Heart block and mesothelioma of the atrioventricular node

Case Reports Heart Block and Mesothelioma of the Atrioventricular Node* NEIL .

1.

KAMINSKY,

M .D .,

THOMAS KILLII' III,

M .D ., F .A .C .C ., JACK W. C . HAGSTROM, M .D .

DANIEL R . ALONSO, M .D .

and

New York, New York

A

tion of being about to faint." t A month later he had another attack, followed by subsequent attacks once or twice daily for the next month . He was admitted to The Rockefeller Hospital on Dec . 13, 1935 . Physical examination revealed a pulse of 32/nrin, a slightly enlarged heart and a systolic murmur along the left sternal border . During this and several subsequent admissions he had marry episodes of light-headedness and Stokes-Adams attacks . The following note describes a typical episode : "This morning he complained of severe giddiness and faintness . His pulse was exceedingly irregular, jumping from 70 to as low as 10 or 12 beats per minute, and back . During the low rate he was flushed and breathed more rapidly . These changes continued for about an hour during the morning, and an electrocardiogram at one time showed great variation in rate and shape of the ventricular complexes . The auricular rate continued regularly ; the ventricular rate, calculated from the interval between cycles, was sometimes as low as 4 beats per min ."t Numerous electrocardiograms showed that the atrioventricular conduction pattern varied from first to third degree block with very slow idioventricular response . In 1936, the patient was referred to The New York Hospital . At that time he noted only occasional episodes of light-headedness and minimal dyspnea on exertion, Throughout the remainder of his life, frequent electrocardiograms and physical examinations consistently showed complete heart block . The ventricular rate varied from 30 to 40 beats/min . No medication was required . Pacemaker Therapy and Results : In 1955, when he was 63, he began to have angina pectoris during exertion . At age 71 he had his first Stokes-Adams

QUIRED complete heart block occurs most

commonly in patients after the fifth decade . [ In such cases pathologic examination frequently reveals scarring in the region of the atrioventricular node 2 Arteriosclerotic change in the artery supplying the node is often present . Heart block may also occur as a complication of myocardial infarction, but if the patient survives, it is usually transient . 3,4 Other less common causes of acquired heart block have recently been reviewed . 5 Because of the small caliber of the conducting pathway, the atrioventricular node and bundle are highly vulnerable to an infiltrative lesion . Primary or metastatic tumors may invade the atrioventricular septum, and, if strategically placed, impinge on the atrioventricular node or A few cases of acquired comcommon bundle . plete heart block have been reported in which a tiny, vacuolated primary tumor of the heart has been found in the atrioventricular node .° - 11 We are reporting the tenth documented case of a primary cardiac wesothelioma of the atrioventricular node which produced complete heart block that persisted for at least 30 years . CLINICAL HISTORY

A 73 year old Greek-born florist died in The New York Hospital, Sept . 2, 1965, with complete heart block . In 1910, at age 18, he was temporarily denied immigration to the United States because of "something in his heart ." Two insurance companies refused him life insurance in 1934 . In 1936, at age 44, he had a sudden attack of giddiness and almost fell ; "things became dark and gray and he had the sensa-

t Quoted from the records of The Rockefeller Hospital, 1933-34, courtesy of Rockefeller University .

"From the Departments of Medicine and Pathology, The New York Iospital-Cornell Medical Center, New York, N . Y. 248

