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123 coronary dialsysis

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Publicada em: Saúde e medicina
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123 coronary dialsysis

  1. 1. Hossein Eftekhari, MDHossein Eftekhari, MD Morteza Naghavi, MDMorteza Naghavi, MD
  2. 2. Cardiac Dialysis SystemCardiac Dialysis System  Atherosclerosis and its consequencesAtherosclerosis and its consequences  Atherosclerosis and inflammationAtherosclerosis and inflammation  Inflammatory markersInflammatory markers  Designed Cardiac Dialysis SystemDesigned Cardiac Dialysis System
  3. 3. Atherosclerotic cardiovascular diseases is the leading cause of mortality with over 6.3 million deaths worldwide. Every year about 1.5 million people in the United States have heart attacks and more than half of them die.
  4. 4. Mechanisms involved inMechanisms involved in atherosclerosis:atherosclerosis: Lipoprotein pathwayLipoprotein pathway Injury to the vessel wallInjury to the vessel wall Response to injury includingResponse to injury including inflammatory and immune systeminflammatory and immune system
  5. 5. Atherosclerosis and its consequencesAtherosclerosis and its consequences ((plaque ruptureplaque rupture andand thrombosisthrombosis) are) are the leading cause of morbidity andthe leading cause of morbidity and mortality in the US and othermortality in the US and other industrialized countriesindustrialized countries
  7. 7. Some of the characteristics ofSome of the characteristics of atherosclerosisatherosclerosis  Inflammatory diseaseInflammatory disease  Slowly progressive diseaseSlowly progressive disease  Diffuse disease (multi organ involvement)Diffuse disease (multi organ involvement)
  8. 8. Coronary Vulnerable Plaque Killer #1 So, the more specific diagnostic and therapeutic method the more effective
  9. 9. Proposed Histopathological andProposed Histopathological and Clinical Criteria for Definition ofClinical Criteria for Definition of Vulnerable PlaqueVulnerable Plaque •• MajorMajor Criteria:Criteria: • Active Inflammation (monocyte/Active Inflammation (monocyte/ macrophage infiltration)macrophage infiltration) • Thin Cap with Large Lipid CoreThin Cap with Large Lipid Core • Endothelial Denudation with SuperficialEndothelial Denudation with Superficial Platelet AggregationPlatelet Aggregation • Fissured / Wounded PlaqueFissured / Wounded Plaque
  10. 10. Proposed Histopathological andProposed Histopathological and Clinical Criteria for Definition ofClinical Criteria for Definition of Vulnerable PlaqueVulnerable Plaque •• MinorMinor Criteria:Criteria: • Superficial Calcified noduleSuperficial Calcified nodule • Glistening YellowGlistening Yellow • Intraplaque HemorrhageIntraplaque Hemorrhage • Critical StenosisCritical Stenosis • Positive Remodeling?Positive Remodeling?
  11. 11. Major modes of plaqueMajor modes of plaque disruption:disruption: **TheThe rupturerupture (fracture) of the(fracture) of the plaque’s fibrous cap accounting forplaque’s fibrous cap accounting for some two thirds of ACSsome two thirds of ACS **The second mode involves aThe second mode involves a superficial erosionsuperficial erosion of the intimaof the intima
  12. 12. Blood FactorBlood Factor  Antithrombin III deficiencyAntithrombin III deficiency  Protein C or S deficiencyProtein C or S deficiency  Resistance to activated protein C (factor VResistance to activated protein C (factor V Leiden)Leiden)  Antiphospholipid syndromeAntiphospholipid syndrome  Nephrotic syndromeNephrotic syndrome  Platelet polymorphismsPlatelet polymorphisms
  13. 13. Myocardial FactorMyocardial Factor  Different cardiomyopathiesDifferent cardiomyopathies  Valvular diseaseValvular disease  Primary electric disturbancesPrimary electric disturbances  Chest traumaChest trauma  Anomalous origin of coronary arteriesAnomalous origin of coronary arteries  MyocarditisMyocarditis  Myocardial bridgingMyocardial bridging
  14. 14. Plaque stabilization strategiesPlaque stabilization strategies  StatinsStatins  Anti-inflammatory agentsAnti-inflammatory agents  ACE inhibitorACE inhibitor  HDLHDL  Coated stentsCoated stents  Gene therapyGene therapy  Thermal stabilizationThermal stabilization
  15. 15. statinsstatins  StatinStatin therapy reduces the risk of majortherapy reduces the risk of major coronary events by 31%coronary events by 31%  Patients intolerancePatients intolerance  Systemic side effectsSystemic side effects
  16. 16. Stent limitationStent limitation  Re-stenosisRe-stenosis  Inaccessibility of lesions (more than 50%)Inaccessibility of lesions (more than 50%)  More than one stent may be neededMore than one stent may be needed  High costHigh cost
