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Kounis Syndrome   and Intracardiac    Metal DevicesFrom Bedside to Bench!“A hypersensitivity blow up inside the heart”Nich...
Hypersensitivity inflammation             + Acute coronary syndrome
Hypersensitivity inflammation                + Acute coronary syndromeHypersensitivity coronary syndrome(Kounis syndrome)
Hypersensitivity inflammation Acute coronary syndromeHypersensitivity coronary syndrome(Kounis syndrome)
Intracardiac devices Containing     Nickel and Other Metals                     2. Devices for Closure1. Coronary Stents  ...
Kounis syndrome: thehypersensitivity coronary syndrome             What is?“The concurrence of acute coronary syndromes wi...
The vicious cycle of                inflammatory cells                  All these inflammatory cells participate in a  Mac...
Kounis syndrome variantsType I variant: includes patients with normal coronary arteries without predisposing factors for c...
Kounis syndrome:   main actions of main mediators    Cardiac effects of histamine1.Coronary vasoconstriction (histamine te...
Kounis syndrome: cardiac actions of         main mediators: Proteases                 Tryptase                            ...
Kounis syndrome: cardiac actions    of the main mediators     Leukotrienes: Powerful arterial vasoconstrictorsand their bi...
How Kounis syndrome is associated with stent and otherdevices thrombosis? Antigens are necessary and antigens are      pre...
3       THE FACTS: First generation Drug          Eluting Stents components:                1.The metal itself is made fro...
Hypersensitivity to Drug ElutingStents components and Kounis          syndromeHypersensitivity reactions to nickel        ...
Hypersensitivity to Drug Eluting          stents components and Kounis                    syndrome Hypersensitivity reacti...
Hypersensitivity to Drug Eluting          Stents components and Kounis                    syndrome    Hypersensitivity rea...
Hypersensitivity to Drug Eluting Stents components and Kounis           syndromeHypersensitivity reactions of Rapamycin   ...
SECOND GENERATION STENTS:    they are named cobalt-chromium            stents (misleading term?)Xience(everolimus) stentTh...
SECOND GENERATION STENTS:    they are named cobalt-chromium            stents (misleading term?)Xience                    ...
4. Clopidogrel-induced allergic          skin rash
4. Clopidogrel-induced allergic             skin rash  5. Kounis NG, et al. “Myocardialinfarction after aspirin treatment,...
6. Atopic stented individuals areunder the risk of any additional      drug or environmental    exposure which may “join  ...
More than 5 antigens are irreversibly implanted  and some of them apply continuous, persistent,      chronic and repetitiv...
Stents, like magnet, attract          inflammatory cells!1. Stent thrombosis associated with allergic symptoms such   as g...
Types of PFO and ASD ocluders containing            nitinol ( nickel-titanium alloy)AMPLATZER® device - used for PFO repai...
The generators are covered with titanium and the pacing leads are made from MP35N (an alloy of               Ni, Co, Cr, a...
Artificial heart valves: Parts aremade of Co-Cr-W-Ni alloy. Today nickel free-valves are available
The ASD and PFO closure device and Kounis syndrome symptoms and signsThe “Device syndrome”  Eight out of 9 patients with p...
The ASD and PFO closure device and Kounis syndrome symptoms and signsThe “Device syndrome”                                ...
Kounis syndrome and intracardiac DevicesTHE EVIDENCE
-Localized Hypersensitivity and Late          CoronaryThrombosis Secondary to a Sirolimus-Eluting Stent              Shoul...
It has been stated that    “eosinophilic infiltration     of intrastent thrombus    seems to be a common        finding in...
Kounis syndrome and intracardiac device             thrombosis THE MECHANISM
Platelets play a central role in pathogenesis of thrombosis
Stent thrombosis1. Platelet adhesion2. Platelet activation3. Platellet aggregation
LMW Heparin2.PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME                                    Mast cell         ...
LMW Heparin2.PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME                                    Mast cell         ...
PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME                                                LMW Heparin2.      ...
PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME                                                LMW Heparin2.      ...
PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME                                                LMW Heparin        ...
Petrikova M, et al. H1 antihistamines and    activated blood platelets. Inflammation        Res 2006; 55 Suppl 1: S51-S52....
In patients with cardiac pacemakers and defibrillators whodied: Thrombi were found at autopsy in 33% of ventricular       ...
Thrombus after ASD and PFODevice closure Krumsdorf U, et al. JACC 2004;43; 302-9
Mid esophageal 2 (chamber view, 90 degrees).           95-1596Cardona L et al. Circulation 2011;124:1595-1596
Prevention of thrombosis
Fighting against stent thrombosis1.Taking careful history of  adverse drug reactions and  allergies2.Monitoring of inflamm...
Fighting against stent thrombosis1.Taking careful history of  adverse drug reactions and  allergies2.Monitoring of inflamm...
Fighting against stent thrombosis1.Taking careful history of  adverse drug reactions and  allergies2.Monitoring of inflamm...
Future  directions forstents and other     devices
1.Nickel free stainless steel                with numberof blood platelets attached to and 316L stainless steel    after d...
Nickel sensitization (patch test)in North-Eastern Italy(Belluno, Bolzano, Padova, Pordedone,Rovereto,Rovigo, Trento, Tries...
Bioabsorbable Stents• …At 2 years after  implantation the  stent was  bioabsorbed, had  vasomotion  restored, restenosis  ...
Bioabsorbable Stents• …At 2 years after  implantation the                          • ..However, three  stent was          ...
3. Bioabsorbable          Stents: Aself expanding drug-eluting non allergic        poly-lactic acid stent
Medronic’s Official                                                safety informationContraindications                    ...
My euharisties to all of youΣας Εσταριστώ όλοσς σας                      Nicholas Kounis
Nickel: a ubiquitous metalNickel allergy is most commonly associated with earrings and other jewelry forbody piercings tha...
Nickel allergy
People who are severely allergic to nickel as from earrings or belt  buckles, can actually develop a rash from eating food...
Lecce lecture kounis syndrome and intracardiac metal devices
Lecce lecture kounis syndrome and intracardiac metal devices
Lecce lecture kounis syndrome and intracardiac metal devices
Lecce lecture kounis syndrome and intracardiac metal devices
Lecce lecture kounis syndrome and intracardiac metal devices
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Lecce lecture kounis syndrome and intracardiac metal devices

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Lecce lecture kounis syndrome and intracardiac metal devices

  1. 1. Kounis Syndrome and Intracardiac Metal DevicesFrom Bedside to Bench!“A hypersensitivity blow up inside the heart”Nicholas Kounis, Iatros, MD, FESC, FACC
  2. 2. Hypersensitivity inflammation + Acute coronary syndrome
  3. 3. Hypersensitivity inflammation + Acute coronary syndromeHypersensitivity coronary syndrome(Kounis syndrome)
  4. 4. Hypersensitivity inflammation Acute coronary syndromeHypersensitivity coronary syndrome(Kounis syndrome)
  5. 5. Intracardiac devices Containing Nickel and Other Metals 2. Devices for Closure1. Coronary Stents Of Atrial Septal Defects including Bare and Patent Foramen Metal Stents Ovale (BMS) and Drug Eluting Stents 3.Cardiac Pacemakers and (DES) defibrillators 4. Artificial Cardiac Valves
