CARDIAC COMPLICATIONS OF DIPHTHERIA

Beverly C. Morgan, M.D.

Heart Station and Department of Pediatrics, Robert B. Green
Memorial Hospital, San Antonio, Texas

T HE WIDESPREAD routine immunization of Sixty-nine patients were of school age; in

children against diphtheria, pertussis, addition, 10 of the younger children ap-
tetanus, poliomyelitis, and smallpox has re- parently contracted their diphtheria from
sulted in a marked decrease in the mci- school age siblings. Only five patients had
dence of these diseases in the United States. received a basic series of three diphtheria
A current textbook of pediatric cardiology immunizations, and of these only two had
comments : “Since the infection has been had a booster injection. The 95 patients
eliminated almost totally by immunization, who were included in this study met the
an opportunity to study a diphtheritic heart following criteria: ( 1) positive nasopharyn-
is rarely presented.” In other parts of the geal smear for diphtheria, (2) positive
world, however, and even in certain areas throat culture for Corynebacterium diph-
of the United States, preventable communi- theriae. Information regarding the type of
cable diseases remain relatively common. diptheria organism was not available. In
Diphtheria attack rates have actually in- addition, each patient had a chest x-ray
creased recently in some sections of the and one or more electrocardiograms avail-
United States.2 In the past 5%-year-period, able for analysis. All patients admitted to
98 patients with diphtheria were admitted the study after November 15, 1960, (42 of
to the Robert B. Green Memorial Hospital. 95 cases) had serial electrocardiograms
The cardiovascular findings were reviewed taken every other day during hospitaliza-
to determine incidence, type of involve- tion and additional tracings 1, 2, and 3
ment, efficacy of modern treatment, and months following discharge from the hos-
prognosis of the cardiac complications in pital. All electrocardiograms were 12 or 13
this disease. lead tracings obtained on a Sanbom Twin
Beam photographic machine except for the
MATERIAL AND METHODS bedside records which were taken with a
During the 5%-year period, January 1, Cambridge Simple-Scribe direct writing in-
1957, through June 30, 1962, 98 patients strument. Post-hospitalization follow-up
with diphtheria were seen at the Robert B. was obtained for all but six patients and
Green Memorial Hospital, a 330-bed city- ranged from 1 month to 5 years.
county hospital. Ninety-five were evaluated
clinically, while three were dead on arrival CLINICAL FINDINGS
with history and postmortem findings of The duration of symptoms ranged from
diphtheria. a few hours to 11 days prior to admission.
There were three Negro and three Cau- The usual history was that of sore throat
casian patients; the remainder were Latin and fever, often with swelling of the neck;
American. Forty-nine of the 98 patients several patients, in addition, complained of
were male. Three children had diphtheria shortness of breath. On physical examina-
and rubeola concurrenfly. The age distribu- tion all children had nasopharyngeal find-
tion ranged from 14 months to 17 years. ings compatible with diphtheria, including

(Received February 18; accepted for publication April 6, 1963.)

This study was partially supported by a grant from the National Heart Institute, Public Health Service
Grant HTS-5539.
ADDRESS: (B.C.M.) Department of Pediatrics, University of Washington School of Medicine, Seattle
5, Washington.
PEDIATRICS, October 1983
549

