Cardiovascular manifestations of systemic lupus

erythematosus
Neil E. Doherty, M.D., and Robert J. Siegel, M.D. Los Angeles, Calif.

Systemic lupus erythematosus (SLE) is a disease of The discovery of the LE ce1115rl6 and its causation
unknown etiology, thought to be autoimmune in by antibodies directed against cell nuclei in the mid
nature, characterized by malar and discoid rashes, 1950’s17pla profoundly changed the concept of syste-
photosensitivity, oral ulcers, nonerosive arthritis, mic lupus erythematosus from a rare fulminant dis-
pleuritis, pericarditis, Raynaud’s phenomenon, ease to an uncommon, but not rare, pleomorphic re-
renal disease, seizures, psychosis, hemolytic anemia, current disease. The spectrum of lupus widened as
leukopenia, lymphopenia, thrombocytopenia, and the diagnosis was made more often clinically, in-
immunologic abnormalities including antinuclear stead of pathologically, and subsequent series were
antibodies, the LE cell phenomenon, anti-DNA not weighted so heavily by overwhelming disease.‘*
antibodies, and a false positive serologic test for In the past 40 years, management of lupus has
syphilis. Because of the pleomorphic nature of this steadily improved, and survival has been greatly
malady, its cardiovascular manifestations have not prolonged. The introduction of antibiotics in the
always been stressed. In recent years, however, with early 1940’s curtailed infections which had previous-
prolonged survival and improvement in diagnostic ly been the primary cause of death among lupus
modalities, the cardiovascular manifestations of patients. Treatment of SLE with steroids began in
SLE have become more apparent. the late 1940’s and dramatically improved survival,
especially when high-dose corticosteroids were
HISTORY
applied to CNS lupus, beginning in 1955. The
The earliest descriptions of lupus erythematosus advent of hemodialysis in 1963 decreased mortality
described it solely as a cutaneous disease (Biett, from renal failure. While most patients still die of
1828; Hebra, 1845; Caxeneve, 1851; Kaposi, 1872).1-6 infection or renal failure, the incidence of cardiovas-
Osler (1895, 1904)7*8 noted endocarditis and pericar- cular morbidity and mortality in SLE is rising, and
ditis as part of the recurrent manifestations of the is now the third leading cause of death in SLE.1s-2z
“exudative erythema” group of diseases. Libman
PERICARDIAL DISEASE
and Sacks (1924)s brought attention to the cardiac
manifestations of lupus, with their description of Pericarditis is the most common cardiovascular
four cases of nonbacterial “verrucous” endocarditis. manifestation of SLE. Evidence of pericarditis has
Gross (1932, 1940)10zl1 went on to describe the been found at autopsy in over 62 % of lupus patients,
cardiac pathology of lupus in greater detail. In but only 25% of cases clinically manifest pericardi-
addition to the verrucous valvular lesions, Gross tis (Table I). s,11,13,14*24-34The clinical diagnosis is
pointed out the significance of the pericardial and frequently difficult and depends on a constellation
myocardial lesions associated with this syndrome. of clinical findings. These include: precordial chest
Thus, it became apparent that cardiac involvement pain, pericardial rub, fever, and tachycardia. How-
in SLE was a “pancarditis.” Subsequent pathologic ever, pericarditis may be painless and clinically
studies in the pre steroid era also demonstrated the silent. The erythrocyte sedimentation rate is ele-
presence of endocarditis, pericarditis, and myocardi- vated. The ECG demonstrates diffuse ST segment
tis in l~pus.‘~-‘~ elevation with evolutionary T wave changes. Sinus
tachycardia and atria1 arrhythmias are frequent, but
From the Division of Cardiology, Cedars-Sinai Medical Center. sinus bradycardia may be seen. The white blood cell
Received for publication July 8, 1985; accepted Aug. 6, 1985.
count is normal unless there is infection, such as
Reprint requests: Robert J. Siegel, M.D., Division of Cardiology, Room
5314, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA purulent pericarditis, or unless the patient is on
90048. steroids.

1257
 December, 1985
1258 Doherty and Siegel American Heart Journal

Table I. Pericarditis

Series author Clinical incidence Autopsy incidence Complications

Libman and Sacks (1924)9 4/4 (100%) 4/4 (100 %I )

Gross (1940)” 14/23 (61%)
Humphreys (1948)l’ 9/21 (43%)
Griffith and Vural (1951)” 11/18 (61%)
Jessar et al. (1953)24 lo/44 (23 % ) 7/15 (47%)
Harvey et al. (1954)25 lPT, 2PP
Armaz-Cruz et al. (1958Y 13/108 (12 %)
Shearn (1959Y 26/83 (31%) 7/16 (44% ) 1PT
Brigden et al. (1960)28 20/27 (74 !‘0 )
Kong et al. (1962)“l 14/30 (47 70 ) 4PT
Hejtmancik et al. (1964)30 24/142 (17 70 ) 11/16 (69%) 2PT, lPP, 1CP
Estes and Christian (1971)” 29/151 (20%) 2PT
Bulkley and Roberts (1975)‘* 19/36 (53 % ) 2PP
Dubois (1976)” 159/520 (30.5% )
Ropes (1976Y 41/142 (29%) 48/58 (83 70 ) 1PT
Total 306/1194 (25.6%) 164/254 (62.1% )

Abbreviations: PT = number of cases of pericardial tamponade-total = 11/1332 (0.8% ); PP = number of cases of purulent pericarditis-total = 5/1332
(0.4’, ); CP = number of cases of constrictive pericarditis-total = l/1332 (O.l?<x ).

