1. Tricuspid Valve Disease & Endocarditis Department of Thoracic & Cardiovascular Surgery Seoul National University Hospital

2. Tricuspid Valve  Anatomy Normal tricuspid valve area ; 10.5 cm 2 Normal valve diameter ; 40 - 45 mm No actual tricuspid annulus ; attached to AV junction Tricuspid valve ring is related to the base of AV, membranous septum, CFB, RCA, CS, bundle of His

3. Tricuspid Valve View of tricuspid valve and surgical importance  Anatomy

4.  Pathophysiology The most common presentation of tricuspid regurgitation is secondary, functional rather than organic from mostly MS, MR or in isolated aortic valve disease As pulmonary hypertension develops leading to right ventricular dilation, tricuspid annulus will dilate The circumference of annulus lengthens primarily along the attachments of the anterior and posterior leaflets. The septal leaflets is fixed between the fibrous trigones, preventing lengthening. As the annular & ventricular dilation progresses, chordal papillary muscle complex becomes functionally shortened This combination prevents leaflet apposition, resulting in valvular incompetence Tricuspid Regurgitation

5. Tricuspid Valve Disease  Etiology Mostly secondary (functional) to valve pathology Eisenmenger’s syndrome Primary pulmonary hypertension Marfan syndrome and other myxomatous disease Blunt or penetrating chest trauma Dilated cardiomyopathy in the late stages Infectious endocarditis Carcinoid syndrome Rheumatic disease of the tricuspid valve is always associated with mitral valve

6. Functional Tricuspid Regurgitation Pathological process of tricuspid annular dilatation. Arrows designate the intercommissural distance that increases with dilatation and that is measured intraoperatively.  Process of annular dilatation

7. Functional Tricuspid Regurgitation  Prerequisite For the tricuspid valve to leak, the tricuspid annulus and hence the right ventricle has to be dilated In addition to tricuspid dilatation, three important factors determine whether TR occurs: the preload, afterload, and right ventricular function. This may explain why TR is difficult to accurately assess because these factors can interfere with regard to the severity of TR under different conditions.

8. Functional Tricuspid Regurgitation  Controversies Early investigators advocated a conservative approach, arguing that functional TR, often secondary to pulmonary hypertension and concomitant mitral valve disease, should spontaneously improve after mitral valve repair Subsequent studies, however, have demonstrated that TR does not necessarily regress after repair of left- sided valve lesions Uncorrected TR increases both postoperative morbidity and mortality and is associated with poor long-term results with medical management alone

9. Tricuspid Regurgitation  Clinical presentation Fatigue & weakness related to reduction of cardiac output Right heart failure lead to ascites, venous engorgement, hepatospenomegaly, pulsatile liver, pleural effusions & peripheral edema In late stage, cachexia, cyanosis, jaundice & AF is common

10. Tricuspid Regurgitation  Signs

11. Tricuspid Stenosis  Clinical presentation Most commonly rheumatic, rare isolated stenosis Fatigue & malaise related to reduction of CO As the right atrial pressure increases, venous congestion leads to distention of jugular veins, hepatomegaly, ascites, pleural effusion, & peripheral edema Anatomic features are similar to mitral stenosis with fusion and shortening of chordae & leaflet thickening The right atrial wall thickens and chamber dilates

12. Tricuspid Valve Disease  Indications for surgery Repair of tricuspid stenosis is indicated for class III-IV symptoms, including hepatic congestion, ascites, and peripheral edema that are refractory to medical treatment Repair of tricuspid regurgitation is indicated for severe symptoms or when moderate-to- severe functional TR is present at left-sided valve surgery. Repair is especially important if PVR is elevated.

