International Journal of Cardiology 172 (2014) e303
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Patent foramen ovale, transient ischemic attack and Kounis syndrome George D. Soufras a, Nicholas G. Kounis b,⁎ a b
Department of Cardiology, “Saint Andrews” State General Hospital, Patras, Achaia, Greece Department of Medical Sciences, Patras Highest Institute of Education and Technology, Patras, Greece
a r t i c l e
i n f o
Article history: Received 3 November 2013 Accepted 28 December 2013 Available online 8 January 2014 Keywords: Cryptogenic stroke Kounis syndrome Nickel allergy Patent foramen ovale Transient ischemic attack
In their important meta-analysis of Ntaios et al.'s study published in this Journal [1], concerning all randomized control trials of patent foramen ovale closure versus medical treatment, the authors found no benefit in the prevention of cryptogenic shock and transient ischemic attack with implantation of unselected devices. However, in a subgroup analysis, selected closure devices may be superior to medical therapy without increasing the risk of new-onset atrial fibrillation. Indeed, in the CLOSURE trial [2] the rate of stroke, transient ischemic attack, or death did not diminish and the risks of major vascular events and atrial fibrillation were increased despite closure of patent foramen ovale, with the StarFlex device, in comparison with the best medical treatment. The benefits of closure seem to be offset by the use of devices acting as antigenic complexes inside the heart which are able to induce the hypersensitivity associated with Kounis syndrome [3]. StarFlex consists of a 4- or 6-arm metallic framework, Dacron fabric, and self-centering mechanism achieved by nitinol microsprings and it has been incriminated for 7.1% of thrombus formation in the first 4 weeks after insertion [4]. Nitinol is a titanium–nickel alloy. Nickel and titanium ions acting as antigens can activate platelets to release proinflammatory, prothrombotic, adhesive and aggregatory mediators in order to induce thrombus formation. Platelet activation ensues from stimulation of some known receptors in the platelet surface such as receptors for adenosine diphosphate, thromboxane, thrombin, serotonin, and epinephrine and some less known receptors such as receptors for platelet activating
⁎ Corresponding author at: Queen Olgas Square, 7 Aratou Street, Patras 26221, Greece. Tel./fax: +30 2610 279579. E-mail address: [email protected] (N.G. Kounis). 0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.189
factor, histamine and high affinity and low affinity IgE receptors FCεRI and FCεRII [5]. Nickel allergy to intracardiac devices has caused systemic allergic reactions confirmed by patch tests to nitinol, which necessitated the removal of these devices [6]. A “device syndrome” resembling Kounis syndrome and consisting of chest discomfort, exertional dyspnea, palpitations, asthenia, atrial fibrillation has been reported in 8 of 9 patients following Amplatzer implantation. These patients had positive patch skin tests to nickel [7]. All commercially available closure devices (ASDOS, Angel Wings, Cardio SEAL, StarFlex, Amplatzer, Helex, PFO-Star) contain nitinol, polyurethane and polyester, which are all well known antigens. Therefore, it is urgent to develop and implant either antigen-free devices or to use the best available medical treatment. Such nickelfree devices have been already developed but concern only artificial metallic cardiac valves [8]. Acknowledgments The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. References [1] Ntaios G, Papavasileiou V, Makaritsis K. Michel P. PFO closure vs medical therapy in cryptogenic stroke or transient ischemic attack: A systematic review and metaanalysis Int J Cardiol 2013;169(2):101–5. [2] Furlan AJ, Reisman M, Massaro J, et al. CLOSURE I Investigators. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012;366:991–9. [3] Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol 2006;110:7–14. [4] Krumsdorf U, Ostermayer S, Billinger K, et al. Incidence and clinical course of thrombus formation on atrial septal defect and patient foramen ovale closure devices in 1,000 consecutive patients. J Am Coll Cardiol 2004;43:302–9. [5] Kounis NG, Giannopoulos S, Tsigkas GG, Goudevenos J. Eosinophilic responses to stent implantation and the risk of Kounis hypersensitivity associated coronary syndrome. Int J Cardiol 2012;156:125–32. [6] Dasika UK, Kanter KR, Vincent R. Nickel allergy to percutaneous patent foramen ovale occluder and subsequent systemic nickel allergy. J Thorac Cardiovasc Surg 2003; 125:2112–3. [7] Rigatelli G, Cardaioli P, Giordan M, et al. Nickel allergy in interatrial shunt devicebased closure patients. Congenit Heart Dis 2007;2:416–20. [8] Lusini M, Barbato R, Spadaccio C, Chello M. Aortic valve replacement in a patient with severe nickel allergy. J Card Surg 2011;26:618–20.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Patent foramen ovale, transient ischemic attack and Kounis syndrome George D. Soufras a, Nicholas G. Kounis b,⁎ a b
