1. Art and Diseño

HEART-REACTIVE ANTIBODY, VIRAL ILLNESS, AND THE
POSTPERICARDIOTOMY SYNDROME
Correlates of a Triple-Blind, Prospective Study
By MARY ALLEN ENGLE, M.D.* AND (BY INVITATION) JOHN B.
ZABRISKIE, M.D.** AND LAURENCE B. SENTERFIT, D.Sc.***
NEW YORK
The postpericardiotomy syndrome (PPS) is a common postoperative
event that occurs in 20-30% of patients following cardiac surgery in
which the pericardium is entered. '3 The syndrome is recognized by the
presence, or by the persistence, beyond the first postoperative week of
f'ever and signs of pericardial and often pleural reaction, sometimes with
effusions. Rarely it recurs late postoperatively. Aside from the discomfort
and prolongation ot' postoperative morbidity that it causes, its significance lies in the confusion with other causes of postoperative fever (such
as endocarditis, the postperfusion syndrome of lymphocytosis and
hepatosplenomegaly,45 atelectasis, or pneumonia) or of cardiomegaly
(such as cardiac failure). Diagnosis is made by excluding these conditions as well as by identifying signs of the syndrome.6 Presently,
management of this self'-limited but sometimes prolonged illness is
entirely empiric since the cause is not known. In mild instances rest in
bed is ef'fective management. In the sick patient, with large pericardial
eff'usion, pericardiocentesis may be required for cardiac tamponade.
Therapy with salicylates or with steroids has been employed with varying
results.
A similar syndrome occurs following myocardial infarction7 and after
penetrating8' 9 or blunt10 pericardial trauma. Features common to these
three settings for the syndrome (intrapericardial surgery or trauma or
myocardial infarction) include damage to heart muscle and the opportunity for intrapericardial bleeding.
Two theories proposed for etiology of the syndrome are that it
represents i!n autoimmune reaction or that it is a viral illness.2 3 10 11
Possibly both factors are involved: an inapparent virus in the host may
* Department of Pediatrics, The New York Hospital-Cornell
University Medical
College. New York New York 10021
** Rockefeller University, New York, New York 10021
*Department of Microbiology, The New York Hospital-Cornell University Medical
College, New York, New York 10021
This work was supported by NHLI Research Grant #1 ROI HL 16246
147
148
ENGLE, ZABRISKIE AND SENTERFIT
be activated by the trauma of surgery and an organ-antibody reaction
may result. We have had an opportunity to test these hypotheses.
PLAN OF STUDY
Subjects for the investigation were consecutive, longterm survivors of
intrapericardial surgery in the pediatric age group. Concurrent analyses
were made on a triple-blind basis preoperatively and postoperatively at
prescribed intervals in the hospital and after discharge, for circulating
antiheart and antiviral antibody and of clinical signs of the syndrome.
The samples of blood were obtained the day before surgery and
postoperatively on the seventh and tenth days, in the third and fifth
weeks and additionally as indicated. The antiheart antibody was
determined from serum by an immunofluorescent technique and was
ranked 0 to 4+, based on intensity of staining. On the same sample of
serum in which heart-reactive antibody was determined, complementfixation studies were performed to a battery of eight viruses (adenovirus,
Coxsackie B 1-6, cytomegalovirus) and to Mycoplasma pneumoniae.
Clinical course of the patients was evaluated by at least two pediatric
cardiologists, one of whom was the principal investigator, and presence
or absence of the syndrome was noted. When present, as judged by strict
criteria, it was rated mild, moderate, or severe, depending on duration
and intensity of manifestations. Physical examination was performed
daily in the hospital and on visits for postoperative followup. Electrocardiogram and teleoroentgenogram of' the chest were obtained according to
the schedule for blood sampling. Echocardiogram was recorded when
pericardial effusion was suspected.
