PEDIATRICS Vol. 111 No. 2 February 2003, pp. e183-e187
Myocardial Infarction and Transient Ventricular Dysfunction in an Adolescent With Sickle Cell Disease
Andreas J. Deymann, MD and
Kenneth K. Goertz, MD
From the Department of Pediatrics, Division of Pediatric Critical Care and Cardiology, University of Kansas Medical Center, Kansas City, Kansas
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ABSTRACT
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We report a case of an adolescent who had sickle cell disease
and previous evidence of myocardial damage and presented with
abdominal pain and rapid progression to cardiogenic shock and
subsequent development of myocardial infarction. To our knowledge,
this represents only the second report of a case of acute myocardial
ischemia and subsequent infarction resulting transient ventricular
dysfunction reported in a child with sickle cell disease successfully
treated with exchange transfusion. The pathophysiology of this
complication remains unclear, and cardiac complications may
remain undetected as lung, bone, and brain infarcts are more
common and the pain associated with sickle cell crisis may mask
the ischemic symptoms. Multiple factors may contribute to ischemia
in addition to the presence of a vaso-occlusive crisis or infection.
Acute or chronic myocardial ischemia are probably more prevalent
than currently known.
Key Words: sickle cell disease • myocardial infarction • ischemia • exchange transfusion
Abbreviations: ECG, electrocardiogram • EF, ejection fraction
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INTRODUCTION
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Vascular injury that leads to thrombosis and hyperplastic remodeling
of large arterial vessels
1 is believed to be the cause of ischemic
or embolic stroke in sickle cell disease. Pathologic examination
of the affected cerebral vasculature reveals intimal proliferation
with a break-up of the elastic lamina. Endothelial cells repopulate
denuded areas only in monolayers, and the hyperplastic intima
consists of fibroblasts, fibrous tissue, and scattered smooth
muscle cells leading to a narrowed vascular lumen and increased
fragility of the affected cerebral vessels. In comparison with
stroke, myocardial infarction is rare in young adults with sickle
cell disease
2–10 and may be attributable in large part
to acute microvascular occlusion of small vessels. Epicardial
coronary artery disease is notably uncommon in sickle cell disease.
Several mechanisms may lead to impairment of microvascular circulation.
In addition to impairment of circulation by sickled cells, thrombosis
of small vessels is thought to be the result of endothelial
damage attributable to shear injury and resulting procoagulant
state and embolization of endothelial cells into the microvasculature.
3,11,12 Fibromuscular dysplasia of small cardiac vessels has been demonstrated
in patients with sickle cell disease and may explain chronic
ischemic changes and apoptosis in myocytes.
3,12 Echocardiographic
and electrocardiogram (ECG) changes may be more prevalent in
sickle cell disease than currently known. Myocardial necrosis
has been observed by autopsy in 1 child with hemoglobin sickle
cell disease
13 and has been reported in adults.
3,12 Chronic
myocardial dysfunction can occur and may be complicated by volume
overload of anemia and coexisting renal and lung disease.
2 Myocardial
ischemia may be a cause of chest pain during crisis in adults
8,14 and is a possible cause for chest pain in children with sickle
cell disease. Only 1 previous report of myocardial dysfunction
with signs of myocardial infarction suggests reversibility of
ischemia after exchange transfusion.
1,15 We report an adolescent
who had previous evidence of myocardial dysfunction with findings
suggesting acute myocardial infarction and rapid development
of severe cardiac dysfunction and who responded to exchange
transfusion.
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CASE REPORT
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A 16-year-old, 53-kg black male with homozygous hemoglobin S
disease and previous admissions for pain crisis and priapism
was evaluated for chest pain at age 13. At that time, he was
found to have ECG abnormalities consistent with left ventricular
hypertrophy and an abnormal stress test with angina 7 minutes
into the test as well as 2-mm ST depression in the inferior
lateral leads. A resting echocardiogram showed a moderately
decreased ejection fraction (EF) of 42% with no focal wall abnormality.
After exercise, multiple segmental wall motion abnormalities
could be seen (hypokinetic apical, midanterior, midanterolateral
and midanteroseptal areas) and a Cardiolite single photon emission
computed tomography study subsequently revealed a reversible
perfusion defect of the inferior portion of the cardiac apex
(Fig
1). Thereafter, he was lost to follow-up until the day
of admission, when he presented with nausea, abdominal pain,
and diaphoresis. He was afebrile and had no detectable focus
of infection. His initial vital signs revealed a pulse of 102,
respiratory rate of 32, a blood pressure of 88/48 mmHg, and
96% oxygen saturation on room air. His initial chest radiograph
revealed a minimal prominence of pulmonary vascular markings.
Prochlorperazine (Compazine) was given for nausea, and his oxygen
requirement increased rapidly after arriving on the ward. After
receiving a 1 L of normal saline fluid bolus over 1 hour, he
developed respiratory failure and was intubated as he rapidly
developed cardiogenic shock and ventricular dysrhythmia. Aggressive
inotropic support with dopamine, milrinone, and norepinephrine
was required to maintain his blood pressure in the low normal
range. Ventricular tachycardia was treated with lidocaine during
the initial phase of myocardial ischemia.
