Kounis syndrome type I in a victim of cardiopulmonary arrest after hymenoptera sting

Abstract

Kounis syndrome is a relatively rare entity in which allergic or hypersensitivity reactions (including anaphylaxis) coexist with acute coronary syndromes. We report a case of Kounis syndrome type I variant in a 51-year-old male, victim of an out-of-hospital cardiac arrest a few minutes after a hymenoptera sting. Ιn-hospital cardiopulmonary resuscitation was provided and return of spontaneous circulation was achieved. The post-resuscitation electrocardiogram revealed ST-segment elevation in leads II, III, aVF, and ST depression in leads V₂, V₃, and V₄. After administration of corticosteroids, antihistamines, nitrates, and a calcium-channel blocker the electrocardiogram rapidly returned to normal. There was no elevation in markers of myocardial necrosis and the coronary angiography revealed normal coronary arteries. According to the clinical course and the laboratory findings the diagnosis of Kounis syndrome type I variant was made. Only a few cases of Kounis syndrome in the setting of cardiopulmonary arrest have been published. We believe that in these cases, the recognition of the main underlying cause that lead to arrest (acute coronary syndrome or severe anaphylactic reaction) plays an important role in the choice of the most appropriate treatment for the patient.

<Learning objective: Kounis syndrome is a rare clinical condition. However, every cardiologist should be capable of diagnosing it, because under specific circumstances it can be life-threatening.>

Introduction

Kounis syndrome is defined as the concurrence of acute coronary syndromes with conditions associated with mast cell activation, involving interrelated and interacting inflammatory cells, and including allergic or hypersensitivity and anaphylactic or anaphylactoid insults [1], [2].

We describe a case of Kounis syndrome type I variant in a 51-year-old male with no past medical history and normal coronary arteries, who survived cardiac arrest after a hymenoptera sting and developed transient inferior ST-segment elevation after return of spontaneous circulation without increase of markers of myocardial necrosis.

Case report

A 51 year-old male, victim of out-of-hospital cardiac arrest, was brought to the emergency room. Out-of-hospital cardiopulmonary resuscitation (CPR) had been delivered. He was found unconscious, and apneic at the side of the road 15 min earlier. It was reported that the patient had a hymenoptera sting a few minutes earlier on the big toe of the left foot. The patient was a smoker (10 pack-years), had no past medical history, and did not take any medication. He had experienced hymenoptera stings several times in the past without any severe allergic reaction or chest pain.

In emergency department the patient was in cardiopulmonary arrest with pulseless electrical activity and cyanotic. In-hospital CPR was immediately initiated and the patient was intubated. Arterial blood gases before the intubation showed: arterial pH, 7.05; PCO2, 66 mmHg; PaO2, 27 mmHg; [HCO₃⁻], 17 mEq/L. After 4 min of CPR and IV administration of 1 mg of epinephrine, spontaneous circulation was established. Post-resuscitation vital signs were the following: blood pressure, 140/80 mmHg; oxygen saturation, 94%; heart rate, 140/min; body temperature, 37 °C (98.6 °F). The electrocardiogram (ECG) revealed sinus tachycardia with ST-segment elevation in leads II, III, aVF, and ST-segment depression in precordial leads V₂, V₃, and V₄ (Fig. 1). A large red allergic rash on the left foot was also present. From the rest physical examination nothing abnormal was found.

Fig. 1.

Electrocardiogram after the return of spontaneous circulation. ST segment elevation in leads II, III, aVF, and ST segment depression in V₂, V₃, and V₄.

The patient was admitted to intensive care unit. IV fluids, corticosteroids, antihistamines, nitrates, and verapamil were administered. A few minutes later the ECG returned to normal (Fig. 2). The patient also underwent therapeutic hypothermia for 24 h in order to prevent ischemic encephalopathy after cardiac arrest.

Fig. 2.

Normal electrocardiogram a few minutes after administration of nitrates and calcium-channel blocker.

Blood analysis showed results within normal values, in respect of complete blood count and markers of renal and liver function. No elevation in markers of myocardial necrosis was revealed. A chest X-ray and an echocardiogram showed no abnormal findings. As the ST-segment elevation was transient and the markers of myocardial necrosis did not increase, coronary angiography was performed after the patient had been hemodynamically stabilized.

