Myocardial Sarcoidosis Presenting as Acute Mitral Insufficiency

concealed His bundle depolarizations, and repetitive block in both the A-V node and His-Purkinje system during Wenckebach periods. 9 •10 The present case is a new manifestation of concealed conduction. Atrial premature beats were blocked distal to the His bundle recording site. The actual anatomic site of block could not be delineated but was within the His bundle (in or distal to the H recording site) or within both bundle branches. When these blocked atrial premature beats were interpolated, the next conducted beat was conducted with "splitting" of H potentials producing P-R prolongation. Splitting of H potentials, the recording of two high frequency His bundle electrograms separated by a variable interval, was reported by Narula11 as suggestive of disease within the His bundle. Subsequent pathologic studies by Bharati and co-workers 12 have confirmed this, by demonstrating pathologic lesions in the His bundle in patients with split H potentials. However, split H potentials do not have to reflect pathologic changes in the His bundle. Schuilenburg and Durrer13 and also Wu et alH have reported that functional block may be produced within the His bundle with coupled extrastimuli, resulting in H potential splitting. This type of functional block would be most likely in a patient with a short A-V nodal functional refractory period, allowing consecutive impulses with short coupling intervals to enter the His bundle. The splitting of H potentials in the present case, does not necessarily reflect a diseased conduction system. The surface electrocardiogram in the present case was misleading, since it suggested antegrade concealed conduction to the A-V node. The demonstration of concealed conduction to the His bundle, could only be documented with recording of His bundle electrograms. We predict that many other examples of both antegrade and retrograde concealed conduction to the His bundle will be found.

fu:FEREN'crs 1 Langendorf R: Concealed A-V conduction: The effect of

2 3 4

5

blocked impulses on the fonnationiand conduction of subsequent impulses. Am Heart J 35:542-552, 1948 Langendorf R, Piclc A: Concealed conduction. Further evaluation of a fundamental aspect of propagation of the cardiac impulse. Circulation 13:381-399, 1956 Dhingra RC, Rosen KM, Rahimtoola SH: Normal conduction intervals and responses in sixty-one patients using His bundle recording and atrial pacing. Chest 64:55-59, 1973 Hoffman BF, Cranefield PF, Stuclc:ey JH: Concealed conduction. Circ Res 9:194-203, 1961 Moe GK, Abildskov JA, Mendez C: An experimental study of concealed conduction. Am Heart J fn :338-356, 1964

6 Moore EN: Microelectrode studies on concealment of multiple premature atrial responses. Circ Res 18:660-672, 1966 7 Moore EN: Observation on concealed conduction in atrial fibrillation. Circ Res 21:201-208, 19fn 8 Damato AN, Lau SH: Concealed and supernormal atrioventricular conduction. Circulation 43:9fn-970, 1971 9 Rosen KM, Rahimtoola SH, Gunnar RM: Pseudo A-V block secondary to premature nonpropagated His bundle depolarizations. Circulation 42:3fn-373, 1970

452 ZONERAICH ET AL

10 Dhingra RC, Rosen KM, Rahimtoola SH: Wenclc:ebach periods with repetitive block: Evaluation with His bundle recording. Am Heart J 86:444-448, 1973 11 Narula OS, Scherlag BJ, Samet P, et al: Atrioventricular block. Localization and classification by His bundle recordings. Am J Med 50:146-165, 1971 12 Bharati S, Lev M, Wu D, et al: Pathophysiologic correlations in two cases of split His bundle potentials. Circulation 49:615-623, 1974 13 Schuilenburg RM, Durrer D: Rate-dependency of functional block in the human His bundle and bundle branchPurkinje system. Circulation 48:526-540, 1973 14 Wu D, Denes P, Dhingra R, et al: Observations on the nature of the "gap" phenomenon. Circ Res 34:682-692, 1974

