Nicholas G. Kounis

Acute anterior myocardial infarction after multiple bee stings. A case of Kounis syndrome

A 58-year-old man with no history of cardiac diseases or cardiovascular risk factors was stung by honeybees. Soon after, he gradually developed signs of an allergic reaction followed by severe retrosternal pain. Electrocardiographic, echocardiographic evidence and positive biochemical markers were consistent with an acute anterolateral myocardial infarction. Coronary arteriography showed a left anterior descending artery thrombotic lesion. This is a case of Kounis syndrome, which is the concurrence of acute coronary syndromes with conditions associated with mast cell activation including allergic or hypersensitivity reactions as well as anaphylactic or anaphylactoid insults. The clinical implications and pathophysiology of this dangerous association are discussed.

Kounis syndrome: a manifestation of drug-eluting stent thrombosis associated with allergic reaction to contrast material.

Stent components acting as potential antigens and promoting intracoronary mast cell activation can lead to catastrophic intrastent thrombosis. Patients with drug-eluting stent (DES) implantation are prone to hypersensitivity reactions from five potential antigens namely, nickel strut, polymer coating, eluted drug, as well as, concomitant drugs clopidogrel and aspirin. These events may be more common than suspected because it is hard to document them, unless they become systemic, in which case they manifest themselves as the Kounis syndrome characterized by the concurrence of acute coronary events with hypersensitivity reactions. This report concerns of a patient with implanted DES who developed an acute myocardial infarction in the stent area following an allergic reaction to contrast material.

Hypersensitivity to proton pump inhibitors: Lansoprazole-induced Kounis syndrome

Proton pump inhibitors are commonly used in clinical practice for the treatment of peptic ulcer and gastroesophageal reflux and are well tolerated by the patients. Their use is rarely associated with hypersensitivity and anaphylactic reactions. According to the reports in the Uppsala Monitoring Center database the frequency of hypersensitivity reactions out of all reported adverse reactions for proton pump inhibitors and H2-histamine receptor antagonists was between 0.2% and 0.7%. A few cases of hypersensitivity to lansoprazole have been reported. We report a patient who developed Kounis syndrome after taking 30 mg of lansoprazole. This is the first report of Kounis syndrome associated with lansoprazole administration in the world literature.

The conundrum of hypersensitivity cardiac disease: Hypersensitivity myocarditis, acute hypersensitivity coronary syndrome (Kounis Syndrome) or both?

Abstract Hypersensitivity or allergic inflammatory processes can affect the cardiac structures during allergic insults. The myocardium, the conduction system and the coronary arteries can be the targets of these insults resulting in Kounis syndrome (hypersensitivity coronary syndrome) or hypersensitivity myocarditis. Kounis syndrome and hypersensitivity myocarditis can be clinically indistinguishable and masquerade each other. Simultaneous occurrence of both entities has not been reported. We report on a patient who presented with signs and symptoms of type I variant of Kounis syndrome but cardiac magnetic resonance imaging showed that he had hypersensitivity myocarditis.

Combined etiology of anaphylactic cardiogenic shock: amiodarone, epinephrine, cardioverter defibrillator, left ventricular assist devices and the Kounis syndrome.

Anaphylactic shock is a life-threatening condition which needs detailed and mediculous clinical assessment and thoughtful treatment. Several causes can join forces in order to degranulate mast cells. Amiodarone which is an iodine-containing highly lipophilic benzofuran can induce allergic reactions and anaphylactic shock in sensitized patients. Epinephrine is a life saving drug, but in sulfite allergic patients it should be given with caution due its metabisulfite preservative. Metals covering cardiac defibrillators and pacemakers can act as antigens attached to serum proteins and induce allergic reactions. In anaphylactic shock, myocardial involvement due to vasospasm-induced coronary blood flow reduction manifesting as Kounis syndrome should be always considered. Clinically, combined treatment targeting the primary cause of anaphylaxis together with protection of cardiac tissue seems to be of paramount importance.

