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  • Pulmonary Thromboembolic DiseaseRisk Stratification & Approach For Management Majdy M Idrees

    Division of Pulmonary MedicineRiyadh Armed Forces Hospital10th Advanced Medicine SymposiumNovember 2006RMH, Riyadh

  • An Expert:A man who has stopped thinking:He Knows!!

  • Pulmonary EmbolismRisk Stratification & Approach of Management Venous thrombosis is always a severe disease and is often fatal, because fragments of the thrombi may detach and occlude branches of the pulmonary artery... the occlusion of the main branches of the pulmonary artery causes a striking rise of the blood pressure in these vessels. This rise, which the right heart might fight in order to ensure circulation, may sometimes lead to cardiac arrest.

    Picot 1884Lecons de Clinique Mdicale

  • It is a clinical syndrome of high mortality characterized by acute pulmonary arterial occlusion with resultant sudden elevation in pulmonary artery pressure and right ventricular failure DefinitionPulmonary EmbolismRisk Stratification & Approach of Management

  • SimpleComplicatedSubmassiveMassive Pulmonary EmbolismRisk StratificationPulmonary EmbolismRisk Stratification

  • Complicated Pulmonary EmbolismMassive Pulmonary EmbolismPerfusion defect >50%Filling defect / obstruction in 2 lobar arteriesObstruction of main (R/L) PA 2. Hemodynamic instability 1. Severe refractory hypoxic3. Acute RV failure4. Tissue hypoperfusion (low urine output)Visual ScoringFunctional Scoring

  • Predicting PE Perfusion DefectsGalle Thromb Haemost 2001; 86:1156-60< 30%30% - 50%>50%

    Resp rate/min172228Heart rate/min9599100(A-a)O2 kPa3.64.46.3D-dimer ug/L273160907950 4000ug/L33%67%94%< 4000ug/L67%33%6%US proximal DVT(+) 33%(+) 76%(+) 66%(-) 67%(-) 24%(-) 34%

  • PE Severity: Echo Assessment% Obstruction Mastora Eur Radiol 2003; 13:29-35

  • CT Severity AssessmentSevere PENon-severe PE(Lysis/Embolectomy)(Heparin tx) Collomb Eur Radiol 2003; 13:1508-14

  • RV Pressure LoadRV DecompensationIncrease RV Volume Septal Shift Pericardial RestrictionDecrease LV DistensiblityDecreased LV Preload Decrease RV OutputIschemiaObstructionNeuro-hormonal COP / MAPDecreased RV CPP VO2 Wall stressPathophysiology

  • Vascular Obstruction and Acute Pulmonary HypertensionMcIntyre Am J Card 1971; 28:288-294Pulmonary Arterial Mean Pressure (mmHg)Pulmonary Vascular Obstruction Angiogram (%)1020304010305070

  • Vascular Resistance vs ObstructionMiller indexTPVR(mmhg.1.min.m)Petitpretz Circ 1984; 70:861-866.

  • InterventionDiagnostic Therapeutic Approach

  • SeverityEmbolism size Cardiopulmonary Status100

    70

    30

    100MortalitySudden DeathCardiac ArrestShockOutcome in Pulmonary EmbolismRisk StratificationHemodynamically Stable & RV NormalInfliction Point

  • SeverityEmbolism size Cardiopulmonary Status100

    70

    30

    100MortalitySudden DeathCardiac ArrestShockOutcome in Pulmonary EmbolismRisk StratificationHemodynamically Stable & RV Normal

  • Sudden Death in Massive PE Mortality is almost 100% No intervention measure has proven effective

  • Cardiac Arrest

  • SeverityEmbolism size Cardiopulmonary Status100

    70

    30

    100MortalitySudden DeathCardiac ArrestShockOutcome in Pulmonary EmbolismRisk StratificationHemodynamically Stable & RV Normal

  • Echo and Cardiac Arrest48 patients in/out hospital cardiac arrestDiagnosis obtained via TEEMyocardial infarction 21Cardiac tamponade 6Pulmonary embolism 6Aortic dissection/rupture 5Papillary muscle rupture 1Absence of cardiac structural abnormalities 7Other diagnosis 2Sensitivity 93% specificity 50%, positive predictive value 87%31% major therapeutic decisions based upon TEEJACC 30:780-783, 1997

  • Thrombolysis in CPRMajority of PE deaths within 1st hour of symptomsBolus thrombolysis in arrest- ReportedInitiated after failure of conventional CPRStabilization Minimal bleeding complicationsMicrocirculatory Reperfusion77% Stabilized67% SurvivedBottiger Fibrinolysis and Proteolysis, 1997

  • Shock

  • SeverityEmbolism size Cardiopulmonary Status100

    70

    30

    100MortalitySudden DeathCardiac ArrestShockOutcome in Pulmonary EmbolismRisk StratificationHemodynamically Stable & RV Normal

  • In acute diseases,,, coldness of the extremities,, is a very bad sign.The Aphorisms of Hippocrates

  • Pulmonary EmbolismShock vs. Non-Shock MortalityStudyTreatmentShock MortalityNon-Shock Mortality