Myocardial Sarcoidosis Presenting as Acute Mitral Insufficiency• S. Zcmeraich, M.D.;•• M.P. Gupta, M.D.;t ]. Mehta, M.D.;t 0. Zcmeraich, M.D.;§ and Z. Wessely, M.D. II

A young patient with IICUte mitral lnsufliciency with a rapid and fatal coune is presented. On autopsy, ditlmJe sarcoid granulomatous Infiltration was found in the anterior and posterior walls of the left veutricle, In the interventricnlar ~~eptmn and in both papillary m1111Cles. Sarcoidosis as a cause of valvular involvemeat shoulcl be considered in patleJds with the sudden ap~ of mitral incompetence, conduction defects and arrllythmlas.

S

arcoidosis is a disease of unknown etiology involving practically every organ of the body. The incidence of myocardial sarcoidosis is about 20 percent of patients with this disease1 and 0.025 percent of total autopsies as reported by Bashour et al. 2 The diagnosis is very often missed antemortem because of sudden death and other fatal cardiac arrhythmias and conduction disturbances. I-s There are several case reports of sarcoidosis involving the heart in the English literature. However, to the best of our knowledge, only one case with acute mitral insufficiency has been attributed to papillary muscle dysfunction secondary to in.6ltration by sarcoid granulomas seen on autopsy.• Here we present the case of a young woman who had a brief cardiac history, severe mitral incompetence and suddenly died. The autopsy revealed several foci of noncaseating granuloma in the papillary muscles and in the left ventricular wall. °From the Departments of Medicine and Pathology, Division of Cardiology, Queens Hospital Center, Long Island Jewish-Hillside Medical Center Afllliation, Clinical Campus of the School of Medicine, State University of New York, Medical School at Stony Brook, Stony Brook, NY. 0 0 Associate Professor of Medicine; Head, Division of Cardiology. tAssistant Professor of Medicine and Physician-in-Charge, Cardiac Catheterization Unit. :j:Fellow in Cardiology. §Associate Professor of Medicine. IIAssociate.Professor of Pathology, Associate Director, Department of Pathology. Reprint requeals: Dr. Zoneraich, Long Island ]ewish-Hillaide Medical Center, ]af'TIIJ1ca, New York 11432.

CHEST, 66: 4, OCTOBER, 1974

CASE REPoRT

A 29-year-old Negro woman was in good health until November 1970, when she started having palpitations. There was no history of chest pain or shortness of breath. The patient denied any history of rheumatic heart disease, high blood pressure or any knowledge of a cardiac murmur. A local physician prescribed pills for her heart which she did not take regularly. About five months later, the patient developed progressive exertional shortness of breath, palpitation, orthopnea and nonproductive cough. One month later, she noted swelling over her legs and was admitted to Queens Hospital Center in respiratory distress. Physical examination revealed a pulse rate of 120/min and irregular, blood pressure 110/80 mm Hg and the jugular veins were full. Cardiac examination revealed the point of maximum impulse in the 5th intercostal space in the midclavicular line, a systolic thrill, s3 and s. gallops and a grade 5/6 holosystolic murmur audible at the apex and radiating to the left axilla. The liver was enlarged 4 em below the costal margin and there was 2+ peripheral pitting edema. Laboratory Data

Electrocardiogram showed a sinus tachycardia with vertical axis and P-wave suggestive of left atrial enlargement and multiple ventricular premature contractions. Hematocrit value was 38 percent, white blood cell count 5,900/em with a normal differential count. Blood urea nitrogen, creatinine, cholesterol, serum enzymes ( SGOT, SGPT, LDH and alkaline phosphatase) were within normal limits. Electrolytes were normal. Urinalysis showed 3+ proteinurea with 12-13 white blood cells/high power field. Chest x-ray film showed moderate enlargement of the heart in transverse diameter, prominent pulmonary artery conus and bilateral congestive changes. Systolic time intervals were measured from simultaneous recordings of carotid pulse, apexcardiogram, phonocardiogram and electrocardiogram ( Fig 1 ) . Left ventricular ejection time ( LVET) and pre-ejection period ( PEP) were corrected (C) for heart rate using Weissler formula.ll.6 In our patient, LVETc was 376 msec and PEPc was 164 msec. (Normal LVETc female 418±10 msec and PEPc female 133±10 msec. The PEPc, LVETc ratio was 0.40 [normal 0.34]. Isovolumetric contractions time (ICT) was 50 msec.