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Mesothelioma of

249

A-V Node

4q v L

mom 14-wo

V 2

11

V 5

11 Fin. I , ElectrocarJ¢ogram obtained March 1965 when the patient was 73 years, after 30 years of proved complete heart block and prior to surgical insertion of an artificial pacci naker . A, standard 12-lead tracing recorded as 3 groups of 4 simultaneously inscribed leads, demonstrates complete heart block . B, occasional extrasystoles interrupt the idioventricular rhyth,n . Atria) rate, 75 beats/min . Ventricular rate, 42 beats/min . Time lines, 0.10 ice . attack in 23 years . Isoproterenol and digitalis were administered but no significant improvement was shown . When incapacitated by 10 to 30 boats of angina pectoris and innumerable light-headed spells each day, he reluctantly agreed to implantation of an artificial cardiac pacemaker (Fig . 1) . On Mar . 26, 1965, a bipolar catheter was passed from the right external jugular vein into the right ventricle, and a fixed rate . battery-powered pacemaker was implanted in the right pectoral region . Pacemaker capture of the ventricles was complete, and the patient's symptoms abated markedly . Five months later he was readmitted because of fatigue, light-headedness and the recurrence of an intermittent, slow pulse . An electrocardiogram demonstrated alternation between pacemaker capture and idioventricular rhythm ; the latter was predominant . A unipolar pacemaker catheter was passed transvenously into the right ventricle, and pacing was initiated from an external battery-powered source, Forty-eight hours after admission ventricular tachycardia suddenly developed followed by ventricular fibrillation . Following precordial shock an idioventricular rhythm eventually vot.1ME 20, sums' 1967

returned, but neither pacemaker captured the ventricle . Although the transjugular, bipolar pacemaker was replaced with another unit, hypotension persisted and the patient died in cardiac and renal failure three days later . Death occurred 30 years after complete heart block was first recognized . N ECROPSY FINDINGS

The significant pathologic findings were limited to the heart . It weighed 440 gm . The left ventricle was hypertrophied and dilated, and old and recent infarcts were present in its anterolateral wall . The lumens of all of the coronary arteries were severely narrowed by atheromatous plaques, most severe in the anterior descending branch of the left coronary artery, which was almost completely occluded . No abnormalities in the areas of distribution of the cardiac conduction system were observed by gross inspection . Two blocks of the heart containing the sinoatrial node, and the atrioventricular node, con, mon bundle, bundle of His and the right and Icft bundles were serially sectioned according to the

2 50

Kaminsky

et

al.

Photomicrograph of atriorentricular erode shows replacement of noruial tissue by curds and glandlike elements of the nicsothelioina . tllematoxylin and eosin, X 95 reduced by 18c .) FIG . 2 .

methods of Lev 14 and Hudson.15,1 G Approximately 100 sections were examined . Microscopic Sections: The sinoatrial node was normal ; the lumen of the sinus node artery was narrowed by thickened intima . The atrioventricular node, proximal to penetration of the fibrous body, was intact . Beyond the point of penetration (anterior), the node was progressively replaced by a neoplasm that was composed of multiple irregular cysts, solid cellular cords and gland-like structures (Fig . 2 and 3) . All these structures were formed by the same type of cell . The cells lining the cysts were flat ; those in the cords or acini were cuboid . No stratification of cells or cilia was present . The nuclei were large, ovoid or elongate, and the scanty cytoplasm was finely granular and cosinophilic . In routine sections the lumens of the acini and cysts contained an amorphous, finely granular, pink staining material . Sections stained with mucicarmine were negative for mucin . In some sections, a few reinnants of the atrioventricular node remained in the midst of the tumor, while in others the node was completely replaced by the tumor . In sections from the anterior portion of the bundle of His, the right bundle branch originated from the tumor and a left fascicle was identified . The over-all dimensions of the lesion were approximately 21 by 3 by 1 .5 mm . The anatomic diagnosis was mesothelioma of the atrioventricular node . DtscusstoN In the patient under consideration, complete

heart block became manifest at age 40 along with recurrent Stokes-Adams attacks . At first, the block was intermittent and associated with marked ventricular slowing . After the block became established, symptoms disappeared . The ventricular rate, documented at frequent clinical visits, was usually about 40 beats/min . during the next 25 years . When angina and heart failure developed, associated with progressive coronary arteriosclerosis, the patient again had bouts of intermittent light-headedness and recurrent Stokes Adams attacks . He died one year after the return of symptoms front the combination of ischemic heart disease and arrhythmia . Autopsy revealed extensive coronary atherosclerosis and recent and old myocardial infarcts . No gross lesions were present in the area of the conduction system . However, microscopic sections contained a mesothclioma precisely confined to the atrioventricular node . This tumor caused documented complete heart block for 30 years . In view of the patient's postponed immigration, it may have produced abnormalities in rhythm for an even longer period . Nine cases of primary mesothelioma of the atrioventricular node have been described previously .s -ls In 8, the tumor caused complete heart block, but in 1, clinical documentation is inadequate .(' Table t lists comparative data for THE AMERICAN JOURNAL OF CARDIOLOGY