13. Tricuspid Valve Repair Plicating the annulus along the posterior leaflet Flexible ring placed, ring can be above coronary sinus  Bicuspidalization

14.  Tricuspid valve annuloplasty Tricuspid Regurgitation

15. Modified DeVega annuloplasty  Tricuspid valve annuloplasty

16. Tricuspid Regurgitation Suture bicuspidization is performed by placement of a 2-0 pledget- supported Ethibond mattress suture from the anteroposterior to the posteroseptal commissures along the posterior annulus.  Tricuspid valve annuloplasty

17. Tricuspid Regurgitation Carpentier-Edwards ring annuloplasty  Tricuspid valve annuloplasty

18. Tricuspid Valve Annuloplasty  Cosgrove-Edwards System Annular sutures extend from the posteroseptal to the anteroseptal commissure and are placed through the polyester velour band of the annuloplasty system

19. Tricuspid Valve Annuloplasty A measured plication of the annulus adjacent to the anterior & posterior leaflets is achieved and the conduction system is not jeopardized.  Cosgrove-Edwards System

20. Traumatic Tricuspid Regurgitation Surgical steps of the clover technique  Clover technique

21.  Tricuspid valvuloplasty Partial Commissure Closure & Leaflet Cleft Repair Tricuspid Regurgitation

22.  Partial annuloplasty Tricuspid Regurgitation

23. Tricuspid Valvuloplasty  Edge-to-edge valve plasty A U-shaped 5-0 polypropylene stitch reinforced with small pericardial pledgets passes through the middle point of the free edges of the tricuspid leaflets. The anterior leaflet is anchored to the facing edges of posterior and septal leaflets to create a triple orifice tricuspid valve.

24.  Operative management Results be interpreted with early & late results of mitral & double valve procedures Indications ; NHYA functional class III & IV TV repair is preferable to valve replacement - Due to unfavorable complications of TVR (TE, thrombosis, anticoagulation problems) Tricuspid Valve Disease

25. Tricuspid Valve Annuloplasty  Risk factors for late failure Greater preoperative TR grade Preoperative TR without concomitant MR Higher postoperative PASP NYHA, preoperative PASP, preoperative RV dysfunction, recurrent MR were not significant risk factors.

26. Tricuspid Regurgitation  Results of operative treatment Clinical and surgical management of tricuspid valve disease have evolved from conservative approaches, that is, spontaneous regression after correction of left- sided lesions, to a more interventionist care. At present, it is well known that tricuspid regurgitation grades 3+ and 4+ that are not surgically corrected or that reappear after operation are prognostic factors of poor long-term outcome. Dysfunction after tricuspid valve repair requiring reoperation was associated with a high hospital mortality

27. Tricuspid Valve Replacement  Prosthetic valve choice The choice of prosthesis follows the algorithm similar to that used for valve replacement in other cardiac valve positions ( demonstrating equality ) The patient’s age, anticoagulation considerations in women and social issues must be considered Degenerative changes were less for bioprosthesis in the tricuspid position than in the mitral, however, thrombus and pannus formation were more frequent in the tricuspid position Prostheses with more than 27mm internal diameter do not have clinically significant gradient Recommend a mechanical valve to young patients who do not have a contraindication to anticoagulation

28. Tricuspid Valve Replacement  Mitral homograft

29. Prosthetic Valve Endocarditis

30. Infective Endocarditis  Introduction Rates of infective endocarditis in the general population have remained relatively constant and are estimated to be 5.0 to 7.0 cases per 100,000 person- years in the United States Contemporary causes of infective endocarditis include intravenous drug use (IVDU), use of prosthetic valves, sclerotic disease in the elderly, and nosocomial infection Although high mortality remains associated with infective endocarditis, surgical treatment has greatly increased survival versus antibiotic treatment alone Early aggressive surgical intervention is often indicated to optimize surgical results

31. Infective Endocarditis  Development Endocarditis usually develops in individauls with underlying structural cardiac defects who develop bacteremia with organisms likely to cause endocarditis Surgical and dental procedures and instrumentations involving mucosal surfaces or contaminated tissue cause transient bacteremia that rarely persists for more than 15 minutes Bacteremia may lodge on damaged or abnormal heart valves or on the endocardium or the endothelium near anatomic defects, resulting in bacterial endocarditis or endarteritis. Although bacteremia is common following many invasive procedures, only certain bacteria commonly cause endocarditis