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550 1)1 PHTI-IERIA

TABLE I peared to be respiratory. Three additional

ELuc’raocutDIooItAi’uIc FINDINUN IN patients were dead on arrival with history
95 PATIENTS WITH DIPHTHERIA and postmortem findings diagnostic of
diphtheria but without pathological evi-
Patients with dence of myocarditis. The over-all mortality
Electrocardiographic
Findings*
These Findings
(9 of 98 cases) was 9%. All deaths occurred
within the first fourteen days of illness.
Surrived Died
Four of 95 patients developed electro-
Normal electrocardiogram 64 0 cardiographic and clinical evidence of se-
T-wave changes in or more leads 18 3 vere myocarditis (case reports in appendix).
ST-segmentshift more than 1 mm 14 3
Three of these patients succumbed while
Minor P-wave abnormality 3 0
Prolonged QT interval 6 3 the fourth survived.
Prolonged PR interval 4 1 The most frequent auscultatory findings
Sinus bradycardia 7 0 in patients with carditis was cardiac ir-
Atrial premature contractions 1 0
regularity which occurred at some time
Ventricular premature contrac-
during the course of the illness in each of
tions 1
Low atrial rhythm I 0 these four patients. Heart sounds were de-
Nodal rhythm 1 1 scribed as “indistinct,” “poor,” or “distant”
Left bundle-branch block I in three of these four children, while gallop
Right bundle-branch block 0 2
rhythm was observed in one. Tachycardia
A-V dissociation I 2
0 1
and bradycardia were seen in children with-
Complete heart block
out other evidence of carditis as frequently
* The electrocardiographic abnormalities occurred as in those who had this complication. The
in 31 patients, of whom 27 are considered not to have presence or absence of heart murmurs was
had significant myocarditis.
not found to be helpful. Physiologic mur-
murs were present in several children who
membrane formation; most were febrile on had no electrocardiographic or clinical evi-
admission with variable degrees of tempera- dence of myocarditis. No child with carditis
ture elevation. Fifteen patients had suffi- had a murmur at any time. Two of the chil-
cient respiratory embarrassment to require dren with carditis developed congestive
tracheostomy at or soon after admission. heart failure and both succumbed despite
Six patients developed palatal paralysis, digitalization and other anti-congestive
one transient ocular palsy, and one paraly- measures. One of these also received steroid
sis of the left hemi-diaphragm; no other therapy without apparent effect on the
neurological complications were observed. course of his disease; complete heart block
No patient initially had evidence of cardiac developed and this patient succumbed. Two
abnormality on physical examination. The patients become hypotensive terminally,
five children who had been immunized but shock was not otherwise observed.
against this disease all had mild diphtheria. The electrocardiographic abnormalities
All patients were treated with parenteral in 95 patients are summarized in Table I.
penicillin and many received additional an- Each of the four children with clinical evi-
tibiotic therapy. All patients received diph- dence of severe myocarditis developed
theria antitoxin in doses ranging from complete bundle-branch block; two had left
40,000 units to 80,000 units after appropri- bundle-branch block, one right, and one
ate skin testing; this was administered in- child had a right bundle-branch shifting
travenously in severe cases and intramus- terminally to left. In addition three of these
cularly in mild ones. patients showed atrioventricular dissocia-
There were six deaths among the 95 pa- tion while the fourth developed complete
tients admitted to the hospital. Three of heart block.
these deaths were cardiac and three ap- One patient had electrocardiographic

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 ARTICLES 551

findings of particular interest without other

evidence of myocarditis. This 9-year-old
Negro girl had serial electrocardiograms re-
vealing ST-segment shifts of 1 to 2 mm in
lflulti1)le leads in the frontal and horizontal
l)lane; in addition, she had a prolonged PR
interval. These findings were present at the
time of admission for diphtheria in Novem-
l)er, 1960, and were still present in August,
1962. In the absence of other evidence of
carditis, these findings were not thought to
l)e related to her episode of diphtheria.
There were no other major electrocardio-
graphic abnormalities . Minor deviations
from normal were observed transiently in
26 additional cases, and included sinus 1:’
bradycardia, atrial premature contractions,
ventricular premature contractions, minor
ST-segment shifts, T-wave changes in two
OI more leads, minor P-wave abnormalities,
and minimal prolongation of the PR or QT
interval (Table I). Normal electrocardio-
grains were subsequently obtained in all of
these children. No patient developed clini-
cal or pathological evidence of myocarditis
without significant electrocardiographic
changes.
Each of the three children who had both
rubeola and diphtheria developed transient
electrocardiographic abnormalties. One had
minimal prolongation of the PR interval,
minor ST-segment shifts, and T-wave . .:
changes in two leads. A second child had
FIG. 1. Case 1. Anteroposterior film of the chest
frequent atrial premature contractions, pro-
(above) on admission, and (below) shortly before
longation of the QT interval and minor ST-
death (increased heart size).
segment changes. The third child who de-
veloped both of these diseases concurrently exotoxin liberated by the diphtheria bacii-
developed mild ST segment elevation in the lus and not to the effect of the organism it-
mid precordial leads and T-wave changes self. It is said to occur clinically in about
in three leads. 10% of affected patients and is the most
Chest x-rays were obtained in each case. common cause of death in this disease.’
The four patients who had severe myo- The mortality is reported to be 62% in a
carditis developed cardiomegaly (
Figs. 1 & series of 496 cases.#{176}
4). The surviving patient has had regres- Electrocardiographic abnormalities have
sion of his mild cardiac enlargement. Sig- been reported in from 16.5% to 84% of all
nificant cardiac enlargement was not ob- patients with 8 while most ob-
served in any other patient. servers place the figure at about 25%,, ‘#{176}
a