  6. 6. Kounis syndrome: thehypersensitivity coronary syndrome What is?“The concurrence of acute coronary syndromes with conditions associated with mast cell activation, involving interrelated and interacting inflammatory cells, and including allergic orhypersensitivity and anaphylactic or anaphylactoid insults”. “It is caused by inflammatory mediators such as histamine, neutral proteases, arachidonic acid products, platelet activating factorand a variety of cytokines and chemokines released during the activation process.” “A subset of platelets bearing FCεRI and FCεRII receptors are also involved in the activation cascade” Mast cells Macrophages T-cells Mast cells
  7. 7. The vicious cycle of inflammatory cells All these inflammatory cells participate in a Macrophages vicious inflammatory cycle and via multidirectional signals: 1. Mast cells can enhance T cell activation1 Mast cells 2. T cells can mediate mast cell activation and proliferation2Macrophages 3. Inducible macrophage protein-1α can activate mast cells3 4. mast cells can activate macrophages4 T-cells 5. T cells can regulate macrophage activity5Macrophages 1. Nakae S, et al. J Immunol 2006; 176: 2238 2. Mecori YA, et al. Clin Immunol 1999; 104: 517 3. Miyazaki D, et al. J Clin Invest 2005; 115: 434 4. Salari H, et al. J Immunol 1989; 142: 2821 5. Doherty TM. Curr Opin Immunol 1995; 7: 400
  8. 8. Kounis syndrome variantsType I variant: includes patients with normal coronary arteries without predisposing factors for coronary artery disease in whom the acute release of inflammatory mediators can induce either coronary artery spasm without increase of cardiac enzymes and troponins or coronary artery spasm progressing to acute myocardial infarction with raised cardiac enzymes and troponin Nikolaidis LA, et al. Can J Cardiol 2002; 18: 508Type II variant: includes patients with culprit but quiescent pre-existing atheromatous disease in whom the acute release of inflammatory mediators can induce either coronary artery spasm with normal cardiac enzymes and troponins or plaque erosion or rupture manifesting as acute myocardial infarction Nikolaidis LA, et al. Can J Cardiol 2002; 18: 508 Type III variant: includes patients with coronary artery stent thrombosis in whom aspirated thrombus specimens stained with hematoxylin-eosin and Giemsa demonstrate the presence of eosinophils and mast cells respectively Biteker M. Expert Rev Clin Immunol 2010; 6: 777-88
  9. 9. Kounis syndrome: main actions of main mediators Cardiac effects of histamine1.Coronary vasoconstriction (histamine test)2. Induces tissue factor expression and activity3. Activates platelets and potentiates the aggregatory response of agonists e.g. adrenaline, 5-hydroxytryptamine, and thrombin4. Intimal thickening5. Inflammatory cell modulation6. Modulates the activity of neutrophils, monocytes, and eosinophils7. Proinflammatory cytokine production8. P-selectine upregulation9. Sensitizites nerve endings in coronary plaques
  10. 10. Kounis syndrome: cardiac actions of main mediators: Proteases Tryptase Chymase 1. Activates the zymogen forms of 1. Converts angiotensin I to metalloproteinases such as angiotensin II and angiotensin II interstitial collagenase, gelatinase, receptors are found in the medial and stromelysin and can promote muscle cells of human coronary plaque disruption or rupture. arteries. Thus, angiotensin II 2. Degrates the pericellular matrix generated by chymase could act components fibronectin and synergistically with histamine and vitronectin and neuropeptides, aggravate the local spasm of the such as vasoactive intestinal infarcted coronary artery. Chymase peptide (VIP) and calcitonin gene also can remove cholesterol from related peptide (CGRP) HDL 3. Tryptase can degrade HDL 2. Activates MMP-1,-2,-9 and plays a 4. Activates neighboring cells by major role in the physiologic cleaving and activating protease- degradation of fibronectin and activated receptor (PAR)-2, and thrombin thrombin receptors 3. Releases latent TGF-β1 from the extracellular matrix 4. Inhibits smooth muscle growth Cathepsin D 5. Induces apoptosis of arterial smooth 1. Angiotensin II-forming protease muscle cells and endothelial cells 2.Degrates both fibronectin and VE-cadherin which arenecessary for adhesion of endothelial cells to their basement membrane and to each other