FIGURE 1. Phonocardiogram at apex with low (A) and high frequency ( B) shows prolonged Q-S1 interval, pansystolic murmur, and presence of Ss and S4 gallops. Also simultaneous recordings of carotid pulse (CAR) and apex cardiogram (A(X;) phonocardiogram and electrocardiogram for measurements of systolic time intervals. Interval between vertical lines equal 100 msec. Paper speed 75 mm/sec.

Hospital Course

as the epicardium. Special stains ruled out tuberculosis and fungal diseases. Examination of the involved areas with crossed polars excluded birefringent foreign materials as

The patient was treated with digoxin, furosemide, and potassium supplements. However, she suddenly developed ventricular tachycardia four days after admission and died. Autopsy revealed an enlarged heart ( 440 gm) within a smooth and glistening epicardium. A yellow-white ovoid, rough area of about 2 x 1em was noted on the basal portion of the posterior wall of the left ventricle. On sectioning, both atria and ventricles were found to be hypertrophied. Several grey-white areas varying from a few mm to 1.5 em were noticed in the anterior and posterior walls of the left ventricle and interventricular septum. Both papillary muscles showed multiple whitish areas. The mitral valve revealed mild edematous edges and slight roughening of the endothelium at the base of the anterior leaflet. Chordae tendineae were thin and delicate. All three coronary arteries showed delicate walls and widely patent lumina. Microscopic examination of these grey-white areas showed diffuse replacement of myocardium by noncaseating granulomas with numerous giant cells and extensive fibrosis (Fig 2). The granulomas also involved the endocardium as well

FIGURE 2. Microscopic examination of heart shows myocardial cells replaced by non-caseating granulomas. H and E stain magnification (original magnification X 630).

CHEST, 66: 4, OCTOBER, 1974

MYOCARDIAL SARCOIDOSIS 453

a cause of granulomata. Multiple noncaseating granulomas were also found in the liver, spleen, lungs and hilar lymph nodes.

DISCUSSION

Cardiac sarcoidosis usually has a brief course. Sudden death seems to be a common occurrence. Various cardiac arrhythmias like multiple atrial, nodal and ventricular premature contractions, wandering pacemaker and atrial and ventricular tachycardia have been reported. H, 1 •8 Conduction disturbances varying from first degree A-V block to advanced second degree heart block and complete heart block are fairly common. 2 Patients have occasionally presented with neuropsychiatric manifestations due to altered cerebral circulation, possibly on the basis of cardiac arrhythmias. 7 These arrhythmias usually are difficult to control with conventional drugs and patients have a rapid and fatal course. 10 Systolic time measurements as a noninvasive technique to assess left ventricular function have been used widely in the past decade. It was shown by WeisslerM that in mitral insufficiency, even in the presence of large stroke volume, prolonged LVETc is uncommon. 5 •6 Prolonged PEPc, shortened LVETc and increased PEPc, LVETc ratio strongly suggest abnormal left ventricular function. In our case, diffuse myocardial inffitration by sarcoidosis was responsible for left ventricular dysfunction, which was clinically suspected by presence of S3 and S, gallops. Congestive heart failure, either due to primary diffuse involvement of the myocardium or secondary to chronic lung disease, occurs in about 80 percent of the patients.1·8 In the review by Bashour et al, 2 14 out of 16 cases had congestive heart failure with or without cardiomegaly. Nonspecific ST-T wave changes to transmural myocardial infarction patterns have been described secondary to myocardial inffitration by sarcoidosis. 2 • 11 The pericardium can also be involved in sarcoidosis presenting as recurrent pericardia! effusion. 12 Cardiac murmurs secondary to sarcoid involvement of valves have been reported. In 1966, Raftery et al' described the case of a West Indian woman who presented with acute mitral insufficiency and histology at surgery for mitral valve replacement, and showed diffuse sarcoidosis in the papillary muscles. This patient had a rather prolonged course and died almost five years after the onset of acute mitral insufficiency. In the same . study, sarcoidosis accounted for only one of the total 23 cases described presenting with acute mitral insufficiency} Ghosh et al 3 reported another patient who had granulomatous involvement of the aortic valve. In review of cardiac sarcoidosis by Gozo et al11 in 1971, they described another sarcoidosis patient, who was found to have a holosystolic murmur, which they attributed to probable valvular sarcoidosis. Autopsy revealed that our patient had a loud holosystolic murmur secondary to papillary muscle dysfunction caused by sarcoid inffitration of the papillary muscles. The patient had a brief course lasting six months after the onset of symptoms. We feel, though not a common disease, sarcoidosis should be considered in the differential diagnosis in

