Keywords
Allergic coronary artery syndrome - coronary artery vasospasm - Kounis syndrome
Introduction
Kounis syndrome is defined as the concurrence of acute coronary syndromes (ACSs) such
as coronary spasm, acute myocardial infarction, and stent thrombosis, with conditions
associated with mast-cell and platelet activation involving interrelated and interacting
inflammatory cells in the setting of allergic or hypersensitivity and anaphylactic
or anaphylactoid insults.[1]
Although many questions about the exact pathophysiologic mechanism of Kounis syndrome
remain unanswered, the increasing number of cases published shows that this condition
should be considered in the differential diagnosis of ischemic heart disease.
Case Report
A 25-year-old female patient with a history of asthma, allergic rhinitis, and migraine
headaches presented to the emergency department with recurrent episodes of chest pain.
She had no cardiovascular risk factors. The patient had an uncomplicated vaginal delivery
6 months prior. She began complaining of intermittent substernal chest pain, described
as a pressure sensation, lasting a few seconds to an hour, with radiation to the back.
Symptoms were associated with diaphoresis and dyspnea but had no apparent triggers
such as exertion, emotional stress, food consumption, or environmental exposure.
On the day of admission, the patient was first seen at an outside facility with similar
complaints. A 12 lead electrocardiogram was performed showing 2 mm ST-elevation in
leads V3 and V4 with reciprocal inferior lead changes [Figure 1]. A diagnostic left heart cardiac catheterization (LHC) revealed significant mid
left anterior descending (LAD) and right coronary artery (RCA) stenosis consistent
with coronary vasospasm that resolved with administration of intracoronary nitroglycerin
and nicardipine [Figure 2]a, [Figure 2]b,[Figure 2]c, [Figure 2]d. However, the patient's chest pain did not resolve and was transferred to our facility
for further evaluation.
Figure 1: 12 lead electrocardiogram showing ST‑segment elevation at V3–V4 with reciprocal
changes at lead II and III
Figure 2: Coronary angiography at the time of her presentation at the outline hospital.
(a) Severe stenosis at mid right coronary artery. (b) Repeat angiography after nitroglycerin
infusion with near complete resolution of the right coronary artery stenosis. (c)
Moderate‑severe stenosis at proximal left anterior descending artery. (d) Repeat angiography
after nitroglycerin infusion with near complete resolution of the left anterior descending
coronary stenosis
A repeat LHC showed mild to moderate residual stenosis involving the mid-RCA and mild
stenosis involving the proximal LAD. No coronary intervention was required. During
her hospitalization, the patient's troponin T, creatine kinase and creatine kinase-MB
peaked at 6.2 ng/ml, 2897 U/L and 285.4 ng/ml, respectively. Her urine drugs screen
was negative. Transthoracic echocardiogram revealed a depressed left ventricular ejection
fraction (LVEF) of 35% with severe hypokinesis of the anterior and anterolateral walls
consistent with an infarct of the LAD distribution. Cardiac magnetic resonance imaging
revealed a LVEF of 29% and late gadolinium enhancement showing transmural infarction
in the distal LAD territory and evidence of microvascular obstruction [Figure 3]a and [Figure 3]b.
Figure 3: Cardiac magnetic resonance imaging, (a) Mid ventricular short axis slice
demonstrating transmural infarct (red arrows) of the anterior septum with evidence
of microvascular obstruction (white arrows) on delayed gadolinium. (b) Two-chambers
view showing transmural infarction (red arrows) of the anterior septum with evidence
of microvascular obstruction (white arrows) delayed gadolinium
On admission, the patient was noted to have eosinophilia of 10% (1.54 absolute eosinophils
count), which peaked at 25% (2.52 absolute eosinophils count) on day 6 with leukocytosis
of 15.7 on admission only. Laboratory workup vasculitis including cytoplasmic-anti-neutrophil
cytoplasmic antibodie (C-ANCA), perinuclear-ANCA (P-ANCA), and atypical P-ANCA were
all negative. IgE and tryptase levels were within the reference range. The patient
suffered recurrent daily episodes of chest pain with ST-segment elevation on the cardiac
monitor. These episodes were resolved with sublingual nitroglycerin in 5–10 min interval
[Figure 4]a and [Figure 4]b.