All parameters of postoperative care were maintained as standard as
possible. Antibiotics were administered for the f'irst five days and not
thereafter, unless in a rare circumstance there was clear evidence of' a
bacterial infection. In the first 100 patients, ambulation was delayed
until the patient was afebrile for 48 hours; earlier ambulation as
tolerated was permitted in subsequent patients. Diuretics (furosemide)
were used in most patients with effusions. Neither salicylates nor steroids
were employed except in twelve subjects with severe syndrome, to be
mentioned later. Patients were discharged when they were afebrile for
two days on ambulation and effusions were subsiding.
In a pilot study prior to undertaking this investigation we looked for
the development of' antiheart antibody in a control group of' patients
undergoing surgery that was intrathoracic but not intrapericardial, or
that involved extensive muscle injury or that required large volumes of
transfused blood. In addition, during the course of' this study, we
performed immunologic studies on approximately 40 patients with
POSTPERICARDIOTOMY SYNDROME
149
pericarditis of other etiology (uremia, rheumatoid arthritis, or of
unknown origin), and with miscellaneous conditions such as collagen
disorder, cardiomyopathy, bacterial endocarditis, and rheumatic fever.
Included were four with postmyocardial infarction syndrome and one
with postpericardial trauma syndrome.
RESULTS
Clinical Evaluation.-Of 300 consecutive survivors of intrapericardial
surgery, 83 patients had the postpericardiotomy syndrome (PPS). It was
judged to be mild in one third, moderate in slightly more and severe in
slightly less than one third of the patients. The last abnormality to
disappear was electrocardiographic evidence of pericarditis. Four patients were readmitted within a month of discharge because of exacerbation of the syndrome. Three of these presented as severely ill children
with cardiac tamponade.
Immunologic Studies.-Preoperative sera and control sera were negative for heart-reactive antibody. However, in 191 subjects an antibody
appeared toward the end of the first week. In 89, the staining was greater
than 2+ and the antibody could ')e detected into the second month or
beyond. This response was called positive. In 102 patients, the antibody
rise began at the same time but the staining was less intense, and the
antibody disappeared after one month (intermediate group).
In the sera of the other nonoperated patients studied, heart-reactive
antibody in high titer developed during the course of the illness only in
the few patients with postmyocardial infarction syndrome and in the one
child with postpericardial trauma syndrome.
The antiheart antibody (AHA) was specific for cardiac and for skeletal
muscle but it was not species specific for human cardiac muscle. There
was little binding to smooth muscle and none to other organs such as
lung, liver, thymus, spleen, or kidney. Unlike the heart-reactive antibody
demonstrated in patients with rheumatic fever which binds to Group A
streptococcal membrane, this antiheart antibody did not.
Virologic Studies.-In 180 patients studied, an elevation of viral titer
to one or more viruses was measured in 76 subjects. Twenty-five had a
high titer on admission that did not change during the course, whereas 51
had a four-fold or greater rise in titer and then decline during the period
of observation.
Correlation of Triple-Blind Data.-Results of clinical evaluation of
PPS and determination of antiheart antibody were compared in each
patient, as in Figure 1.
When the comparisons for all subjects were analyzed, it was found that
none of the patients with negative antiheart antibody had the syndrome
150
ENGLE, ZABRISKIE AND SENTERFIT
MODERATE P. P.S
-
S. V., T,
TEMPERIATURLDG.
U
37L
us
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FRICTION fr
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FIG. 1. Graph of hospital course and the month after discharge of a child operated upon
f'or tetralogy of' Fallot. Postoperative fever persisted for four weeks, while pericardial
friction rub was present in the second postoperative week and signs of pericardial effusion
appeared on the fifth postoperative day and disappeared after three weeks. Pleural effusion
was present from the tenth to sixteenth days. The elevated white blood cell count dropped
below 10,000 at the end of three weeks. Heart-reactive antibody, negative preoperatively
and on the fourth postoperative day rose to 2+ or higher by the eighth day, declined in the
third week and disappeared by one month postoperatively.
whereas all of' those with positive antibody had PPS (Figure 2). There
does indeed appear in the serum of certain postoperative subjects a
heart-reactive antibody that correlates closely with clinical evidence of
the PPS.
