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She was cachectic (weight 43 kg.), obtunded and dehydrated. There was severe limitation
to passive as well as active movement of all peripheral joints and to exion and extension
of the neck. There was marked ulnar deviation of both wrists and fusiform swelling of
the metacar pal-phalangeal joints. The heart was enlarged and both atrial and ventricu lar
gallops were audible. Agrade 3/6 ejection type systolic murmur which radiated into
the neck was audible over the cardiac base, a grade 2/6 high-pitched blowing diastolic
murmur was heard over the left sternal border and a grade 2/6 blowing pansystolic
murmur which radiated into the left axilla was heard over the cardiac apex.
The blood hematocrit was 40 per cent and the white blood cell count was 8,200
per cu. mm. The serum total protein was 6.7 gm. with albumin 2.1 gm. per 100 ml.
Blood electrolytes and urea nitrogen were normal. Chest roentgenogram (Figure1)
showed cardiomegaly, a small left pleural effusion and arthritic changes in the
shoulders. Electrocardiogram (Figure2) showed normal sinus rhythm, left bundle
Figure 1 Roentgenograms demonstrating progressive cardiomegaly. The lower
roentgenograms were made one day before death.
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CASE 65 QUADRIVALVULAR RHEUMATOID HEART DISEASE
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Figure 2 Electrocardiogram recorded one day before death. Left bundle branch
block and rst degree heart block are present.
Figure 3 The opened heart. Left, the aortic root, aortic valve and left ventricle
(L.V.) are shown. Each of the aortic valvular cusps as well as the anterior mitral
leaet (A.) is diffusely thickened. The aortic cusps also are contracted, and prolapse
slightly toward the left ventricle. No lesions are present in the aorta itself. Right, the
left atrium (L.A.), mitral valve and left ventricle (L.V.) are shown. Both anterior (A.)
and posterior mitral leaets are diffusely thickened, but the chordae tendineae are
normal and neither commissure is fused. Focal areas of thickening are visible on the
endocardial surface of the left atrium.
branch block and a prolonged P-R interval (0.26 second). (Electrocardiogram in
August1963 had been normal.) Breathing became labored and she died two days
after admission.
At autopsy (No. 66A-129) the pericardial space was obliterated by brous
and a few brinous adhesions. Within the adhesions and in the subepicardial
fat numerous rm, yellow nodules measuring up to 1.5cm. were found, and on
microscopic examination these were typical rheumatoid granulomas. The heart
weighed 550 gm. All chambers were dilated and the walls of both right (0.7cm.
thick) and left (1.5cm. thick) ventricles were hypertrophied (Figure3 through 10).
The aortic and mitral valvular leaets were markedly thickened, and the normal
cuspal tissue was replaced by innumerable rheumatoid nodules. The thickening
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Figure 4 Gross (left) and histologic section (right) of wall of left atrium (L.A.) and
left ventricle (L.V.), and posterior mitral leaet (P.M.L.). The basal portion of the left
ventricular myocardium and the caudal portion of the left atrial endocardium are
replaced by rheumatoid nodules which appear white (left). The visceral and parietal
pericardia are adherent to one another. Aclose-up of the area enclosed by the blacklined rectangle is shown in Figure5. Hematoxylin and eosin stain (right), original
magnication × 2.5.
Figure 5 Left atrial wall. The endocardium is markedly thickened by the presence
of rheumatoid nodules. The dashed line separates the endocardium from the myocardium. Hematoxylin and eosin stain, original magnication × 28.
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CASE 65 QUADRIVALVULAR RHEUMATOID HEART DISEASE
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of these cusps almost certainly prevented them from closing completely. Similar
rheumatoid nodules were localized discretely at the basal attachments of the septal
and anterior tricuspid leaets and of two of the three pulmonic valvular cusps.
Function of these right-sided valves, however, would not appear to have been
altered. In addition to the rheumatoid nodules in the mitral and aortic leaets, the
process extended into the myocardium in the basal portion of the left ventricular
free wall, into the adipose tissue of the left atrioventricular sulcus, and down the
membranous septum to the cephalad portion of the muscular ventricular septum.
Remnants of the atrioventricular bundle were found, but the proximal portion of
the left bundle branch was completely interrupted by the granulomatous process.