Acute symptomatic
_ - pericarditis is frequently reviewed, and in three case reports.51-53 All patients
associated with pericardial effusions. However, had been on steroids. Staphylococcus aureus was
asymptomatic pericardial effusions are also com- identified in six cases and tuberculosis was found in
mon. Clinical evidence of a large effusion includes: 1 case. Patients needed to be treated by surgical
decreased heart sounds, jugular venous distension, drainage, parenteral antibiotics, and generally had
pulsus paradoxus, and Ewart’s sign. The ECG may been continued on steroids until pericarditis
demonstrate diminished voltage and electrical alter- resolved.
nans. Chest x-ray films may demonstrate progres- Chia et a1.37 reported pericardial thickening by
sive enlargement of the cardiac silhouette. Echocar- echocardiographic study in 29% of unselected SLE
diographic studies demonstrate effusion in 21% to subjects. However, constrictive pericarditis is
46 % of nonselected SLE patients.35-38 The incidence exceedingly rare in lupus, and was apparently not
in symptomatic SLE patients has not been re- reported before the use of steroids. Only five cases
ported. have been reported in the literature,30v”-57 including
Pericardial tamponade, an unusual complication, one case of procainamide-induced lupus syndrome
was reported in 11 of 1332 patients (0.8% 1 of the treated with steroids.5g
combined series (Table I). However, there have been Treatment of SLE pericarditis depends on its
several case reports. 3g-47Tamponade has also been severity and is similar to that for viral or idiopathic
reported in drug-induced lupus syndromes with pericarditis. Asymptomatic hemodynamically insig-
isoniazid,48 procainamide,4g and hydralaxine.50 Pul- nificant pericardial effusions are generally not
sus paradoxus hypotension, jugular venous disten- treated. Symptomatic pericarditis is usually treated
sion, and hepatic enlargement, in addition to other with nonsteroidal anti-inflammatory agents (e.g.,
signs of pericarditis, may be present to suggest the aspirin, 1 gm every 4 hours, or indomethacin, 50 mg
diagnosis. thrice daily). More serious cases may be treated with
Echocardiographic indicators of tamponade steroids (e.g., prednisone, 20 to 80 mg daily). There
include: right atrial collapse, right ventricular expi- is no clear-cut role for intrapericardial steroid
ratory collapse, as well as paradoxic septal motion. administration. It has been recommended that peri-
While large effusions are usually present, tampon- cardiocentesis not be performed, except in life-
ade may occur with acute accumulation of small to threatening tamponade, or to resolve a serious diag-
moderate volumes in the pericardial space. Hemody- nostic dilemma such as the need to rule out purulent
namic corroboration of tamponade physiology, i.e., pericarditis (Dubois and Wallace, personal commu-
equalization of right- and left-sided diastolic pres- nication). Four deaths have been attributed to myo-
sures, is useful. cardial laceration,%* 5g and one death has been
Purulent pericarditis is a rare complication, ascribed to laceration of the left anterior descending
occurring in only five cases among the 15 series coronary arteryzs during pericardiocentesis.
Volume 110
Number 6
When pericardiocentesis is performed, the peri-
cardial fluid is generally an exudate that may be
clear to hemorrhagic, with normal glucose, and that
contains numerous leukocytes-primarily polymor-
phonuclear cells. 27,41~43~46~ 60-63 There is marked immu-
nologic activity in the pericardial fluid, including:
LE cells, antinuclear antibodies, anti-DNA antibod-
ies, rheumatoid factor, and immune complexes, with
activation of classical and alternative complement
pathways and low complement levels.“, 45*47,56,64,65
MYOCARDIAL DISEASE
Whether there is a cardiomyopathy directly
attributable to lupus is unresolved. Most series cite a
high incidence of heart failure but attribute it to
multiple problems, including: fever, infections, ane-
mia, uremia, hypertension, steroids, and accelerated
atherosclerosis. At least two studies, however, have
provided evidence supporting the concept of a pri-
mary lupus cardiomyopathy. de1 Rio et al.66 studied
systolic time intervals in 25 patients with SLE and
found that these patients had a shorter left ventric-
ular ejection time and a longer pre-ejection period
than control subjects, suggesting impaired left ven-
tricular systolic function.
Strauer et al.67 performed extensive hemodynamic
evaluations in five young patients without clinically
evident heart disease and found significant abnor-
malities of cardiac function in all five. These inves-
tigators demonstrated minimally impaired systolic
pump function but advanced diastolic dysfunction
and marked abnormalities of coronary vascular
reserve. These findings were demonstrated in the
absence of cardiomegaly, hypertrophy, or symptoms
of heart failure. Strauer et al. concluded that lupus
cardiomyopathy may exist even without clinical
signs or symptoms of cardiac dysfunction and may
represent abnormalities of the intrinsic contractile
and relaxation properties of the myocardium.
Kohler et a1.68demonstrated that resting hemody-
namics were generally normal in young SLE
patients, but with exercise there was an inordinate
rise in systemic, pulmonary, and pulmonary capil-
lary wedge pressures associated with an appropriate
rise in cardiac output. At a workload of 90 W, the
pulmonary capillary wedge pressure rose from 8.0 f
4.1 to 21.4 +- 6.2 mm Hg despite a rise in cardiac
index from 4.7 f 0.9 to 11.6 f 1.1 L/min/m2, sug-
gesting diastolic dysfunction but normal systolic
function.
Echocardiographic studies also support the pres-
ence of a subclinical or asymptomatic cardiomyopa-
thy. Kanaya et al.‘js noted a hyperkinetic state, along
with a constellation of abnormalities suggesting
Cardiovascular manifestations of SLE 1259
diastolic impairment. Ito et al.36 found increased
cardiac chamber size and decreased ejection fraction
in patients who had had a pericardial effusion, and
noted that disease activity was related to the pres-
ence of pericardial effusions. They suggested a rela-
tionship between pericarditis and myocarditis, caus-
ing myocardial systolic dysfunction in lupus. In
normotensive patients, chamber size and myocardial
function returned to normal as pericardial effusions
abated, but this did not hold true in hypertensive
patients, in whom chamber dilation and hypokinetic
wall motion persisted, suggesting an interaction
between autoimmune and hypertensive damage to
the heart. Chia et a1.37did not find any relationship
between echocardiographic abnormalities and previ-
ous hypertension, anemia, or renal failure, but Kou-
Chine found that many aspects of cardiac function
were significantly worsened by these risk factors in
lupus patients.
Various etiologies have been proposed for lupus
cardiomyopathy. Das and Cassidy70 detected anti-
heart antibodies in 20 of 32 patients with SLE and
proposed that these antibodies might be involved in
the genesis of myocardial dysfunction in lupus.
Bidani et a1.71 demonstrated immune complexes in
the myocardium in 9 of 10 necropsies. They pro-
posed that immune complex deposition led to com-
plement activation, inflammation, and myocardial
damage. Either mechanism (anti-heart antibodies or
immune complex deposition) may provoke the small
vessel vasculitis, focal myocarditis, fibrosis, and
myocardial necrosis that is seen at autopsy in many
SLE hearts. Further evidence is needed, however, to
establish the link between these pathologic findings,
immunologic abnormalities, and cardiac dysfunction
in vivo.
There is a large disparity between clinical and
autopsy series in recognizing myocarditis. Clinical
investigators have diagnosed myocarditis in less
than 10% of most series (Estes and Christian, 8.0% ;
Dubois, 7.3%; Ropes, 10.0%),3133*3’ compared to an
overall incidence of 40% in autopsy series (Table
II). 14,25*27,2g,30,32,33,58 Clinically, these patients may
present with heart failure, cardiomegaly, ventricular
arrhythmias, sinus tachycardia, or merely nonspe-
cific ECG changes. Cardiac enzymes and endomyo-
cardial biopsy should improve diagnostic sensitivi-
ty.
On endomyocardial biopsy and at autopsy, there
is perivascular and interstitial invasion by mononu-
clear cells, along with myocardial degeneration,
fibrosis, and scarring in more advanced cases. Bor-
enstein et a1.72 reported five cases of myocardi-
tis associated with myositis and antibodies to ri-
 December, 1985
1260 Doherty and Siegel American Heart Journal