A striking difference was noticed in incidence of syndrome and in
antiheart antibody between the inf'ants one year of age or less and those
two years of' age and older (Figure 3). Only one baby out of 74 had the
syndrome and positive antibody, an incidence of' 1.3%. Beyond two years,
the incidence was comparable at all ages, ranging from 29 to 40%. One
difference between the babies and those older than two years is the
relatively brief' opportunity for exposure to viral illness in the infants.
POSTPERICARDIOTOMY SYNDROME
151
Among the 180 patients tested for antibody to viruses were 25 patients
who had antibody to one or more viruses prior to surgery but no change
throughout the period of study. They were evenly distributed among the
three types of responses to antiheart antibody. They constituted 17-19%
of those with negative, intermediate, and positive response. In contrast
were 51 children in whom a significant rise, four-f'old or greater, and then
a drop in titer occurred. This rise was observed in 5% of patients with
negative antiheart antibody and no syndrome; in 16% of those with
intermediate antiheart antibody and no syndrome; but in 80% of subjects
with positive AHA and with the syndrome (Figure 4).
The numbers of patients with a significant rise in titer to each viral
agent and the percentage who had postpericardiotomy syndrome are
shown in Figure 5. Most had no detectable antiviral antibody prior to
surgery. In six subjects there was demonstrable titer to Mycoplasma
pneumoniae but no rise in titer. Among the 51 patients with a significant
rise in viral titer, this elevation was to one agent only in 24 but to 2 agents
in five children, to 3 viruses in another 3 patients, and to 4 agents
257 PATIENTS
4 Severe (16)
PPS SYNDROME Moderate (28)*
Mild (22)E
None (191)
100
L
LU
80
a
cD
-
& 60
E
Z
40
20
n
11,
Negaulve iniermeaiate Positive
ANTIHEART ANTIBODY
FIG. 2. In the first 257 consecutive survivors, none of the subjects with negative
antiheart antibody had clinical syndrome, whereas all with positive antiheart antibody had
the syndrome. It was severe in 16 and moderately so in 28. Among those with intermediate
rise of antibody were two with mild syndrome. These same results now extend to 300
consecutive survivors.
AGE DISTRIBUTION OF 257 OPERATED PATIENTS
M-1
out syndrome (191)
syndrome (66)
80
,
60
0
a
9O
E 40
z
20
-
......
nv
0-1 2-5 6-10 11-15 16 &>
Age in years
FIG. 3. The relationship of age to the occurrence of the postpericardiotomy syndrome is
such that babies aged less than two years have a low incidence of only 1.6% of the
postoperative complication, whereas the incidence in the pediatric age groups beyond two
years is about the same, 30-40%.
ANTIHEART ANTIBODY AND RISE IN VIRAL
TITER IN 137 PATIENTS
bu
a. 50
5%
| No rise in titer (106)
Rise in titer (31:
15%
t1
_ 40
L-
o
*
E
30
M
20
10
n
v
Negative Intermediate rositive
FIG. 4. In 137 patients with concurrent measurement of antiheart and antiviral
antibody, only 5%, of those with negative antiheart antibody (AHA) and no postpericardiotomy syndrome had a significant rise in titer to one or more viral agents, whereas 68% of
those with positive AHA and with postpericardiotomy syndrome had a fourfold or greater
rise in titer. In those with intermediate AHA, 15% had a rise in antiviral antibody (AVA).
152
153
POSTPERICARDIOTOMY SYNDROME
RISE IN TITER, VIRAL AGENTS IN 137 PATIENTS
n1'1
without syndrome (10) A?O
PPS syndrome (2
71%
7_
71-To
67%
El
LA
r_6
.T
I
a
'a
a.
z
0
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I
£
4
Coxsackie B
A
:2
0
r,
Cytomegalo-
virus
FIG. 5. In 137 patients with concurrently measured AHA and AVA in figure 4, the
numbers of patients with postpericardiotomy syndrome and with a significant rise in titer
to specific viral agents tested are approximately the same. Though none of the first 137
tested had a measurable rise to Coxsackie B4, several of the more recently studied subjects
did have.
