- Email: [email protected]
Heart Block in “Oddball” Diseases
an active participant in phagocytosis in certain diseases involving other systems.
Wilfrido M . Sy, M.D. o and Monte Malach, M.D., F.C .C.P. oo Brooklyn, NY Director, Nuclear Medicine Service, Department of Radiology, Brooklyn-Cumberland Medical Center and Clinical_ Ass_istant Professor, Department of Radiology, State UmversJty of New York Downstate Medical School. 00 Attending, Department of Medicine, Brooklyn-Cumberland Medical Center, and Clinical Associate Professor of Medicine, State University of New York Downstate Medical School. Reprint requests: Dr. Sy, Nuclear Medicine, Brooklyn Hospital, Brooklyn 11201 0
REFERENCES
1 Klingensmith W III, Ryerson TW: Lung uptake of 99mTc sulfur colloid. J Nucl Med 14:201-204, 1973 2 Mikhael MA, Evens RG: Migration and embolization of macrophages to the lung: A possible mechanism for colloid lung uptake in the lung during liver scanning. J Nucl Med 16:22-27, 1975 3 Chaudhuri TK, Evans TC, Chaudhuri TK: Autoradiographic studies of distribution of the liver of I98Au and llll"'Tc sulfur colloids. Radiology 109:633-637, 1973
Heart Block in "Oddball" Diseases various degrees of atrioventricular (A V) block are known as concomitants of a large number of systemic diseases, including several neuromuscular disorders, such as primary muscular dystrophy, 1 Friedreich's ataxia, 2 myotonic dystrophy, 3 and a variety of syndromes which have in common the feature of progressive external ophthalmoplegia (PEO). The report by Clark et al in this issue (see page 727) adds significantly to the literature on one of the PEO disorders, the Keams-Sayre syndrome. KeamsSayre syndrome 4 is a rare nonfamilial disorder, usually presenting in childhood or adolescence with ptosis, external ophthalmoplegia, and visual loss; it is associated with facial weakness and, in some patients, a generalized myopathy, neurosensory deafness, abnormally small stature, diffusely abnormal electroencephalogram, myopathic spindles on the electromyogram, and an elevated spinal fluid yglobulin.5 The proliferation of reports of "new" syndromes characterized by PEO led Drachman6 in 1968 to note the considerable overlap of associated features in several neurodegenerative disorders which could be loosely grouped under the designation "ophthalmoplegia plus." Disturbances of AV conduction occur in a number of these, including Keams-Sayre syndrome, progressive external ophthalmoplegia 614 EDITORIALS
(ocular myopathy), chronic PEO and muscular dystrophy, abiotrophic ophthalmoplegia extema, spongiform encephalopathy, Shy's syndrome, and Refsum's disease. 6 Progression of conduction disease ( bifascicular block progressing to second and third degree AV block) has been documented in some cases of Keams-Sayre syndrome, and symptomatic complete heart block was the mode of death in a majority of reported patients in whom conduction disturbances were shown. In contrast to patients with progressive muscular dystrophy, congestive heart failure has been present in a minority of reported cases of Keams-Sayre syndrome, and normal hemodynamics were found in a case investigated by Uppal. 5 The present report by Clark et al represents the second documentation of the site of block in KeamsSayre syndrome with His bundle recordings, 7 and the first cardiac electrophysiologic-pathologic correlation in this condition. The authors identified lesions consisting of vacuolization of Purkinje cells and fibrofatty infiltration of the distal His bundle and proximal left bundle branch. The histologic changes and their location resemble those found in a growing body of pathologic studies in cases of conduction disease, in which the site of block was correctly predicted by intracardiac recordings during life. It has been shown, for example, that second or third degree AV block proximal to the His recording site (A V nodal block) is associated with lesions involving the AV node and its approaches, that the occurrence of "split" His potentials correlates with lesions of the His bundle and that patients with bifascicular block and His~ven tricle ( H-V) interval prolongation or block, or both, distal to the His bundle recording site ( trifascicular block) have extensive lesions involving the His bundle and proximal portions of both bundle branches."·" However, a recent report of a major discordance between the presence of extensive pathologic lesions in the His bundle and bundle branches of a patient with aortic stenosis and only transient AV conduction disturbances 12 indicates that careful documentation of the site of block during life and correlations with anatomic structure by serial section should continue when such opportunities present themselves. The present electrophysiologic-pathologic report is, therefore, most opportune.