  11. 11. Kounis syndrome: cardiac actions of the main mediators Leukotrienes: Powerful arterial vasoconstrictorsand their biosynthesis is enhanced in the acute phase of unstable angina Thromboxane: A potent mediator of platelet aggregation with vasoconstricting properties Platelet activating factor: In myocardialischemia acts as proadhesive signalling molecule or via activation of leucocytes and platelets to release other mediators. In experimental anaphylaxis reproduces the electrical and mechanical effects observed in allergic reactions such as ST changes and arrhythmias acting either through the release of leukotrienes or as a direct vasoconstrictor
  12. 12. How Kounis syndrome is associated with stent and otherdevices thrombosis? Antigens are necessary and antigens are present not only throughout stenting process but also after implantation of devices containing nickel, polymers and other metals the Facts the evidence the mechanism
  13. 13. 3 THE FACTS: First generation Drug Eluting Stents components: 1.The metal itself is made from stainless steel which contains: nickel, chromium, manganese, titanium and molybdenum 2.The polymer coating 3.The antineoplastic Paclitaxel 3.The antiproliferative Rapamycin All these are strong allergens and constitute the “stent antigenic complex” Kounis NG, et al. J Am Coll Cardiol 2006; 48: 592
  14. 14. Hypersensitivity to Drug ElutingStents components and Kounis syndromeHypersensitivity reactions to nickel allergic contact dermatitis baboon syndrome (erythema in the buttocks and upper inner thighs resembling the red bottom of baboons) bronchial asthma dependent edema diffuse exanthema fever flexural dermatitis itching erythema pericarditis pompholyx formation rosacea sarcoid granuloma (delayed hypersensitivity) Kounis NG. Hahalis G, Theoharides TC. J Interven Cardiol 2007; 20: 314
  15. 15. Hypersensitivity to Drug Eluting stents components and Kounis syndrome Hypersensitivity reactions with the use of polymers and Latex -allergic conjunctivitis -allergic rhinitis -allergic allergic stomatitis -facial angioedema -generalized anaphylactic reaction -generalized urticaria -interstitial asthma -neurodermatitis -stomatitis venenadaKounis NG. Hahalis G, Theoharides TC. J Interven Cardiol 2007; 20: 314
  16. 16. Hypersensitivity to Drug Eluting Stents components and Kounis syndrome Hypersensitivity reactions with the use of paclitaxel -angioedema -atrioventricular block -bronchospasm -cutaneous flushing -diaphoresis -Kounis syndrome -left bundle branch block -ventricular tachycardia -urticariaKounis NG. Hahalis G, Theoharides TC. J Interven Cardiol 2007; 20: 314
  17. 17. Hypersensitivity to Drug Eluting Stents components and Kounis syndromeHypersensitivity reactions of Rapamycin -acrocyanosis -angioedema -flushing -pruritus -interstitial pneumonitis -Schonlein-Henoch purpura -localized eczematiform eruption -palpable purpura due to leucocytoplastic vasculitis -paradoxic coronary vasoconstriction Kounis NG. Hahalis G, Theoharides TC. J Interven Cardiol 2007; 20: 314
  18. 18. SECOND GENERATION STENTS: they are named cobalt-chromium stents (misleading term?)Xience(everolimus) stentThe information we have obtained fromthe manufacturer indicates that the alloycomposition of the Xience stent is 55%cobalt 20% chromium, 15% tungsten,10% nickel Min. MaxCarbon 0.05 0.15Manganese 1.00 2.00Silicon -- 0.40Phosphorus -- 0.040Sulfur -- 0.030Chromium 19.00 21.00Nickel 9.00 11.00Tungsten 14.00 16.00ron -- 3.00Cobalt* Balance Balance•