(cytomegolovirus or adenovirus and several of the Coxsackie B group) in
two subjects. No patient in the first 137 studied showed a rise to
Coxsackie B 4, but 11 of the next 43 patients studied this spring and
summer showed a four-f'old or greater rise to this agent. The data
obtained suggested the possibility of' viral invasion, or reactivation of
latent virus, of cardiac muscle at the time of surgery.
Types of Surgery Performed.-We questioned whether the type of
operation and the amount of' myocardial trauma incident to the repair
bore any relation to incidence of' the syndrome. The same types of
operation were performed in all age groups (Figure 6). The most frequent
anomaly operated upon was tetralogy of Fallot, in which a right
ventriculotomy was performed for excision of infundibular pulmonic
stenosis and f'or closure of' the ventricular septal defect with a patch of
tef'lon f'elt. Next most common was atrial septal defect. There appeared
to be no difference in the response of patients with a simple secundumtype defect and those with an ostium primum who had a cleft in the
mitral valve sutured at the same time; so these two types of atrial septal
defect were combined for the analysis. Surgical repair was through a
right atriotomy. A teflon felt patch was used to close all the primum
defects and for the large secundum defects. Simple ventricular septal
defect (VSD), closed with a teflon f'elt patch and usually through a small
right ventriculotomy, was the next most common anomaly; while repair
of' a VSD plus some other lesion such as transposition and/or pulmonic
stenosis was the fourth most common surgical procedure. In the patients
with immunologic and with virologic studies (Figure 6), those with repair
154
ENGLE, ZABRISKIE AND SENTERFIT
OPERATION & POSITIVE ANTI HEART ANTIBODY
257 PATIENTS
60
144%)
Without sydrome
*17%)
m0
PPS syndrome
40
12%
39%
30
0%
20
18%
EL10
E
0
40
31%
OPERATION & VIRAL RISE
137 PATIENTS
II 6%39
~~9%
30
20
~~$0%
10
10
Tetralogy ASD
VSD
only
VSD
plus
TGA
only
Valvar
PS
FIG. 6. The types of operations most frequently performed are shown in order of
decreasing frequency at the bottom of the figure. The percentage with postpericardiotomy
syndrome is indicated at the bottom of each bar for the 257 measured AHA (at top of
figure) and for the 137 with concurrently measured AVA (bottom portion of figure). The
syndrome occurred with higher frequency in those with tetralogy of Fallot and with
ventricular septal defect plus some other anomaly than it did in those wherein there was
less damage to cardiac muscle (ASD=atrial septal defect; VSD only=ventricular septal
defect; TGA=transposition of great arteries undergoing emplacement of intrapericardial
baffle; valvar PS = valvar pulmonic stenosis undergoing pulmonary valvotomy via a
pulmonary arteriotomy).
of tetralogy of Fallot and of VSD plus another lesion (the two conditions
with the greatest potential for myocardial trauma) had the highest
incidence of the syndrome, while none of those with only transposition of
the great arteries repaired by use of an intra-atrial pericardial baffle had
the PPS.
Management.-In a self-limited condition of' uncertain etiology, it is
difficult to judge the effect of treatment, such as rest and diuretics and
the two modalities often recommended: salicylates or steroids.
Early ambulation as tolerated, in contrast to that which was delayed
until the child was afebrile for 48 hours, did not increase the incidence of
the syndrome in the last 190 patients as compared with the first 110
POSTPERICARDIOTOMY SYNDROME
155
individuals in the study. However, when they were febrile or did not feel
well with the syndrome, some of the children permitted early ambulation
voluntarily limited their activity. We do not think it advisable for
patients with moderate or large effusion to be active; three patients
discharged with decreasing pericardial effusion returned critically ill
with pericardial tamponade.