32. Active Infective Endocarditis  Introduction Depending on how promptly the disease is diagnosed and appropriate antibiotics are started, on the virulence of the microorganism, and on whether the infected valve is native or prosthetic, surgery may become indispensable to save the patient’s life and eradicate the infection Staphylococcus aureus was the most common microorganism, & less virulent streptococcus viridans, always respond to antibiotics alone is erroneous, because these bacteria can cause extensive damage to a heart valve and surrounding tissues if inadequately treated

33. Infective Endocarditis Modified Duke Criteria [Major criteria] Blood culture positive for IE (A) Typical microorganisms consistent with IE from 2 separate blood cultures: (1) Viridans streptococci, Streptococcus bovis, HACEK group, staphtlococcu aureus; or (2) Community-acquired enterococci, in the absence of a primary focus (B) Microorganisms consistent with IE from persistently positive blood cultures, defined as follows; (1) At least 2 positive cultures of blood samples drawn 12h apart; or (2) All of 3 or a majority of ＞ 4 separate cultures of blood (with first and last sample drawn at least 1h apart) (C) Single positive blood culture for Coxiella burnetii or antiphase I IgG antibody titer e ＞ 1:800 Evidence of endocardial involvement (A) Echocaridiogram positive for IE (TEE recommended in patients with prosthetic valves, rated at least “possible IE” by clinical criteria, or complicated IE [paravalvular abscess]; TEE as first test in other patients), defined as follows; (1) Oscillating intracardiac mass on valve of an alternative anatomic explanation; or (2) Abscess; or (3) New vavular regurgitation (worsening or changing of pre-existing murmur not sufficient) [Minor criteria] (A) Predisposition: predisposing heart condition or injection drug use (B) Fever: temperature ＞ 38 ℃ (C) Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway’s lesions (D) Immunologic phenomena: glomerulonephritis, Osle’s nodes, Roth’s spot, and rheumatoid factor (E) Microbiological evidence: positive blood culture but does not meet a major criterion as noted above or serological evdence of active infection with organism consistent with IE

34. Infective Endocarditis Modified Duke Criteria (Diagnosis) Definite infective endocarditis Pathologic criteria (1) Microorganisms demonstrated by culture or histologic examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen; or (2) Pathologic lesions; begetation or intracardiac abscess confirmed by histologic examination showing active endocarditis Clincal criteria (1) 2 major criteria; or (2) 1 major criterion and 3 minor criteria; or (3) 5 minor criteria Possible infective endocarditis (1) 1 major criterion and 1 minor criterion; or (2) 3 minor criteria Rejected (1) Firm alternate diagnosis explaning evidence of infective endocarditis; or (2) Resolution of infective endocarditis syndrome with antibiotic therapy for ＜ 4 days; or (3) No pathologic evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for ＜ 4 days; or (4) Dose not meet criteria for possible infective endocarditis, as above

35. Infective Endocarditis  Situations of high complication Prosthetic cardiac valves Left-sided infective endocarditis Fungal infective endocarditis Previous infective endocarditis Prolonged clinical symptoms(>3 months) Cyanotic congenital heart disease Patients with systemic to pulmonary shunt Poor clinical response to antimicrobial therapy

36. Infective Endocarditis  Need for surgical intervention  Vegetation Persistent vegetation after systemic embolization Increase in vegetation size after 4 weeks of antimicrobial therapy  Valvar dysfunction Acute aortic or mitral regurgitation with ventricular dilatation Heart failure unresponsive to medical therapy Valve perforation or rupture  Perivalvar extension Valvar dehiscence, rupture, or fistula New heart block Large abscess or extension of abscess despite appropriate antibiotic therapy

37. Prosthetic Valve Endocarditis Early Late Onset 60 days Organism Staphylococci; Streptococci; S.epidermidis,aureus. S.viridans, Gr D. Gr(-) organisms. Staphylococci. Fungi, Diphteroids. Fungi, Diphteroids Streptococci. * Risk of PVE: greatest at 5wks following valve implantation