  19. 19. SECOND GENERATION STENTS: they are named cobalt-chromium stents (misleading term?)Xience Endeavor(everolimus) stent (zotarolimus) stentThe information we have obtained fromthe manufacturer indicates that the alloycomposition of the Xience stent is 55%cobalt 20% chromium, 15% tungsten,10% nickel Min. MaxCarbon 0.05 0.15Manganese 1.00 2.00Silicon -- 0.40Phosphorus -- 0.040Sulfur -- 0.030Chromium 19.00 21.00Nickel 9.00 11.00Tungsten 14.00 16.00ron -- 3.00Cobalt* Balance Balance•
  20. 20. 4. Clopidogrel-induced allergic skin rash
  21. 21. 4. Clopidogrel-induced allergic skin rash 5. Kounis NG, et al. “Myocardialinfarction after aspirin treatment,and the Kounis syndrome”. J R Soc Med 2005; 98: 296
  22. 22. 6. Atopic stented individuals areunder the risk of any additional drug or environmental exposure which may “join forces” with the previous 5agents and trigger the cascade of intrastent thrombosis
  23. 23. More than 5 antigens are irreversibly implanted and some of them apply continuous, persistent, chronic and repetitive allergic irritation! Allergic inflammation is initiated by allergens cross-bridging their corresponding, receptor- bound, immunoglobin IgE or IgG antibodies on “ IgE antibodies with different the surface of the mast cells or basophils. A total of 1000 bridges are necessary to trigger specificities can have an the cell out of maximal number of some 500 000 additive effect i.e. if mast cells -1 000 000 IgE molecules on the cell surface. It are sensitized with small, even might be possible to accumulate the critical number of bridges by more than one noncross- subthreshold numbers of IgE reactive allergen and its corresponding IgE antibody antibodies of different specificities they can “join forces” and trigger the cells to release its mediators,if the patient is simultaneously exposed to corresponding allergens” Nopp A, et al. Allergy 2006; 61: 1336MacGlashan DW, et al. J Immunol 1997; 158: 1438
  24. 24. Stents, like magnet, attract inflammatory cells!1. Stent thrombosis associated with allergic symptoms such as glottis edema, cold sweat, and tongue enlargement followed a flavonate-propyphenasone administration a week after stent implantation. Int J Cardiol. 2009; 134: e45-6.2. Acute myocardial infarction, in the stented area, coincided with allergic reaction following intravenous administration of the non-anionic contrast material iopromide during a routine excretory urography . Int J Cardiol 2010; 139: 206-9.3. Intrastent thromboses have also been reported following insect and larvae sting allergic reactions. Cases J. 2009; 2: 7800
  25. 25. Types of PFO and ASD ocluders containing nitinol ( nickel-titanium alloy)AMPLATZER® device - used for PFO repair GORE HELEX Septal Occluder - used for PFO repair
  26. 26. The generators are covered with titanium and the pacing leads are made from MP35N (an alloy of Ni, Co, Cr, and Mo)
  27. 27. Artificial heart valves: Parts aremade of Co-Cr-W-Ni alloy. Today nickel free-valves are available
  28. 28. The ASD and PFO closure device and Kounis syndrome symptoms and signsThe “Device syndrome” Eight out of 9 patients with proven, by skin tests, allergy to nickel developed a syndrome the 2nd and 3rd posroperative day after implantation a full nitinol Aplatzer occluder and low nitinol Premere closure system consisting of: -exertional dyspnea -palpitations -worsening of headache -asthenia -leukocytosis -atrial fibrillation (2 patients with negative skin patch testing but with occluder system implantation)Rigatelli G, et al. Congenit Heart Dis 2007;2:416–20