figure comparable to the 32% (31 of 95) of

COM MENT the children in this series who developed
Myocarditis in diphtheria is due to the abnormalities in one or more tracings

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552 DIPHTHERIA

-: ::: iIrr iJ:

L

I: 4:L L

4 i-j A;’1It
tttt NL

. 41#{149} #{149} H ffttLt:i zi f

vs
,-.

TriI1j: i
-
/s
.
1
‘

1-
:‘

:L±’
: #{149}#{149}

FIG. 2. Case 1. Electrocardiogram 6 hours before death, showing A-V dissocia-

tion and marked widening of QRS complexes.

( Table I). The most common electrocardio- tion of the QT interval, sinus bradycardia,
graphic abnormality is flattening or inver- low voltage, slurring of the QRS complexes,
sion of the T waves; this variation and ST- axis shift, bizarre P waves, and extra
segment shifts are probably the earliest systoles.8’2

findings.9 Prolongation of the PR-interval Among the more serious electrocardio-

has been observed in about 5% of affected graphic abnormalities, varying conduction
1( Other nonspecific abnormalities defects and arrhythmias have been de-
have been reported and include prolonga- scribed. Atrial fibrillation and flutter occur

4$
-
_ __ - j$

- iPIIA
‘ H . . !i; 1

L1

I1jl_l -? , . V I
r r #{149}T#{149} ‘ ksb$ L

FIG. 3. Case 2. Electrocardiogram one day before death showing left bundle-branch
block and A-V dissociation.

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 ARTICLES 553

but are unusual in this disease.’3 The de-

velopment of A-V dissociation or complete
heart block is ominous prognostically; mor-
tality with these findings is reported in
from 54% to 100% of the es’ ‘ Bundle-
branch block is also a serious complication
with a similar 14 Two children
in the present series developed right bun-
dle-branch block, and one of these shifted
terminally from right to left bundle-branch
block; both patients ultimately showed
rhythm disturbances ( one A-V dissociation,
one complete heart block) and succumbed
(Figs. 2 & 5). Of the two patients who had
left bundle-branch block, both developed
A-V dissociation; one child died while the
other survived (Figs. 3 & 6). The survivor is
now attending school regularly and is
asymptomatic 3 years following his illness;
left bundle-branch block persists.
In clinically evident diphtheria, the pres-
ence of marked electrocardiographic ab-
normalities such as bundle-branch block,
A-V dissociation, and complete heart block
are diagnostic of diphtheritic myocarditis.
In addition, patients with these findings
also have evidence of myocarditis on phys-
ical examination and generally show cardio-
megaly on chest x-ray as well.
The occurrence of transient less marked
electrocardiographic abnormalities without
progression is more difficult to interpret.
Such nonspecific variations as prolongation
of the PR or QT interval, ST-segment and
T-wave abnormalities, and abnormal P
waves have been reported in a variety of FIG. 4. Case 3. Anteroposterior film of the chest

infectious diseases including 5

( above) on admission, and (below) two days before
death (showing increased heart SIZ(’ Ifl(l piralysis
poliomyelitis,16 typhoid fever,17 and lobar of left hemi-diaphragm).
pneumonia17 as well as diphtheria. These
variations occurred in patients who also had scarcely be doubted, their interpretation re-
more severe electrocardiographic changes quires considerable caution.”
and succumbed to diphtheritic myocarditis; It is possible that diphtheritic myocarditis
however, no patient with these findings as may lead to myocardial fibrosis which re-
the only electrocardiographic abnormalities sults in congestive failure later in life.19’ 20

had clinical or pathological evidence of This has not been proven. Some observers
myocarditis. The exact cause of these believe that many of the cases of complete
changes and their significance remain un- heart block which are first noted in the
clear. It has been suggested that “although sixth decade of life and beyond are sequelae
the presence of histologic or electrocardio- of diphtheritic myocarditis.21 As evidence
graphic changes in infectious disease can against this, 100 patients who had suffered