38. Prosthetic Valve Endocarditis  Pathology Mechanical valve; Sewing ring, valve ring abscess, valve dehiscence, paravalvular leak Tissue valve; Valve leaflets –greater success of antibiotic therapy

39.  Paraannular ring abscess Infective Endocarditis

40.  Causes of negative blood cultures Rt-sided endocarditis Bacteria free-stage: very “chronic” SBE Uremia Poor bacteriologic sampling techniques Fastidious organisms needing special growth requirements Prior administration of antibiotics Nonbacterial causes of endocarditis

41. Native Valve Endocarditis  Surgical indications Presence of moderate-to-severe CHF Persistent sepsis Evidence of local extension producing annular or myocardial abscesses, conduction disturbance, or intracardiac fistula Systemic embolization Enlarging vegetations, threatened embolization

42. Infective Endocarditis  Surgical indications Progressive heart failure Significant heart failure: fails to improve Major embolism, large vegetation ( >1cm ) Persistent bacteremia despite antibiotics Fungal endocarditis Patients with intravascular devices Heart block PV dehiscence or obstruction Relapse

43. Infective Endocarditis  Tricuspid valve lesion Increasing due to rising incidence of IV drug abuse Surgical treatment is necessary when continued sepsis, moderate to severe HF, multiple pulmonary emboli(+) Intensive medical Tx, valvectomy, valve replacement; aggressive counseling should be offered due to high incidence of recidivism

44. Endocarditis Prophylaxis  Cardiac conditions  High-risk category Prosthetic cardiac valves, including bioprosthetic and homograft valves Previous bacterial endocarditis Complex cyanotic congenital heart disease Surgical systemic pulmonary shunt or conduits  Moderate-risk category Most other congenital cardiac malformations Acquired valvar dysfunction Hypertrophic cardiomyopathy Mitral valve prolapse with valve regurgitation and/or thickened leaflets

45. Endocarditis Prophylaxis  Cardiac conditions  Negative-risk category (not greater than general) Isolated secundum ASD Surgical repair of ASD, VSD, or PDA ( without residua beyond 6 months ) Previous coronary artery bypass graft surgery Mitral valve prolapse without regurgitation Physiologic, functional, or innocent heart murmur Previous Kawasaki disease without valve dysfunction Previous rheumatic fever without valvar dysfunction Cardiac pacemakers( intravenous and epicardial ) and implanted defibrillators

46.  Prophylactic regimens for procedures Situation Agent Regimen Srandard general Amoxicillin Adult; 2.0g orally 1 hour before procedure Child; 50mg/kg orally Unable to oral intake Ampicillin Adult; 2.0g IM or IV, 30 m before procedures Child; 50mg/kg 30 min. before Allergic to penicillin Clindamycin Adult; 600mg, Child; 20mg/kg 1 h before Cephalexin Adult; 2g, Child; 50mg/kg 1 h before Azithromycin Adult; 500mg, Child; 15mg/kg 1 h before or Clarithromycin Allergic & unable to Clindamycin or Oral intake Cefazolin Adult; 1g, Child; 25mg/kg 30 min. before procedure Infective Endocarditis

47. Bioprosthetic Mechanical Durability less more Bleeding Cx. less more Thromboemboism less more Rheology   Indication pregnant woman most pts, old age Focus(BE) leaflet sewing ring Prosthetic Heart Valve

48. Prosthetic Valve Endocarditis Tissue ValveMechanical Valve  Gross findings

49. Redo Cardiac Valve Operation  Considerations Careful preoperative study Chest lateral, Chest CT, Cardiac catheterization & angiography Femoral dissection Blood-saving procedure Autotransfusion, cell saver, aprotinin Automatic implantable cardioverter defibrillator Tissue valve(cusp tear) > mechanical valve(TE, SBE)