  17. 17. Based on Biochemical and EpidemiologicalBased on Biochemical and Epidemiological evidencesevidences Atherosclerosis is an inflammatory diseaseAtherosclerosis is an inflammatory disease
  18. 18. Although Acute phase reactantAlthough Acute phase reactant such assuch as CRPCRP is non-specific but itis non-specific but it is very sensitive marker ofis very sensitive marker of inflammationinflammation
  19. 19. Prospective studies haveProspective studies have consistently demonstrated aconsistently demonstrated a positive association between hs-positive association between hs- CRPCRP and the future coronary eventsand the future coronary events
  20. 20. Each standard deviation increase in hs-Each standard deviation increase in hs- CRPCRP was associated with a 45%was associated with a 45% increase in the relative risk of nonfatalincrease in the relative risk of nonfatal MI or cardiac deathMI or cardiac death
  21. 21. CRPCRP is not only an epiphenomenonis not only an epiphenomenon A casual relationship has beenA casual relationship has been suggested betweensuggested between CRPCRP andand inflammatory reaction in the vesselinflammatory reaction in the vessel wallwall
  22. 22. Inflammatory roles ofInflammatory roles of CRPCRP Activation of complement pathwayActivation of complement pathway Enhancement of thrombosisEnhancement of thrombosis Enhancement of tissue injuryEnhancement of tissue injury Chemotactic for monocytesChemotactic for monocytes Facilitation uptake of LDL by MACFacilitation uptake of LDL by MAC Induction of adhesion moleculesInduction of adhesion molecules Impairment endothelial functionImpairment endothelial function
  23. 23. Potential preventive therapies forPotential preventive therapies for high CRP-levelhigh CRP-level Although no specific therapies have beenAlthough no specific therapies have been developed to decreasedeveloped to decrease hs-CRPhs-CRP **************************************** ButBut AspirinAspirin andand statinsstatins are effective inare effective in decreasing the incidence of future coronarydecreasing the incidence of future coronary events in those with highevents in those with high CRPCRP
  24. 24. CRPCRP level can be modified bylevel can be modified by statins, which reflects the antistatins, which reflects the anti inflammatory effect by 18%inflammatory effect by 18% reduction of plasmareduction of plasma CRPCRP
  25. 25. These findings suggest:These findings suggest:  Statins also may has anti-inflammatoryStatins also may has anti-inflammatory characteristics in addition to its anti-hypercharacteristics in addition to its anti-hyper lipidemic potentiallipidemic potential  Aspirin is not only anti platelet agent but alsoAspirin is not only anti platelet agent but also is an anti-inflammatoryis an anti-inflammatory
  26. 26. StatinStatin therapy reduces the risk oftherapy reduces the risk of major coronary events bymajor coronary events by 31%,all cause mortality by 21%31%,all cause mortality by 21%
  27. 27. Focusing primarily on LDL-CFocusing primarily on LDL-C lowering revealed only 20% to 40%lowering revealed only 20% to 40% relative risk reduction in CV mortalityrelative risk reduction in CV mortality so there should be other potentialso there should be other potential reasons for CV events.reasons for CV events.
  28. 28. NO standard treatment has been established forNO standard treatment has been established for patient who continues to maintain LDL-c levelpatient who continues to maintain LDL-c level in excess of 160 mg/dl after diet and drugin excess of 160 mg/dl after diet and drug therapy.therapy. To date therapy has consisted of a variety ofTo date therapy has consisted of a variety of measures including combination drug therapy,measures including combination drug therapy, plasmapheresis, and partial ileal by pass andplasmapheresis, and partial ileal by pass and even liver transplantation.even liver transplantation.
  29. 29. NOW!NOW! It is the time of developing,It is the time of developing, implementing, and clinical trials ofimplementing, and clinical trials of new frontier anti -atherogenic policynew frontier anti -atherogenic policy
  30. 30. TheThe LDL aphaeresisLDL aphaeresis waswas developed to provide therapy fordeveloped to provide therapy for patients who fail to responds topatients who fail to responds to provided therapy especially whenprovided therapy especially when patients who have existing CADpatients who have existing CAD
