fu:FEREN~
1 Hinson K.FW, Moon AJ, Plummer !'l{S: Bronchopulmonary aspergillosis: A review and a report of eight new cases. Thorax 73:317, 1952 2 Spotnitz M, Overholt EC: Mucoid impaction of the bronchi associated with aspergillus. Dis Chest 52:92, 1967 3 Goodman DH: Bronchiectasis, eosinophilia, asthma and pneumonitis, BEAP syndrome. Ann Allergy 33:289, 1974 4 Goodman DH: Bronchiectasis in allergic aspergillosis (BEAP syndrome). Ariz Med 31:91-93, 1975 5 Liebow AA: The J Burns Amberson lecture-Pulmonary angiitis and granulomatosis. Am Rev Respir Dis 108: 1, 1973 6 Katzenstein AL, Liebow AA, Friedman PJ: Bronchocentric granulomatosis, mucoid impaction, and hypersensitivity reactions to fungi. Am Rev Respir Dis III:497537, 1975 7 Scadding JG : The bronchi in allergic aspergillosis. Scand J Resp Dis 48:372, 1967
Intermittent Complete Atrioventricular Block Masquerading as Epilepsy in the Mitral Valve Prolapse Syndrome* David Woodley, M.D. ;•• Ward Chambers, M.D.;t Helen Starke, M.D.; Barry Dzindzio, M.D.; and Alan D. Forker, M.D. FIGURE 2. Mucoid impaction of the bronchus in the region of the lingula.
constitutes the BEAP syndrome. 3 • 4 Mucoid impaction of the bronchi ( MIB) is a frequent concomitant feature of the syndrome.2 The bronchi in allergic bronchopulmonary aspergil]osis are damaged at the site of lodgement of the mucous plugs which contain Aspergillus mycelia, the antigenic source of the formation of precipitins. The Aspergillus antigen-antibody complexes created within the impacted mucus cause a type 3 Arthus reaction resulting in a destructive inflammatory reaction of the bronchial wall. 7 This may result in bronchiectasis and bronchocentric granulomatosis. Bronchocentric granulomatosis represents a distinctive microscopic lesion associated with ABPA, MIB and the BEAP syndrome. Patients with bronchocentric granulomatosis in whom noninvasive fungi have been found invariably have chronic asthma with eosinophilia, mucoid impaction and central bronchiectasis.6 Pulmonary cavitation can also occur with advanced allergic bronchopulmonary aspergillosis and bronchocentric granulomatosis. A cavity could represent abscess, cavitated granuloma or marked dilated bronchi. 6 In patients with chronic asthma, any of the following should suggest the diagnosis of allergic bronchopulmonary aspergillosis: the occurrence of more than one episode of pneumonitis, transitory pulmonary infiltrates with eosinophilia, atelectasis resulting from mucous plugs, upper lobe fibrosis, "central" bronchiectasis and/ or pulmonary cavitation.
CHEST, 72: 3, SEPTEMBER, 1977
A 24-year-old white man had a history of "epDepsy" since the age of eight years. Prolapse of the mitral valve was documented by auscultation and echocardlographic and left ventriculographic studies. At 120 hours after st0pping therapy with phenobarbital and diphenylhydantoin (Dilantin) sodium, continuous electrocardiographic monitoring (Holter monitor) revealed episodes of coinplete atrioventricular block lasting up to 23 seconds. 1be results of hemodynamic studies were normal. 1be patient's symptoms were all totally corrected by implantation of an epicardial demand pacemaker. 1bis report raises the possibillty that sudden death in association with the mitral valve prolapse syndrome may be due to intermittent severe disturbances in conduction, in addition to ventricolar arrhythmias.
S
udden death has recently been emphasized as a complication of the mitral valve prolapse syndrome. 1 • 2 Fortunately, this complication is a relatively rare manifestation of this common syndrome. A recent editorial by Jeresaty 1 reviewed the 12 known cases of sudden death. The mechanism of sudden death is thought to be ventricular tachycardia and 6brillation. i-s This report describes a case of prolapse of the mitral valve in which •From the Cardiovascular Division and Cardiovascular Center, University of Nebraska Medical Center, Omaha. • 0 lntemal Medicine Resident. tcardiology Fellow.