  29. 29. The ASD and PFO closure device and Kounis syndrome symptoms and signsThe “Device syndrome” The Kounis syndrome Eight out of 9 patients with proven, by skin tests, allergy to nickel • -Chest discomfort developed a syndrome the 2nd and • -Acute chest pain 3rd posroperative day after • -Dyspnea implantation a full nitinol Aplatzer • -Faintness occluder and low nitinol Premere • -Nausea • -Vomiting closure system consisting of: • -Syncope -exertional dyspnea • -Pruritus -palpitations • -Urticaria -worsening of headache • -Hypotention -asthenia • -Diaphoresis -leukocytosis • -Pallor • -Palpitations -atrial fibrillation (2 patients with • -Bradycardia negative skin patch testing but • -Tachycardia with occluder system implantation) Kounis NG, et al. Br J Clin Pract 1991;45:121–8Rigatelli G, et al. Congenit Heart Dis 2007;2:416–20
  30. 30. Kounis syndrome and intracardiac DevicesTHE EVIDENCE
  31. 31. -Localized Hypersensitivity and Late CoronaryThrombosis Secondary to a Sirolimus-Eluting Stent Should We Be Cautious?- Virmani et al. Circulation 2004; 109: 701 Focal strut malapposition with aneurysmal dilatation (double arrows in D and F) and occlusive luminal thrombosis E Extensive inflammation consisting primarily of eosinophils and lymphocytes, with a focal giant cell reaction around stent strut (*) and surrounding polymer. Marked inflammation is similarly present in intima, media, and adventitia in J (left box in E). K and L (Luna stains) show giant cells (arrowheads) around a polymer remnant that has separated from stent numerous strut and eosinophils within arterial wall
  32. 32. It has been stated that “eosinophilic infiltration of intrastent thrombus seems to be a common finding in stented patients and is not a peculiarity”Zavalloni D, et al. J Cardiovasc Med 2009;10: 942
  33. 33. Kounis syndrome and intracardiac device thrombosis THE MECHANISM
  34. 34. Platelets play a central role in pathogenesis of thrombosis
  35. 35. Stent thrombosis1. Platelet adhesion2. Platelet activation3. Platellet aggregation
  36. 36. LMW Heparin2.PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME Mast cell HIRUDIN Mast cell BIVALIRUDIN Eosinophil Triflusal Aspirin Ticagrelor TXA2 Clopidogrel Prasugrell thrombin Ticlopidin ADP (P2Y12) 2. ACTIVATION GP IIb/ IIIa receptors serotonin serotonin Pl changes from discoid to spiculated form Fibrinogen Degranulation epinephrine Mediators GP IIb/ IIIa inhibitors Adhesive (vWF, fibrinogen) ME 1. ADHESION Prothrombotic (V,XI, PAI-1) DA Proinflammatory (PDGF, PF4) Via interaction of Aggregatory (ADP, ATP, Ca, Mg) TO 3. AGGREGATION GP IIb/II/a and vWF RS
  37. 37. LMW Heparin2.PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME Mast cell HIRUDIN Mast cell BIVALIRUDIN Eosinophil Triflusal Aspirin PAF Ticagrelor TXA2 Clopidogrel Prasugrell thrombin Ticlopidin ADP (P2Y12) 2. ACTIVATION GP IIb/ IIIa receptors serotonin serotonin Pl changes from discoid to spiculated form Fibrinogen Degranulation epinephrine Mediators GP IIb/ IIIa inhibitors Adhesive (vWF, fibrinogen) ME 1. ADHESION Prothrombotic (V,XI, PAI-1) DA Proinflammatory (PDGF, PF4) Via interaction of Aggregatory (ADP, ATP, Ca, Mg) TO 3. AGGREGATION GP IIb/II/a and vWF RS
  38. 38. PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME LMW Heparin2. Mast cell Mast cell HIRUDIN BIVALIRUDIN Eosinophil Triflusal Aspirin PAF histamine Ticagrelor TXA2 Clopidogrel Prasugrell thrombin Ticlopidin ADP (P2Y12) 2. ACTIVATION GP IIb/ IIIa receptors serotonin serotonin Pl changes from discoid to spiculated form Fibrinogen Degranulation epinephrine Mediators GP IIb/ IIIa inhibitors Adhesive (vWF, fibrinogen) ME 1. ADHESION Prothrombotic (V,XI, PAI-1) DA Proinflammatory (PDGF, PF4) Via interaction of Aggregatory (ADP, ATP, Ca, Mg) TO 3. AGGREGATION GP IIb/II/a and vWF RS