50. Infective Endocarditis  Management in septic shock Nitric oxide has been implicated in these derangements. Exposure to endotoxin and cytokines can trigger a de novo synthesis of the inducible, calcium-dependent isoform of nitric oxide synthase. Methylene blue inhibits this process by decreasing intracellular cyclic guanosine monophosphate concentrations through guanylate cyclase inhibition, thus blocking its vasodilator properties. Methylene blue increases arterial pressure, systemic vascular resistance, and left ventricular stroke work but does not increase cardiac output, oxygen delivery, or oxygen consumption. 4

51. Infective Endocarditis  Indications for surgery Infective endocarditis have continued to evolve, but frequently include new severe valvular regurgitation, intractable heart failure, abscess formation, conduction abnormalities, recurrent embolic events, organism involved(fungal endocarditis), and presence of prosthetic material While mortality has improved from 30% to 15% over the past two decades, it remains substantial

52. Infective Endocarditis  Echocardiographic diagnosis Three echocardiographic findings are considered to be major criteria for the diagnosis of endocarditis: (1) presence of vegetations defined as mobile echodense masses implanted in a valve or mural endocardium; (2) presence of abscess; or (3) presence of a new dehiscence of a valvular prosthesis With the development of TEE imaging, the noninvasive detection of vegetations has substantially improved

53. Infective Endocarditis  Causes of operative deaths Often multifactorial, but the main reasons were multiorgan failure, low cardiac output syndrome, intractable sepsis, coagulopathy, technical errors, stroke, pulmonary embolism, acute myocardial infarction, ruptured aortic root, valve dehiscence, retroperitoneal bleeding, and right ventricular failure The predictors of operative mortality includes preoperative shock, prosthetic valve endocarditis, S aureus, and paravalvular abscess.

54. Infective Endocarditis  Results of operative treatment Surgery for endocarditis continues to be challenging & associated with high operative mortality & morbidity Age, shock, prosthetic valve endocarditis, impaired ventricular function, and recurrent infections adversely affect long-term survival Long-term survival is satisfactory, particularly for patients with native valve endocarditis & differences between native and prosthetic valve endocarditis are likely multifactorial and include higher operative mortality, more complex operations, and such patient variables as older age and worse ventricular function

55. Anticoagulation

56. 1. Mechanical valves: All patients should be anticoagulated with coumadin. In addition, all patients would receive aspirin and persantine. Persantine is discontinued after 3 months. 2. Porcine or bovine valves: a) Aortic valve replacement: Aspirin and persantine starting on the 5th postoperative day for 3 months. No anticoagulants per se need be given. b) Mitral and tricuspid valve replacement: ⅰ ) Children with chronic atrial fibrillation or proven intra-atrial clot should be anticoagulated with coumadin, sapirin and persantine permanently. ⅱ ) Patients in sinus rhythm should be anticoagulated with coumadin, aspirin, and persantine for a period of 3 months. All drugs to be discontinued at 3 months. c) Pulmonary valve replacement: No anticoagulants are required. ASA is recommended indefinitely. 3. Homograft pulmonary or aortic valve: No anticoagulants are required. ASA is recommended indefinitely.  Policy for prostheisis

57. Anticoagulation  Protocol for children British Columbia children’s Hospital Policy 1. Mechanical valve: All patients with mechanical valve on the left side of the circulation should be anticoagulated with coumadin for three months. Coumadin is discontinued after three months and replaced by ASA(10 ㎎ / ㎏ per day) plus persantine (3 ㎎ / ㎏ /day) indefinitely. Patients in atrial fibrillation or with a history of thromboembolism require life time anticoagulation (coumadin). Patient is then fully anticoagulated with coumadin when 18 years of age. 2. Porcine or bovine valves: All patients require coumadin for three months. Coumadin is discontinued after 3 months and replaced by ASA(10 ㎎ / ㎏ per day) and persantine (3 ㎎ / ㎏ /day). 3. Homograft valve replacement: all patients require ASA(10 ㎎ / ㎏ per day). N.B. no heparin is given postoperatively as coumadin is started after 48 hours (per mouth or Nasogastric tube). Prothrombin time is to be kept between 1-¹/ ₂ to 2 times normal (15-20second)