Reprint requests: Dr. Forker, University of Nebraska Medical Center, 668 South 4lst Street, Omaha 68105
INTERMITIENT COMPLETE AV BLOCK 369
FIGURE 1. Echocardiogram showing pansystolic prolapse of mitral valve (black am>u>s) . IVS, Intervenbicular septum; and AML, anterior mitral leaJlet.
intermittent, recurrent complete heart block was documented and masqueraded as "epilepsy" for 16 years. Sudden death in some patients with prolapse of the mitral valve may conceivably be secondary to intermittent severe abnormalities of conduction.
chest and neck and occasionally by a sensation of palpitations. Throughout childhood and adolescence, he was thought to have epilepsy. In November 1975, the patient had an evaluation at another hospital, where an electroencephalogram, brain scan, skull x-ray films, treadmill electrocardiogram, 24-hour continuous electrocardiographic monitoring ( Holter monitor) , and 24-hour urinary levels of vanillylmandelic acid and 5hydroxyindoleacetic acid were normal. The patient was started on a trial of therapy with diphenylhydantoin ( Dilantin) sodium ( 300 mg daily). Soon after, his blackout spells
CASE REPORT
A 24-year-old man had been troubled with "blackout spells" since the age of eight years. He noted that each spell of unconsciousness was preceded by a vague feeling in his
'----
. /'--
. / ~/
~
7 . . ____
.
7 i._ . . , .-
~,/'
..
~~ . •·
.
-...
F1cURE 2. Continuous rhythm strip documents intermittent complete abiovenbicular block
( numbers in background should be ignored).
370 WOODLEY ET AL
CHEST, 72: 3, SEPTEMBER, 1977
changed character to include generalized tonic-clooic contractions, unconsciousness, and mild postictal nausea. Each episode lasted approximately 20 seconds. In December 1975, therapy with phenobarbital ( 60 mg twice daily) was added; the patient was free of "sei%ures" up until the time of his admission to the neurology service at the University of Nebraska Medical Center on Feb 9, 1976. Other than a questionable history of a seizure disorder affecting his maternal grandmother, the family history was unremarlcable. The findings from physical examination were essentially normal, except for a soft, mid-late grade 1-2/6 systolic murmur, which became more prominent with standing. A systolic click was never heard. The resting ECG was nonnal. A treadmill exercise ECG was normal, with the patient reaching a maximum heart rate of 176 beats per minute without symptoms, disturbance in rhythm, or ST-segment changes. An echocardiogram revealed pansystolic prolapse of both leaflets of the mitral valve (Fig 1 ) . The transducer was in the third intercostal space, perpendicular to the chest wall. At 96 hours after stopping all medications, an EEG, brain scan, and the results of computemed axial tomographic studies of the brain were normal. A chest x-ray film and the findings from general laboratory tests, serum protein electrophoresis, determinations of antinuclear antibody, and latex fixation test were all normal. At 120 hours after stopping all medications, continuous electrocardiographic monitoring (Holter monitor) revealed episodes of complete atrioventricular bloclc with an extremely slow junctional escape pacemaker (Fig 2). The atrial rate accelerated to sinus tachycardia during heart bloclc. During the episodes the patient was prone in bed and did not lose consciousness but felt very lightheaded. With continuous monitoring in the intensive care unit, similar episodes of highdegree atrioventricular block were documented, lasting up to 23 seconds. No change in position or vagal maneuvers was related to the episodes. An epicardial demand pacemaker was implanted without complications. After one month of followup with no medications, the patient has been free of "seizures" or blackout spells. A complete cardiac catheterization was performed on April 16, 1976. This revealed normal coronary arteries with a right dominant system, a normal ventriculogram (except for a moderate pro}apse of the posterior leaflet of the mitral valve), and normal results on hemodynamic studies. The results of a study of the His bundle were also normal; throughout the latter study, the patient's epicardial pacemaker was suppressed by his own intrinsic rate of over 75 beats per minute. DISCUSSION