Serum CXCL10 and CXCL12 chemokine levels are associated with the severity of coronary artery disease and coronary artery occlusion

BACKGROUND Cardiovascular disease constitutes a major cause of death worldwide. Inflammation plays an important role in atherosclerosis formation, coronary artery disease progression, acute coronary thrombosis and occlusion. Chemokines are inflammatory mediators disposing several bio-functions, as leukocyte migration towards inflammatory signals and vascular injuries. The present study was designed to evaluate the potential correlation between serum levels of chemokines CXCL-10 and CXCL-12 and the degree of coronary artery occlusion. METHODS Eighty eight patient candidates for coronary angiography with coronary artery disease symptoms and potentially high risk of coronary artery occlusion were recruited. Chemokine serum levels were measured with the ELISA method and patients underwent coronary angiography. All patients with coronary artery disease (CAD) were divided into four groups according to the Gensini score. Data were presented as mean±SD. All P values <0.05 were considered significant. RESULTS Our demographic data showed that of the 88 patients, 46 were male and 42 female. The mean age of patients was 57.95±11.13. Following increased coronary artery occlusion the serum levels of chemokines were significantly increased (CXCL-10 and CXCL-12; P<0.0001 and P<0.0001, respectively). CONCLUSION In this novel study, a significant correlation between the serum levels of CXCL-10 and CXCL-12 and the severity of coronary artery occlusion was found. This could be attributed to the role of these chemokines in the processes of angiogenesis and angiostasis, a biological phenomenon that can play key role in the development of collateral circulation.

Serum IgE levels in coronary artery disease.

The development and progression of atherosclerosis and its predisposition for unstable angina, myocardial infarction and stroke is associated with traditional risk factors such as family history, cigarette smoking, hypertension, dyslipidemia, diabetes mellitus, obesity, imbalance of the hemostatic/fibrinolytic system and sedentary lifestyle. However, much of the variability in atherosclerosis and its manifestations still remains unexplained. Nowadays, there is increasing evidence that immunologic mechanisms play a major role in etiology, prediction of coronary plaque instability and foreseeing severe reaction leading to an actual coronary event. Cells of the immune system such as macrophages, mast cells and T-lymphocytes are major components of human atheromatous plaque. These cells participate in a vicious immune cycle and activate each others via bidirectional stimuli. For example, mast cells can activate macrophages and may enhance T-cell activation. Inducible macrophage protein 1a may activate mast cells, while CD169+ macrophages activate CD8 T cells. T cells may mediate mast-cell activation and proliferation and regulate macrophage activity. Mediators secreted by these cells, including histamine, neutral proteases, arachidonic acid products, platelet activating factor and a variety of cytokines and chemokines, can induce coronary artery spasm and atheromatous plaque erosion and rupture, culminating in the development of acute coronary syndromes.

Pathways of platelet activation and unexplained clopidogel variability: Causes of poor response to clopidogrel