Effect of salicylates and steroids.-It is the group of patients with
severe illness who are of particular concern for optimal management. We
studied the clinical response and the effect on antiheart antibody in 12
such patients. Six patients who received salicylates for several weeks
soon became afebrile and began to improve gradually. The heart-reactive
antibody did not drop immediately but instead, followed the usual
curve of decline. Six other patients who received steroids in the form
of prednisone in a dose of 2 mgm./kg. the first week, half that for the
second week, and a quarter of that for the third week before the
medication was discontinued, had a more impressive response. Promptly
the clinical manifestations subsided, and the antiheart antibody dropped
to intermediate levels and disappeared earlier than expected.
Prevention.-We know of no means as yet of prevention of the
syndrome in an individual patient undergoing intrapericardial surgery.
In one boy with vascular hemophilia, steroids in therapeutic dosage were
administered for one week prior to repair of his tetralogy of Fallot and in
diminishing doses for the first postoperative week. Nonetheless in the
second and third weeks he developed moderately severe syndrome with
high titer of antiheart antibody. Avoidance of the complication, with
reduction in overall incidence of the condition, has come about recently
with the trend to early open repair of severe congenital cardiovascular
anomalies in infancy, the period when there is the least likelihood of
developing postpericardiotomy syndrome.
DISCUSSION
Antibodies which react to nonhuman myocardium were detected in
patients with the PPS by Robinson and Brigden12 and by van der Geld13
in a manner similar to the finding by Kaplan14 and by Zabriskie et a 15 of
heart-reactive antibody associated with rheumatic fever. Kaplan and
Frengley16, Fowler"7, Kirsh and associates"8, Roberts and Lessof19, Das et
al20, as well as Roses, Rose and Rappaport2I have presented thoughtful
reviews on the topic of autoimmunity of the heart and the possible
connection to the postpericardiotomy syndrome. Our early studies on
antiheart antibody confirm an association.22
Concerning the question of the role of viruses, Kahn et al thought
Parainfluenza virus, strain 3, might be significant in pathogenesis of the
156
ENGLE, ZABRISKIE AND SENTERFIT
syndrome.23 In 1970 Burch and Colcolough suggested from their work
with cardiotropic viruses that the syndrome might be caused by
reactivation of a latent virus infection when there is trauma to
myocardium.24 Lerner, Wilson, and Reyes in 1975 reviewed the subject of
enteroviruses and the heart and especially emphasized the probably rolc
of Coxsackie viruses, Group B, Types 15. 2 They set forth criteria for
establishing an association of' a virus infection with an acute or chronic
myocardiopathy.26
SUMMARY AND CONCLUSIONS
This study has demonstrated that a heart-reactive antibody appears in
the serum of' some patients undergoing intrapericardial surgery and that
its presence in high titer correlates with clinical evidence of the
syndrome. This correlation is sufficiently high that it constitutes a
diagnostic test. Furthermore, a rise in viral titer to one or more of the
eight viruses tested occurred in 80% of the patients with the syndrome
but in only 5% and 16% of those with no syndrome and negative or
intermediate levels respectively of heart-reactive antibody.
The freedom from the syndrome in infants may be related to their
short period of' experience with exposure to viruses and to viral illness; so
they do not react immunologically to this new stress by having the
postpericardiotomy syndrome.
The greater chance of' having the syndrome with elevation of antiheart
antibody and rise in titer that patients with tetralogy of Fallot (large
VSD and severe pulmonic stenosis) or with VSD plus some other
anomaly showed may be due to a greater amount of myocardial injury in
those situations than in the other operations, resulting in greater release
of potential antigens.
It is interesting that the last clinical sign of the syndrome to disappear
is the electrocardiographic abnormalities and that the antibody is still
present but in diminished amounts at this time. Just as the elevation of
temperature and white blood cell count seem to parallel one another, so
too do the electrocardiographic abnormalities and elevation of antiheart
antibody. The eff'ect of' steroids in apparently shortening the course of
illness and depressing the level of' antiheart antibody suggests that
prednisone halted antibody production and that we measured the decline
of' the antibody that had already been produced.