  39. 39. PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME LMW Heparin2. Mast cell Mast cell HIRUDIN BIVALIRUDIN Eosinophil Triflusal Aspirin PAF histamine FCεRI-FCεRII Ticagrelor TXA2 Clopidogrel Prasugrell thrombin Ticlopidin ADP (P2Y12) 2. ACTIVATION GP IIb/ IIIa receptors serotonin serotonin Pl change from discoid to spiculated form Fibrinogen Degranulation epinephrine Mediators GP IIb/ IIIa inhibitors Adhesive (vWF, fibrinogen) ME 1. ADHESION Prothrombotic (V,XI, PAI-1) DA Proinflammatory (PDGF, PF4) Via interaction of Aggregatory (ADP, ATP, Ca, Mg) TO 3. AGGREGATION GP IIb/II/a and vWF RS
  40. 40. PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME LMW Heparin Mast cell HIRUDIN MAST CELL INHIBITORS Mast cell BIVALIRUDIN Eosinophil Triflusal Aspirin PAF histamine FCεRI-FCεRII Ticagrelor TXA2 Clopidogrel Prasugrell thrombin Ticlopidin ADP (P2Y12) 2. ACTIVATION GP IIb/ IIIa receptors serotonin serotonin Pl changes from discoid to spiculated form Fibrinogen Degranulation epinephrine Mediators GP IIb/ IIIa inhibitors Adhesive (vWF, fibrinogen) ME 1. ADHESION Prothrombotic (V,XI, PAI-1) DA Proinflammatory (PDGF, PF4) Via interaction of Aggregatory (ADP, ATP, Ca, Mg) TO 3. AGGREGATION GP IIb/II/a and vWF RS
  41. 41. Petrikova M, et al. H1 antihistamines and activated blood platelets. Inflammation Res 2006; 55 Suppl 1: S51-S52.Antihistamines Dithiaden, Loratadine and Bromadylinhibited platelet activation-aggregation in 3experimental systems: 1. Whole human blood from healthy male donors 2. Platelets in plasma 3. Isolated plateletsDespite their stimulation withadenosine-5`-diphosphate (ADP)It was thought that this action was on cytosolicphospholipase A2 at arachidonate cascade rather than atspecific histamine receptors (!)
  42. 42. In patients with cardiac pacemakers and defibrillators whodied: Thrombi were found at autopsy in 33% of ventricular and 48% on atrial leads Novak M, et al. Europace. 2009; 11: 1510-6
  43. 43. Thrombus after ASD and PFODevice closure Krumsdorf U, et al. JACC 2004;43; 302-9
  44. 44. Mid esophageal 2 (chamber view, 90 degrees). 95-1596Cardona L et al. Circulation 2011;124:1595-1596
  45. 45. Prevention of thrombosis
  46. 46. Fighting against stent thrombosis1.Taking careful history of adverse drug reactions and allergies2.Monitoring of inflammatory mediators after stent or device insertion3.Performing antibody and skin testing when and where appropriate4.Performing macrophage and T-cell activation studies5.Considering desensitization strategies6.Considering the use of mast cell stabilizers and steroidsKounis NG, et al. J Am Coll Cardiol 2006; 48: 592Kounis NG, et al N Engl J Med 2006; 354: 20767.Measuring of acute phase reactans8.Periprocedural antiinflammatory therapyGaspardone A, Versaci F. Am J Med 2005; 96: 65L
  47. 47. Fighting against stent thrombosis1.Taking careful history of adverse drug reactions and allergies2.Monitoring of inflammatory mediators after stent or device insertion3.Performing antibody and skin testing when and where appropriate4.Performing macrophage and T-cell activation studies5.Considering desensitization strategies6.Considering the use of mast cell stabilizers and steroidsKounis NG, et al. J Am Coll Cardiol 2006; 48: 592Kounis NG, et al N Engl J Med 2006; 354: 20767.Measuring of acute phase reactans8.Periprocedural antiinflammatory therapyGaspardone A, Versaci F. Am J Med 2005; 96: 65L
  48. 48. Fighting against stent thrombosis1.Taking careful history of adverse drug reactions and allergies2.Monitoring of inflammatory mediators after stent or device insertion3.Performing antibody and skin testing when and where appropriate4.Performing macrophage and T-cell activation studies Which means that allergic5.Considering desensitization strategies predisposition6.Considering the use of mast may help in prediction of cell stabilizers and steroids the risk for stentKounis NG, et al. J Am Coll Cardiol 2006; 48: 592Kounis NG, et al N Engl J Med 2006; 354: 2076 thrombosis7.Measuring of acute phase reactans8.Periprocedural antiinflammatory therapyGaspardone A, Versaci F. Am J Med 2005; 96: 65L