  • Major Pulmonary EmbolismDiagnostic & Therapeutic Approach ShockECHOTEE/TTERV Pressure Overload?Alternative DX Resuscitate & Stabilize Establish DiagnosisNoYesStart HeparinCertain DiagnosesEmboli in PAAMI / Aortic Dissection / TamponadeSpiral CTV/QAngio-+Peruse other dx

    Lysis Candidate

    NoEmbolectomy YesLytic Rx

  • Measures to Improve HemodynamicsFlow (Cardiac Output)

  • Patients with shock or major disability due to Pulmonary Embolism were excluded because random assignment to a placebo group was considered unethical.Exclusion Criteria PIOPEDPIOPED Investigators CHEST 1990; 97:528-33Heparin Therapy

  • Management Massive PE With Shock Heparin TherapyThe efficacy of heparin is attributed to an impairment of clot propagation and the prevention of recurrent PE Recurrent PE is reported to be the most common cause of death in hemodynamically stable patients Prog Cardiovasc Dis 17,257-270 An inability to establish an early therapeutic level for aPTT is associated with a higher rate of recurrence and impairs the efficacy of anticoagulation therapy with warfarin It is recommended that heparin therapy be given for 7 to 10 days and that the initiation of warfarin therapy be delayed until the aPTT is at a therapeutic level for 3 days.

  • Thrombolytic Therapy

  • Thrombolists Perspective Works GreatHastens thromboembolic resolution

    Removes pulmonary thromboemboli more completely

    Hastens dissolution of thrombi in legs

    May decrease mortality from pulmonary embolism

    May diminish the incidence of chronic thromboembolic pulmonary hypertensionSasahara J Cardiovascular Medicine 1980

  • Traditionalists Perspective UnfulfillingDoes fibrinolytic therapy decrease mortality in acute PE?What is the impact of fibrinolytic therapy on short and long term recovery from acute PE?Does fibrinolytic therapy decrease the rate of recurrent PE?How do the complications and Cost of fibrinolytic therapy compare with those of heparin?Available data does not support the FDA conclusion that fibrinolytic agents are indicated for massive PE there is insufficient data to determine whether the second approved indication for fibrinolytic therapy PE accompanied by failure to maintain BP without supportive measures is appropriate.Dalen J Cardiovascular Medicine 1980

  • Thrombolytic TherapyPutative Benefits

    Accelerated Clot Lysis Recurrent EmbolismAngiogramsPerfusion scans Chronic Pul HTNPul capillary blood volume Quality of LifeHemodynamic ImprovementPulmonary pressuresSymptomsEchocardiogram Mortality

    PROVENSPECULATIVE

  • Early Resolution Rate Lytic vs HeparinStudy/YrAgentTime PostResolutionMetric

  • Angiographic Severity UPETUPET JAMA 1970; 214:2163-2172321032104Heparin UrokinaseHeparin UrokinaseBaseline24 HoursSevereModerateNormalMinimalN = 57N = 57Complete (91-100%)Marked (61-90%)Moderate (31-60%)Slight Improvement ( 30%)No change

  • Rate and Extent Clinical-Hemodynamic Resolution Reported in UPETUPET JAMA 1970; 214:2163-2172HeparinUrokinaseBaseline24 hours 24 hours Baseline

  • Total Pulmonary Resistance EvolutionMeneveau European Heart Journal 1997; 18:1141-1148 0-40-20-60024681012Time (h)% change from baselinert-PAStreptokinaseHeparin

  • Right Ventricular Ejection Fraction EvolutionMeneveau European Heart Journal 1997; 18:1141-11488070602030405010024681012Time (h)% change from baselinert-PAStreptokinaseHeparin

  • Recurrent PE With Thrombolytic TherapyStudyAgentHeparinLyticDalen Venous Thromboembolism Lung Biology in Health and Disease 2003

    UPET 1973Urokinase9.0% (7)6.1% (5)Levine 1990rt-PA0%0%PAIMS 2rt-PA0%5% (1)Goldhaber 1993rt-PA3.6% (2)0%Konstantinides 2003rt-PA2.9% (4)3.4% (4)Totalsrt-PA2.3% (5)2.6% (6)

  • Thrombolytic Therapy Hemorrhagic ComplicationsMajor hemorrhage 8-12%Similar amongst agentsFatal hemorrhage 1-2%Intra-cranial hemorrhage 1.2-2.1%Fatal in 50%Arcasoy Chest 1999; 115:1695-1707

  • Allows rapid and complete removal of the clot Survival rate in retrospective review 40-60% Ann Thorac Surg 1991Cardiac arrest is the most preoperative prognostic factorIndicated when Thrombolysis is contraindicated or failed Unyeilding hypotension despite max therapy for > 1 h Ongoing/intermittent cardiac arrest Management Massive PE With ShockSurgical Embolectomy

  • Infliction PointEmboli in TransitRV Dysfunction Submassive Pulmonary Embolism

  • SeverityEmbolism size Cardiopulmonary Status100

    70

    30

    100MortalitySudden DeathCardiac ArrestShockOutcome in Pulmonary EmbolismRisk StratificationHemodynamically Stable & RV NormalInfliction Point RV Dysfunction Troponin T NDH

  • Isolated RV DysfunctionRV dysfunction has long been recognized as a marker for poor outcome in patients with PE, especially in those with hemodynamic instability RV dysfunction in hemodynamically stable patients has been identified as a predictor of worse outcome and appears to be related to the pres