While it is possible that neither the appearance of antiheart antibody
nor the rise in viral titer has any connection with the syndrome or with
each other; it seems to us that a reasonable working hypothesis at this
time is as f'ollows. The postpericardiotomy syndrome is the result of an
immunologically determined response of' the epicardial layer of myocar-
POSTPERICARDIOTOMY SYNDROME
157
dium, with inf'lammation and effusion and with "neighborhood" involvement of pleura. Heart-reactive antibody in high titer appears in the sera
of' a certain number of individuals (25-30%) who because of their age and
previous immunologic experience react to epicardial and myocardial
injury incurred at pericardiotomy. This reaction may be triggered by a
latent or fresh viral illness.
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2. ITO, T., ENGLE, M. A. AND GOLDBERG, H. P.: Postpericardiotomy syndrome following
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13. VAN DER GELD, H.: Anti-heart antibodies in the postpericardiotomy and the postmyocardial-infarction syndromes. Lancet 2: 617, 1964.
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ENGLE, ZABRISKIE AND SENTERFIT
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DISCUSSION
DR. JOHN MERRILL (Boston): Have you attempted to see whether specific viral antibody
in any of the viruses you mentioned will block immunofluorescence to your specific heart
reactive antibody?
DR. ENGLE: That's a very good question. This is an ongoing prospective study, and we
do hope to do that. We have not as yet.
DR. NOBLE 0. FOWLER (Cincinnati): This is an area that interests us very much. As Dr.
Engle knows, there are several types of heart and pericardiol damage that may look rather
similar to the post-pericardiotomy syndrome. These include the so-called idiopathic
pericarditis syndrome, the Dressler syndrome, and post-radiation syndrome. It is of interest
to us that living in an area where people occasionally get a little bit excited, we have
observed instances of the same syndrome following both direct and indirect trauma to the
heart of a nonsurgical nature. The syndrome may follow for example a stab wound to the
precordium, and one instance followed just a needle puncture of the heart. This raises the
question again about the relation of intrapericardial bleeding to this syndrome. Are there
any common antigens between heart muscle and red cells? This is one question I would
raise. The other question is have you looked at the idiopathic pericarditis syndrome with
the test mechanism that you used.
DR. ENGLE: Thank you Dr. Fowler. I know that Noble has had a long experience and
interest in this condition. The situations he mentioned really are clinically identical. They
are called by other descriptive terms just because of their settings, post-myocardial
infarction syndrome, post-pericardial trauma syndrome. In our few patients studied with
POSTPERICARDIOTOMY SYNDROME
159
these conditions we have found elevated heart reactive antibody of just this same level that
is indistinguishable from postpericardiotomy syndrome. All these syndromes have the
components of myocardial damage and intrapericardial bleeding. I don't know beyond that
what the common ingredient is. We're looking for antibody against tropomyosin. Because
the anti-heart antibody test is so specific for this condition that it is really helpful in diagnosis, but it is awkward to do, we would like to develop a radioimmunoassay technique that
could be read off as so many nanograms and used everywhere, but we need the optimal
antigen-antibody to do it. We don't know those answers, yet.
DR. JOSEPH JOHNSON, III (Winston-Salem): I'd like to congratulate you upon this very
nice paper. You've alluded by implication already to the problem of assigning pathogenicity to this particular antibody. It is always a question as to whether a particular antibody is
a cause of disease or an effect. I wonder whether this antibody is cytotoxic or if it fixes
complement. Is there any evidence which would support a pathogenic potential for this
antibody?
DR. ENGLE: We are working on establishing a cell line in which direct cytotoxicity can be
tested. The early studies by Dr. Zabriskie were not rewarding. We were not even certain
whether it was against pericardium per se or the different components of pericardium that
merged with myocardium. Thus far we have answered certain questions by putting little
pieces of a jigsaw puzzle together, but the total picture is by no means clear. It's just a little
iarther along, and the possibilities are intriguing, as you suggest.
