Abbreviations
CICU, Cardiac ICU
CTCA, Computed tomography coronary angiogram
ECG, Electrocardiogram
KS, Kounis syndrome
LAD, Left anterior descending
INTRODUCTION
Kounis and Zavras in 1991 first described the phenomenon of acute coronary syndrome following mast cell activation from allergic, hypersensitivity or anaphylactoid reactions. This has been referred to as "allergic angina" or "allergic myocardial infarction".1 The mechanism of Kounis syndrome (KS) involves release of inflammatory cytokines through mast cell activation, which leads to coronary artery vasospasm and/or atheromatous plaque erosion or rupture.2 It is not a rare disease but is difficult diagnosed condition. The emergency department incidence is 0.0194% in all patients and 3.4% in patients with allergies.3 We report a case of KS from anaphylaxis to contrast manifesting as an inferior ST elevation myocardial infarction.
CASE
A 56-year-old man presented to the emergency department with chest pain that started the previous day. He has a medical history of diabetes mellitus, hypertension, hyperlipidemia and gallstone disease. He is also a chronic smoker and has no known drug allergies. The chest pain history was non-specific with no exertional component. The initial electrocardiogram (ECG) revealed a normal sinus rhythm with no ischemic changes or arrhythmias. Two sets of troponin I sent 6 hours apart were performed and was not elevated. A diagnosis of non-anginal chest pain was made and given his intermediate to high cardiovascular risk profile, he was planned for a computed tomography coronary angiogram (CTCA) and transthoracic echocardiogram.
He remained stable in the general ward and was sent for CTCA on the 3rd day of admission. During the imaging procedure, 60 cc of Iopromide (Ultravist) contrast was injected at 6 cc/sec as per standard protocol. The patient became acutely unwell with symptoms of significant giddiness and abdominal pain. The blood pressure dropped drastically from a systolic of 116 to 47 mmHg and patient was in a peri-arrest state. Examination revealed generalised flushing with periorbital edema. A 12 lead ECG was done showing inferior ST segment elevations, no pathological Q wave (Figure 1A) and this was also seen on the continuous cardiac monitoring screen. A decision was made to intubate the patient and peripheral vasopressors were started to support his blood pressure. Adrenaline 0.5 mg, hydrocortisone 200 mg, and diphenhydramine 50 mg were promptly given for suspected anaphylactic shock.
Figure 1.
(A) Initial electrocardiogram showing sinus rhythm, 1-2 mm ST elevation in the inferior leads and T inversion in V4-6. (B) Repeat electrocardiogram revealed resolution of ST segment elevation.
The CTCA images were reviewed which showed a coronary calcium score of 27. There were minor plaques in the left anterior descending (LAD), left circumflex and right coronary artery with no significant stenosis (Figure 2). There was no aortic dissection as well. In view of these findings, emergent invasive coronary angiography was not performed, and patient was sent to the cardiac ICU (CICU) for treatment of anaphylactic shock. A repeat ECG upon arrival in the CICU showed resolution of the ST segment elevations (Figure 1B). The formal transthoracic echocardiogram showed a preserved ejection fraction of 60% with no regional wall motion abnormalities.
Figure 2.
Computed tomography (CT) coronary angiogram revealed minimal coronary calcification with no major obstructive disease. LAD, Left anterior descending.
The patient’s hemodynamic status improved with supportive therapy in the subsequent days. Troponin I levels were sent which showed an acute rise from 5 to 424 ng/L. The clinical allergist’s consult was sought, and the diagnosis of anaphylaxis complicated by possible KS was established. This was further supported by significantly elevated serum tryptase levels of 85.7 ug/L one-hour post contrast exposure (normal range: < 11.4 ug/L). His symptoms resolved the following day and was subsequently transferred out of the CICU. He was discharged 5 days after the anaphylaxis event. The patient underwent skin prick and intradermal allergy testing to contrast agents for which the results came back as strongly positive for Iopromide. A medical alert was raised to avoid Iopromide based contrast agents indefinitely to prevent recurrence of anaphylaxis and KS.
Hypersensitivity reactions to contrast media include both Ig E and non-Ig E-mediated anaphylaxis, with activation of mast cells, coagulation, kinin and complement mechanisms, inhibition of enzymes, and platelet aggregation.