Supraventricular and ventricular ectopic beats, atrial tachyarrhythmias, and ventricular tachycardia are wellknown complications of prolapse of the mitral valve.1 • 1 The most common disturbance in rhythm is ventricular premature contractions. 3- 5 Sudden death associated with prolapse of the mitral valve has been attributed to ventricular arrhythmias. 1 • 2 •8 Bradyarrhythmias are less well recogni7.ed as complications of the mitral valve prolapse syndrome. 5 •7 •8 Leighbnan et al8 have reported the findin~ in a family of 11 patients with a high prevalance of prolapse of the mitral valve; seven of the members of the family had
CHEST, 72: 3, SEPTEMBER, 1977
documented bradyarrhythmias.8 Three patients had recurrent syncope produced by simple uptilting of the head. One patient had sinus arrest and sustained asystole produced by tilting up the head. Studies of the His bundle revealed prolonged atrio-His intervals; atrial pacing revealed an inability to maintain I: I conduction when paced at 120 beats per minute. Bradyarrhythmia and sinus arrest were thought to be due to excessive vagal tone. In two of these patients, the condition was successfully controlled by permanent demand pacing. Disturbances in conduction have been least emphasized as associated features of the mitral valve prolapse syndrome. Of all the abnormalities of conduction, firstdegree atrioventricular block is the most common.11• 12 Left anterior hemiblock, 11 •12 left anterior hemiblock plus right bundle branch block,11,12 right bundle branch block,9,lt-13 and left bundle branch block9·12.H have also been described. Second-degree atrioventricular block has been rare. 9 •12 Complete heart block has been reported in fourcases.e,12,u In this report, we describe a patient with prolapse of the mitral valve who had episodic complete atrioventricular block which induced seizure-like spells and was corrected by implantation of a permanent pacemaker. The mechanism of this disturbance in conduction is unknown, but this report emphasizes the possibility that sudden death in association with the mitral valve prolapse syndrome may be due to intermittent severe disturbances in conduction, in addition to ventricular arrhythmias. Repeated and prolonged electrocardiographic monitoring may be necessary before the mechanism for the symptoms and arrhythmia or for the disturbance in conduction (or both) is documented, as demonstrated in this case.
fu:FERENCFS 1 Jeresaty RM: Sudden death in the mitral valve prolapseclick syndrome. Am J Cardiol 37:317, 1976 2 Ritchie JI.., Hammermeister KE, Kennedy JW: Refractory
3
4 5
6 7
8
ventricular tachycardia and fibrillation in a patient with a pro}apsing mitral leaflet syndrome: Successful control with overdrive pacing. Am J Cardiol 37 :314-316, 1976 Gooch AS, Vicencio F, Maranhao V, et al: Arrhythmias and left ventricular asynergy of the prolapsing mitral leaflet syndrome. Am J Cardiol 29:611-620, 1972 Winkle RA, Lopes MG, Fitzgerald JW, et al: Arrhythmias in patients with mitral valve prolapse. Circulation 52:7381, 1975 DeMaria AM, Amsterdam EA, Vismara LA, et al: Arrhythmias in the mitral valve pro}apse syndrome: Prevalence, nature, and frequency. Ann Intern Med 84:656660, 1976 Rakowski H, Waxman MB, Wald RW, et al: Mitral valve prolapse and ventricu1ar fibrillation. Circulation 52 (suppl 3) :Ill-93, 1975 Barlow JB, Pocock WA: The problem of nonejection systolio clicks and associated mitral systolic murmurs: Emphasis on the billowing mitral leaftet syndrome. Am Heart J 90:636-655, 1975 Leighbnan D, Nelson R, Gobel F, et al: Bradyarrhythmia in familial mitral valve prolapse syndrome: A potential mechanism of sudden death. Circulation 52 (suppl 2) : 11-
- INTERMITTENT COMPIDE AV BLOCK 371
92, 1975 9 Gulotta SJ, Gulco L, Padmanabhan V, et al: The syndrome of systolic click, munnur, and mitral valve prolapse: A cardiomyopathy? Circulation 49 :717-728, 1974 10 Pocock WA, Barlow JB : Etiology and electrocardiography features of the billowing posterior mitral leaflet syndrome. Am J Med 51:731-739, 1971 11 Willems J, Roelandt J, de Gust H, et al: Late systolic murmurs and systolic non-ejection clicks. Acta Cardiol 24 :456-481, 1969 12 Schaal SS, Fontana ME, Wooley CF: Mitral valve prolapse syndrome: Spectrum of conduction defects and arrhythmias. Circulation 50 (suppl 3):111-97, 1974 13 Leon DF, Leonard JJ, Kroetz FW, et al: Late systolic munnurs, clicks and whoops from the mitral valve. Am Heart J 73:325-336, 1966 14 Jeresaty RM : Mitral valve prolapse-click syndrome. Prog Cardiovasc Dis 14:623-652, 1973 15 Martin C: Mid-systolic click, late systolic murmur syndrome associated with complete heart block. J Electrocardiol 8: 191-194, 1975