58. Anticoagulation  Prothrombin time & INR Determine by % INR(international normalized ratio) Mechanical vs. bioprostheis Cardiac rhythm ; atrial fibrillation Location of valve; aortic, mitral, tricuspid Age ; old or young

59.  Prothrombin time & INR Anticoagulation

60.  Drug interaction with warfarin Potentiation Inhibition No Effect Acetaminophen Azathioprine Alcohol (if no liver D.) Alcohol(if liver D.) Barbiturates Antacids Amiodarone Carbamazepine Atenolol Chloral hydrate Chlordiazepoxide Bumetanide Cefazolin Cholestyramine Diltiazem Cimetidine Cyclosporine Famotidine Clofibrate Narcillin Ibuprofen Erythromycin Sucralfate Ketorolac Floxin antibiotics Ketoconazole Fluconazole Metoprolol Isoniazid Nizatidine Lovastatin Ranitidine Metronidazole Vancomycin Omeprazole Phenylbutazone Phenytoin Propranolol Quinidine Tamoxifen Anticoagulation

61. Mechanical Valve Implantation  Pathogenesis of thromboembolism The pathogenesis is a complex phenomenon, occurring through an interaction of a of prosthesis-related and patient-related factors Damaged perivalvular tissue and deposition of fibrinogen on the valve surface activate platelets as soon as blood starts flowing across the valve and this leads to immediate platelet adhesion and aggregation, and within 24 hours after surgery, platelet deposition on the Dacron sewing ring can be imaged radiographically Coagulation factors are also directly activated after valve implantation, leading to further clot formation as a result of the inherent thrombogenicity of the prosthetic material and sites of denuded tissue (valve excision site) Transprosthetic turbulent flow leads to regional increases in shear stress, structurally damaging the endocardium, causing a loss of local resistance to thrombosis.

62. Mechanical Valve Implantation  Thromboembolic mechanism Strong risk factor for thromboembolic complications, especially in the first three to six months after surgery First, the pathologic sequelae of the patients' inherent valvular disease (atrial fibrillation, dilated left atrium, and dilated left ventricle) may predispose to areas of stasis and thrombus formation Second, the increased thromboembolic risk early reflect incomplete endothelial proliferation on the raw intracardiac surfaces, sewing ring, and suture knots in the initial postoperative period Early thromboembolic risk can also be attributed to inconsistencies of oral anticoagulation management. During the first six months, the thromboembolic risk is up to seven times greater than in the after months and years.

63. Mechanical Valve Implantation  Early thromboembolic risk The early thromboembolic risk associated with the placement of a mechanical prosthesis depends on the complex interactions between the recipient and valve, the intrinsic thrombogenic properties of the mechanical valve components, and the diligent management of postoperative anticoagulation. Variable or inadequate anticoagulation, defined as an INR 25% or more below the therapeutic range, has been demonstrated to increase the incidence of thromboembolism 2 to 6 times, especially in the postoperative period

64. Mechanical Valve Implantation  Anticoagulation therapy In patients not receiving anticoagulation therapy, the average rate of major thromboembolism is estimated to be 4 to 8 per 100 patient-years and this risk is reduced to 2.2 per 100 patient-years with antiplatelet therapy, and further reduced to 1 per 100 patient-years with oral warfarin Recommended, in their most recent guidelines, that contemporary mechanical valves in the aortic position be anticoagulated with a target INR of 2.0 to 3.0, and mechanical valves in the mitral position be anticoagulated with a target INR of 2.5 to 3.5 [.