Christopher R. Wyndham, M.B. 0 Chicago Associate in Medicine, Section of Cardiology, Department of Medicine, Abraham Lincoln School of ~1edicine, University of Illinois at the Medical Center. Reprint requests: Dr. Wyndham, Section of Cardiology 840 ' South Wood Street, Chicago 60612 0
CHEST, 68: 5, NOVEMBER, 1975
REFERENCES
2 3 4
5 6 7 8
9
10
11 12
James TN : Observations on the cardiovascular involvement, including the cardiac conduction system, in progressive muscular dystrophy. Am Heart J 63:48, 1962 James TN, Fisch C : Observations on the cardiovascular involvement in Friedreich's ataxia. Am Heart J 66 :164, 1963 Bulloch RT, Davis JL, Hara M: Dystrophia myotonica with heart block: A light and electron microscopic study. Arch Pathol 84: 130, 1967 Keams TP : External ophthalmoplegia, pigmentary degeneration of the retina, and cardiomyopathy : A newly recognized syndrome. Trans Am Ophthalmol Soc 63:559625, 1965 Uppal SC : Kearn's syndrome, a new form of cardiomyopathy. Br Heart J 35 :766-769, 1973 Drachman DA : Ophthalmoplegia plus: The neurodegenerative disorders associated with progressive external ophthalmoplegia. Arch Neurol18 :654-674, 1968 Morris JH, Eugster GS, Nora JJ, et al: His bundle recordings in progressive external ophthalmoplegia. J Pediatr 81 :1167, 1972 Rosen KM, Rahimtoola SH, Gunnar RM, et al : Transient and persistent atrial standstill with His bundle lesions : Electrophysiologic and pathologic correlations. Circulation 44 :220-236, 1971 Rosen KM, Rahimtoola SH, Gunnar RM, et a! : Site of heart block as defined by His bundle recording: Pathologic correlations ' in three cases. Circulation 45 :965-987, 1972 Hunt D, Lie JT, Vohra J, et al : Histopathology of heart block complicating myocardial infarction: Correlation with the His bundle electrogram. Circulation 48 : 12521261, 1973 Bharati S, Lev M, Wu D, eta! : Pathophysiologic correlations in two cases of split His bundle potentials. Circulation 49 :615-623, 1974 Rosen KM, Wu D, Kanakis C Jr, et al: Return of normal conduction after paroxysmal heart block : Report of a case with major discordance of electrophysiological and pathological findings . Circulation 51 :197-204, 1975
BCG-osis
J n their case report in this issue (see page 725) ,
Sparks et al add to the list of complications of BCG vaccine following its use as a therapeutic agent against neoplastic disease. Malignant melanoma nodules in their patient completely regressed following systemic and intratumor injections of BCG vaccine, but a severe generalized skin erruption with granulomas ensued. The rash was transient and apparently responded favorably to the administration of steroids and isoniazid. Complications of BGG vaccination vary widely. 1-a The severity of the local reaction depends upon the number of previous vaccinations. Systemic reactions include chills, fever, myalgias and arthralgias.
CHEST, 68: 5, NOVEMBER, 1975
Progressive infection with the Calmette-Guerin bacillus has been documented in regional lymph nodes and pleura; miliary caseating granulomas have been reported. Acid-fast organisms identified as CalmetteGuerin bacilli have been cultured from autopsy specimens of liver and lung. Scarification and multiple puncture techniques have less morbidity than intradermal injections. lntratumor injection is the most hazardous, and severe hypersensitivity reactions have been observed following the intralesional administration of BCG vaccine. Two patients have died from apparent reactions to intratumor injection of BCG vaccine. The complications of BCG therapy for neoplastic disease raise difficult and largely unanswered questions. Do the untoward reactions reflect host hyperreactivity, hyporeactivity, or disseminated tuberculous infection? Small consolation can be found in the realization that all Calmette-Guerin organisms currently in use are sensitive to standard antituberculosis chemotherapy. But, as Sparks et al ask, does isoniazid therapy decrease the antineoplastic effect of BCG immunotherapy? Finally, does tumor growth acceleration ever occur following BCG vaccination? Because of the uncertain indications and significant untoward reactions that include death, BCG vaccination for cancer patients is not recommended for use in general practice. BCG vaccination of a terminal cancer patient as part of "medical last rites" definitely is not indicated and is potentially harmful. Well-controlled clinical investigation hopefully will answer some of the immunologic questions and identify the indications for BCG therapy for cancer patients and, thereby, control and make more acceptable "BCG-osis," the complications of BCG therapy.