Pulmonary Fibrosis a~er Prolonged Therapy with 1,3-Bis (2-chloroethyl)1-nitrosourea * David Crittenden, M.D.; .. Bill L. Tranum, M.D.;t and Arthur Haut, M.D.t
A 43-year-old man with metastatic malignant melanoma
was treated with 1,3-bis(2-cbloroethyl)-1-nitrosourea
be came to the University of Arkansas Medical Center with widespread metastases to multiple subcutaneous sites and to the supraclavicular and axillary lymph nodes. A chest x-ray film was nonnal. Chemotherapy with BCNU ( 150 mg/sq m intravenously on the first day of every other course), with imidazole carboxamide ( 150 mg/sq m intravenously for five days in each course of treatment), and with bydroxyurea ( 1,480 mg/sq m orally for five days in each course of treatment) was planned according to an investigational protocol.2 In error, during the first course of treatment, the patient received five daily doses of BCNU, rather than only one. The total dose of BCNU in the first course of treatment was 750 mg/sq m. Myelosuppression was severe. Transfusions of red blood cells and platelets were given. Nevertheless, the patient had a very favorable response to this regimen. After only one course of therapy, there was greater than 50 percent regression of lymphadenopathy, and malignant cells were no longer found on biopsy of a previously involved cutaneous site. A complete remission was achieved after two courses of therapy. The planned therapy was continued at six-week intervals. A single dose of BCNU was given with every other course. In August 1973, after having received 1,800 mg of BCNU over a period of 22 months, chest x-ray films disclosed bilateral pulmonary infiltrates in the upper lobes, which were worse on the right side of the chest. The patient remained asymptomatic. A search for mycobacteria and fungi revealed no organisms. There was no history suggestive of aspiration. Later the patient developed cough, dyspnea, and fever, and he was treated with penicillin for bacterial pneumonia. Symptoms resolved, but the pulmonary infiltrates persisted bilaterally as before (Fig 1). Multiple cultures of sputum and bronchoscopic and mediastinoscopic examinations failed to reveal an etiology for the infiltrate.
(BCNU) in combination with imidazole carboumide and bydroxyurea. He achieved complete remission. After 22 months of chemotherapy, the patient developed bilateral pulmonary infiltrates. Open lung biopsy showed sclerosing alveolltls. Long-term therapy with BCNU may cause pulmonary fibrosis, as has been seen with other cytotoxic drugs. disseminated malignant melanoma, 1,3-bis I n (treating 2-chloroethyl )-1-nitrosourea ( BCNU ) is a chemotherapeutic agent of some value, both as a single agent1 and in combination chemotherapy. 2 Its chief toxic effect is myelosuppression. This report describes a patient with metastatic malignant melanoma who developed pulmonary fibrosis, a side effect heretofore unrecognized after chemotherapy with BCNU and two other drugs. CASE REroRT
A 43-year-old white man had a malignant melanoma removed from his right flanlc in July 1971. In October 1971, °From the Division of Hematology and Oncology, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock. Supported in part by research grant CA-03400 from the National Cancer Institute. 0 °Clinical Instructor in Medicine. tAssistant Professor of Medicine. !Professor of Medicine; Director, Division of Hematology and Oncology. Reprint requests: Dr. Crittenden, University qf Arkansas Medical Sciences, 4301 West Markham, Little Rock 72201
372 CRITTENDEN, TRANUM, HAUT
FicURE 1. Posteroanterior chest x-ray film taken prior to lung biopsy. There are bilateral pulmonary infiltrates in upper lobes. Apparent loss of volume in right upper lobe is consistent with fibrotic process, with subsequent pulling of trachea and mediastinum to right.