65. Mechanical Valve Implantation  Antiplatelet therapy In the absence of anticoagulation, antiplatelet therapy seems to be insufficient to prevent thrombi. Because platelet aggregation occurs despite anticoagulation, the co-administration of antiplatelet agents with anticoagulation has been advocated to reduce the frequency of thromboembolic complications Recommended that the addition of aspirin (80 to 100 mg/day) to warfarin be strongly considered for all patients with mechanical valves, for patients who have had an embolus while on warfarin therapy, those with vascular disease, or those with hypercoagulability

66. Mechanical Valve Implantation  Early anticoagulation strategies The three common early postoperative anticoagulation strategies (1) oral warfarin starting on postoperative day one, without the use of therapeutic heparin anticoagulation; (2) intravenous unfractionated heparin beginning in the early hours after surgery, oral warfarin starting on postoperative day one, and the continuation of heparin until a therapeutic INR has been achieved; (3) low molecular weight heparin (LMWH) beginning in the early hours after surgery, oral warfarin starting on postoperative day one, and the continuation of LMWH until a therapeutic INR has been

67. Mechanical Valve Implantation  Strategies Oral warfarin alone Aanticoagulation with oral warfarin alone has been advocated as the safest regimen Intravenous unfractionated heparin and oral warfarin Because the risk of thromboembolism is greatest in the early postoperative period (within 24 hours), with oral anticoagulation starting on the first postoperative day 3. Low molecular weight heparin and oral warfarin Better safety profile with less thrombocytopenias, less bleeding, a more predictable and rapidly reached anticoagulant effect, the possibility of self-administration without laboratory monitoring, and shorter hospital stays

68. Anticoagulation  Thromboembolic level (TEL) TEL 1; Presence of nonobstructive thrombus in the vicinity of the prosthetic valve as identified by clinical imaging (echocardiography); TEL 2; Documented evidence of peripheral limb and visceral embolization (solid organs, coronary thrombus); TEL 3; Documented evidence of central nervous system embolization (transient ischemic attack or cerebrovascular accident); TEL 4; Prosthesis thrombosis requiring thrombolysis or emergency surgery; TEL 5; A fatal thromboembolism.

69. Anticoagulation  Bleeding level (BL) BL 1; Mild bleeding such as recurrent epistaxis or periodontal bleeding (more than two events) and gastrointestinal bleeds not requiring hospitalization or transfusions; BL 2; Documented large pericardial effusion (>1 cm thickness on echocardiography); BL 3; G-I bleeding requiring hospitalization, transfusion, endoscopic intervention or surgery; BL 4; Documented cardiac tamponade requiring intervention; BL 5; Documented CNS hemorrhage BL 6; Fatal bleeding.

70. Anticoagulation  Tissue valved conduit replacement Small patients with a greater mismatch between conduit size and normal valve size, prophylactic anticoagulation is recommended. Due to the initially good overall performance, the Contegra bovine jugular vein conduit has become our preferred device for RVOT reconstruction. Anticoagulated with heparin during their hospital stay followed by aspirin (10 mg/d) after discharge until they gain a weight of 5 to 6 kg. Since the introduction of this regimen we have not observed any other case of conduit valve thrombosis

71. Anticoagulation  Systemic-pulmonary shunt PTFE conduit in Fontan patient received warfarin for 6-12 months for anticoagulation to maintain an INR between 2.5 and 3.0. In addition, they were administered aspirin (5 mg/kg per day), which was continued indefinitely. Trend in recent years toward using smaller shunts has contributed to a decrease in perioperative mortality due to excessive pulmonary blood flow but perhaps also to an increase in the incidence of shunt thrombosis Shunt size is made more difficult by variations in technique such as the location of the proximal end of the shunt and its length

72. Anticoagulation  Tissue valve implantation Warfarin was given to patients in sinus rhythm for the first 3 months postoperatively, then aspirin at a dose of 150 mg. Keep on warfarin in patients in chronic atrial fibrillation and maintain the INR between 2.5 and 3.5. Aanticoagulate our patients with tissue valves for the first 3 months postoperatively because the thromboembolic risk outweighs the risk of bleeding in this group of patients Thromboembolic rates in patients with aortic pericardial valves parallel those observed in patients with aortic porcine valves

73. Ideal Anticoagulation  Factors of clinical situations Valve replacement MVR, AVR, DVR, TVR Mechanical vs. tissue Bentall operation Mitral ring annuloplasty Graft replacement of large vein Pulmonary embolism, deep vein thrombosis Atrial fibrillation, LA thrombi