Table II. Incidence of myocarditis in SLE butww The diagnosis of Libman-Sacks endocarditis
series) is primarily made at autopsy. Table III summarizes
data pertaining to these lesions from 13
Griffith and Vural (1951)14 14/18
Harvey et al. (1954)*5 21138 autopsy series, which found verrucae in 47% of
Shearn (1959)*’ 8116 322 autopsied patients between 1924 and
Larson ( 1961)58 8152 1982. 9.11-14.24,25,21-3%32,32 Ml four v&,es may be
Kong et al. (1962)29 15/30 involved, but the mitral valve is most commonly
Hejtmancik et al. (1964)‘O 13/16
involved, especially the recess between the posterior
Bulkley and Roberts (1975)” 3136
Haserick (per Dubois, 1956)73 15/30 mitral valve leaflet and the ventricular wall.
Total 100/236 Physical examination and echocardiography may
suggest verrucae, but are nondiagnostic. Murmurs
SLE = systemic lupus erythematosus.
may be caused by fever, tachycardia, hypertension
or anemia, rather than by verrucae in SLE. Con-
bonucleoprotein (RNP). Most patients re- versely, Libman-Sacks verrucous endocarditis is fre-
sponded to high-dose steroids, but some required quently reported at autopsy in patients who were
the addition of azathioprine. These authors noted never reported to have had murmurs on physical
that myocarditis was less responsive than myositis. examination 14925,21-2% 33,34,13 With echocardiography,
Hypertension may predispose to myocardial dys- mitral valve thickening suggestive of verrucae has
function, The incidence of hypertension in lupus is been reported in 3 % to 4 % of cases,35’3s,7gbut
estimated at between 14 % and 69 % .14,25*27,28*32-34,I3 vegetations are ordinarily too small to detect. Only
Lupus, per se, is not thought to cause hypertension, unusually large Libman-Sacks verrucous vegeta-
but renal failure and steroids are thought to precip- tions may be visualized clearly with echocardiogra-
itate or aggravate hypertension in many cases. dw.so
Dubois13-16 found that steroids caused a significant The incidence of Libman-Sacks endocarditis
and reversible increase in blood pressure in 10% to seems to have declined in the last 30 years. Steroids
19% of SLE patients. The impact of nonsteroidal may have caused this decrease. As can be seen from
anti-inflammatory drugs has not been evaluated. Table III, 59% of autopsied patients in the pre-
steroid era had verrucous lesions, compared to 36%
VALVULAR DISEASE in the steroid era. This would be consistent with an
Libman-Sacks verrucous vegetations are the immune complex etiology of these lesions, as pro-
pathognomonic valvular lesions of SLE.gs l1 The ver- posed by Shapiro and colleagues.77 Another possible
rucae may appear as pea-sized, flat or slightly raised, explanation is that in former years many patholo-
granular, gray or pinkish projections, densely adher- gists considered the endocardial lesions requisite to
ent to the endocardium, occurring most frequently the diagnosis of lupus erythematosus, since these
at the valve rings and commissures, spreading over lesions represented the most specific postmor-
both valve surfaces, the valve pockets, and even onto tem finding. In later years, the diagnosis was more
the atria1 and ventricular mural endocardium, chor- often made antemortem by clinical criteria includ-
dae tendineae, and papillary muscles. Infrequently, ing the LE ce1115*‘6* l8 and antinuclear antibody
11,81,85
they may become massive thrombotic lesions, up to t&S.
10 mm, or even larger, which tend to occur at Libman-Sacks endocarditis probably predisposes
commissures, and may in rare instances obstruct a to infective endocarditis.83,s4 Review of 15 studies
valve orifice.” (Table III) demonstrates that 4.9% of autopsied,
Microscopically, the vegetations consist of prolif- and 1.3% of clinical cases were complicated by
erating and degenerating cells, fibrin, fibrous tissue, infective ~~~~~~~~~~~~9,11-14,24,25,21-30,32,34,85 This is a

and occasional hematoxylin bodies. There may be
variable amounts of inflammation, with a mild
scattering of plasma and large mononuclear cells.
Shapiro et alI7 demonstrated selective deposition of
immunoglobulins and complement along the vessel
walls of verrucae, suggesting that circulating
immune complexes may be involved in the growth
and proliferation of Libman-Sacks verrucous vege-
tations.
much higher percentage than that encountered in
the general population or with other collagen vascu-
lar diseases.s5
Thromboembolism is a rare consequence of Lib-
man-Sacks endocarditis. Pritzker et al.% report one
case of myocardial infarction studied at necropsy
with normal coronary arteries and thrombotic occlu-
sion of the left circumflex coronary artery in the
setting of a Libman-Sacks aortic valve vegetation.
Volume 110
Number 6 Cardiovascular manifestations of SLE 1261

Table 111.Libman-Sacks endocarditis (LSE)

Incidence Vu/aloesIn~rolued
No. of LSEI
Autopsy series No. of Autopsies s, MV AV TV F’V

Pre-steroid era
Libman and Sacks (1924j9 414 100
Gross (194O)l’ 17123 74
Klemperer et al. (1953)‘> 12120 60
Humphreys (1948)” 12121 57
Griffith and Vural (1951)14
6/18 33
Pre-steroid era (Total) 51186 59