In their very interesting paper, Dr Marco Cattano [1] referred to known factors affecting clopidogrel action such as diet, smoking, alcohol, noncompliance, demographic factors, co-medicationwith statins, calcium channel blockers and proton pump inhibitors, pre-treatment platelet hyperreactivity and polymorphisms in the enzymes converting clopidogrel to active metabolite. Despite the exclusion or control of the above factors clopidogrel variability remains unexplained in about 82% of cases and only 18% of the variation of clopidogrel activemetabolite is attributed to identifiable factors according to a recent study [2]. The author correctly concluded that the best laboratory test in monitoring clopidogrel action still needs to be identified. However, he did not elaborate on other pathways which may explain this variability and lead to platelet adhesion, activation, aggregation and thrombosis, beyond the clopidogrel way of action. It is known that only 15% of administered clopidogrel is converted to active metabolite and inhibits the adenosine diphosphate receptor P2Y12 [3]. It is anticipated that patients with high on-treatment platelet reactivity would be at high risk for thrombotic events and therefore the unclear variations may be future therapeutic targets. Adenosine diphosphate, thromboxane, thrombin and glycoprotein IIb/IIIa receptors constitute current therapeutic targets for prevention of thrombosis. However, platelet surface membrane, apart from these well known receptors carries also other receptors such as receptors for platelet activating factor and histamine [4]. Additionally, flow cytofluorometric analysis has revealed that 20% of platelets express Fc γ receptor (FcγR) I, FcγRII and high FCεRI and low FRεRII affinity IgE receptors [5]. This percentage increases up to 50% in patients with IgE-dependent atopic diathesis [6]. It is known that platelets show the capacity to get activated upon local and systemic hypersensitivity reactions [7]. It has been shown that in platelets isolated fromatopic patients, immunological stimulation with anti-IgE antibodies induces platelet aggregation and release of histamine [8]. In experiments with human blood platelets which were stimulated with adenosine diphosphate inwhole human blood fromhealthy donors, in plasma and in isolated platelets, their aggregation was inhibited by antihistamines [9]. In other experiments in hamsters, late thrombotic events, induced by diesel particles, were abrogated by mast cell stabilization with disodium cromoglycate or dexamethazone and this was attributed to the prevention of release of histamine frommast cells [10]. All of the above denote that there are other pathways leading to thrombotic events and that inhibition of adenosine diphosphate receptor

Nickel Allergy, Amplatzer Atrial Septal Occluder Device, and the Risk of Kounis Syndrome

In a very interesting report published in this journal1 concerning a 52-year-old woman with an Amplatzer atrial septal occluder device implantation, the authors reported that the patient experienced repeated attacks of severe, burning left-sided chest pain which disappeared following explantation of the device. The Amplatzer occluder device is made from nitinol which is a nickel-titanium alloy. Although the electrocardiographic findings during the chest pain attacks have not been given, the patient’s chest pain is characteristic for Kounis hypersensitivity coronary syndrome.2 It is known that hypersensitivity reactions to nickel occur in up to 17.2% of the population and are the most frequent cause of allergic contact dermatitis.3 In patients undergoing percutaneous atrial septal defect and patent foramen ovale closure, nickel allergy can be the cause of systemic reactions such as chest discomfort, palpitation, and migraine headache with or without aura.4 Local nickel allergy from intracardiac devices and subsequent systemic allergic reactions confirmed by patch tests as an allergy to nitinol have necessitated the removal of these devices.5 Reports concerning hypersensitivity reactions to various metals used in orthodontics have also been published and nickel was the metal provoking the most severe responses.6 Delayed hypersensitivity reactions to nickel and molybdenummight be part of the inflammatoryprocess and one of the triggering factors for development of in-stent restenosis.7 The rate of nickel allergy following initial stent implantation has been estimated to be 9.2%.8 Skin clips containing nickel, chromium, molybdenum, cobalt, and titanium can induce allergic reactions and may be the cause of delayed wound healing.9 It is known that the metal strut in coronary stents is made from 316L stainless steel containing nickel, chromium, manganese, titanium, and molybdenum. Based on the above clinical observations, we believe that nickel allergy history should be ascertained in all patients prior to undergoing Amplatzer device or coronary stent implantation. Indeed, newer stent devices (eg, Endeavor with zotarolimus(Medtronic,Minneapolis, MN) and Xience V with everolimus eluting drugs (Abbott Laboratories, Abbott Park, IL)), avoid nickel struts and use cobaltchromium struts which are less allergenic, thus following our recommendations.10 The same should be applied in the newer Amplatzer atrial septal occluder devices.

Ascites and other extracardiac manifestations associated with right atrial myxoma : A case report

Right atrial myxomas are rare intracardiac tumors that often pose difficulties in diagnosis. Right ventricular failure and ascites ensuing from tricuspid valve orifice obstruction are potentially dangerous complications. Early diagnosis of cardiac myxoma is important since surgical treatment leads to disappearance of all symptoms with a low rate of recurrence and good long-term survival. Nonspecific extracardiac symptoms, signs, complications, and laboratory findings may be the initial manifestations contributing to misdiagnosis of these rare but totally treatable atrial tumors.