74. Ideal Anticoagulation  Ideal levels of INR Mitral valve replacement( 2.5 to 3.5 INR ) Aortic valve replacement(2.0 to 3.0 INR) Tricuspid valve replacement Pulmonary valve replacement Annuloplasty rings Extracardiac conduit Fontan operation Prosthetic angioplasties

75. Anticoagulation  Choice of prosthesis The incidence of anticoagulation-related complications such as bleeding and thromboembolic events increase sharply with advanced age Oral anticoagulation is required lifelong, some may argue that implantation of bioprostheses should be preferred instead of mechanical prostheses in order to reduce the risk of anticoagulation-related complications with advanced age

76. Postoperative Blood Loss  Factors Prior intake of antiplatelet drugs Endothelial response to cardiopulmonary bypass Systemic inflammatory response Systemic hypothermia Heparin excess and heparin rebound Platelet dysfunction and fibrinolysis Type of operation, reoperation, duration of CPB Presurgical anticoagulation status

77. Hemostasis  Physiology Vascular function, which consists of three discrete layers; intima, media, and adventitia. The intima comsists of a monolayer of nonthrombogenic endothelial cells and an internal elastic membrane. The media consists of smooth muscle cells and the adventitia, external elastic lamina and membrane and supportive connective tissues. The platelets, which must be normal in both number and function The plasma protein, which include procoagulants, anticoagulants, and fibrinolytic proteins

78. Anticoagulants  Warfarin Interfere with vitamin K –mediated formation of clotting factors, including prothrombin as well as factor II, VII, IX and X, ; warfarin may also block the release of prothrombin from the liver The absorption of vitamin K, as well as warfarin, is influenced by bile salts, dietary fat and in addition, affected by gastrointestinal tract transit time and intrinsic hepatic function and oral antibiotics that alter the gut flora The maximam teratogenic action occurs between 6 and 9 weeks of pregnancy(oral anticoagulants cross the placenta and produces fetal abnormality)

79. Anticoagulants  Warfarin Action; interfere with hepatic synthesis of vitamin K – dependent coagulation factors(II, VII, IX,X) Stability; protect from light in IV form(inject over 1-2 minutes) Dose adjustment in hepatic disease Dietary consideration; foods in high vitamin K inhibit anticoagulant effect Contraindications; hypersensitivity to warfarin or any components of formulation of bleeding tendency Adverse reaction; bleeding is major and others nonspecific & some allergic

80. Warfarin  Pharmacokinetics Onset of action; anticoagulation effect from oral 36-72 hours, peak therapeutic effect 5-7 days, INR increase in 36-72 hours, IV administer as a slow bolus injection 2-5mg/day Absorption; rapid, oral Stability; protect from light in IV form(inject over 1-2 minutes) Duration; 2-5 days Metabolism; hepatic Half life elimination; 20-60 hours

81. Aspirin  Pharmacokinetics Mechanism of action;Inhibits prostaglandin synthesis, acts on the hypothalamus heat-regulating center to reduce fever, blocks prostaglandin synthetase action which prevents formation of the platelet-aggregating substance thromboxane A2 Duration; 4-6 hours, rapid absorption, & rapid dstribution and cross the the placenta and enter fetal circulation and also enters breast milk Metabolism; hydrolyzed to salycylate(active) by esterase in GI mucosa, RBC, blood; primarily by hepartic conjugation; metabolic pathways are saturable

82. Aspirin  Actions  Mechanism Aspirin inhibits platelet aggregation by irreversible inhibition of platelet cyclooxygenase and thus inhibits the generation of thromboxane A2  Child dose Antiinflammatory, 60-80mg/day/Kg in every 4-6 hours Antiplatelet effects; 3-5mg/Kg– 5-10mg/Kg in single dose Mechanical prosthetic valve 6-20mg/Kg in single dose  Adult dose 75-325mg/day in CABG, 80-325mg/day in PTCA, 160- 325mg in stent, 30-325mg/day to prevent stroke(upto 1300mg)