His first ECG revealed 4-mm ST depression in V
4 to V
6 and loss
of R waves in V
1 and V
2. His cardiac enzymes (Fig
2) were highly
abnormal, suggesting myocardial tissue damage. Electrolytes
were normal with an HCO
3 of 20 mmol/L and glucose of 9.88 mmol/L
(178 mg/dL). A moderate degree of hemolysis was present with
a hemoglobin of 7.2g/L and absolute reticulocyte count of 156
10
3/µL, uncorrected of 6% and corrected of 2.6% combined
with a total bilirubin of 65 µmol/L (3.8 mg/dL), direct
bilirubin 5.13 µmol/L (0.3 mg/dL). His white blood cell
count was 23.7
x 10
9/L, and his temperature was 35.2°C orally.
He was started on Ceftriaxone (Rocephin) and low molecular weight
heparin.
At this time, the decision was made to perform an exchange transfusion
to improve microvascular circulation in light of myocardial
ischemia and dysfunction. The resulting hemoglobin S after exchange
transfusion was 30% with a total hemoglobin of 10.5 mg/dL. Before
exchange transfusion, his echocardiogram showed paradoxical
septal motion, severe global akinesis of the myocardium, and
an unmeasurable EF on transthoracic echocardiogram. Three hours
after exchange transfusion, his myocardial contractility was
dramatically improved and his EF was estimated to be 46%. During
the next 24 hours, his cardiogenic shock improved and he was
weaned off inotropes on hospital day 4. He was extubated on
hospital day 5. His ECG changes resolved within the first 24
hours, and his ECG pattern returned to his baseline abnormalities
with absent R waves in V
1 and V
2. His ST segment changes had
resolved (Figs
3–
5). On hospital day 10 a stress perfusion
scan revealed no fixed or reversible perfusion deficits and
an EF of 40% (Figs
2 and
6). He was started on ß-blockers
and angiotensin-converting enzyme inhibition. Incidentally,
the patient disclosed after extubation that he had experienced
chest pain on the day of admission during physical exercise.
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DISCUSSION
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We conclude that our patient experienced myocardial injury in
the past and had transient myocardial ischemia with necrosis
of myocardium during this admission, resulting in severe myocardial
dysfunction. Infection could not be documented, and myocarditis
was deemed unlikely. His impaired myocardial function and significant
area under the curve for creatine kinase-MB release from myocytes
suggest infarction. Focal myocardial scarring is likely to have
occurred in the past as preexisting ECG changes and a cardiac
perfusion scan suggest (Figs
3–
6). Although thallium scintigraphy
may not detect nontransmural or microinfarcts, it is a highly
sensitive test of malperfusion and excludes the likelihood of
epicardial vessel disease. His EF, measured before discharge,
may have been artificially increased as inotropic support with
dobutamine and milrinone are known to exert inotropy for some
time after discontinuation. The interesting resolution of previous
perfusion deficits on Cardiolite perfusion scanning after exchange
transfusion before discharge suggests improved microvascular
flow as a result of the absence of significant amounts of sickled
red blood cells (Figs
1 and
6).
The true incidence of myocardial ischemia in sickle cell disease remains unknown. The pathophysiologic mechanism of acute and chronic microvascular occlusion, complicated by endothelial dysfunction as a result of endothelial cell damage by sickled red blood cells, can occur in any vascular bed. The heart seems to be protected by an unknown mechanism, especially when taking into consideration the high cardiac oxygen extraction as hypoxemia promotes sickling of red blood cells.
Acute exchange transfusion seems to have improved myocardial dysfunction promptly in our case. Thrombolytic agents have not been adequately tested in sickle cell disease, although there is evidence of altered homeostasis and presence of a procoagulant state.11 Anticoagulation was initiated with low molecular weight heparin as anticoagulation therapy for myocardial infarction, but its value has not been established in ischemia associated with sickle cell disease. It is noteworthy that antiplatelet therapy remains unproved as well in sickle cell disease, and currently no evidence-based therapeutic regimen can be recommended for the treatment or prevention of cardiac complications of sickle cell disease. However, experience drawn from stroke prophylaxis in sickle cell disease suggests initiating a hypertransfusion regimen with the goal of a hemoglobin S level of 30% or less for patients with sickle cell disease and signs of myocardial ischemia. Hypertransfusion is known to prevent sickling and normalizes abnormal levels of pro- and anticoagulants in sickle cell disease, indicating decreased endothelial damage. This case and the previous case report suggest that aggressive support of cardiac function in conjunction with immediate exchange transfusion improves cardiac function probably as a result of improvement of microvascular circulation. Long-term prevention could include hypertransfusion, hydroxyurea administration, or bone marrow transplantation, but their roles remain to be demonstrated in the treatment of sickle cell disease-related complications.10,16–20
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FOOTNOTES
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Received for publication Apr 22, 2002; Accepted Sep 23, 2002.
Reprint requests to (A.J.D.) Department of Pediatrics University of Kansas, Kansas City, KS 66160. E-mail: adeymann{at}kumc.edu
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PEDIATRICS (ISSN 1098-4275). ©2003 by the American Academy of Pediatrics
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ABSTRACT
INTRODUCTION
