VTE & Medical Patients: Case Scenario

Transcription

1 The Saudi Association for Venous Thromboembolism SAVTE The 2 nd SAVTE Symposium 1-3 May, 2012 Casablanca, Morocco VTE & Medical Patients: Case Scenario Majdy Idrees Riyadh, Saudi Arabia Majdy M Idrees, MD Gulf Thoracic Meeting Abu Dhabi, UAE MArch 18 20, 2010

2 The 2 nd SAVTE Symposium Disclosure Honoraria for lecturing for Actelion, BSP, pfizer, AstraZeneca, MSD & GSK Research grant from pfizer & Actelion Multi-national RCT sponsored by Actelion, BSP, and pfizer

3 The 2 nd SAVTE Symposium 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 1884 Lecons de Clinique Médicale

4 The 2 nd SAVTE Symposium The aphorisms of Hippocrates In acute diseases, coldness of the extremities,, is a very bad sign

5 The 2 nd SAVTE Symposium 74 year old lady presented with progressive shortness of breath (WHO functional class IV) over 10 day period She had one attack of syncope 2 days before his presentation Recent surgery (appendectomy 3 weeks earlier)

6 The 2 nd SAVTE Symposium BP 155/88, PR 92/min, O 2 sat 84% on r/a and 92% on 4 L/min Physical examination revealed Rt. heart strain Doppler US negative EKG revealed sinus tachycardia with T wave inversion in the anterior precordial leads NT pro BNP 4200

7 The 2 nd SAVTE Symposium Echocardiography: Dilated RV Severe TR spap 84 mmhg Small posterior PE

8 The 2 nd SAVTE Symposium Management issues: How severe is this patient s PE?.1 What is the risk of mortality? Risk stratifying.2 Is the pathobiology different from massive PE?.3 What is the best management approach?.4

9 Outcome in Pulmonary Embolism 100 Sudden Death 70 Cardiac Arrest Mortality 30 Infliction Point Shock 10 RV Dysfunction 0 Severity Cardiopulmonary Status Embolism size

10 Outcomes in hemodynamically stable, RVstrained PE treated with Heparin Study Year Number PE Death % Mortality Goldhaber % Grifoni % Hamel % Giannitsis % Viellard-Baron % Pruszczyk % Pruszczyk % Kucher % %

11 The 2 nd SAVTE Symposium Different Pathophysiology Massive Pulmonary Embolism Sub massive Pulmonary Embolism Well understood Obstructive shock Poorly understood

12 Hemodynamic PE Systemic Arterial Pressure COP 0-10 Guyton Cir Res 1954; 2: RAP Zero Occlusion Total Occlusion Progressive PR occlusion

13 PE: Vascular resistance vs. obstruction 30 PVR Petitpretz Circ 1984; 70: Miller index

14 Thrombolytic therapy in massive PE Randomized trial Aimed for 40 patients Patients with massive PE (SBP<90) IV bolus of SK Vs Heparin The study was prematurely Terminated. Throm Thrombolysis 1995

15 Thrombolytic therapy in massive PE 100 Survival Heparin Streptokinase 20 0 J Throm Thrombolysis Conclusion: Although a small study, it strongly support the current indication for thrombolytic therapy in massive PE.

16 Non shock mortality thrombolytic therapy Patients Mortality Study Lytic Heparin Lytic % (N) Heparin % (N) UPET 73 Urokinase % (2) 8.2% (6) Marini 88 Urokinase % 0% PIOPED 90 rt-pa % (1) 0% Levine 90 rt-pa % (1) 0% PAIMS 2 92 rt-pa % (2) 6.3% (1) Goldhaber 93 rt-pa % 3.6% (2) Konstantinides 02 rt-pa % (4) 2.2% (3) Total % (10) 3.7% (12)

17 Thrombolytic therapy in patients with non shock pulmonary embolism? Randomized, DB, multicenter trial 256 pt PE confirmed by HP V/Q scan, spiral CT or angiogram Normal BP RV dysfunction (Echo, ECG or SG catheter) Primary endpoint: In hospital mortality Worsening circulation Need for additional therapy Secondary endpoint: 30 days mortality Recurrent PE American Journal of Cardiovascular Drugs, 4 (2) 2004, 69-74

18 Thrombolytic Therapy in patients with non shock pulmonary embolism? 25 5 Composite PEP % P = % 2.1 % P = NS 2.4 % In hospital Mortality Heparin TPA Heparin Am J of Cardiovascular Drugs, 4 (2) 2004, Alteplase

19 Non shock PE: Pathobiology Observations: Clinical observation Lack of response to anti obstructive lytic treatment Science: Inflammatory neurohormonal mediators release bilateral pulmonary vasoconstriction, bilateral V/Q mismatch PVR RV dysfunction Stein M, Prog Cardiovasc Dis 1974; 17: Malik AB, Physiol Rev 1983; 63: Alpert JS, Chest 1978; 73:

20 Novel approach for the management of sub massive pulmonary embolism Methods: Inhaled Iloprost used in 11 patients with Submassive PE, who refused to receive thrombolytic therapy NYHA III to IV for duration between 1 14 day Helical CT angiogram was confirmatory Echocardiography was used to evaluate the RV All patients were stable hemodynamically Beside anticoagulation, all patients received inhaled Iloprost, µg every 4 hours for 3 weeks. Idrees et al, ATM, submitted

21 Prostanoids Vessels Platelets Leukocytes SMC fibroblasts platelets monoc PMN T cells vasodilation anticoagulation antiproliferation matrix secretion burst elastase leukotrienes NFkB TNF IL 1 IL 10 MAPK inos TNF IFN IL 2 Olschewski et al. Pharmacol Ther, 2004

22 Novel approach for the management of sub massive pulmonary embolism End points: Improvement in echocardiographic parameters for right ventricular strain/ph Functional class improvement Improvement in dyspnea score Exercise improvement Biomarker (Pro BNP) Improvement in oxygenation Mortality Idrees et al, ATM, Submitted

23 Results P = 0.01 P < P = 0.03 P = 0.01 P < m 520 m X VIII VI IV II 0 Vlll ll IV III II I 0 lll + l + spap NT Pro 6MWT Dyspnea NYHA BNP Score Pre Iloprost Idrees et al, ATM, Submitted Post Iloprost

24 Conclusion: Novel approach for the management of sub massive pulmonary embolism In sub massive pulmonary embolism, directing therapy towards decreasing PVR is effective in improving the hemodynamics derangement associated with this condition. This strategy might turn to be the most effective approach for treating this condition and probably safer than thrombolytic therapy. However, these conclusion should be confirmed in a large, randomized, placebo controlled study Idrees et al, ATM, Submitted

25 The 2 nd SAVTE Symposium Take Home Messages

26 Summary Pulmonary embolism could be a fatal disease Diagnostic Therapeutic approach based on risk stratification is probably the most important step in the management RV Dysfunction Shock Cardiac arrest Sudden arrest

27 Summary Thrombolytic therapy in M PE: Accelerated clot lysis Hemodynamic improvement May improve Recurrent embolism CTEPH Quality of life Symptoms Mortality Thrombolytic therapy in SM PE: Controversial issue Administrating early in the course of submassive pulmonary embolism prevents worsening of the disease In SM PE Directing therapy towards PVR rather than clotting lysis might be the ideal approach in this patients population Need to be tested in randomized clinical studies

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