta, Ga. Classification system for human T-lymphotropic virus type III/lymphadenopathyassociated virus infections. Ann Intern Med 1986;105:234-7. Navarro V, Navarro R, Juan G, Nieto A, Minguez J, Lloret T. Tuberculosis en pacientes adictos a drogas por via parenteral (ADVP) con infection por HTLV-III. Arch Bronconeumol i986,22155. Cohen IS, Anderson DW, Virmani R, Reen BM, Macher AM, Sennesh J, Di Lorenzo P, Redfield RR. Congestive cardiomyopathy in association with the acquired immunodeficiency syndrome. N Engl J Med 1986;315:628-30.
Hepatoma mass
presenting
as a right atrigl
Daniel L. Miller, M.D., Nevin M. Katz, M.D., and Randolph S. Pallas, M.D. Washington, D.C. A large right atria1 masswas diagnosedby echocardiography in a young man. At surgery the masswasfound to be a From the Departments of Medicine and Surgery, Georgetown University Hospital. Reprint requests: N&n M. Katz, M.D., Department of Surgery, Georgetown University Hospital, 3800 Reservoir Rd. NW, Washington, DC 20007.
Fig. 1. Two-dimensional echocardiographic apical fourchamber view demonstrates the large tumor (T) within the right atrium.
direct
extension
of a hepatocellular
carcinoma.
We are
reporting this casebecauseprecisepreoperative diagnosis was difficult, and to our knowledge, only one other surgical casehas been described.’ A 36year-old white man with a history of psoriasis developed fever, malaise, proximal muscle weakness, abdominal distension, and lower extremity edema. On admissionto the hospital he was in respiratory distress, heart rate was 120 bpm, and pulsesparadoxus of 25 mm Hg was present. Jugular venous distension was absent. Heart sounds were muffled. There was marked ascites with hepatomegaly and pretibial edema to midcalf. ECG revealed right atrial enlargement with sinus tachycardia. Liver function test results were abnormal: direct bilirubin 2.0 mg/dl, total bilirubin 5.3 mg/dl, alkaline phosphatase 393Ill/L (normal <88), SGOT 52 IU/L (normal <42), and SGPT 89 IU/L (normal <60). Serum cy-fetoprotein was normal. An abdominal computerized tomographic scan with contrast material was negative for tumor. A twodimensional echocardiogram showed a 5 by 6 cm right atrial massoccupying a major portion of the right atrium (Fig. 1). Intermittent obstruction of the tricuspid valve and inferior vena caval orifice was seen. At operation through a median sternotomy there was marked thickening along the medial aspect of the right atrioinferior vena caval junction. The patient was cooled on cardiopulmonary bypass to 18’ C with venous drainage via the right atria1 appendageand right femoral vein. On
Volum* Number
114 4, Part 1
Brief
Communications
907
Fig. 2. The right atrium mass represented extension of a hepatocellular carcinoma through the diaphragm almost completely obstructing the inferior vena cava (WC) orifice and the orifice of the tricuspid valve. The intrathoracic portion of the tumor was excised and the right atriocaval wall was reoonstructured with a 4 by 6 cm oval patch of Gore-Tex. (WC = superior vena cava.)
exploration via a right atriotomy it was found that a large tumor massoccupied more than half of the interior of the right atrium (Fig. 2). The masswas densely adherent to the medial wall of the right atrium at its junction with the inferior vena cava. External to this the diaphragm was intimately adherent to this area. The tumor masswas excised by mobilizing a collar of atriocaval junction. Dissection was carried through the diaphragm and the column of tumor wasdivided by electrocautery. An inferior vena caval thrombus, separatefrom the tumor column, was removed by balloon catheter. Under a secondperiod of circulatory arrest the right atrioinferior vena caval junction was reconstructed with a Gore-Tex patch (W.L. Gore & Associates,Inc., Elkton, Md.) After surgery a good hemodynamic state was present and there was normal pulmonary and renal function, no evidence of neurologic deficit, and a gradual resolution of lower body edema. Anticoagulation was employed. Arteriography demonstrated extensive tumor involvement of the liver and venography showed residual thrombus in the infrarenal vena cava. The patient is now 6 months postoperative, moderately active, and undergoing a combined program of radiotherapy and immunotherapy.