Mesothelioma of A-V Node

251

y Fte . 3 .

lire niesothetioma in the atriocentricntar node . Note irregular cysts through tutnor . (Hernatoxylin and eosin, X 95 reduced by 18c_; .)

Pholornicrograph

randoudv scattered

of

the 10 known cases, including the present report . The sex distribution has been approximately equal . The age of onset (recognition of heart block) has varied froth 4 to 71 years . In 3 cases rhythm disturbances were intermittent, but in 6 the block, once established, was permanent . It is notable that in 7 of the 9 cases with documented heart block, abnormal conduction developed at or before the age of 40 . Onset of heart block before the fifth decade may suggest the presence of a primary mesotheliona of the atrioventricalar node, in the absence of other possible causes . In none of the cases reported to date had the lesion been suspected prior to its discovery at necropsy . Survival following the onset of symptoms has varied from 2 months to 30 years . Six patients died during Stokes-Adams seizures . Intermittent rather than established block is more likely to be a cause of death . Patients with congenital complete heart block generally have a good prognosis, and their ventricular rates tend to be faster than those of older patients with acquired heart block . These observations suggest that, if the ventricular rate is over 35 beats/min ., the heart block is not associated with serious impairment of the circulation, providing there are no associated diseases which may disturb cardiac function . The long course of the patient reVOLUME 20, AUGUST

1967

ported herein is in accord with this view ; once the block became permanent, lie functioned without symptoms until another form of heart disease supervened . Two anatomically distinct types of intracardiac One type, located epithelial tumors are recognized .

in the superficial myocardium, is a thin-walled, cystic lesion lined by ciliated epithelium, and is always an incidental finding at necropsy . The second type, in the interatrial septum, is composed of cords and "cysts" lined by primitive cuboidal epithelium and has been ascribed as the cause of heart block in 10 cases, including the present report . Lanks et al . 17 recently described a case in which the former type of cystic lesion was found . They believe that it is a result of the isolation of a bit of esophageal pritnordiunt prior to the sixth week of gestation . The heterotopic tissue then continues to differentiate and grow for a short period in an aberrant location . The histogenetic origin oj' the second type of tumor,

has not been established . Armstrong et al .' and Perry and Rogerss all believed the lesion is a true neoplasm originating from the lymphatic channels in the area of the atrioventricular node . Rezak 9 and Leichcr" concluded that the tumor represented an abnormal (dysontogenctic) growth of heterotopic entodermal primordium . Mahaimto was the. first to suggest

rnesothelioma,



2 52

Kaminsky et al . TABLE I

Clinical and Pathologic Data on 10 Reported Cases of Mesothcliorna of Atrioventricular Node

Case

Authors

Sex

Age of Onset of Block (yr .)

1

Armstrong & Monckehergs 1911 Lloyd7 1929

M

4%

3

Perry & Rogerss 1934

F

4

4

Rezek9 1938

F

71

Angina & CFIF

ECG-CHB with irregular idioventricular rhythm and rate ECG -CHB & 1st degree

5

Mahaim'0 1945 Leicher" 1948 Leicher" 1948

F

12

None

ECG-CHB

F

23

S-A attacks

ECG-CHB

F

34

S -A attacks

None

8

Rabson & Thill" 1948

F

29

9

Wolf & Bing" 1965 Kaminsky et al. 1966

M

67

EGG-CHB

M

40

10 sec . episodes of dizziness, angina, CHF S-A attacks, angina, CHF

2

6 7

10

39

Symptoms of Conduction Disturbance S-A attacks

Documentation of Block Simultaneous radial & jugular pulse recording ECG-1st & 2nd degree