Steroid era
.Jessar et al. (1953Y 5115 33 l/44
Harvey et al. (1954)2” 12138 32 2138
Shearn (1959)*’ 4116 25 O/83
Brigden et al. (196O)2* 13127 48 10 4 1 1 2160
Kong et al. (1962)19 4130 13 4 0 0 0
Hejtmancik et al. (1964))O S/l6 50 8 2 1 1 21142
Bulkley and Robert (1975)‘* 18136 50 18 2 1 0
Ropes (1976)‘4 22158 38 22 3 4 1 21142
Lehman et al. (1983)” 61571
(L.1 I’( 1
Steroids era (Total) 86/236 36 71178 15/1180
(3.Y1, ) (1.31, )
Total 1371322 43 76 17 17 10 191264 15/1180
(4.9”, i (l.ac, )
MV = mitral valve; AV = aortic valve; TV = tricuspid valve; PV = pulmonic valve

There has also been one documented embolic cere- scarring of the valve leaflets against the mural
brovascular accident, presumably due to Libman- endocardium. Two cases of mitral regurgitation were
Sacks embolized verrucae.87 associated with aortic insufFicienc~gg and two
Hemodynamically significant regurgitant lesions additional cases of mitral regurgitation were associ-
may affect the aortic or mitral valve in SLE. Aortic ated with mitral stenosis.100~105
insufficiency is the most common serious problem, Pritzker et al.& reported two cases of aortic steno-
with at least 36 cases in the English literature, and sis due to massive thrombi. Vaughton et a1.‘06report-
may be due to multiple causes, in addition to ed a case of mitral stenosis secondary to massive
verrucous endocarditis, including: valvulitis, thrombi, requiring valve replacement. There are 10
fibrosis, mucoid degeneration and fenestrations, cases of mitral stenosis in the earlier literature
bacterial endocarditis, and aortic dissec- attributed to Libman-Sacks lesions, but few of these
tion.‘*, 25,28,30,34*71,80,ea-looRisk factors for aortic insuffi- were hemodynamically significant.“, 25,28
ciency in these patients include: systemic hyperten- Dajee, Hurley, and Szarnicki’O” reported three
sion, steroid therapy, bicuspid aortic valves, and cases and reviewed nine additional cases from the
rheumatic fever. literature on valve replacement (six aortic valve and
Nine cases of hemodynamically significant mitral six mitral valve replacements). Their report sub-
regurgitation have been reported in SLE.32, 9~.lo1-lo3 stantiates the viability of surgical valve replace-
Mitral regurgitation may be due to: thickening and ment, but documents a 26% overall surgical mortal-
calcification of the mitral valve leaflets and chordae ity in SLE patients. There are inadequate data
tendineae scarring, fibrosis, fibrinoid necrosis of comparing mechanical and tissue bioprostheses.
papillary muscles, and rupture of chordae tendineae. While tissue valves may avoid the need for anticoag-
Bulkley and Robert~‘~* attributed three cases of ulation, there is concern that they may be predis-
mitral regurgitation to steroids, postulating that posed to verrucous vegetation and accelerated
they caused healing of the verrucae and subsequent degeneration.
 December, 1985
1262 Doherty and Siegel American Heart Journal

Table IV. SLE and coronary artery disease in 33 young tors. The presence of a lupus anticoagulant was
patients (135 years old) noted in two patients. In these reports107-121there was
limited information concerning cholesterol; an ele-
Age of diagnosis
SLE 3-27 yr (18.0 + 7.4)* vated cholesterol level was documented in only one
CAD 5-35 yr (26.5 f 6.6)* patient.l13 Acute myocardial infarction was the most
Coronary risk factors? common initial cardiac manifestation, followed, in
Hypertension 14124 order, by heart failure, sudden death, and angina.
“Steroids”1 19124
Extracardiac manifestations of SLE were common
Cigarettes 5124
Lupus anticoagulant 2124
but were not always present. The incidence of
Cardiac manifestations atherosclerosis and arteritis was similar: 12 patients
Myocardial infarction 30/33 had atherosclerosis, seven had arteritis, and six had
CHF 9/33 stenosis, but no distinction was made between ath-
Sudden death 4133
erosclerosis or arteritis. Small vessel hyaline arterio-
Angina 2133
Presence of active extracardiac SLE 23128 lar disease probably caused myocardial infarction in
Coronary artery lesions two cases.118l121Coronary artery embolization from
Atherosclerosis 12128 Libman-Sacks vegetations appears rare and was
Arteritis 7128 reported in one patient less than 35 years old.86 The
Embolus l/28
left anterior descending coronary artery was
Hyaline arteriolar disease 2128
Thrombosis present 12/25
involved in most cases of coronary disease, and
Coronary artery involved thrombosis was frequently noted. There has been
Left anterior descending 18/22 little discussion of therapy, but Homey et allo did
Left circumflex 9122 note successful treatment of arteritis with steroids
Right 8122
in one patient and coronary bypass surgery for
CAD = coronary artery disease; CHF = congestive heart failure. atherosclerotic disease in one patient.107121 At our
*Mean ? standard deviation. institution, bypass surgery has been performed in
See text for discussion of cholesterol.
YSteroids” = Quotation marks are used because the role of steroids as a one SLE patient and angioplasty was done in anoth-
risk factor is still questionable. er patient with good early results.
$Based on angiography or necropsy; in 6 cases stenosis noted but no Haider and Roberts122 studied at necropsy coro-
distinction made between atherosclerosis or arteritis.
nary artery disease in 22 lupus patients aged 16 to 37
years. Hypertension and hypercholesterolemia were
significant risk factors. The mean cholesterol level of
CORONARY ARTERY DISEASES
382 mg/dl in SLE patients with severe coronary
The apparent incidence of coronary artery disease narrowing was significantly higher than the mean
in SLE has been increasing. There has been a recent cholesterol level of 290 mg/dl in those with no
rise in the proportion of deaths due to myocardial significant coronary artery narrowing. Unlike the
infarction and its cardiovascular sequelae.1g-23 Both clinical case reports in young SLE patients, these
coronary arteritis and atherosclerosis may occur in authors point out the significance of hypercholester-
SLE. Arteritis is a pathologic diagnosis, but certain olemia as a coronary risk factor. Arterial blood
angiographic features suggest it. Aneurysmal dilata- pressure of 175/118 mm Hg in severely diseased
tion or any abrupt change from a previously normal patients was also significantly greater than the level
arteriogram may be seen in arteritis.107s121 These of 151/93 mm Hg in patients with no severe coronary
lesions may improve after treatment with high-dose narrowing. The higher frequency of pericardial
steroids. Atherosclerotic obstructions, however, are adhesions and mitral valvular disease in SLE
better treated with standard therapy: nitrates, beta- patients with severe coronary narrowing suggested
blockers, calcium channel antagonists, angioplasty, that an immunologic factor may also have contrib-
and coronary bypass surgery. For management pur- uted to the development of coronary disease in these
poses, therefore, differentiation between arteritis individuals.
and atherosclerosis is important.
SUMMARY
There have been numerous case reports of signifi-
cant coronary artery disease in young lupus SLE affects most aspects of cardiac function, and
patients.33s 1o7’-121
Table IV summarizes salient fea- recent studies have reported increasing cardiovascu-
tures of 33 patients less than 35 years old with SLE lar morbidity and mortality.1gs21 Pathologically, SLE
and coronary disease. Hypertension, steroids, and is characterized by a pancarditis involving pericardi-
cigarettes were the most commonly cited risk fac- um, myocardium, endocardium, and coronary arte-
Volume 110
Number 6 Cardiovascular manifestations of SLE 1263