DR. THOMAS MATTINGLY (Columbia): My comment relates to the problem of blood in the
pericardium in these syndromes. I do not believe that this factor should be ignored in spite
of the brilliant work which you have presented here today. In my experience, I know of no
instance in these syndromes where the presence of blood in the pericardial sac or in the
mediastinum about the pericardium did not exist. My earliest observations go back to the
late forties with the beginning of anticoagulant administration in the management of acute
myocardial infarctions. Hemopericardium occasionally occurred as a complication, producing tamponade and requiring paracentesis. In such instances, the presence of blood in the
pericardium was well established. The clinical features of so-called post-myocardial
infarction were observed to follow these instances of hemopericardium. Again, in 1958, I well
remember during the presentation of an exhibit on nonpenetrating and penetrating trauma
to the heart which included instances of hemopericardium and recurrent pericarditis,
pleuritis, effusion and fever similar to the syndromes you have described here today, Dr.
Dressler was presenting his first exhibits on his collection of cases which he described as the
"post-myocardial infarction" or "Dresslers syndrome" at the same meeting. He came over
and reviewed our exhibit and stated "Your patients have my disease." My reply was "I
think it's vice-versa, I think your patients have our disease, namely blood in the
pericardium."
When one reviews all these syndromes, bleeding in the pericardium sac or in the
mediastinum around the sac is a common denominator, including the post-operative
cardiomyotomies where the pericardium is either closed or left open. Dr. Fowler, in all
probability had bleeding in the pericardial sac following his paracentesis from needle injury
to the myocardium. What is needed are some well designed experimental studies where
blood is placed in the pericardial sac without any of the other factors present and observe
for the clinical syndromes and the antibody responses. This may provide the answer to the
crucial question of blood in the pericardium as a factor.
DR. ENGLE: I certainly agree with you, Dr. Mattingly. We started out believing the
reaction was either an autoimmune response or an unusual viral illness. I now think it's
both, and one of the reasons why some people respond one time and not another to the same
kind of trauma (some people have to undergo cardiac surgery a second time, as you know) is
perhaps the role played by the viral illness. If that too is there at a certain time, then the
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syndrome is triggered in 25 percent of the patients. The role of bleeding certainly is
possible in all of these and its role isn't clarified yet.
DR. LOCKHART MCGUIRE (Charlottesville): Two questions Dr. Engle. In terms of the
definition of the clinical syndrome, do you require a quiescent, afebrile latent period in
which the direct inflammatory response to immediate trauma and blood has been
eliminated, before you will say that this syndrome exists, or do you include an entire
continuum from the immediate post-operative period? I think if you include both you are
talking about two different diseases.
DR. ENGLE: I think I'm not talking about two different diseases, and we do define it as
one of two things, persistence or reappearance. It was thought at first that it occurred late
and only in those people who were readmitted to the hospital after discharge. But in looking
closely, there were evidences of pericardial involvement earlier. We think that they became
worse, or relapsed or that the syndrome recurred. We define the postpericardectomy
syndrome as the persistence beyond the first post-operative week of fever and signs of
pericardial reaction. Within that first week one gets into surgical pericarditis, which is as
you say a completely different thing.
DR. McGuIRE: I would agree with that. Either persistence or appearance. That's a good
phraseology for the definition. The other question was the role of an infectious agent in
eliciting in some way this syndrome, I was going to ask you if you see it in epidemics. Does
it correlate with other viral syndromes in your hospital population?
DR. ENGLE: We are fortunate to have a virologist who works in Long Island who does such
studies and keeps records of which viruses are prevalent at certain times, and we are trying
to correlate our work with his. For instance, you will notice that there was no rise in titer to
Cocksacki B4 with this syndrome in our first 137 patients but concurrent and coincident
with the new B4 epidemic in the New York City area, we have several cases with B4
antibody now. This might suggest that it is a fresh illness, at least in some patients.