The lungs were edematous, and rm well circumscribed yellow nodules up
to 0.5cm. in diameter were found in both lower lobes and in the middle lobe of
the right lung. The nodules demonstrated the characteristic histologic features of
rheumatoid granulomas.
The articular cartilages of the knee joints were destroyed and the bone on
the articular surfaces of the tibial and femoral condyles was focally eroded. The
Figure 6 Cut sections depicting aortic root and surrounding structures. Left, this
block includes an aortic valvular cusp (A.V.), membranous and muscular ventricular
septa (V.S.), septal tricuspid valvular leaet (T.V.) and portion of right atrial wall
(R.A.). The entire membranous and the cephalad portion of the muscular septum are
virtually replaced by rheumatoid granulomas which appear white. The granulomatous process extends into the tricuspid valve ring through the membranous septum.
Right, this section includes an aortic valvular cusp, anterior mitral leaet (A.M.L.),
aorta and left atrial wall (L.A.). The “core” of both mitral and aortic valvular cusps
are replaced by the innumerable granulomas which appear white. Acircumscribed
rheumatoid nodule (arrow) is located between the aortic and left atrial walls.
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Figure 7 Histologic sections depicting extensive inltration of the cardiac valves
and adjacent structures by rheumatoid nodules. Left, this section was prepared from
the tissue block shown in Figure6, left. The membranous and cephalad tip of the
muscular ventricular septum (V.S.) are replaced by rheumatoid granulomas. In
addition, a rheumatoid nodule is present at the base of the tricuspid valve (T.V.), and
others extend up the right atrial wall (R.A.). Middle, the aortic valvular cusps (A.V.),
anterior mitral leaet (A.M.L.) and portions of aortic and left atrial (L.A.) walls are
extensively inltrated by rheumatoid granulomas. Right, close-up of aortic valvular
cusp shown on middle photograph. The “core” of the cusp is uniformly necrotic. The
margins of the cusps are relatively well preserved. Hematoxylin and eosin stains,
original magnication × 7 (left), × 3.5 (middle) and × 19 (right).
Figure 8 Close-up of most cephalad portion of ventricular septum. The area is
extensively inltrated by rheumatoid granulomas, but portions of the atrioventricular
bundle (enclosed by dashed line) remain. The proximal portions of the left bundle
branch (the area enclosed by dashed parallel lines), however, are completely disrupted
by the granulomatous process. Elastic tissue stain, original magnication × 18.
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CASE 65 QUADRIVALVULAR RHEUMATOID HEART DISEASE
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synovia of these joints was thickened, and histologic sections disclosed organizing
connective tissue containing bone chips and pigment-laden macrophages, with
proliferation of villi. In addition, inactive and involuting rheumatoid nodules were
identied in the synovia of the knee joints and immobile subcutaneous nodules
were found over both elbows.
Special stains including Brown and Brenn, Fite, methenamine silver and stains
for acid-fast organisms were applied to selected sections of heart and lung; no
organisms were found.
COMMENTS
Since the rst description by Baggenstoss and Rosenberg in 1941 of cardiac nodules
morphologically similar to those seen in the subcutaneous tissues of patients with
rheumatoid arthritis, a number of reports describing the heart in this disease have
appeared.
the heart in only 1 to 3 per cent of patients with rheumatoid arthritis who come to
autopsy.
1–27
Although specic for this condition, rheumatoid nodules are found in
2
Other nonspecic types of cardiac lesions, however, have been observed
at necropsy in these patients, including pericarditis, myocarditis, coronary arteritis
and patchy valvular brosis (Table 1). In addition to these specic and nonspecic
cardiac lesions which have been considered to be manifestations of rheumatoid
disease, other types of heart disease have been identied as being more common
in patients with rheumatoid arthritis than in control groups, although these lesions
in themselves are not considered to be part of the rheumatoid process. Lebowitz
4
found a higher over-all incidence of cardiac disease, especially calcic aortic
stenosis and valvular sclerosis, at autopsy among patients with rheumatoid arthritis
than in control subjects matched for age and sex. He noted a similar incidence of
arteriosclerotic heart disease, including myocardial infarction, in the two groups
and a lower incidence of systemic hypertension and hypertensive heart disease
among the patients with rheumatoid arthritis. There was a comparable incidence
of previous rheumatic heart disease in the two groups. These observations differ
from those of Sokoloff who found a higher incidence of what he called rheumatic
heart disease or heart disease indistinguishable from rheumatic heart disease in
patients with rheumatoid arthritis.