Hepatocellular carcinoma represents 1% to 2.5 % of all malignanciesin the United States2 Right atrial metastases occur in 1% to 4% of patients with hepatoma.3 Steffens’ reported the first echocardiographicdiagnosisof metastatic hepatocellular carcinoma to the heart. To the best of our knowledge, only four cases of metastatic hepatocellular carcinoma to the right atrium have been diagnosedby echocardiography antemortem.5*6In our case two-dimensional echocardiographyprovided the diagnosis of a right atria1 massleading to surgical exploration. The computerized tomographic scan of the abdomen in our patient was performed to rule out an extracardiac source for the right atria1 masssuch asrenal cell carcinoma. The computerized tomographic scandid not detect the hepatoma despite its extensive involvement. Hepatomasmay be isodensewith normal hepatic parenchyma, thus alluding detection by computerized tomographic scan unless hepatic contour is altered. This is especially true in well-differentiated hepatocellular carcinoma as in our patient. Dynamic computerized tomography has made it possible to identify isodensetumors whose recognition was difficult on conventional computerized tomographic scans7 Arteriography is the best method of detecting
90%
Brief
Communications
American
small tumors, particularly by the technique of infusion hepatic angiography.8The reported caseof surgical excision of a right atria1 metastatic hepatoma was diagnosed by arteriography.’ With regard to our surgical approach, femoral vein cannulation avoided direct contact of the drainage cannula with the tumor and permitted exploration of the orifice of the inferior vena cava. Circulatory arrest with profound hypothermia was employed for part of the resection and reconstruction because subtotal occlusion of the caval orifice precluded adequate visualization. Ralloon catheter occlusion of the atriocaval junction during the latter part of the procedure shortened the period of circulatory arrest. Gore-Tex was usedfor patch reconstruction. Similar techniques have been usedfor resection of hypernephroma with involvement of the inferior vena cava.g It was anticipated that the Gore-Tex patch material would provide a barrier to recurrent extension of the tumor and, if hepatic resection were feasible, provide a well-defined margin for the superior resection. REFERENCES
1. Ehrlich DA, Widmann JJ, Berger RL, Abelmann WH. Intracavitary cardiac extension of hepatoma. Ann Thorac Surg 19’75;19:206-11. 2. Alpert E. Primary tumors of the liver: etiologic and diagnostic features. View Dig Dis 1982;14:9-11. 3. Tokuda K. Pathomorphological study on hepatocellular carcinoma. Kurume Med J 1978:41:1044-51. 4. St&ens TG. Echocardiographic diagnosis of a right ventricular metastatic tumor. Arch Intern Med 1980;140:122-4. 5. Chua SO, Chiang CW, Lee YS, Lin SH, Liaw YF. Moving right atria1 mass associated with hepatoma. Chest 1986; 8914%50. 6. Chia BL, Choo MH, Tan L, Tan A, Oon CJ, Chiw PH. Two-dimensional echocardiographic abnormalities of the right atria1 metastatic tumors in hepatoma. Chest 1985;87: 399-401. 7. Kunstlinger F, Federle MP, Marlos W. Computed tomography of hepatocellular carcinoma. AJR 1980;134:431-7. 8. Takashima T, Matsui 0, Suzuki M, Ida M. Infusion hepatic angiography in the detection of small hepatoce!lular carcinomas. Radiology 1980;137:321-5. 9. Katz NM, Spence JJ, Wallace RB. Reconstruction of the inferior vena cava with a polytetrafluoroethylene tube graft after resection for hypemephroma of the right kidney. J Thorac Cardiovasc Surg 1984;87:791-7.
Increased procainamidq plasma concentrations caused by cquhidh: drug interaction
A new
Beverly Hughes, M.D., Jo Ellen Dyer, Pharm. D., and Alan B. Schwartz, M.D. Davis and Martinez, Calif. From the Department of Medicine, University of California, Davis,and the Medical Service, Veterans Administration Hospital, Martinez. Reprint requests: A. B. Schwartz, M.D., Veterans Administration Medical Center
(lllB),
150 Muir
Rd.,
Martinez,
CA 94553.
October 1987 Heart Journal
The class IA ant&rhythmic agents procainamide and quinidine have similar cardiac electrophysiologic effects but differ in their extracardiac side effects.’ Despite these similar electrophysiologic effects, patients’ responsesto one of these agentsmay not predict their responsesto the other.2 Becausetheir extracardiac effects are doserelated and specificto each agent, it hasbeensuggestedthat when either quinidine or procainamide is ineffective because extracardiac side effects limit maximal administration, combination therapy with lower tolerable dosesof each of these may avoid these adverse effects and may be more effective than either drug alone at maximal doses.3While using combination therapy of high (but submaximal)-dose procainamide and quindine to treat a patient with sustained ventricular tachycardia, we observed increased plasmaprocainamide concentrations after the administration of quinidine, a previously unreported drug interaction. Kim et als treated patients with frequent ventricular ectopy first with maximal doses of procainamide and quinidine alone and then with the combination at submaximal dosesof each drug. Plasma concentrations of procainamide were not followed. It is thus not known if the addition of quinidine resulted in increasedprocainamide levels, although in that study3further QRS and QTc prolongation resulted with the combination compared with each drug alone. A 53-year-old man with sustained ventricular tachycardia was treated with sustained-release procainamide hydrochloride (Procan SR) after an electrophysiologic study
indicated
that
his arrhythmia
was suppressed
by
high-doseintravenous procainamide with a corresponding high plasmalevel (11.9 rig/ml). Oral sustained-releaseprocainamide was progressively increased.Steady-state concentrations
(at least 4% half-lives
at each dose level) were
measured2 to 3 hours after a dose.Determinations were made at 4,6,8, and 12 gmlday. At 12 &day (3 gm every 6 hours) plasma levels similar to those that suppressed the induction of ventricular tachycardia by programmed electrical stimulation
were achieved. The initial
QTc and QRS
durations were 562 and 192msecand increasedto 688 and 240 msec,respectively, with this regimen. Becauseof the concern for drug toxicity, procainamidewasdecreasedto 8 gm/day (2 gm every 6 hours), and quinidine gluconate (Quinaglute), 324 mg every 8 hours, was added. After 4% half-lives, a similar steady-state concentration of procainamide wasdetermined. The QTc and QRS durations were 678 and 232 msec.When compared with the levels with 8 to 9 gmlday of procainamide alone, the combination with quinidine produced substantially greater levels of procaim&de and N-acetylprocainamide (Table I). The QTc and QRS intervals and 228 msec.
at 8 gmlday
of procainamide
were 648
No medications were added or discontinued during this period. The only concomitant medication was diltiazem, 30 mg every 6 hours, the dose of which remained unchanged. Hepatic and renal function were normal before and during these measurements. The baseline (before antiarrhythmic drugs) left ventricular ejection fraction
was 11% . Steady-state
concentrations
of procain-