two bone marrow elements: The “tart” ceil and the “LE.”
ries. In autopsy series, pericarditis has been found in
cell. Proc Staff Meet Mayo Clin 23:25. 1948.
43 % to 100 % (mean 62 % , Table I), and myocarditis 16. Hargraves MM: The LE cell phenomenon Proc Statf Meet.
was found in 8% to 78% (mean 40%) Table II), but Mayo Clin 27:419, 1952.
both have been underdiagnosed clinically. Libman- 17. Tan EM, Schur PH, Carr RI, Kunkel HG: Deoxyribonucleic
Acid (DNA1 and antibodies to DNA in the serum of patients
Sacks lesions have been noted in 25% to 100% with systemic lupus erythematosus. .I (‘Iin invest &:17X!,
(mean 43% ) and infective endocarditis in 1.1% to 1966.
4.9% of clinical and autopsy studies (Table III). 18. Dubois EL: The etfect of the L,.E. cell test on the clinical
picture of systemic lupus erythematosu.+. Arch Intern Med
Coronary disease may be due to arteritis, which 38:1265, 1953.
should be treated with high-dose steroids, or it may 19. Urowitz MB, Bookman AAM, Koehler BE. Gordon DA,
be due to atherosclerosis, which is amenable to med- Smythe HA, Ogryzto MA: The binodal mortality pattern ot
systemic lupus erythematosus. Am ,J Med 60:221 1976.
ical or surgical therapy.‘07,121 Valvular disease has 20. Karsh J, Klippel JH, Barlow JE, Decker cJl,: Mortality in
been treated surgically, but with a combined sur- lupus nephritis. Arthritis Rheum 22:764. 1979.
gical mortality as high as 25% .l”) Aortic insufficien- 21. Wallace DJ, Podelt T, Weiner .I. Klinenhrrg .JR, Forouzesh
S, Dubois EL: Systemic lupus ervthemaiosus---Survival
cy and mitral regurgitation are the most common patterns. Experience with 609 patienis -7.4M.4 245:944.
valvular problems, although aortic and mitral ste- 1981.
22. Rosner S, Ginzler EM, Diamond HS, Weiner M, Schlesinger
nosis have also been reported. Hypertension has M. Fries JF. Wasner C. Medsger TA <Jr. Zeialer G. Kliauel
been noted in 14% to 69% ,14,25,27-33and heart failure JH, Hadler ‘NM, Albert DA, ‘Hess EV. Spencer-Green’G.
in 5% to 44% .14,24j27-33Evidence for a lupus cardio- Grayzel A, Worth D, Hahn BH, Barnett E: A multicentrr
myopathy, which may be subclinical, is re- study of outcome in systemic lupus ervthematosus. 11.
Causes of death. Arthritis Rheum 25:61?. 1982.
viewed.36*66-6g While steroids may ameliorate SLE 23. Cheigh JS, Stenzel KH, Rubin AL, Chami .1. Sullivan dF:
pancarditis, they have also been associated with hy- Systemic lupus erythematosus in patients with chronic renal
pertension, LV hypertrophy, purulent and constric- failure. Am cJ Med 75:602, 1983.
24. Jessar R, Lamont-Havers R, Ragan C: Natural history 01’
tive pericarditis, mitral regurgitation, and perhaps lupus erythematosus disseminatus. Ann Intern Med 38:717,
accelerated atherosclerosis.22, lo4It remains to be seen 1953.
if improved diagnosis and treatment of the cardio- 25. Harvey A, Shulman L, Tumulty l’, (‘onley t’. Scheinrick E:
Svstemic lupus erythematosus: Review of the literature and
vascular manifestations of SLE can enhance survival. clinical analvsis of 138 cases. Medicine 33:%1. 1954.
26. Armaz-Cruz”R, Harnecker J, Ducach G, ,Iwlil J, (Gonzales F:
REFERENCES
Clinical diagnosis of systemic lupus rryt hcmatosus. Am .I
1. Hiett T: Quoted in Abrege Pratigue des Maladies de la Peau Med 25:409, 1958.
by Casenave A, and Schedel HE. Paris, 1828, p 386 (Quoted 27. Shearn M: The heart in systemic 1up11s erythematosus. Ahf
in Harvey et al, ref. 25, 1954, pg 293). HEART J 58:4X, 1959.
2. Hebra F: “Hautkrankheiten.” Wien, B.3, Theil 1:40, 1845. 28. Brigden W, Bywaters EGL, Lessof MH, Ross 11’: The heart
3. Hebra F, Kaposi M: On diseases of the skin including the in systemic lupus erythematosus. Br Heart .J 22:l. 1960.
exanthema. Translated and edited by W Tay. London, 1875, 29. Kong TQ, Kellum RE, Haserich ,112: Clinical diagnosis of
The New Sydenham Society, vol 4. cardiac involvement in systemic lupus erythematosus: A
4. Cazenave A: Lupus erythemateux (Erytheme centrifuge). correlation of clinical and autopsy findings in thirty
Ann Malad Peau Syph 3:297, 1850-1851. patients. Circulation 26:7, 1962.
5. Cazenave ,4. Chausit M: Du lupus. Ann Malad Peau Syph 30. Hejtmancik M. Wright J. Quint R. clemmings I+ The
4:113, 1852. cardiovascular manifestations of’ systemit, Iiipus erqthema-
6. Kaposi M: Neue beitrage zur Kenntnis des lupus erythema- tosus. AM HEART ,J 68:119, 1964.
tosus. Arch Dermat U Syph 4:36, 1872. 31 Estes D, Christian CL: The natural history of systemic lupus
7. Osler W: On the visceral complications of Erythema exuda- erythematosus hy prospective analysis. Medicine 50:85.
tivum multiforme. Am J Med Sci 110:629, 1895. 1971.
8. Osler W: On the visceral manifestations of the erythema :i2. Butkley BH, Roberts WC: The heart in systemic lupus
group of skin diseases. Am J Med Sci 127:1, 1904. erythematosus and the changes induced in it by corticoste-
9. Libman E, Sacks B: A hitherto undescribed form of valvular roid therapy: A study of 36 necropsy patients. Am J Med
and mural endocarditis. Arch Intern Med 33:701, 1924. 58:243, 1975.
10. Gross I,: The heart. in atypical verrucous endocarditis 33. Dubois E: Lupus erythematosus: A review of the current
(Libman-Sacks): Contributions to the medical sciences in status of discoid and systemic lupus rrythematosus and
honor of Dr Emanuel Libman by his pupils, friends, and their variants. ed 2, revised. Los Angeles. !976, Ifniversity of
colleagues. Vol 2. New York, 1932, International Press, pg Southern California Press.
527. 34. Kopes M: Systemic lupus erythematosus. Cambridge, Mass.,
11. Gross L: The cardiac lesions in Libman-Sacks disease with a 7976, Harvard University Press.
consideration of its relationship to acute diffuse lupus 35. Maniscalco BS, Felner JM, Mc(lans .lL, Chiapella JA:
erythematosus. Am J Pathol 16:375, 1940. Echocardiographic abnormalities in systemic lupus erythe-
12. Klemperer P, Potlack AD, Baehr G: Pathology of dissemi- matosus (abstr). Circulation 52 (Suppl 11):211, 1975.
nated lupus erythematosus. Arch Path01 92:789, 1953. 36. lto M, Kugiyama Y, Omura 1, Hiramatsu Y, Kurata E,
13. Humphreys E: The cardiac lesions of acute disseminated Kanaya S, Ito S, Fujino T, Kusaba ‘I?, Jimi S: Cardiovascular
lupus erythematosus. Ann Intern Med 28:12, 1948. manifestations in systemic lupus erythematosus. ,Jpn Circ J
14. Griffith GC, Vurat IL: Acute and subacute disseminated 43:985, 1979.
lupus erythematosus: A correlation of clinical and postmor- 37. Chia BL, Mah EPK, Feng PH: Cardiovascular abnormali-
tem findings in eighteen cases. Circulation 3:492, 1951. ties in systemic lupus erythematosus. .I Clin Ultrasound
15. Hargraves MM, Richmond H, Morton R: Presentation of 9.‘2’37
.I , 1981.
,