CHEST, 72: 3, SEPTEMBER, 1977
1 Hinson K.FW, Moon AJ, Plummer !'l{S: Bronchopulmonary aspergillosis: A review and a report of eight new cases. Thorax 73:317, 1952 2 Spotnitz M, Overholt EC: Mucoid impaction of the bronchi associated with aspergillus. Dis Chest 52:92, 1967 3 Goodman DH: Bronchiectasis, eosinophilia, asthma and pneumonitis, BEAP syndrome. Ann Allergy 33:289, 1974 4 Goodman DH: Bronchiectasis in allergic aspergillosis (BEAP syndrome). Ariz Med 31:91-93, 1975 5 Liebow AA: The J Burns Amberson lecture-Pulmonary angiitis and granulomatosis. Am Rev Respir Dis 108: 1, 1973 6 Katzenstein AL, Liebow AA, Friedman PJ: Bronchocentric granulomatosis, mucoid impaction, and hypersensitivity reactions to fungi. Am Rev Respir Dis III:497537, 1975 7 Scadding JG : The bronchi in allergic aspergillosis. Scand J Resp Dis 48:372, 1967
Intermittent Complete Atrioventricular Block Masquerading as Epilepsy in the Mitral Valve Prolapse Syndrome* David Woodley, M.D. ;•• Ward Chambers, M.D.;t Helen Starke, M.D.; Barry Dzindzio, M.D.; and Alan D. Forker, M.D. FIGURE 2. Mucoid impaction of the bronchus in the region of the lingula.
constitutes the BEAP syndrome. 3 • 4 Mucoid impaction of the bronchi ( MIB) is a frequent concomitant feature of the syndrome.2 The bronchi in allergic bronchopulmonary aspergil]osis are damaged at the site of lodgement of the mucous plugs which contain Aspergillus mycelia, the antigenic source of the formation of precipitins. The Aspergillus antigen-antibody complexes created within the impacted mucus cause a type 3 Arthus reaction resulting in a destructive inflammatory reaction of the bronchial wall. 7 This may result in bronchiectasis and bronchocentric granulomatosis. Bronchocentric granulomatosis represents a distinctive microscopic lesion associated with ABPA, MIB and the BEAP syndrome. Patients with bronchocentric granulomatosis in whom noninvasive fungi have been found invariably have chronic asthma with eosinophilia, mucoid impaction and central bronchiectasis.6 Pulmonary cavitation can also occur with advanced allergic bronchopulmonary aspergillosis and bronchocentric granulomatosis. A cavity could represent abscess, cavitated granuloma or marked dilated bronchi. 6 In patients with chronic asthma, any of the following should suggest the diagnosis of allergic bronchopulmonary aspergillosis: the occurrence of more than one episode of pneumonitis, transitory pulmonary infiltrates with eosinophilia, atelectasis resulting from mucous plugs, upper lobe fibrosis, "central" bronchiectasis and/ or pulmonary cavitation.
CHEST, 72: 3, SEPTEMBER, 1977
A 24-year-old white man had a history of "epDepsy" since the age of eight years. Prolapse of the mitral valve was documented by auscultation and echocardlographic and left ventriculographic studies. At 120 hours after st0pping therapy with phenobarbital and diphenylhydantoin (Dilantin) sodium, continuous electrocardiographic monitoring (Holter monitor) revealed episodes of coinplete atrioventricular block lasting up to 23 seconds. 1be results of hemodynamic studies were normal. 1be patient's symptoms were all totally corrected by implantation of an epicardial demand pacemaker. 1bis report raises the possibillty that sudden death in association with the mitral valve prolapse syndrome may be due to intermittent severe disturbances in conduction, in addition to ventricolar arrhythmias.
S
udden death has recently been emphasized as a complication of the mitral valve prolapse syndrome. 1 • 2 Fortunately, this complication is a relatively rare manifestation of this common syndrome. A recent editorial by Jeresaty 1 reviewed the 12 known cases of sudden death. The mechanism of sudden death is thought to be ventricular tachycardia and 6brillation. i-s This report describes a case of prolapse of the mitral valve in which •From the Cardiovascular Division and Cardiovascular Center, University of Nebraska Medical Center, Omaha. • 0 lntemal Medicine Resident. tcardiology Fellow.
