Download Myocardial Infarction?

CLIN. CHEM. 25/10,
1853-1856
-
(1979)
Myocardial Infarction?-A Conflict between Electrocardiographic
Changes and Biochemical Data
William Z. Borer, John S. Gottdiener,1 and Nicholas M. Papadopoulos
We present a case of hypovolemic
by electrocardiographic
changes
shock accompanied
classically
associated
with acute myocardial infarction. Prompt therapeutic intervention, which included correction of the hypovolemic
shock, resulted in stabilization
of the patient’s clinical
course. Increased activities of the cardiac-specific
enzymes in serum were not documented. Serial electrophoretic determinations
of the isoenzymes of serum lactate dehydrogenase
did not show the characteristic
changes associated with myocardial infarction. Accurate
determination
of the serum isoerizymes provided valuable
diagnostic information which, accompanied
by the patient’sclinical improvement, militated strongly against the
occurrence of myocardial infarction.
Acute
myocardial
infarction
is a straightforward
diagnosis
in the patient
who presents with typical substernal
electrocardiographic
abnormalities
that include
chest
pain;
the sudden
development
of abnormal
Q waves, or ischemic ST segment
and T-wave changes; and increased
serum
activity
of the
cardiac-specific
enzymes.
Indeed, some may make the diagnosis if any two of these three abnormalities
are confirmed
(1).
Occasionally,
however,
conflicting
data preclude
accurate
diagnosis
until the complete clinical picture has evolved. Here
we present
a case that illustrates
these difficulties.
Case History
The patient,
Clinical
Center
granulomatosis.
man, was admitted
to the NIH
and treatment
of lymphomatoid
a 66-year-old
for evaluation
Past
medical
history
revealed
that
he had
been a heavy cigarette
smoker for 40 years. A few years before
this admission
he had been noted to have an irregular
cardiac
rhythm and was subsequently treated with procainamide for
ventricular premature contractions. No other history of serious illness was elicited.
Physical
examination
and hepatosplenomegaly.
were normal.
Laboratory
increased
revealed
Results
fever,
abdominal
of examination
evaluation
erythrocyte
sedimentation
kocyte count. No source of infection,
demonstrated
rate,
tenderness,
of the heart
anemia,
and a normal
leu-
to explain the fever, was
The values for routine clinical chemical determinations
were all within
the expected ranges. The electrocardiogram
found.
ClinicalPathology Department
and1 National Heart, Lung and
Blood Institute,
National
Institutes
of Health,
Bethesda,
MD
20205.
Received June 11, 1979; accepted July 5,1979.
was normal except for low voltage
amplitude
in the limb
leads.
Treatment
with cyclophosphamide
and prednisone
was
begun, and at first the patient showed clinical improvement.
However, after the 60th hospital day he became increasingly
short of breath and developed edematous swelling of the feet
and legs. Supplemental
oxygen
improved
his respiratory
status. That the deep veins of the left leg were obstructed was
demonstrated
by venography. A presumptive diagnosis of
deep-vein
thrombosis
with pulmonary
embolism
was made
and anticoagulation
therapy was instituted with heparin and
warfarin.
On the
72nd
hospital
day
the
electrocardiogram
(Figure 1A) was unchanged from admission.
On the 79th hospital day the hematocrit
and hemoglobin
showed persistent
anemia. The leukocyte count had dropped
to 22004tL.
Alkaline phosphatase (EC 3.1.3.1) activity was
increased
and lactate dehydrogenase
(EC 1.1.1.27) activity
was 494 U/L (expected normal 115-340 U/L), while the bilirubin, alanine aminotransferase
aminotransferase
(EC 2.6.1.1)
expected
range.
(EC 2.6.1.2), and aspartate
values remained within the
At this time, extensive pulmonary
involvement
with softtissue masses was demonstrated by chest roentgenography
and computerized
axial
tomography.
Because
of the rapidly
advancing
primary
disease process, we began more aggressive
therapy,
in the form of radiation
and antibiotics.
Because of
severe hypotension,
with values for systolic blood pressure in
the range of 8.0 to 9.3 kPa (70 to 80 mmHg),
and respiratory
impairment
on the 91st hospital day, the patient was intu-
bated and mechanically
ventilated.
An electrocardiogram
at
this time revealed pathological
Q waves in precordial leads
V1-V5(Figure 1B). A ventilation-perfusion
scan was not
suggestive
of pulmonary
embolism.