2
The differences in the incidences of the cardiac
diseases associated with rheumatoid arthritis reported by these two investigators
can probably be explained by differences in criteria used for the cardiac diagnoses.
Goehrs etal.
5
found cardiac hypertrophy in twenty-ve of thirty-six autopsy patients
with rheumatoid arthritis, and only seven of them had systemic hypertension.
Asai found that the incidence of S-T segment depression and/or inverted or at T
waves was signicantly greater among 158 patients with rheumatoid arthritis than
among 182 apparently healthy control subjects.
6
In those with rheumatoid arthritis
changes were most marked in the patients with high levels of serum beta or gamma
globulins, and he speculated that dysproteinemia could be a factor in causing the
electrocardiographic abnormalities.
At least twenty-one patients with rheumatoid granulomas involving cardiac
valves or valve rings have been described in the literature.
4, 5, 7–16
The aortic
valve alone was involved in four patients, the mitral valve alone in ten and both
aortic and mitral valves in three. The tricuspid valve alone was involved once,
and in another patient both mitral and tricuspid valves were affected. Three
valves (aortic, mitral and pulmonic) were involved in one patient and all four
in another. In nine of the twelve patients in whom cardiac size was recorded
the heart weighed over 300 gm.; in the other three it weighed less than 300 gm.
Of the nine patients in whom blood pressure determinations were reported,
three had systemic hypertension (≧ 140/90mm. Hg). The presence or absence
of a precordial murmur was recorded in fteen of these twenty-one subjects. Six
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Figure 9 Gross (left) and histologic section (right) of rheumatoid nodule in right
ventricular (R.V.) myocardium at the base of a pulmonic valvular cusp (P.V.). P.T.,
pulmonic trunk. Hematoxylin and eosin stain (right), original magnication × 9.
Figure 10 Close-up of cardiac rheumatoid granuloma. This nodule is representative of the many in the heart; this particular one was located at the base of a pulmonic cusp. Hematoxylin and eosin stains, original magnication × 160 (left), × 628
(right).
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CASE 65 QUADRIVALVULAR RHEUMATOID HEART DISEASE
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Table 1: Rheumatoid heart disease
Rheumatoid granulomas (3%)
Valve rings and valve leaets
Myocardium
Complete heart block
Ventricular septum
Pericardium
Nonspecic inammatory lesions
Pericarditis (40%)—Fibrous
Myocarditis (20%)
Coronary arteritis (20%)
Acute and chronic valvulitis (5%)
NOTE: The percentages quoted in this table are from the paper by Sokoloff in 1953.
patients had precordial murmurs which appeared to be related to the presence of
granulomas in the cardiac valves, and another patient (not included in the total
of twenty-one) had a murmur typical of aortic regurgitation with rheumatoid
nodules in the wall of the dilated aortic root but none in the aortic valve itself.
In each of these six patients the murmurs were interpreted as representing either
mitral regurgitation or aortic stenosis or regurgitation. Three of the other nine
patients had precordial murmurs which did not appear to be caused by valvular
granulomas, and six patients had no murmur despite the presence of valvular
lesions at necropsy. The precordial murmurs when secondary to valvular
granulomas tended to indicate that a cardiac valve was extensively involved, but
did not correlate with the number of valves containing granulomas. The only
patient described with rheumatoid granulomas in all four cardiac valves had no
precordial murmur. The murmurs in the present patient were almost certainly
the result of incompetent mitral and aortic valves which were not able to close
completely because of diffuse thickening of the leaets. There may also have been
some element of aortic valvular stenosis in the present patient, the result of the
inability of the thickened cusps to open properly.
The feature which distinguishes our patient from those previously described
is the extent and severity of the cardiac involvement. Rheumatoid granulomas
were observed in all four valves, in the mural endocardium, in the myocardium
and in the pericardium. The mitral and aortic leaets were diffusely and uniformly
thickened by granulomas, but only focal lesions were observed on the tricuspid
leaets and at the base of the pulmonic valvular cusps. The rheumatoid lesions in
the previously described patients were generally focal, usually small and widely
scattered. The granulomatous process involved the central portion of the valvular
leaets with relative sparing of the margins. This involvement of the “core” of the
valvular leaets is in direct contrast to the valvular involvement in carcinoid heart
disease in which the valve itself remains normal and the atypical brous tissue is
deposited on the surface of the valvular cusp.