  49. 49. Future directions forstents and other devices
  50. 50. 1.Nickel free stainless steel with numberof blood platelets attached to and 316L stainless steel after dipping in fresh human blood plasma for 25 min and 3 hours Yang K, Ren Y. Sci Technol Adv Mater 2010; 11: 1-13
  51. 51. Nickel sensitization (patch test)in North-Eastern Italy(Belluno, Bolzano, Padova, Pordedone,Rovereto,Rovigo, Trento, Trieste)31.6% in women (9771)10.0% in men (4693)The overall prevalence 24.6%
  52. 52. Bioabsorbable Stents• …At 2 years after implantation the stent was bioabsorbed, had vasomotion restored, restenosis prevented and was clinically safe, suggesting freedom from late thrombosisSerruys PW, et al. Lancet; 2009; 373: 897
  53. 53. Bioabsorbable Stents• …At 2 years after implantation the • ..However, three stent was “mores” are bioabsorbed, had needed: more vasomotion patients, more restored, restenosis follow-up, and prevented and was more experience clinically safe, in complex suggesting freedom from late thrombosis lesions Colombo A, Sharp A. Lancet. 2009; 3 73:Serruys PW, et al. Lancet; 2009; 373: 897 869
  54. 54. 3. Bioabsorbable Stents: Aself expanding drug-eluting non allergic poly-lactic acid stent
  55. 55. Medronic’s Official safety informationContraindications WarningsThe Endeavor Sprint Zotarolimus- Please ensure that the inner Eluting Coronary Stent System is package has not been opened or contraindicated for use in: damaged, as this indicates the 1. Patients with a known sterile barrier has been breached. hypersensitivity to zotarolimus or The use of this product carries the structurally-related compounds. risks associated with coronary 2. Patients with a known artery stenting, including hypersensitivity to the cobalt- subacute thrombosis, vascular based alloy (cobalt, nickel, complications, and/or bleeding chromium, and molybdenum). events. 3. Patients with a known This product should not be used in hypersensitivity to patients who are not likely to Phosphorylcholine polymer or its comply with the individual Components and in recommended antiplatelet 4.patients with a known therapy hypersensitivity or allergies to aspirin, heparin, clopidogrel or ticlopidine
  56. 56. My euharisties to all of youΣας Εσταριστώ όλοσς σας Nicholas Kounis
  57. 57. Nickel: a ubiquitous metalNickel allergy is most commonly associated with earrings and other jewelry forbody piercings that contain some nickel. Common sources of nickel exposureinclude:Jewelry for body piercingsOther jewelry, including rings, bracelets, necklaces and jewelry claspsWatchbandsClothing fasteners, such as zippers, snaps and bra hooksBelt bucklesHairpinsEyeglass framesCoinsKitchen utensilsPaper clipsPensKeysTools, such as hammers and screwdriversDental fillingsArtificial body parts (prostheses), such as artificial heart valvesDrinking waterAlkaline batteriesCell phonesNickel is also found in some foods, such as oatmeal, chocolate, nuts, beans and driedfruit. Nickel may also be found in canned foods
  58. 58. Nickel allergy
  59. 59. People who are severely allergic to nickel as from earrings or belt buckles, can actually develop a rash from eating foods high in nickel. In particular, chronic hand dermatitis has been associated witheating foods high in nickel in patients with a known allergy. If you are allergic to nickel and have a chronic rash, especially of your hands, then consider a nickel-free diet. Try to avoid: -Chocolate -Potatoes -Salmon -Nuts and Legumes (beans, lentils) -Any canned food or canned fruit -Hot water from the tap -Anything acidic (like tomatoes) cooked in a stainless steel pan -Leafy green vegetables

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