454 DYE, LAFORET

patients with sudden and unexplained cardiac murmurs, arrhythmias and conduction defects. ACKNOWLEDGMENTS: The authors wish to thank Mr. Floyd Jackson, Miss Ada Fauntroy and Mrs. Karen Franklin for their technical assistance. REFERENCFS

1 Porter GH: Sarcoid heart disease. N Eng! J Med 263: 1350-1357, 1960 2 Bashour FA, McConnel T, Skinner W, eta!: Myocardial sarcoidosis. Dis Chest 53:413-429, 1968 3 Ghosh P, Fleming HA, Gresham GA, et al: Myocardial sarcoidosis, Br Heart J 34:769-773, 1972 4 Raftery EB, Oakley CM, Goodwin JP: Acute subvalvular mitral incompetence. Lancet 2:360-365, 1966 5 Weissler AM, et a!: Systolic time intervals in heart failure in men. Circulation 37:149-153, 1968 6 Weissler AM, et al: The systolic time intervals as a measure of left ventricular performance in man. Progr Cardiovasc Dis. In print 7 Rajasenan V, Cooper ES: Myocardial sarcoidosis. Bouts of ventricular tachycardia. Psychiatric manifestations and sudden death. J Nat Med Assoc 61:306-309, 1969 8 Forbes G, Usher A: Fatal myocardial sarcoidosis. Br Med J 2:771-773, 1962 9 Duvemoy WFC, Garcia R: Sarcoidosis of the heart presenting with ventricular tachycardia and atrioventricular block. Am J Cardiol23:348-352, 1971 10 Stein MH, Gross JM, Shulman M: A case of cardiac sarcoidosis manifested by uncontrollable ventricular tachycardia. Review of cardiac manifestations in 16 cases of sarcoidosis. Am J Cardiol10:864-870, 1962 11 Hines JD, Sancetta SM: Myocardial sarcoidosis simulating healed myocardial infarction. Ohio State Med J 59: 689-692, 1963 12 Schiff AD, Blatt CJ, Colp C: Recurrent pericardia! effusion secondary to sarcoidosis of the pericardium. N Engl J Med 281:141-143, 1969 13 Gozo EG, Cosnow I, Cohen HC, et al: The heart in sarcoidosis. Chest 60:379-388, 1971

Esophageal Rupture: Diagnosis by Pleural Fluid pH* Robert A. Dye, M.D. •• and Eugene G. Laforet, M.D.t

Failure to appreciate the significance of a pleural fluid pH of 5 led to delay in establishing a diagnosis of esophageal rupture. In a subsequent study the pH of 56 pleural Ouid specimens from 50 patlellts with coDdl•From the Department of Medicine and the Thoracic Surgery Service, Newton-Wellesley Hospital, Newton Lower Falls, Mass.; presented in part at the joint meeting of the New England States Chapter, American College of
CHEST, 66: 4, OCTOBER, 1974