In the present patient the left bundle branch block was the result of disruption
by rheumatoid granulomas of the left bundle branch as it emerged from the
atrioventricular bundle. Complete heart block has been reported in at least two
necropsy patients with rheumatoid arthritis, and in one a single rheumatoid nodule
was located in the area of the atrioventricular bundle.
had granulomas in cardiac valves and appropriate histologic sections were not
prepared to determine the precise cause of the heart block.
↗
↘
Left bundle branch block
2
17, 18
Neither of these patients
7
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REFERENCES
1. BAGGENSTOSS, A. H. and ROSENBERG, E. F. Cardiac lesions associated with
chronic infectious arthritis. Arch. Int. Med., 67: 241, 1941.
2. SOKOLOFF, L. The heart in rheumatoid arthritis. Am. Heart J., 45: 635, 1953.
3. SOKOLOFF, L. Cardiac involvement in rheumatoid arthritis and allied disor-
ders: current concepts. Mod. Concepts Cardiovasc. Dis., 33: 847, 1964.
4. LEBOWITZ, W. B. The heart in rheumatoid arthritis (rheumatoid disease). Ann.
Int. Med., 58: 102, 1963.
5. GOEHRS, H. R., BAGGENSTOSS, A. H. and SLOCUMB, C. H. Cardiac lesions in
rheumatoid arthritis. Arthritis& Rheumat., 3: 298, 1960.
6. ASAI, K. Electrographic changes in rheumatoid arthritis. Jap. Heart J., 6: 367, 1965.
7. WEINTRAUB, A. M. and ZVAIFLER, N. J. The occurrence of valvular and myo-
cardial disease in patients with chronic joint deformity. Am. J, Med., 35: 145, 1963.
8. BAGGENSTOSS, A. H. and ROSENBERG, E. F. Unusual cardiac lesions associ-
ated with chronic multiple rheumatoid arthritis. Arch. Path., 37: 54, 1944.
9. ELLMAN, P., CUDKOWICZ, L. and ELWOOD, J. S. Widespread serous mem-
brane involvement by rheumatoid nodules. J. Clin. Path., 7: 239, 1954.
10. SCHOENE, R. H. and RISSE, G. B. Rheumatoid heart disease. Ohio State M. J., 60:
37 7, 1 9 64.
11. SKOGRAND, A. Visceral lesions in rheumatoid arthritis. Acta Rheumat.
Scandinav., 2: 17, 1956.
12. GRUENWALD, P. Visceral lesions in a case of rheumatoid arthritis. Arch. Path.,
46: 59, 1948.
13. BYWATERS, E. G. L. The relation between heart and joint disease including
“rheumatoid heart disease” and chronic post-rheumatic arthritis (type Jaccoud).
Brit. Heart J., 12: 101, 1950.
14. LASSITER, G. S. and TASSY, F. T. Malignant rheumatoid disease with aortic ste-
nosis. Arch. Int. Med., 116: 930, 1965.
15. CRUICKSHANK, B. Heart lesions in rheumatoid disease. J. Path. Bact., 76: 223,
1958.
16. SOKOLOFF, L. and BUNIM, J. J. Vascular lesions in rheumatoid arthritis.
J. Chron. Dis., 5: 668, 1957.
17. GOWANS, J. D. C. Complete heart block with Stokes-Adams syndrome due to
rheumatoid heart disease. New England J. Med., 262: 1012, 1960.
18. HANDFORTH, C. P. and WOODBURY, J. F. L. Cardiovascular manifestations of
rheumatoid arthritis. Canad. M. A. J., 80: 86, 1959.
19. HOFFMAN, F. G. and LEIGHT, L. Complete atrioventricular block associated
with rheumatoid disease. Am. J. Cardiol., 16: 585, 1965.
20. LEBOWITZ, W. B. The heart in rheumatoid disease. Geriatrics, 21: 194, 1966.
21. SINCLAIR, R. J. G. and CRUICKSHANK, B. Aclinical and pathological study of
sixteen cases of rheumatoid arthritis with extensive visceral involvement (rheumatoid disease). Quart. J. Med., 25: 313, 1956.