Reprint requests: Dr. Forker, University of Nebraska Medical Center, 668 South 4lst Street, Omaha 68105
INTERMITIENT COMPLETE AV BLOCK 369
FIGURE 1. Echocardiogram showing pansystolic prolapse of mitral valve (black am>u>s) . IVS, Intervenbicular septum; and AML, anterior mitral leaJlet.
intermittent, recurrent complete heart block was documented and masqueraded as "epilepsy" for 16 years. Sudden death in some patients with prolapse of the mitral valve may conceivably be secondary to intermittent severe abnormalities of conduction.
chest and neck and occasionally by a sensation of palpitations. Throughout childhood and adolescence, he was thought to have epilepsy. In November 1975, the patient had an evaluation at another hospital, where an electroencephalogram, brain scan, skull x-ray films, treadmill electrocardiogram, 24-hour continuous electrocardiographic monitoring ( Holter monitor) , and 24-hour urinary levels of vanillylmandelic acid and 5hydroxyindoleacetic acid were normal. The patient was started on a trial of therapy with diphenylhydantoin ( Dilantin) sodium ( 300 mg daily). Soon after, his blackout spells
CASE REPORT
A 24-year-old man had been troubled with "blackout spells" since the age of eight years. He noted that each spell of unconsciousness was preceded by a vague feeling in his
'----
. /'--
. / ~/
~
7 . . ____
.
7 i._ . . , .-
~,/'
..
~~ . •·
.
-...
F1cURE 2. Continuous rhythm strip documents intermittent complete abiovenbicular block
( numbers in background should be ignored).
370 WOODLEY ET AL
CHEST, 72: 3, SEPTEMBER, 1977
changed character to include generalized tonic-clooic contractions, unconsciousness, and mild postictal nausea. Each episode lasted approximately 20 seconds. In December 1975, therapy with phenobarbital ( 60 mg twice daily) was added; the patient was free of "sei%ures" up until the time of his admission to the neurology service at the University of Nebraska Medical Center on Feb 9, 1976. Other than a questionable history of a seizure disorder affecting his maternal grandmother, the family history was unremarlcable. The findings from physical examination were essentially normal, except for a soft, mid-late grade 1-2/6 systolic murmur, which became more prominent with standing. A systolic click was never heard. The resting ECG was nonnal. A treadmill exercise ECG was normal, with the patient reaching a maximum heart rate of 176 beats per minute without symptoms, disturbance in rhythm, or ST-segment changes. An echocardiogram revealed pansystolic prolapse of both leaflets of the mitral valve (Fig 1 ) . The transducer was in the third intercostal space, perpendicular to the chest wall. At 96 hours after stopping all medications, an EEG, brain scan, and the results of computemed axial tomographic studies of the brain were normal. A chest x-ray film and the findings from general laboratory tests, serum protein electrophoresis, determinations of antinuclear antibody, and latex fixation test were all normal. At 120 hours after stopping all medications, continuous electrocardiographic monitoring (Holter monitor) revealed episodes of complete atrioventricular bloclc with an extremely slow junctional escape pacemaker (Fig 2). The atrial rate accelerated to sinus tachycardia during heart bloclc. During the episodes the patient was prone in bed and did not lose consciousness but felt very lightheaded. With continuous monitoring in the intensive care unit, similar episodes of highdegree atrioventricular block were documented, lasting up to 23 seconds. No change in position or vagal maneuvers was related to the episodes. An epicardial demand pacemaker was implanted without complications. After one month of followup with no medications, the patient has been free of "seizures" or blackout spells. A complete cardiac catheterization was performed on April 16, 1976. This revealed normal coronary arteries with a right dominant system, a normal ventriculogram (except for a moderate pro}apse of the posterior leaflet of the mitral valve), and normal results on hemodynamic studies. The results of a study of the His bundle were also normal; throughout the latter study, the patient's epicardial pacemaker was suppressed by his own intrinsic rate of over 75 beats per minute. DISCUSSION