The next days the ventilatory and hemodynamic status of the patient was stable and improving and on the sixth day the patient was extubated. The mental status of the patient returned to normal within a few hours. He experienced no symptoms of chest pain, the ECGs were completely normal, and the coronary angiography revealed normal coronary arteries (Fig. 3).

Fig. 3.

Coronary angiography. Normal left and right coronary artery. Right coronary artery was spastic without provocation test.

According to the clinical course (hymenoptera sting and rash) and the laboratory findings (no elevation of markers of myocardial necrosis), coronary vasospasm was considered to be the most possible cause of the inferior ST-segment elevation and the diagnosis of Kounis syndrome type I variant was made. The patient was transferred to the Cardiology Ward and on the ninth day he was discharged home. At the 3- and 6-month visits, he was free of symptoms.

Discussion

In 1991, Kounis and Zavras first described the syndrome of allergic angina and allergic myocardial infarction, as the concurrence of acute coronary syndromes and allergic reactions. Since then three types of the Kounis syndrome have been described:

• •Type I variant includes patients with normal coronary arteries in whom coronary artery spasm occur, with or without increase of markers of myocardial necrosis.
• •Type II variant includes patients with culprit but quiescent pre-existing atheromatous disease in whom plaque erosion or rupture occur, manifesting as acute myocardial infarction.
• •Type III variant includes patients with coronary thrombosis (including stent thrombosis) [3] in whom histologically stained aspirated thrombus specimens reveal the presence of eosinophils and mast cells.

The main pathophysiologic mechanism of the syndrome is thought to be the hypercontractility of vascular smooth muscle that leads to coronary vasospasm and the endothelial injury that leads to plaque erosion or rupture. These may be the result of mast cell activation and release of vasoconstrictor and inflammatory mediators, including histamine, serotonin, endothelin, neutral proteases, arachidonic acid products, and platelet activating factor [4], [5].

A variety of causes, including medications, medical conditions, and environmental exposures, have been reported [6], [7].

The clinical presentation of the syndrome varies, including symptoms of both an acute coronary syndrome and an allergic reaction, e.g. chest pain, nausea, vomiting, dyspnea, pallor, diaphoresis, pruritus, and hypotension [8]. Most of the cases refer to patients with consciousness and relative hemodynamic stability and only few cases with patients in the setting of cardiopulmonary arrest [9], [10].

The key question in these rare cases, in which cardiopulmonary arrest and Kounis syndrome coexist, is what the main cause of the arrest is. Is it the acute coronary syndrome, that can cause a life-threatening arrhythmia or/and cardiogenic shock, or the severe anaphylactic reaction, that can cause anaphylactic shock or/and airway obstruction? We believe that the answer is rather difficult but crucial for the physician in order to cope with the right reversible cause and improve the outcome of the patient.

In our case, based on the clinical course (no cardiac history, non-“shockable” arrest rhythm, rapid resolution of post-resuscitation ischemic electrocardiographic changes), the absence of elevation of cardiac markers and the normal coronary angiogram, we believe that the main cause of the arrest was probably the severe allergic reaction to the hymenoptera sting. We considered coronary vasospasm to be the cause of the transient inferior ST-segment elevation and consequently we set the diagnosis of Kounis syndrome type I variant.

Generally, we believe that Kounis syndrome is likely an underdiagnosed and probably life-threatening entity that requires immediate and specific treatment. It is important for the physicians to be aware of and able to suspect and diagnose this syndrome in order to provide effective treatment. Additional research in this field is necessary to elucidate the pathophysiological mechanisms of this syndrome and provide more effective treatment.

The main limitations of our case are the inability to perform intravascular ultrasound or optical coherence imaging due to the lack of the necessary equipment and the fact that we did not perform test of vasospasm.

In conclusion, Kounis syndrome has a variant etiology and clinical presentation and in rare cases may coexist with cardiopulmonary arrest. In these cases it is crucial to identify the underlying cause of the arrest, i.e. an acute coronary syndrome or an allergic reaction, since this will determine the the choice of the correct treatment.

Conflict of interest

The authors declare that there is no conflict of interest.