1264 Doherty and Siegel
38. Kou-Ching J: Echocardiographic findings in systemic lupus
erythematosus (in Chinese). Formosan Med Assoc 80:1227,
1981.
39. Curtis AC, Horne SF: Disseminated lupus erythematosus
with pericardial effusion. Ann Intern Med 30:209, 1949.
40. Williams C. Soutter L: Pericardial tamaonade. Diaenosis
and treatment. Arch Intern Med 94:571: 1958. - I. Ortiz-Vazauez J: Mvocardial involvement in svstemic
41. Bergen SS: Pericardial effusion, a manifestation of systemic
lupus erythematosus. Circulation 22:144, 1960.
42. Schoenfield MR. Messeloff CR: Cardiac tamnonade in
systemic lupus erythematosus. Circulation 27:98, 1963.
43. Lerer RJ: Cardiac tamponade as an initial finding in
systemic lupus erythematosus. Am J Dis Child 124:436,
1972.
44. Hunder GG, Muller BJ, McDuffie FC: Complement in
pericardial fluid of lupus erythematosus. Ann Intern Med
80:453, 1974.
45. Glovsky MM, Louie JS, Pitts WH, Alnty A: Reduction of
pleural fluid complement activity in patients with systemic
lupus erythematosus and rheumatoid arthritis. Clin Immu-
no1 Immunopathol 6:31, 1976.
46. Askari AD: Pericardial tamponade with hemorrhagic fluid
in systemic lupus erythematosus. JAMWA 33:111, 1978.
47. Quismorio FP: Immune complexes in the pericardial fluid in
systemic lupus erythematosus. Arch Intern Med 140:112,
1980.
48. Greenberg JH, Lutcher CL: Drug-induced systemic lupus
erythematosus. A case of life-threatening pericardial tam-
ponade. JAMA 222:191, 1972.
49. Anderson RJ, Genton E: Procainamide induced pericardial
effusion. AM HEART J 83:798, 1972.
50. Carey RM, Coleman M, Feder A: Pericardial tamponade. A
major presenting manifestation of hydralazine induced
lupus syndrome. Am J Med 54:84, 1973.
51. Knodell RG, Manders SJ: Staphylococcal pericarditis in a
patient with systemic lupus erythematosus. Chest 85:103,
i974. - sus: A comparative evaluation of corticosteroids and their
52. Gould K, Barnett JA, Sanford JP: Purulent pericarditis in
the antibiotic era. Arch Intern Med 134:923. 1974.
53. Dorlon RE, Smith JM, Cook EH, Loebl DH; Mealing HG,
Bailey JP: Staphylococcal pericardial effusion with tampon-
ade. J Rheumatol9:813, 1982.
54. Yurchak PM, Levine SA, Gorlin R: Constrictive pericarditis
complicating disseminated lupus erythematosus. Circula-
tion 31:113, 1965.
55. Starkey RH, Hahn BH: Rapid development of constrictive
pericarditis in a patient with systemic lupus erythematosus.
Chest 63:448, 1973.
56. Jacobson EJ, Reza MJ.: Constrictive pericarditis in systemic
lupus erythematosus. Arthritis Rheum 21:972, 1978.
57. Sunder SK. Shan A: Constrictive nericarditis in nrocainam-
ide-induced lupus erythematosus-syndrome. Am J Cardiol
36:960, 1975.
58. Larson DL: Systemic lupus erythematosus. Boston, 1961,
Little, Brown & Co.
59. Berbis N, Allen J, Dubois E: Le risque de la pericardicentese
dans le lupus erythemateux dissemine: A propos d’un cas et
revue de la litterature Revue du (in French). Rhumatisme
44:359, 1977.
60. Seaman AJ, Christerson JW: Demonstration of L.E. cells in
pericardial fluid. Report of a case. JAMA 149:145, 1952.
61. Spodick DH. Differential diagnosis of acute pericarditis.
Prog Cardiovasc Dis 14:192, 1971.
62. Wolkove N, Frank H: Lupus pericarditis. CMA J 111:1331,
1974.
63. McCuiston CF, Moser KM: Studies in pericarditis. Differ-
entiation of the acute idiopathic form from that occurring in
disseminated lupus. Am J Cardiol 4:42, 1959.
64. Goldenberg DL, Leff G, Grayzel AI.: Pericardial tamponade
in systemic lupus erythematosus. With absent hemolytic