Supraventricular and ventricular ectopic beats, atrial tachyarrhythmias, and ventricular tachycardia are wellknown complications of prolapse of the mitral valve.1 • 1 The most common disturbance in rhythm is ventricular premature contractions. 3- 5 Sudden death associated with prolapse of the mitral valve has been attributed to ventricular arrhythmias. 1 • 2 •8 Bradyarrhythmias are less well recogni7.ed as complications of the mitral valve prolapse syndrome. 5 •7 •8 Leighbnan et al8 have reported the findin~ in a family of 11 patients with a high prevalance of prolapse of the mitral valve; seven of the members of the family had
CHEST, 72: 3, SEPTEMBER, 1977
documented bradyarrhythmias.8 Three patients had recurrent syncope produced by simple uptilting of the head. One patient had sinus arrest and sustained asystole produced by tilting up the head. Studies of the His bundle revealed prolonged atrio-His intervals; atrial pacing revealed an inability to maintain I: I conduction when paced at 120 beats per minute. Bradyarrhythmia and sinus arrest were thought to be due to excessive vagal tone. In two of these patients, the condition was successfully controlled by permanent demand pacing. Disturbances in conduction have been least emphasized as associated features of the mitral valve prolapse syndrome. Of all the abnormalities of conduction, firstdegree atrioventricular block is the most common.11• 12 Left anterior hemiblock, 11 •12 left anterior hemiblock plus right bundle branch block,11,12 right bundle branch block,9,lt-13 and left bundle branch block9·12.H have also been described. Second-degree atrioventricular block has been rare. 9 •12 Complete heart block has been reported in fourcases.e,12,u In this report, we describe a patient with prolapse of the mitral valve who had episodic complete atrioventricular block which induced seizure-like spells and was corrected by implantation of a permanent pacemaker. The mechanism of this disturbance in conduction is unknown, but this report emphasizes the possibility that sudden death in association with the mitral valve prolapse syndrome may be due to intermittent severe disturbances in conduction, in addition to ventricular arrhythmias. Repeated and prolonged electrocardiographic monitoring may be necessary before the mechanism for the symptoms and arrhythmia or for the disturbance in conduction (or both) is documented, as demonstrated in this case.
fu:FERENCFS 1 Jeresaty RM: Sudden death in the mitral valve prolapseclick syndrome. Am J Cardiol 37:317, 1976 2 Ritchie JI.., Hammermeister KE, Kennedy JW: Refractory
3
4 5
6 7
8
ventricular tachycardia and fibrillation in a patient with a pro}apsing mitral leaflet syndrome: Successful control with overdrive pacing. Am J Cardiol 37 :314-316, 1976 Gooch AS, Vicencio F, Maranhao V, et al: Arrhythmias and left ventricular asynergy of the prolapsing mitral leaflet syndrome. Am J Cardiol 29:611-620, 1972 Winkle RA, Lopes MG, Fitzgerald JW, et al: Arrhythmias in patients with mitral valve prolapse. Circulation 52:7381, 1975 DeMaria AM, Amsterdam EA, Vismara LA, et al: Arrhythmias in the mitral valve pro}apse syndrome: Prevalence, nature, and frequency. Ann Intern Med 84:656660, 1976 Rakowski H, Waxman MB, Wald RW, et al: Mitral valve prolapse and ventricu1ar fibrillation. Circulation 52 (suppl 3) :Ill-93, 1975 Barlow JB, Pocock WA: The problem of nonejection systolio clicks and associated mitral systolic murmurs: Emphasis on the billowing mitral leaftet syndrome. Am Heart J 90:636-655, 1975 Leighbnan D, Nelson R, Gobel F, et al: Bradyarrhythmia in familial mitral valve prolapse syndrome: A potential mechanism of sudden death. Circulation 52 (suppl 2) : 11-
- INTERMITTENT COMPIDE AV BLOCK 371
92, 1975 9 Gulotta SJ, Gulco L, Padmanabhan V, et al: The syndrome of systolic click, munnur, and mitral valve prolapse: A cardiomyopathy? Circulation 49 :717-728, 1974 10 Pocock WA, Barlow JB : Etiology and electrocardiography features of the billowing posterior mitral leaflet syndrome. Am J Med 51:731-739, 1971 11 Willems J, Roelandt J, de Gust H, et al: Late systolic murmurs and systolic non-ejection clicks. Acta Cardiol 24 :456-481, 1969 12 Schaal SS, Fontana ME, Wooley CF: Mitral valve prolapse syndrome: Spectrum of conduction defects and arrhythmias. Circulation 50 (suppl 3):111-97, 1974 13 Leon DF, Leonard JJ, Kroetz FW, et al: Late systolic munnurs, clicks and whoops from the mitral valve. Am Heart J 73:325-336, 1966 14 Jeresaty RM : Mitral valve prolapse-click syndrome. Prog Cardiovasc Dis 14:623-652, 1973 15 Martin C: Mid-systolic click, late systolic murmur syndrome associated with complete heart block. J Electrocardiol 8: 191-194, 1975