Whitney W. Addington, M.D., F.C.C.P. • Chicago •Chairman, Division of Pulmonary Medicine, Cook County Hospital. Reprint requests: Dr. Addington, 1825 West Harrison Street, Chicago 60612 REFERENCES
1 Sparks FC, Silverstein JD, Hunt JS, et al: Complications of BCG immunotherapy in plltients with cancer. New Eng! J Med 289 :827, 1973 2 Bast RC, Zbar B, Borsos T, et al: BCG and cancer. New Eng! J Med 290 :1458, 1974 3 Aungst CW, Sokal JE, Jager BV : Complications of BCG vaccination in neoplastic disease. Ann Intern Med 82:666, 1975
EDITORIALS 615
Wilfrido M . Sy, M.D. o and Monte Malach, M.D., F.C .C.P. oo Brooklyn, NY Director, Nuclear Medicine Service, Department of Radiology, Brooklyn-Cumberland Medical Center and Clinical_ Ass_istant Professor, Department of Radiology, State UmversJty of New York Downstate Medical School. 00 Attending, Department of Medicine, Brooklyn-Cumberland Medical Center, and Clinical Associate Professor of Medicine, State University of New York Downstate Medical School. Reprint requests: Dr. Sy, Nuclear Medicine, Brooklyn Hospital, Brooklyn 11201 0
REFERENCES
1 Klingensmith W III, Ryerson TW: Lung uptake of 99mTc sulfur colloid. J Nucl Med 14:201-204, 1973 2 Mikhael MA, Evens RG: Migration and embolization of macrophages to the lung: A possible mechanism for colloid lung uptake in the lung during liver scanning. J Nucl Med 16:22-27, 1975 3 Chaudhuri TK, Evans TC, Chaudhuri TK: Autoradiographic studies of distribution of the liver of I98Au and llll"'Tc sulfur colloids. Radiology 109:633-637, 1973
Heart Block in "Oddball" Diseases various degrees of atrioventricular (A V) block are known as concomitants of a large number of systemic diseases, including several neuromuscular disorders, such as primary muscular dystrophy, 1 Friedreich's ataxia, 2 myotonic dystrophy, 3 and a variety of syndromes which have in common the feature of progressive external ophthalmoplegia (PEO). The report by Clark et al in this issue (see page 727) adds significantly to the literature on one of the PEO disorders, the Keams-Sayre syndrome. KeamsSayre syndrome 4 is a rare nonfamilial disorder, usually presenting in childhood or adolescence with ptosis, external ophthalmoplegia, and visual loss; it is associated with facial weakness and, in some patients, a generalized myopathy, neurosensory deafness, abnormally small stature, diffusely abnormal electroencephalogram, myopathic spindles on the electromyogram, and an elevated spinal fluid yglobulin.5 The proliferation of reports of "new" syndromes characterized by PEO led Drachman6 in 1968 to note the considerable overlap of associated features in several neurodegenerative disorders which could be loosely grouped under the designation "ophthalmoplegia plus." Disturbances of AV conduction occur in a number of these, including Keams-Sayre syndrome, progressive external ophthalmoplegia 614 EDITORIALS
(ocular myopathy), chronic PEO and muscular dystrophy, abiotrophic ophthalmoplegia extema, spongiform encephalopathy, Shy's syndrome, and Refsum's disease. 6 Progression of conduction disease ( bifascicular block progressing to second and third degree AV block) has been documented in some cases of Keams-Sayre syndrome, and symptomatic complete heart block was the mode of death in a majority of reported patients in whom conduction disturbances were shown. In contrast to patients with progressive muscular dystrophy, congestive heart failure has been present in a minority of reported cases of Keams-Sayre syndrome, and normal hemodynamics were found in a case investigated by Uppal. 5 The present report by Clark et al represents the second documentation of the site of block in KeamsSayre syndrome with His bundle recordings, 7 and the first cardiac electrophysiologic-pathologic correlation in this condition. The authors identified lesions consisting of vacuolization of Purkinje cells and fibrofatty infiltration of the distal His bundle and proximal left bundle branch. The histologic changes and their location resemble those found in a growing body of pathologic studies in cases of conduction disease, in which the site of block was correctly predicted by intracardiac recordings during life. It has been shown, for example, that second or third degree AV block proximal to the His recording site (A V nodal block) is associated with lesions involving the AV node and its approaches, that the occurrence of "split" His potentials correlates with lesions of the His bundle and that patients with bifascicular block and His~ven tricle ( H-V) interval prolongation or block, or both, distal to the His bundle recording site ( trifascicular block) have extensive lesions involving the His bundle and proximal portions of both bundle branches."·" However, a recent report of a major discordance between the presence of extensive pathologic lesions in the His bundle and bundle branches of a patient with aortic stenosis and only transient AV conduction disturbances 12 indicates that careful documentation of the site of block during life and correlations with anatomic structure by serial section should continue when such opportunities present themselves. The present electrophysiologic-pathologic report is, therefore, most opportune.