complement activity in pericardial fluid. NY State J Med
75:910, 1975.
December, 1985
American Heart Journal
65. Ordonez NG, Parem S, Aronson A, Dalton H, Katz AI,
Spargo BH, Kirsten WH: Viral immune complexes in
systemic lupus erythematosus. C-type viral complex deposi-
tion at extrarenal sites. Virchows Arch (Cell Pathol) 25:355,
1977.
66. de1 Rio A, Vazquez JJ, Sobrino JA, Gil A, Barbado J, Mate,
lupus erythematosus. Chest 74:414, 1978. _
67. Strauer BE, Brune I, Schenk H, Knoll D, Perinos I: Lupus
cardiomyopathy: Cardiac mechanics, hemodynamics and
coronary blood flow in uncomplicated systemic lupus ery-
thematosus. AM HEART J 92:715, 1976.
68. Kohler E, Boldt-Gath A, Bremer G, Goeckenjan G, Lako-
mek HJ: Abnormal findings of cardiac function in patients
with systemic lupus erythematosus (in German). Z Kardiol
71:93, 1982.
69. Kanaya S, Fujino T, Hirata M, Kurata E, Kodama T,
Kusaba T, Ito M: Echocardiographic evaluation of cardiac
function in patients with systemic lupus erythematosua J
Cardiogr 9:45, 1977.
70. Das SL, Cassidy JT: Antiheart antibodies in patients with
SLE. Am J Med Sci 285:275, 1973.
71. Bidani AK, Robert JL, Schwartz MM, Lewis EJ: Immuno-
pathology of cardiac lesions in fatal SLE. Am J Med 69:849,
1980.
72. Borenstein DG, Fye WB, Arnett FC, Stevens MB: Myocar-
ditis of SLE: Association with myocarditis. Ann Intern Med
89:619, 1978.
73. Dubois EL: Prednisone and prednisolone in the treatment
of systemic lupus erythematosus. JAMA 161:427, 1956.
‘74. Dubois EL: Triamcinolone in the treatment of systemic
lupus erythematosus. JAMA 167:1590, 1958.
75. Dubois EL: Methylprednisolone (Medrol) in the treatment
of systemic lupus erythematosus. Analysis of results in forty
cases. JAMA 170:1537, 1959.
76. Dubois EL: Current therapy of systemic lupus erythemato-
side effects with emphasis on fifty patients treated with
dexamethasone. JAMA 173:1633, 1960.
77. Shapiro RF, Gamble CN, Wiesner KB, Castles JJ, Wolf AW,
Hurley EJ, Sale1 AF: Immunopathogenesis of Libman-Sacks
endocarditis. Assessment by light and immunofluorescent
microscopy in two patients. Ann Rheum Dis 36:508,1977.
78. Dubois EL, Tuffanelli DL: Clinical manifestations of sys-
temic lupus erythematosus: Computer analysis of 520 cases.
JAMA 190:104,1964.
79. Elkayam U, Weiss S, Laniado S: Pericardial effusion and
mitral valve involvement in systemic lupus erythematosus:
Echocardiographic study. Ann Rheum Dis 36:349, 1977.
80. Richardson PG, Hibbert DH, Oram S: Aortic incompetence
in systemic lupus erythematosus. Br Med J 2:1260, 1976.
81. Schur P: Antinuclear antibodies. N Engl J Med 282:1205,
1970.
82. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ,
Rothfield NF, Schaller JG, Talal N, Winchester RJ: The
1982 revised criteria for the classification of systemic lupus
erythematosus. Arthritis Rheum 25:1271, 1982.
83. Short CL: Case report: Case records of the Massachusetts
General Hospital, Case #39431. N Engl J Med 249:700,
1953.
84. Mills JA: Case report: Case Records of the Massachusetts
General Hospital, Case #8-1968. N Engl J Med 278:441,
1968.
85. Lehman T, Palmeri S, Hastings C, Klippel J, Platz P:
Bacterial endocarditis complicating systemic lupus erythe-
matosus. J Rheumatol 10:655, 1983.
86. Pritzker MR, Ernst JD, Candill C, Wilson CS, Weaver WF,
Edwards JE: Acquired aortic stenosis in systemic lupus
erythematosus. Ann Intern Med 93:434, 1980.
87. Fox IS, Spence AM, Wheelis RF, HeaIey LA: Cerebral
embolism in Libman-Sacks endocarditis. Neurology 30:487,
1980.
Volume 110
Number 6 Cardiovascular manifestations of SLE 1265