Total
serum lactate dehydrogenase
and creatine kinase activities are given in Table
1. On the 92nd
day an electrocardiogram
(Figure
1C)
across all of the precordial
leads
and ST segment
elevation
in precordial
leads V2-V6. These
findings
were believed
to be consistent
with extension
of an
showed
hospital
even deeper
anteroseptal
surements
Q waves
myocardial
were monitored
infarction.
Hemodynamic
with an indwelling
double
mealumen
1)ulmonary arterial catheter. Initial pulmonary-artery
balloon-occlusion
pressure was 1.2 kPa (9 mmHg;
normal,
0.67-1.33 kPa, or 5-10 mmHg). This increased to 2 kPa (15
mmHg) with an intravenous
fluid challenge and was accompanied by a concomitant
normalization
of the arterial blood
pressure (bringing systolic pressures to the range of 16 to 18.6
kPa, or 120-140 mmHg) and improvement
in the urine output.
CLINICAL CHEMISTRY. Vol. 25, No. 10, 1979
1853
I
lu
aVR aVL aVF
V1
V2
V3
V4
V5
V6
A
DAY12
B llrT
DAY91 ____
C
DAY92
0
DAY99
Fig. 1. Electrocardiogram obtained before (A), during (B and
C), and after (D) the patient’s acute hypotensive episode
The hospital day on which eachelectrocardiogram
was made Is indicatd
Adequate blood pressure was maintained by administering
intravenous
fluid and the patient remained stable for the next
10 days. An electrocardiogram
on the 99th
hospital
day
demonstrated the return of normal QRS complexes in the
anterior precordial leads (Figure 1D). Nonspecific ST-segment and T-wave changes, however, persisted. The patient
continued
to require mechanical ventilation to adequately
support
respiration. He was unresponsive to verbal stimuli
and was noted to be severely thrombocytopenic.
Despite
supportive efforts, another severe hypotensive
suIted in death on the 109th hospital day.
An autopsy was not performed.
episode re-
Discussion
In this patient the development of hypotension in the
presence of electrocardiographic
changes consistent with
global infarction was suggestive of cardiogenic shock, However, the documentation
tery-occlusion
pressure,
of an initially
low pulmonary-arthe favorable
response
of the blood
to fluid challenge,
and the subsequent survival of the
patient for several weeks combined to make this possibility
unlikely. More importantly, serum enzyme and isoenzyme
determinations failed to confirm the presumptive diagnosis
of myocardial infarction. The values for the serially measured
activities (Table 1) of total lactate dehydrogenase and total
creatine kinase in the serum show no sharp increases such as
would be expected in a case of massive myocardial infarction
complicated by cardiogenic shock. The lactate dehydrogenase
activity remained increased above the reference range, but no
convincing temporal relationship to electrocardiographic
changes was observed. Total creatine kinase activity remained
within the reference range. The isoenzymes of creatine kinase
(especially CK-M), which may have provided more clinically
useful information, unfortunately were not measured.
The lactate dehydrogenase isoenzymes discussed here were
quantitated by an electrophoretic method (2). Figure 2 shows
the results of the serial determination.
Increased activity of
isoenzymes LD1 and LD2, such as is known to occur after
acute myocardial infarction (3, 4), was not observed in this
case. A more important discriminant of myocardial infarction
pressure
1854 CLINICAL CHEMISTRY,
Vol. 25. No. 10, 1979
is the ratio of LD1/LD2
(5-7). In normal human serum the
ratio of LD1ILD2
is <1, averaging about 0.75. After myocardial infarction,
a characteristic
reversal occurs, the ratio of
LD1/LD2 becoming transiently >1 between 18 and 72 h after
myocardial infarction, with the ratio being highest at about
48 h. Figure 3 shows the serum lactate dehydrogenase isoenzyme patterns obtained in a patient with documented myocardial infarction. Our patient demonstrated no reversal of
the LD1/LD2
ratio.
The persistent above-normal values for
total serum lactate dehydrogenase activity may be a result of
the patient’s primary disease with pulmonary involvement
complicated by hypotension.
Although abnormal Q waves usually indicate myocardial
necrosis, the loss of initial electrical forces thus represented
may be seen in other clinical conditions, such as the actual loss
of viable myocardium,
as may occur with primary myocardial
disease and with infiltrative
cardiomyopathies.