22. MAHER, J. A. Dural nodules in rheumatoid arthritis. Arch. Path., 58: 354, 1954.
23. CATHCART, E. S. and SPODICK, D. H. Rheumatoid heart disease. New England
J. Med., 266: 959, 1962.
24. CHRISTIE, G. S. Pulmonary lesions in rheumatoid arthritis. Aust. Am. Med., 3:
49, 1954.
25. GRAEF, J., HICKEY, D. V. and ALTMANN, V. Cardiac lesions in rheumatoid
arthritis. Am. Heart J., 37: 635, 1949.
26. RAVEN, R. W., WEBER, F. P. and PRICE, L. W. The necrobiotic nodules of rheu-
matoid arthritis. Ann. Rheumat. Dis., 7: 63, 1948.
27. PIRANI, C. L. and BENNETT, G. A. Rheumatoid arthritis. Bull. Hosp. Joint Dis.,
12: 335, 1951.
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CASE 78 CARDIAC VALVULAR LESIONS IN RHEUMATOID ARTHRITIS
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Case 78 Cardiac Valvular Lesions
in Rheumatoid Arthritis
William C. Roberts, MD; James A. Kehoe, MD; Deborah F. Carpenter, MD;
and Abner Golden, MD
Washington, DC, and Bethesda, MD
Nodules, similar to those which occur in the subcutaneous tissue, also may occur
in the respiratory, intestinal hematopoietic, musculoskeletal, and cardiac systems
of patients with rheumatoid arthritis (RA). Recently, we described rheumatoid
nodules in all four cardiac valves of a 65-year-old woman with RA.
was submitted for publication, which was the rst report to describe signicant
quadrivalvular involvement in RA, we have observed similar quadrivalvular cardiac
disease in another patient who died with RA. This paper describes the cardiac lesions
in the latter patient, and compares them with those found in the previously described
subject and with those observed in the more frequent types of valvular heart disease.
PATIENT SUMMARY
A 72-year-old man (GMC, 12-47-82) who died Nov 28, 1966, was well until age 36 when
he suddenly developed right-sided pleuritis with effusion, and several days later,
swelling, redness, pain, and tenderness of both ankles and the metatarsophalangeal
joints of both feet. He was treated with aspirin and the arthritis disappeared
within a six-month period. Thereafter, with the exception of several approximately
six-hour episodes of pain and swelling of the metatarsophalangeal joints, the
patient was completely well and on no medications until age 66 (1960) when acute
arthritis appeared involving initially mainly the right ankle. He was treated with
phenylbutazone with considerable improvement of the joint manifestations, but
signs and symptoms of an active peptic ulcer appeared and the drug was stopped.
Thereafter, he had severe chronic pain, stiffness and swelling, and periodic
tenderness and redness bilaterally of the metacarpo-, metatarso-, and proximal
interphalangeal joints, wrists, elbows, shoulders, knees, and ankles. Despite weekly
intramuscular gold injections, he did not receive complete relief from these joint
manifestations.
At age 68 (February 1963) he was admitted to the Georgetown University
Medical Center for further therapy. Examination disclosed fusiform swelling
of the proximal interphalangeal joints of the hands, tender and swollen ankles,
subcutaneous nodules over both olecranon processes, basilar pulmonary rales,
atrial and ventricular diastolic gallops, and lower leg edema. The patient’s
blood pressure was 120/70mm Hg, the heart was not enlarged, and a grade 1/6
systolic murmur was heard over the cardiac base and over the left sternal border.
Chest roentgenogram disclosed the cardiac silhouette to be at the upper limits
1
Since that report
Received for publication March13, 1968; accepted May6.
From the departments of pathology (Drs. Carpenter and Golden) and medicine (Dr. Kehoe),
Georgetown University Medical Center, Washington, DC, and the Section of Pathology,
National Heart Institute, National Institutes of Health, Bethesda, Md (Dr. Roberts).
Reprint requests to Section of Pathology, National Heart Institute, National Institutes of
Health, Bethesda, Md 20014 (Dr. Roberts).
DOI: 10.1201/9781003409281-9 59
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