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554 DIPHTHERIA
from severe or moderately severe diphtheria sion. Treatment consisted of tracheostomy, diph-
were examined 15 to 20 years after their theria antitoxin, penicillin, and supportive mess-
ures. Chest x-ray on admission was normal, while a
infection; none showed evidence of atrio-
Later film showed cardiac enlargement. An electro-
ventricular or intraventricular block.22 The cardiogram taken on admission showed prolonga-
increasingly common discovery of infants tion of the QT interval and widespread flattening
with complete heart block in this era of of T waves. On the seventh hospital day, a cardiac
arrhythmia was observed clinically at a time when
routine well baby care suggests that con-
the child was complaining of nausea and weak-
genital complete heart block may explain
ness. An electrocardiogram was obtained which
this finding in some adults. revealed that A-V dissociation and left bundle-
Treatment for diphtheritic myocarditis is branch block had developed since the initial tracing.
generally unsatisfactory. Though steroids (Fig. 3)
The cardiac arrhythmia persisted; heart
have been used, the results thus far have sounds were poor and terminally hypotension de-
veloped. He died on the eighth hospital day. Post-
not been encouraging. Digitalis is recom-
mortem examination revealed cardiac dilitation.
mended when heart failure If
Microscopic study of the myocardium showed mono-
recovery from the acute episode of diph- nuclear cell infiltration, interstitial edema, swelling
theritic myocarditis occurs, the prognosis of the muscular fibers, and loss of cross-striations at
appears to be good. different levels.

APPENDIX Case 3 (8-67-96)

Case Reports R. P., an 11-year-old Latin American boy was
admitted to the hospital January 8, 1962, with a
Case 1 (7-33-85)
2-day history of swelling of the neck, sore throat,
F. W., a 4-year-old Caucasian boy, was admitted and fever. He had received no immunizations and
to the hospital August 22, 1980, with a one-day was one of three siblings concurrently hospitalized
history of fever, swelling of the neck, and respira- with diphtheria. Physical examination revealed a
tory difficulty. He had received no immunizations. moderately ill child with evidence of laryngo-
Physical examination revealed an acutely ill child tracheal diphtheria. Auscultation of the heart was
with evidence of laryngotracheal diphtheria. Am- within normal limits. Treatment consisted of diph-
cultation of the heart disclosed no abnormalities theria antitoxin, penicillin and supportive meas-
on admission. Treatment consisted of tracheostomy, ures. Chest x-ray on admission revealed elevation
intravenous diphtheria antitoxin, penicillin and of the left hemi-diaphragm with a normal size
chloramphenicol, digitalization, and supportive heart; a second film on the seventh hospital day
measures. Chest x-rays taken shortly before death showed the development of cardiomegaly (Fig. 4).
revealed an increase in heart size as compared to
The initial electrocardiogram taken on admission
the admission film (Fig. la, b). Two electrocardio- showed normal sinus rhythm with a prolonged QT
grams were obtained. The first, taken on admis- interval and right block. The fol-
bundle-branch
sion, showed prolongation of the QT interval,
lowing day, incomplete atrioventricular block had
nodal rhythm and right bundle-branch block; the developed with prolongation of the PR interval
second, taken 6 hours before death, revealed A-V (Fig. 5, above). Auscultation at that time revealed
dissociation with marked widening of the QRS tachycardia with gallop rhythm. By the seventh
complexes (Fig. 2). The serum potassium value at hospital day, the right bundle-branch block pat-
this time was 8.4 meq./l. Approximately 24 hours
tern had shifted to left bundle-branch block and
prior to death he developed cardiac irregularity complete heart block was present (Fig. 5, below).
and poor heart sounds. Despite all therapy he died At this time he had developed nausea, weakness,
on the fourth hospital day. Permission for post- and lethargy. Physical examination revealed brady-
mortem examination was denied. cardia with marked cardiac irregularity and poor
heart tones. Steroid therapy was begun. Hypoten-
Case 2 (7-64-86)
sion and evidence of a moderate degree of con-
J. T., a 6-year-old
Latin American boy was ad- gestive heart failure developed and digitalization
mitted tothe hospital December 9, 1960, with a was initiated. He died on the ninth hospital day.
6-day history of sore throat and fever. He had re- Postmortem examination revealed cardiac dilata-
ceived no immunizations and was one of five sib- tion; the myocardium grossly showed pallor and
lings simultaneously hospitalized with diphtheria. was of flabby consistency. Microscopic studies of
Physical examination revealed a moderately ill boy the heart showed interstitial edema, mononudear
with findings of laryngotracheal diphtheria. Am- cell infiltrates, and foci of degeneration in the
pultatjon of the heart was unremarkable on admis- myocardium.