Christopher R. Wyndham, M.B. 0 Chicago Associate in Medicine, Section of Cardiology, Department of Medicine, Abraham Lincoln School of ~1edicine, University of Illinois at the Medical Center. Reprint requests: Dr. Wyndham, Section of Cardiology 840 ' South Wood Street, Chicago 60612 0
CHEST, 68: 5, NOVEMBER, 1975
REFERENCES
2 3 4
5 6 7 8
9
10
11 12
James TN : Observations on the cardiovascular involvement, including the cardiac conduction system, in progressive muscular dystrophy. Am Heart J 63:48, 1962 James TN, Fisch C : Observations on the cardiovascular involvement in Friedreich's ataxia. Am Heart J 66 :164, 1963 Bulloch RT, Davis JL, Hara M: Dystrophia myotonica with heart block: A light and electron microscopic study. Arch Pathol 84: 130, 1967 Keams TP : External ophthalmoplegia, pigmentary degeneration of the retina, and cardiomyopathy : A newly recognized syndrome. Trans Am Ophthalmol Soc 63:559625, 1965 Uppal SC : Kearn's syndrome, a new form of cardiomyopathy. Br Heart J 35 :766-769, 1973 Drachman DA : Ophthalmoplegia plus: The neurodegenerative disorders associated with progressive external ophthalmoplegia. Arch Neurol18 :654-674, 1968 Morris JH, Eugster GS, Nora JJ, et al: His bundle recordings in progressive external ophthalmoplegia. J Pediatr 81 :1167, 1972 Rosen KM, Rahimtoola SH, Gunnar RM, et al : Transient and persistent atrial standstill with His bundle lesions : Electrophysiologic and pathologic correlations. Circulation 44 :220-236, 1971 Rosen KM, Rahimtoola SH, Gunnar RM, et a! : Site of heart block as defined by His bundle recording: Pathologic correlations ' in three cases. Circulation 45 :965-987, 1972 Hunt D, Lie JT, Vohra J, et al : Histopathology of heart block complicating myocardial infarction: Correlation with the His bundle electrogram. Circulation 48 : 12521261, 1973 Bharati S, Lev M, Wu D, eta! : Pathophysiologic correlations in two cases of split His bundle potentials. Circulation 49 :615-623, 1974 Rosen KM, Wu D, Kanakis C Jr, et al: Return of normal conduction after paroxysmal heart block : Report of a case with major discordance of electrophysiological and pathological findings . Circulation 51 :197-204, 1975
BCG-osis
J n their case report in this issue (see page 725) ,
Sparks et al add to the list of complications of BCG vaccine following its use as a therapeutic agent against neoplastic disease. Malignant melanoma nodules in their patient completely regressed following systemic and intratumor injections of BCG vaccine, but a severe generalized skin erruption with granulomas ensued. The rash was transient and apparently responded favorably to the administration of steroids and isoniazid. Complications of BGG vaccination vary widely. 1-a The severity of the local reaction depends upon the number of previous vaccinations. Systemic reactions include chills, fever, myalgias and arthralgias.
CHEST, 68: 5, NOVEMBER, 1975
Progressive infection with the Calmette-Guerin bacillus has been documented in regional lymph nodes and pleura; miliary caseating granulomas have been reported. Acid-fast organisms identified as CalmetteGuerin bacilli have been cultured from autopsy specimens of liver and lung. Scarification and multiple puncture techniques have less morbidity than intradermal injections. lntratumor injection is the most hazardous, and severe hypersensitivity reactions have been observed following the intralesional administration of BCG vaccine. Two patients have died from apparent reactions to intratumor injection of BCG vaccine. The complications of BCG therapy for neoplastic disease raise difficult and largely unanswered questions. Do the untoward reactions reflect host hyperreactivity, hyporeactivity, or disseminated tuberculous infection? Small consolation can be found in the realization that all Calmette-Guerin organisms currently in use are sensitive to standard antituberculosis chemotherapy. But, as Sparks et al ask, does isoniazid therapy decrease the antineoplastic effect of BCG immunotherapy? Finally, does tumor growth acceleration ever occur following BCG vaccination? Because of the uncertain indications and significant untoward reactions that include death, BCG vaccination for cancer patients is not recommended for use in general practice. BCG vaccination of a terminal cancer patient as part of "medical last rites" definitely is not indicated and is potentially harmful. Well-controlled clinical investigation hopefully will answer some of the immunologic questions and identify the indications for BCG therapy for cancer patients and, thereby, control and make more acceptable "BCG-osis," the complications of BCG therapy.
Whitney W. Addington, M.D., F.C.C.P. • Chicago •Chairman, Division of Pulmonary Medicine, Cook County Hospital. Reprint requests: Dr. Addington, 1825 West Harrison Street, Chicago 60612 REFERENCES
1 Sparks FC, Silverstein JD, Hunt JS, et al: Complications of BCG immunotherapy in plltients with cancer. New Eng! J Med 289 :827, 1973 2 Bast RC, Zbar B, Borsos T, et al: BCG and cancer. New Eng! J Med 290 :1458, 1974 3 Aungst CW, Sokal JE, Jager BV : Complications of BCG vaccination in neoplastic disease. Ann Intern Med 82:666, 1975
EDITORIALS 615