Department of Cardiology, “Saint Andrews” State General Hospital, Patras, Achaia, Greece Department of Medical Sciences, Patras Highest Institute of Education and Technology, Patras, Greece
a r t i c l e
i n f o
Article history: Received 3 November 2013 Accepted 28 December 2013 Available online 8 January 2014 Keywords: Cryptogenic stroke Kounis syndrome Nickel allergy Patent foramen ovale Transient ischemic attack
In their important meta-analysis of Ntaios et al.'s study published in this Journal [1], concerning all randomized control trials of patent foramen ovale closure versus medical treatment, the authors found no benefit in the prevention of cryptogenic shock and transient ischemic attack with implantation of unselected devices. However, in a subgroup analysis, selected closure devices may be superior to medical therapy without increasing the risk of new-onset atrial fibrillation. Indeed, in the CLOSURE trial [2] the rate of stroke, transient ischemic attack, or death did not diminish and the risks of major vascular events and atrial fibrillation were increased despite closure of patent foramen ovale, with the StarFlex device, in comparison with the best medical treatment. The benefits of closure seem to be offset by the use of devices acting as antigenic complexes inside the heart which are able to induce the hypersensitivity associated with Kounis syndrome [3]. StarFlex consists of a 4- or 6-arm metallic framework, Dacron fabric, and self-centering mechanism achieved by nitinol microsprings and it has been incriminated for 7.1% of thrombus formation in the first 4 weeks after insertion [4]. Nitinol is a titanium–nickel alloy. Nickel and titanium ions acting as antigens can activate platelets to release proinflammatory, prothrombotic, adhesive and aggregatory mediators in order to induce thrombus formation. Platelet activation ensues from stimulation of some known receptors in the platelet surface such as receptors for adenosine diphosphate, thromboxane, thrombin, serotonin, and epinephrine and some less known receptors such as receptors for platelet activating
⁎ Corresponding author at: Queen Olgas Square, 7 Aratou Street, Patras 26221, Greece. Tel./fax: +30 2610 279579. E-mail address: [email protected] (N.G. Kounis). 0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.189
factor, histamine and high affinity and low affinity IgE receptors FCεRI and FCεRII [5]. Nickel allergy to intracardiac devices has caused systemic allergic reactions confirmed by patch tests to nitinol, which necessitated the removal of these devices [6]. A “device syndrome” resembling Kounis syndrome and consisting of chest discomfort, exertional dyspnea, palpitations, asthenia, atrial fibrillation has been reported in 8 of 9 patients following Amplatzer implantation. These patients had positive patch skin tests to nickel [7]. All commercially available closure devices (ASDOS, Angel Wings, Cardio SEAL, StarFlex, Amplatzer, Helex, PFO-Star) contain nitinol, polyurethane and polyester, which are all well known antigens. Therefore, it is urgent to develop and implant either antigen-free devices or to use the best available medical treatment. Such nickelfree devices have been already developed but concern only artificial metallic cardiac valves [8]. Acknowledgments The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. References [1] Ntaios G, Papavasileiou V, Makaritsis K. Michel P. PFO closure vs medical therapy in cryptogenic stroke or transient ischemic attack: A systematic review and metaanalysis Int J Cardiol 2013;169(2):101–5. [2] Furlan AJ, Reisman M, Massaro J, et al. CLOSURE I Investigators. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012;366:991–9. [3] Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol 2006;110:7–14. [4] Krumsdorf U, Ostermayer S, Billinger K, et al. Incidence and clinical course of thrombus formation on atrial septal defect and patient foramen ovale closure devices in 1,000 consecutive patients. J Am Coll Cardiol 2004;43:302–9. [5] Kounis NG, Giannopoulos S, Tsigkas GG, Goudevenos J. Eosinophilic responses to stent implantation and the risk of Kounis hypersensitivity associated coronary syndrome. Int J Cardiol 2012;156:125–32. [6] Dasika UK, Kanter KR, Vincent R. Nickel allergy to percutaneous patent foramen ovale occluder and subsequent systemic nickel allergy. J Thorac Cardiovasc Surg 2003; 125:2112–3. [7] Rigatelli G, Cardaioli P, Giordan M, et al. Nickel allergy in interatrial shunt devicebased closure patients. Congenit Heart Dis 2007;2:416–20. [8] Lusini M, Barbato R, Spadaccio C, Chello M. Aortic valve replacement in a patient with severe nickel allergy. J Card Surg 2011;26:618–20.