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 ARTICLES 555

vad .

, --v- -

_J_
v ____ ____
m

FIG. 5. Case 3. Electrocardiogram (above) on third hospital day, showing prolonga-

tion of PR interval and right bundle-branch block; and (below) on seventh hospital
(lay, 2 days before death, showing widespread ST-T abnormalities, left bundle-
branch block, and complete heart block.

Case 4 (6-24-54) tion was noted (Fig. 6, above). At the time of dis-
charge sinus rhythm and left bundle-branch block
G.C., a 9-year-old Latin American boy was ad-
were present, though physical findings were within
mitted to the hospital August 11, 1959, with a
normal limits. His sedimentation rate returned to
history of fever and sore throat of 8 days’ duration.
normal by the tenth hospital day; his serum gin-
Physical examination revealed findings compatible
tamic oxaiacetic transaminase fell slightly but
with nasopharyngeal diphtheria without evidence of
mained elevated to 62 units at the time of dis-
carditis. Treatment consisted of diphtheria antitoxin,
charge on the thirty-sixth hospital day; this has
penicillin, and supportive measures. On the second
subsequently returned to normal. When the patient
hospital day, he developed substernal pain, weak-
was examined in 1962, he was attending school
ness, nausea, and an irregular pulse with heart
regularly and was entirely asymptomatic, but his
sounds which were said to be “fair.” Chest x-ray at
electrocardiographic abnormality of left bundle-
this time revealed significant increase in heart size as
branch block persisted (Fig. 6, below).
compared with his admission film. Serum glutamic
oxalacetic transaminase was 78 units (normal 10-
40) and the erythrocyte sedimentation rate was 40
SUMMARY
mm/hour. At this time his electrocardiogram re- Ninety-eight cases of diphtheria were ob-
vealed normal sinus rhythm with left bundle-branch
served in a 5% year period, and the cardiac
block. On the thirteenth hospital day, he had
developed A-V dissociation which persisted briefly,
findings were evaluated. There were nine
and an occasional premature ventricular contrac- deaths. Three patients were dead on ar-

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556 DIPHTHERIA

.%‘
,jc

I__

FIG. 6. Case 4. Electrocardiogram (above) on thirteenth hospital day

showing A-V dissociation, premature ventricular contraction, and left bundle-
1)ranch l)lOCk; and (below) 3 years later showing normal sinus rhythm
and persistence of left bundle-branch block.

rival at the hospital (without postmortem significance remains unclear. Marked elec-
evidence of myocarditis) while three died trocardiographic abnormalities such as bun-
of diphtheritic myocarditis and three as a dle-branch block, A-V dissociation, and
result of respiratory complications. No child complete heart block are diagnostic of myo-
who succumbed had been immunized carditis in patients with diphtheria.
against diphtheria. Four patients developed
electrocardiographic and clinical evidence REFERENCES
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 CARDIAC COMPLICATIONS OF DIPHTHERIA
Beverly C. Morgan
Pediatrics 1963;32;549

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 CARDIAC COMPLICATIONS OF DIPHTHERIA
Beverly C. Morgan
Pediatrics 1963;32;549

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