None

S-A attacks

ECG-CHB

S-A = Stokes-Adams attack ; ECG = electrocardiogram ; C11n = complete heart block ; and CUT = congestive heart failure .

that the tumor was derived from mesothelium . He called it a coelothelionte and emphasized its In a superb discussion he disbenign character . missed the theory that the tumor was a lymphoangioma since it did not have the histologic charHe acteristics and was a secretary tumor . stated that the tumor did not originate from heterotopic entoderm because of the absence of stratified or ciliated epithelium and had no resemblance to thyroid . He believed that this tumor is histogenetically derived from residual mesoderm, which remains from the developmental stage when the cardiac loop twists . When the primitive epimyocardial tissue surrounds the endocardium during the twisting process, it becomes invaginated and encircles the primitive heart like a collar . This theory explains the location of the tumor in the midst of the intcratrial septum. It also explains the presence of secretions in the dilated tubules, since the epicardium is a mesothelial secretory tissue that produces the pericardial fluid . -Moreover, as

Nicod's originally noted, the histologic appearance of the tumor resembles that of proliferated mesothelium in so-called pericardial milk spots . Wolf and Bing12 have adopted -Mahaim's reasoning in the report of their case . In our tabulation we did not include the case described by Anderson and Dmytryk ' 9 because of the size and the unusual histologic appearance of the tumor . Moreover, there was no description of involvement of the conduction system with the tumor . Although the tumor described by Grant and Camp20 caused complete heart block, it is not included because the histologic diagnosis was angioma of the atrioventricular node . It is provocative to speculate on tfle effects of changing modes of medical treatment on the course of a patient such as the one we describe . If artificial pacemakers had been available in 1935, our patient probably would have been considered a prime candidate for permanent pacing, and a pacemaker would have been surgically iutTHE AMERICAN JOURNAL OF CARDIOLOGY



253

Mesothelioma of A-V Node TABLE

Duration and Constancy of Case Block

2

4

Pathologic FindingsAge (yr .) & Cause of Death

Size (mm .)

Location

Original Diagnosis Lymphangioendothelioma Lymphangioendothelioma

A-V node

8 X 6 X 5

A-V node

15 X 12 X 18

Inferior portion interatrial septom & A-V node

2 (micro .)

Lymphangioendothelionia

7 mo . ; intermittens

Inferior portion interatrial septum & A-V node

? (micro .)

Interatrial Septum & A-V node

15 X 15 X 5

Dysontogenic tumor of epithelial (endodermal) origin Mcsothclioma

8

10

(continued)

1 yr . ; stable 5% S-A attack Sevcralmo . ; 39 interS-A attack mittent 22 yr . ; 26 stable S-A attack

12 yr . ; stable 1 yr . ; stable 2 mo . ; ? intermittent

9

I

2 me . ; ? stable 30 yr . ; stable

'1 Ca . of stomach, lobar pneumonia, subdural hemorrhage 24 Ca . of ovary 24 S-A attack 34 S-A attack 29 Rheumatic heart disease 67 S-A attack 70 Ileart failure, acute renal failure

A-V node

5

Hamartoma

A-V node

10

Hamartoma

Post . junction atrium & vent .