There are three pathophysiological variants of KS that has been previously described.4 Type I includes patients with normal coronary arteries or near-normal coronary arteries in whom an acute allergic insult leads to coronary artery vasospasm. This can lead to angina or infarction with elevation of cardiac biomarkers. This variant represents a manifestation of endothelial dysfunction or microvascular angina.5 The type II variant describes patients with underlying atherosclerotic coronary artery disease where the allergic insult results in plaque erosion or rupture leading to acute myocardial infarction.6,7 The type III variant can be divided into IIIA (stent thrombosis) and IIIB (stent restenosis). Coronary ischaemia from an allergic reaction is a result of the release of inflammatory mediators like histamine, tryptase, cytokines and prostaglandins to name a few. This leads to intense coronary vasospasm and can mimic acute coronary syndromes.8
For our patient, we postulate that his presentation was more in keeping with the type I variant of KS. The cause of the ST segment elevations was promptly identified as to be from an anaphylactic reaction and immediate treatment was given. The resolution of the ST elevations after treatment is possibly contributed by vasospasm. Despite observing ST elevations, the managing team was confident in deferring emergent invasive coronary angiography as to avoid a second hit mechanism leading to devastating outcome. While troponin elevation was observed, early treatment with resolution of coronary vasospasm resulted in minimal damage to the myocardium as evidenced by his preserved ejection fraction and absence of wall motion abnormalities on echocardiography. This case highlights the importance of understanding the therapeutic goals of KS, which is to suppress anaphylaxis and thus improve coronary flow.
LEARNING POINTS
• Kounis syndrome is not rare but a poorly recognized disease. It is an important differential diagnosis in cases of acute coronary syndrome with allergic attack.
• Identification of potential trigger is important to prevent catastrophic complication.
• Referral to allergist early is prudent in the work-up of Kounis syndrome.
DECLARATION OF CONFLICT OF INTEREST
All the authors declare no conflict of interest.
Acknowledgments
Nil.
AUTHORS’ CONTRIBUTIONS
SW: Drafting the manuscript, acquisition of data. MA: drafting the manuscript and supervision.
FUNDING
None.
REFERENCES
- 1.Kounis NG, Zavras GM. Histamine-induced coronary artery spasm: the concept of allergic angina. Br J Clin Pract. 1991;45:121–128. [PubMed] [Google Scholar]
- 2.Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol. 2006;110:7–14. doi: 10.1016/j.ijcard.2005.08.007. [DOI] [PubMed] [Google Scholar]
- 3.Kounis NG. Coronary hypersensitivity disorder: the Kounis syndrome. Clin Ther. 2013;35:563–571. doi: 10.1016/j.clinthera.2013.02.022. [DOI] [PubMed] [Google Scholar]
- 4.Nikolaidis LA, Kounis NG, Gradman AH. Allergic angina and allergic myocardial infarction: a new twist on an old syndrome. Can J Cardiol. 2002;18:508–511. [PubMed] [Google Scholar]
- 5.Guedeney P, Claessen BE, Kalkman DN, et al. Residual inflammatory risk in patients with low LDL cholesterol levels undergoing percutaneous coronary intervention. J Am Coll Cardiol. 2019;73:2401–2409. doi: 10.1016/j.jacc.2019.01.077. [DOI] [PubMed] [Google Scholar]
- 6.Kalkman DN, Aquino M, Claessen BE, et al. Residual inflammatory risk and the impact on clinical outcomes in patients after percutaneous coronary interventions. Eur Heart J. 2018;39:4101–4108. doi: 10.1093/eurheartj/ehy633. [DOI] [PubMed] [Google Scholar]
- 7.Raggi P, Genest J, Giles JT, et al. Role of inflammation in the pathogenesis of atherosclerosis and therapeutic interventions. Atherosclerosis. 2018;276:98–108. doi: 10.1016/j.atherosclerosis.2018.07.014. [DOI] [PubMed] [Google Scholar]
- 8.Desai R, Parekh T, Patel U, et al. Epidemiology of acute coronary syndrome co-existent with allergic/hypersensitivity/anaphylactic reactions (Kounis syndrome) in the United States: a nationwide inpatient analysis. Int J Cardiol. 2019;292:35–38. doi: 10.1016/j.ijcard.2019.06.002. [DOI] [PubMed] [Google Scholar]