Pulmonary Fibrosis a~er Prolonged Therapy with 1,3-Bis (2-chloroethyl)1-nitrosourea * David Crittenden, M.D.; .. Bill L. Tranum, M.D.;t and Arthur Haut, M.D.t
A 43-year-old man with metastatic malignant melanoma
was treated with 1,3-bis(2-cbloroethyl)-1-nitrosourea
be came to the University of Arkansas Medical Center with widespread metastases to multiple subcutaneous sites and to the supraclavicular and axillary lymph nodes. A chest x-ray film was nonnal. Chemotherapy with BCNU ( 150 mg/sq m intravenously on the first day of every other course), with imidazole carboxamide ( 150 mg/sq m intravenously for five days in each course of treatment), and with bydroxyurea ( 1,480 mg/sq m orally for five days in each course of treatment) was planned according to an investigational protocol.2 In error, during the first course of treatment, the patient received five daily doses of BCNU, rather than only one. The total dose of BCNU in the first course of treatment was 750 mg/sq m. Myelosuppression was severe. Transfusions of red blood cells and platelets were given. Nevertheless, the patient had a very favorable response to this regimen. After only one course of therapy, there was greater than 50 percent regression of lymphadenopathy, and malignant cells were no longer found on biopsy of a previously involved cutaneous site. A complete remission was achieved after two courses of therapy. The planned therapy was continued at six-week intervals. A single dose of BCNU was given with every other course. In August 1973, after having received 1,800 mg of BCNU over a period of 22 months, chest x-ray films disclosed bilateral pulmonary infiltrates in the upper lobes, which were worse on the right side of the chest. The patient remained asymptomatic. A search for mycobacteria and fungi revealed no organisms. There was no history suggestive of aspiration. Later the patient developed cough, dyspnea, and fever, and he was treated with penicillin for bacterial pneumonia. Symptoms resolved, but the pulmonary infiltrates persisted bilaterally as before (Fig 1). Multiple cultures of sputum and bronchoscopic and mediastinoscopic examinations failed to reveal an etiology for the infiltrate.
(BCNU) in combination with imidazole carboumide and bydroxyurea. He achieved complete remission. After 22 months of chemotherapy, the patient developed bilateral pulmonary infiltrates. Open lung biopsy showed sclerosing alveolltls. Long-term therapy with BCNU may cause pulmonary fibrosis, as has been seen with other cytotoxic drugs. disseminated malignant melanoma, 1,3-bis I n (treating 2-chloroethyl )-1-nitrosourea ( BCNU ) is a chemotherapeutic agent of some value, both as a single agent1 and in combination chemotherapy. 2 Its chief toxic effect is myelosuppression. This report describes a patient with metastatic malignant melanoma who developed pulmonary fibrosis, a side effect heretofore unrecognized after chemotherapy with BCNU and two other drugs. CASE REroRT
A 43-year-old white man had a malignant melanoma removed from his right flanlc in July 1971. In October 1971, °From the Division of Hematology and Oncology, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock. Supported in part by research grant CA-03400 from the National Cancer Institute. 0 °Clinical Instructor in Medicine. tAssistant Professor of Medicine. !Professor of Medicine; Director, Division of Hematology and Oncology. Reprint requests: Dr. Crittenden, University qf Arkansas Medical Sciences, 4301 West Markham, Little Rock 72201
372 CRITTENDEN, TRANUM, HAUT
FicURE 1. Posteroanterior chest x-ray film taken prior to lung biopsy. There are bilateral pulmonary infiltrates in upper lobes. Apparent loss of volume in right upper lobe is consistent with fibrotic process, with subsequent pulling of trachea and mediastinum to right.
CHEST, 72: 3, SEPTEMBER, 1977