They may also
result from an increase in electrical forces contralateral
to the
recording electrode, associated with hypertrophy
of the ventricular myocardium,
as may occur with idiopathic
hyper-
trophic subaortic stenosis or with left ventricular hypertrophy
accompanying hypertension or aortic stenosis. In the absence
Table 1. Serum Enzyme Activities
Hospital Day
LD(U/L)
CK(U/L)
91
508
78
92
589
90
93
544
52
94
-
34
95
512
38
91
542
38
Reference Range
115-340
50-200
till
+
111
N
1 2 3 45
12345
III
III
(II
93
95
samples 1 and 2demonstrate
to the normal sample
(15), myocardial
91
serum lactate dehydro-
genase isoenzyme patterns
The sample labeled N was obtained from a normal individual; all other samples
were obtained from the patient. The hospital day on which the samples from the
patient were obtained Is Indicated at the right
of myocardial infarction, Q waves may occur transiently
with
clinical events such as cerebral hemorrhage (8), uremia (9),
pancreatitis (10), pulmonary embolism (11, 12), or myocardial
ischemia without frank necrosis (13). Alternatively,
Q waves
subsequent to actual infarction may disappear as soon as five
to 10 days later (14). As the adjacent ischemic myocardium
recovers, sufficient initial electrical forces are generated to
mask Q waves originating
from the necrotic zone.
Q waves
in this patient was
profound
transient
ischemia,
perhaps occasioned by hypotension in the setting of pre-existing
coronary artery disease.
Pulmonary
embolism
is an unlikely cause, because of the anterolateral location of the Q waves. This is consistent with the
ventilation-perfusion
scan, which did not suggest pulmonary
embolism. Although the Q waves of myocardial infarction may
be transient, the electrocardiographic
changes in this patient
suggested extensive necrosis of the left ventricle. It is unlikely
that recovery of bordering ischemic tissue would be sufficient
to mask the Q waves originating
from such an extensive zone
of infarction.
Artifactual
sources of pseudo-Q waves, such as
malposition
of chest electrodes, were excluded by consistent
changes noted on several electrocardiograms
and by physician
supervision of electrode placement.
Loss of electrical activity sufficient to cause
waves has
generally been associated with myocardial necrosis; however,
severe metabolic
alteration
may occur without irreversible
tissue damage (15). Transient patterns of myocardial
infarction have been produced in experimental
animals by intravenous
infusion of norepinephrine
(15) and by experimental coronary artery occlusion (16). Although histological
examination
showed decreased myocardial glycogen and impairment of succinate dehydrogenase
(EC 1.3.99.1) activity
Q
1
2
Fig. 3. Electrophoretically determined lactate dehydrogenase
isoenzyme patterns obtained from the serum of a normal mdividual (AOand from the serum of a patient one day ( 1) and two
days (2) after a documented myocardial infarction
a reversal of the LD1/LD2 ratio when compared
infarction
did not occur. Similarly,
good clinical documentation
determined
The most likely source of the
‘Ii
iit
92
lit
Fig. 2. Electrophoretically
N
in association
with coronary
(13) noted transient abnormal
of transient abnormal
insufficiency.
Haiat
there is
Q waves
and Chiche
Q waves in 15 patients, in eight
of whom myocardial
ischemia
was present without
infarction.
As seen from this case, the clinical differentiation
of transient abnormal Q waves with true infarction from those ascribable
to ischemia or other causes may be extraordinarily
difficult.
Isoenzyme
determinations
that allow one nonin-
vasively to determine the presence of myocardial necrosis are
of key importance
in making such distinctions.
This is illus-
trated by the electrophoretic
technique used here, which is
sensitive and accurate enough to detect pen-operative myocardial infarction in patients who have undergone cardiac
surgery (5). The data obtained from serial electrocardiograms,
isoenzyme determinations, and the clinical course of the patient must then be interpreted together to arrive at the appropriate diagnosis.
References
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heart
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2. Papadopoulos, N.M., and Kintzios, J., Quantitative electrophoretic
determination of lactate dehydrogenase isoenzymes. Am. J. Clin.
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3. Papadopoulos, N. M., Clinical applications of lactate dehydrogenase isoenzymes. Ann. Clin. Lab. Sci. 7, 506-510 (1977).
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