Figure 4: Cardiac monitor rhythm strips. (a) ST‑segment elevation associated with
chest pain when the patient woke up in the morning. (b) Resolution of ST‑segment elevation
and chest pain after two sublingual nitroglycerin 0.4 mg tablets
Due to the extensive LAD infarction in the setting of severe coronary vasospasms,
and the significant eosinophilia; Type 1 Kounis syndrome was suspected. She was started
on prednisone 40 mg daily with a resolution of the eosinophilia and chest pain within
2 days. The patient was started on amlodipine, isosorbide mononitrate, loratidine,
ranitidine, and montelukast before discharge. She was discharged on a prednisone taper
(started with 30 mg with 10 mg dose reduction every day then 5 mg maintenance dose).
On 4 weeks follow-up, the patient denied any symptoms recurrence.
Discussion
Kounis syndrome or “allergic myocardial infraction” is defined as the concurrence
of ACSs (coronary spasm, acute myocardial infarction, and stent thrombosis) in the
setting of mast-cell and platelet activation from allergic or anaphylactic insults.[1]
Three variants have been described.[2] Type I, which our patient most likely had, includes normal coronary arteries without
risk factors for CAD, and with the acute release of inflammatory mediators that may
induce coronary artery spasm with or without cardiac enzymes elevation and subsequent
myocardial infarction. Type II includes culprit but quiescent preexisting atheromatous
disease in which the acute release of inflammatory mediators may induce coronary artery
spasm with or without associated plaque erosion or rupture manifesting as acute myocardial
infarction. Type III includes coronary artery stent thrombosis in which aspirated
thrombus specimens stained with hematoxylin and eosin and Giemsa stain demonstrate
the presence of eosinophils and mast cells, respectively.
Inflammatory mediators such as histamine, neutral proteases, arachidonic acid products,
platelet-activating factor, eosinophils and a variety of cytokines and chemokines
have been implicated in its pathophysiology.[3] Eosinophils synthesize leukotriene C4, a potent stimulant of vasoactivity smooth
muscle contraction. Eosinophils also activates mast cells and basophils to produce
vasoactive substances.[4] Patients with eosinophilia and coronary vasospasm were found to have a high risk
of recurrent coronary events despite treatment.[4]
Treatment is aimed at coronary artery vasodilators and allergic reaction amelioration.
Calcium channel blockers and nitrates are considered the first-line in the management.[5]
Histamine induces tissue factor expression, through H1 receptors, which mediates thrombus
formation in inflammation and vasospasm and hence, H1 receptor blockers may be useful
in the management of Kounis syndrome, variant angina and ACS.[5],[6],[7] H2 receptors blockers use have been suggested in Kounis syndrome.[5] The use of mast cells stabilizers such as sodium cromoglycate and ketotifen has
been suggested; although, their efficacy is not clear.[5]
The use of corticosteroids reported to be effective in cases with refractory vasospastic
angina (VSA).[8] Corticosteroids use found to be effective in treating anginal symptoms and normalizing
the eosinophil count too.[9] Variable corticosteroids doses and regimens have been used. However the optimal
regimen is yet to be determined. In some cases, patients' symptoms relapsed after
dropping the dose below a certain point, while others tolerated being tapered off
completely with no reported symptomatic recurrence.[8]
Conclusion
Kounis syndrome needs to be considered in patients presenting with chest pain, especially
at young age. Coronary vessels vasodilators are considered to be the first line of
treatment. The use of corticosteroids has been described in the literature, especially
in severe or refractory cases with symptomatic relief, but optimal regimen yet to
be determined. Further studies are necessary to determine the long-term efficacy of
each treatment option and thereby establishing the definitive treatment strategy for
refractory VSA.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