Epithelium-like inclusions

A-V node

2

Mcsothehoma

A-V node & common bundle

21 X 3 X 1 .5

Mcsothelioma

Micro = microscopic ; Ca = carcinoma ; Post = posterior ; and vent . = ventricle .

planted . If the pacemaker had had a reliable power source, and the electronic and myocardial connections continued to perform without malfunction for more than three decades (an ideal currently unattained), we might well be reporting this case as a dramatic instance of successful long term aggressive management of heart block . Since pacemakers, wire electrodes and rate stimulating drugs were not available, the patient was treated conservatively and remained in good health until shortly before he died . SUMMARY

A case of a primary uzesothclioma of the atrioventricular node is described . The tumor caused complete heart block for at least 30 years . The 9 previously reported cases are summarized . The microscopic nature of the tumor and the tendency for heart block to occur before the fifth decade of life are emphasized . ACKNOWLEDGMENT

Dr. Maclyn McCarthy, Vice President and PhysicianVOLUME 20 . AUGUST 1967

in-Chief, The Rockefeller University, kindly furnished permission to quote from the records of The Rockefeller Hospital. Mrs . Mary Eitingon provided valuable assistance with sonic of the translations . REFERENCES

1 . GTLetmisT, A . K . Clinical aspects of high-grade heart block. Scottish M . J., 3 : 53, 1958 . 2 . LEV, M . The pathology of complete atrioventricular block . Yrogr . Cardiovas. Dit., 6 : 317, 1964 . 3 . COURTER, S . R ., MOFFA'I, J. and FOWLER, N . O. Advanced atrioventrieular block in acute myocardial infarction . Circulation, 27 : 1034, 1963 . 4 . .IOLTAN, D . G ., VALENTINE, P . A . and MILLER, G . G . Disturbances of rate, rhythm and conduction in acute myocardial infarction . 4m . J. Med., 37 : 915,1964 . 5 . LEv, M . Anatomic basis for atrioventricular block . Am . J. Med., 37 : 742, 1964 . 6 . ARMSTRONG, H . and M6NCRERERG, .1 . G . Herzblock, bedingt durch primaren Ilerztumor, bei einem 5 jahrigen Kinde . Deutsches Arch . klin . .,102 ; 144, 1911 . Med 7 . LLOYD, P . C. Heart block due to primary lymphangio-endothelioma of the atrio-ventricular node . Boll. Johns Hopkins Hop_, 44 : 149, 1929 . 8 . PERRY, C . B . and ROGERS, H . Lymphangio-endo-



254

Kaminsky et al . thelioma of heart causing complete heart block .

14 .

J. Path . & Bact ., 39 : 281, 1934 .

9 . REZex, P . Tibet tine primare epitheliale Geschwulst in der Gegend des Reizleitungs-systems beim Menschen . Virchows Arch . path . Anat., 301 : 305, 1938 . 10 . MAHAIM, I . Les Tumeurs et les Polypes do Coeur, p . 246. Paris and Lausanne, 1945 . Masson and

Roth . F. Zur Pathogenese der primaren epithelialen Tumoren lilt Reizleitungssystem des

11 . LEICHER,

Menschcn . Ztschr. Kreidaaj/orsch ., 37 : 105, 1948 . 12 . WOLF, P . L . and BING, R. The smallest tumor which causes sudden death . J.A .M .A ., 194 : 674, 1965 . 13 . RABSON, S . M . and THILL, L . J . Epithelitmm-like inclusions in the heart . Am . J. Path ., 24 : 655, 1948 .

LEv, M ., WIDRAN, J . and ERICKSON, E . E . Method for histopathologic study of the atrioventricular node, bundle, and branches . Arch . Path ., 52 :

73, 1951 . 15 . HUDSON, R . E . B . The human pacemaker and its pathology . Brit. Heart J ., 22 : 153, 1960 . 16 . HUDSON, R. E . B . The human conducting system and its examination. J. Clin . Path ., 16 : 492, 1963 . 17 . LANxs, K . W . and LAUTSCH, E . V . Pathogenesis of intramyocardial epithelial inclusion cysts . Arch . Path ., 81 ; 365, 1966 . 18 . NICOO, J . L . Cited in Ref . 10 . 19 . ANDERSON, W . A. D. and DMYTRYK, E . '1'. Primary

20 .

tumor of the heart containing epithelium-like elements . Am, J. Path ., 22 :337,1946 . GRANT, R . T . and CAMP, P . 1) . A case of complete heart block due to an arterial angioma . Heart, 16 : 137,1932 .

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