  31. 31. Heparin-induced exteracoporealHeparin-induced exteracoporeal LDL-PrecipitationLDL-Precipitation Other co-precipitated plasma proteins :Other co-precipitated plasma proteins : CRPCRP Lp(a)Lp(a) FibrinogenFibrinogen PlasminogenPlasminogen Anti-thrombinAnti-thrombin Adhesion moleculesAdhesion molecules C3, C4, C1 inhibitorC3, C4, C1 inhibitor ChemokinesChemokines Interlukin-1Interlukin-1 TNF alphaTNF alpha EdotoxinsEdotoxins FerritinFerritin CD 40LCD 40L
  32. 32. Treatment efficacy result of LDL aphaeresisTreatment efficacy result of LDL aphaeresis -58-58-158-158112112270270FibrinogenFibrinogen -18-18-22-22100100123123Apo A-1Apo A-1 -14-14-6-636364242HDL-CHDL-C -49-49-90-909898188188TriglycerideTriglyceride -52-52-88-887676164164Apolipo-BApolipo-B -54-54-111-1118989200200LDL-CLDL-C -47-47-134-134144144287287Total-CTotal-C Percent%Percent%MeanMean mg/dlmg/dlMeanMean mg/dlmg/dlMeanMean mg/dlmg/dl ChangeChangeChangeChangeAfterAfterBeforeBeforeweeklyweekly
  33. 33. Weekly vs. biweekly parameter changesWeekly vs. biweekly parameter changes -18-18 -16-16 -22-22 -19-19 9797 100100 118118 119119 Apo A-1Apo A-1 -15-15 -15-15 -6-6 -6-6 3535 3434 4141 4040 HDL-CHDL-C -53-53 -56-56 -92-92 -104-104 7777 8080 170170 184184 Apolipo-BApolipo-B -47-47 -49-49 -133-133 -161-161 144144 156156 277277 318318 Total-CTotal-C -53-53 -55-55 -111-111 -138-138 9191 104104 202202 242242 LDL-CLDL-C Change (%)Change (%)Change (mg/dl)Change (mg/dl)Post-Post- treatment(%)treatment(%) Pre-Pre- treatment(%)treatment(%)
  34. 34. Effect of 31 LDL aphaeresis treatments onEffect of 31 LDL aphaeresis treatments on CRPCRP and low density cholesterol (LDL)and low density cholesterol (LDL) concentrations in serum of 13 CHD patientsconcentrations in serum of 13 CHD patients <0.001<0.0011. (mmol/l)(mmol/l) <0.001<0.0011. (mg/dl)(mg/dl) P valueP valueAfterAfter aphaeresisaphaeresis BeforeBefore aphaeresisaphaeresis VariableVariable
  35. 35. Six-month trend analysis of pre- andSix-month trend analysis of pre- and post-treatmentpost-treatment hs-CRPhs-CRP levels for fourlevels for four patients on chronic LDL apheresispatients on chronic LDL apheresis therapy.therapy. 6-month6-month
  36. 36. Time course of CRP and LDL recoverTime course of CRP and LDL recover between H.E.L.Pbetween H.E.L.P E.WielandE.Wieland
  37. 37. Change in lipid, fibrinogenChange in lipid, fibrinogen,, CRPCRP across 6 months of LDLacross 6 months of LDL aphaeresisaphaeresis -49%-49%64%64%9 +/-89 +/-8CRPCRP -25%-25%65%65%332 +/-46332 +/-46FibrinogenFibrinogen +8%+8%34%34%190 +/-64190 +/-64TriglycerideTriglyceride +12%+12%25%25%46 +/-1446 +/-14HDL-CHDL-C -9%-9%64%64%275 +/-69275 +/-69LDL-CLDL-C -5%-5%56%56%359 +/-77359 +/-77Total-CTotal-C change afterchange after 6months(%)6months(%) Mean decrease perMean decrease per treatment(%)treatment(%) BaselineBaselineParameter (mg/dl)Parameter (mg/dl)
  38. 38. How to increase the efficiency ofHow to increase the efficiency of LDL aphaeresis machine?LDL aphaeresis machine?  Increasing the spectrum of its clinical useIncreasing the spectrum of its clinical use  Implementing other techniques for IncreasingImplementing other techniques for Increasing its capacity to remove more harmful factorsits capacity to remove more harmful factors from plasmafrom plasma
  39. 39. CLINICALAPPLICATION OF LDLCLINICALAPPLICATION OF LDL APHAERESISAPHAERESIS Acute coronary syndromeAcute coronary syndrome Chronic coronary artery diseaseChronic coronary artery disease
  40. 40. CLINICAL TRIALCLINICAL TRIAL Inclusion criteria:Inclusion criteria: Acute coronary syndromeAcute coronary syndrome Unstable anginaUnstable angina Acute myocardial infarctionAcute myocardial infarction Anti ischemic treatmentAnti ischemic treatment LDL-C> 200 mg/dlLDL-C> 200 mg/dl
  41. 41. End pointsEnd points Primary end point:Primary end point: MACEMACE Secondary end points:Secondary end points: Lipid profileLipid profile CRPCRP FibrinogenFibrinogen Tissue factorTissue factor CytokinesCytokines IL-1, IL-6IL-1, IL-6 TNFTNF CD40/LCD40/L
  42. 42. CLINICAL TRIALCLINICAL TRIAL Patient with ACS HELP + Statin Statin One HELP therapy Weekly HELP for 4w MACE Biochemical changes MACE Biochemical changes MACE Biochemical changes
  43. 43. Safety-adverse eventsSafety-adverse events 110022AcheAche 002233DizzinessDizziness 111133FeverFever 002244NauseaNausea 223355ChillsChills 007777Prolonged PTT orProlonged PTT or ACTACT 222288FatigueFatigue 4410102020HypotensionHypotension 4420203131Access problemAccess problem Number biNumber bi weekly(276weekly(276 treatments)treatments) NumberNumber weekly(575weekly(575 treatments)treatments) Total no. ofTotal no. of eventsevents No=23 ptsNo=23 pts