88. Shulman HJ, Christian CL: Aortic insufficiency in systemic 105. Yates DB, Scott JT: Cardiac inflammatory diseases in
lupus erythematosus. Arthritis Rheum 12:138, 1969. chronic inflammatory disorders of connect.ive tissue. Factors
89. Bernhard GC, Lange RL, Hensley GT: Aortic disease with influencing survival after surgery. Ann Rhenm Dis 34:321.
valvular insufficiency as the principal manifestation of 1975.
systemic lupus erythematosus. Ann Intern Med 71:81, 106. Vaughton KC, Walker DR, Sturridge MF: Mitral valve
1969. replacement for mitral stenosis caused h,v Libman-Sacks
90. Oh WMC, Taylor RT, Olsen EGJ: Aortic regurgitation in endocarditis. Br Heart ,J 41:730, 1979.
systemic lupus erythematosus requiring aortic valve 107. Homey CJ, Liberthson RR, Fallon JT. (iross S, Miller LM:
replacement. Br Heart J 36:413, 1974. Ischemic heart disease in systemic lupus erythematosus in
91. Williams RC: Case report: Case records of the Massachu- the young patient. Am J Cardiol 49:478. 1982.
setts General Hospital, Case #29-1976. N Engl J Med 108. Bor I: Cardiac infarction in the Libman-Sacks endocardit,is.
295:156, 1976. N Engl J Med 279:164, 1968.
92. Cooper PJ. Ferguson R, Toghill PJ, Walker M: Aortic 109. Bickers JN. Buechner HA. Hood Bd. :tlvarez-Chiesa (;:
incompetence in systemic lupus erythematosus. Br Med J Hypersensitivity reaction to ant.ituberculous drugs with
2:1260, 1976. hepatitis lupus phenomenon and mvocartlial infarction. N
93. Isaacs A,J: Aortic incompetence in systemic lupus erythema- Engl J Med 265:131, 1961.
tosus. Br Med J 2:1260, 1976. 110. Aravanis C. Toutouzas P. Yatzidis 1: Fatal mvocardial
94. El-Ghobarey A, Grennan DM, Hadidi T, El-Bodawy S: infarction in lupus erythematosus: Report of a case of a
Aortic incompetence in systemic lupus erythmatosus. Br young female patient. Vascular Dis 1:258. 1964.
Med J 2:915, 1976. 111. Honfiglio TA, Botti RE, Hagstrom JW(‘: i’oronary arteritls
95. Mossard ,JM, Walter P, Brechenmacher C, Voegtlin R: occlusion and myocardial infarction due ii 8 lupus erythemn-
Atteinte cardiaque au tours d’un syndrome la pique. Etude tosus. AM HEART J 83:153, 1972.
clinique et morphologique a propos d’un cas ayant necessite 112. *Jensen G, Sigurd B: Systemic lupus ervthematosus and
un double remplacement valvulaire (in French). Arch Ma1 acute myocardial infarction. Chest 64:65:i. 1973.
Coeur 70:1203, 1977. 113. Simon N. Cohen H. Glick G. Kanter A. Levin B. Pirani Cl,:
96. Walts AE, Dubois EL: Acute dissecting aneurysm of the Clinicopathologic conference. AM HEART .I 86:539, 1973.
aorta as the fatal event in systemic lupus erythematosus. AM 114. Tsakraklides VG, Blieden LC, Edwards cJE: Coronary ath-
HEART J 93:378, 1977. erosclerosis and myocardial infarction associated with sys-
97. Thandroyen FT, Matison RE, Weir EK: Severe aortic temic lupus erythematosus. AM HEART J 87:637, 1974.
incompetence caused by systemic lupus erythematosus. S 115. Benisch BM, Pervez N: Coronary arttlry vasculitis and
Afr Med J 54:166, 1978. myocardial infarction with systemic. 1~~11s erythematosus.
98. Kinney EL, Wynn J, Ward S, Babb JD, Wine-Schaffer C, NY State J Med 74:873, 1974.
Zelis R: Ruptured chordae tendineae. Its association with 116. Meller J. Conde CA. Dennisch LM. l)a)noso E. Dack S:
systemic lupus erythematosus. Arch Path01 Lab Med Myocardial infarction due’ to coronary atherosclerosis in 3
104595, 1980. voung adults with systemic lupus ervthemat,osus. Am .J
99. Rawsthorne L, Ptacin MJ, Choi H, Olinger GN, Bamrah VS: Cardiol 35:309, 1975..
Lupus valvulitis necessitating double valve replacement. 117. Ishikawa S. Seear WE. Gilbert EF. Burkholder PM. Levv
Arthritis Rheum 24:561, 1981. JM: Myocardii infarction in a child with systemic lup\ls
100. Dajee H, Hurley EJ, Szarnicki RJ: Cardiac valve replace- erythematosus. Am J Dis Child 1323696, 1978.
ment in systemic lupus erythematosus: A review. J Thorac 118. Bignold LP, Bailey IK, Kronenberp H: Myocardial infarc-
Cardiovasc Surg 85:718, 1983. tion, papillary muscle dysfunction, and mitral valve incom-
101. Myerowitz PD, Michaelis LL, McIntosh CL: Mitral valve petence in systemic lupus erythematosua. Aust NZ ,I Med
replacement for mitral regurgitation due to Libman-Sacks 10:236, 1980.
endocarditis. Report of a case. J Thorac Cardiovasc Surg 119. Rosenthal T, Neufeld H, Kishon Y. \ elin 0, Many A:
67:869, 1974. Myocardial infarction in a young woman with systemic
102. Paget SA, Bulkley BH, Brauer LE, Seninger R: Mitral valve lupus erythematosus. Angiology 31:573, 1980.
disease of systemic lupus erythematosus: A cause of severe 120. Speira H, Rothenberg RR: Myocardial infarction in four
congestive heart failure reversed by valve replacement. Am young patients with systemic lupus erythpmatosus. .J Rheu-
J Med 59:134, 1975. matol 10:464, 1983.
103. Murray FT, Fuleihan DS, Cornwall CS, Pinals RS: Acute 121. Liberthson RR, Homey C, Fallon JT. (Gross S, Leppo J,
mitral regurgitation from ruptured chordae tendineae in Miller L: Systemic lupus erythematosas and heart disease.
systemic lupus erythematosus. J Rheumatol 2:454, 1975. Primary Cardiol 9:77, 1983.
104. Bulkley BH, Roberts WC: Systemic lupus erythematosus as 122. Haider YS, Roberts WC: Coronary artery disease in SLE:
a cause of severe mitral regurgitation: New problem in an Quantification of degrees of narrowing in 22 necropsy
old disease. Am d Cardiol 35:305, 1975. patients aged 16 to 37 years. Am J Med 70:775. 1981.