1. Isolated Thrombolysis for DVT DVT Treatment with the Trellis ® Peripheral Infusion System Manufacturer’s Registry Report Gerard J. O’Sullivan MD Mahmood Razavi MD

2. Deep Vein Thrombosis 900,000 patients diagnosed annually USA Probably the same number again undiagnosed Treatment has barely altered in 40 years –Bed Rest –Anticoagulation –Anticoagulation does NOT attack the clot, it merely decreases the risk of spread of that clot Interventional Radiology has been at the forefront of more aggressive therapies –Catheter Directed Thrombolysis- CDT- (1994)

3. Catheter Directed Thrombolysis Basically anti clot drugs dripped in through a small garden hose type system over an average of 2-3 days Needs ICU bed/ frequent lab checks/ trips to IR Small risk of bleeding Good results

4. Pharmaco-mechanical thrombectomy (PMT) A combination of –Physical maceration of the clot –Drug dispersal through clot –Aspiration of that clot out of the body

5. Trellis Peripheral Infusion System Designed for single-setting DVT thrombolysis Treatment area isolated within occluding balloons Targeted delivery of thrombolytic agents Mechanical dispersion of infused thrombolytic agents Aspiration following treatment

6. Data Set 827 venous limbs in 771 patients Cases performed between February 2005 and February 2008 362 US and OUS sites All used Trellis Peripheral Infusion System - 8 Fr OD,.035” guidewire - 15 & 30 cm treatment lengths - 80 & 120 cm catheter lengths

7. Thrombolytic Therapy for DVT Patient Benefits Immediate restoration of vein patency Immediate resolution of patient symptoms Preservation of valve function Valves prevent blood from falling back downwards in the leg when the patient is in the erect position –Lower risk of Venous Hypertension –Reduction in recurrent DVT –Lower likelihood of Post Thrombotic Syndrome

8. Vessel Types Treated - Overview Venous771 (94.7%) Arterial 27 ( 3.3%) Bypass Graft 4 ( 0.5%) Dialysis Access 11 ( 1.4%) Not Reported 1 ( 0.1%)

9. Clinical Presentation – Venous Only Number of Patients771 Number of Limbs827 Age 54 +/-30 Gender Female391 (51%) Male351 (45%) Not Reported 29 ( 4%) Clinical Presentation of Clot Acute248 (30%) Acute on Chronic360 (44%) SubAcute 87 (10%) SubAcute on Chronic Chronic 89 (11%) 43 ( 5%) 74% of cases presented acutely based on patient symptoms However, 44% of cases demonstrated venographic evidence of a previous DVT

10. Clinical Presentation (continued) Thrombus Location Lower Extremity N=827 limbs 703 (85.0%) IVC Only Iliac Involvement 4 ( 0.5%) 554 (78.8%) Femoro-Popliteal145 (20.6%) Upper Extremity 111(13.4%) Subclavian Only Subclavian Involvement 100 (90.1%) 11( 9.9%) Other (azygous, portal) 13 (1.6%)

11. Final Patency by Age of Clot Acute Acute on ChronicSubAcute SubAcute on ChronicChronic Grade I8 (3.2%)23 (6.4%)4 (4.6%)10 (11.2%)4 (9.3%) Grade II107 (43.1%)218 (60.6%) 59 (67.8%)48 (53.9%)29 (67.4%) Grade III133 (53.6%)119 (33.1%) 24 (27.6%)31 (34.8%)10 (23.3%) Comb II/III 183 (96.7%)252 (93.7%) 72 (95.4%)60 (88.7%) 32 (90.7%) Lysis Grading Scale 1 Grade III = >95% thrombus removal Grade II = > 50% - 94% thrombus removal Grade I = < 50% thrombus removal 97% Grade II and III lysis with restoration of patency in patients with acute clot 1 Vedantham S et al. “Reporting Standards for Endovascular Treatment of Lower Extremity Deep Vein Thrombosis.” J Vasc. Interv Radiol 2006 17; 417-434.

12. Adjunctive Therapies – All Clots N=771 Adjunctive Measure* None 91 (12%) PTA Alone351 (46%) Stent Alone 33 ( 4%) PTA and Stent211 (27%) CDT 104 (13%) PMT 40 (5%) Other (Embolectomy) 80 (10%) Note: More than one adjunctive maneuver may have been performed during the procedure 77% occurred during primary procedure

13. Reason for Adjunctive Maneuvers Reason Additional vessel treated 39 ( 5.9%) Chronic substrate226 (34.1%) Obstruction/lesion279 (42.1%) Partial Clot Removal118 (17.8%) 76% of maneuvers were due to underlying chronic obstruction or culprit lesion- if this lesion was not treated, high likelihood of recurrence of DVT

14. Single vs. Non-single Setting AcuteAcute on ChronicSubAcute SubAcute on ChronicChronic Single Setting 201 (83.8%)260 (77.2%)64 (77.1%)65 (82.3%)37 (94.9%) Non-single Setting 39 (16.3%)77 (22.8%)19 (22.9%)14 (17.7%)2 (5.1%) Vast majority of cases (> 80%) completed in single setting in less than 2 hours and achieved Grade II or III lysis Average Trellis-use time was 22 minutes

15. Summary of Lytic Doses t-PARetavaseUKTNK Number of Patients*714211223 Average Lytic Dose Per Run 6.0 +/-2.2 mg5.2 +/-2.7 U307k +/-87 U4.8 +/-2.2 mg Total Lytic Dose Per Patient 13.4 +/-6.7 mg12.1 +/-7.4 U690k +/-327 U11.2 +/-7.3 mg 93% of cases used t-PA Compared to CDT, doses are appreciably reduced & delivered in a single setting No reported bleeding complications in acute follow up * N=771, 1 case used heparinized saline as the infusate

16. Case 1 60 year old lady Failed traditional therapy for DVT Left leg massively swollen after 6 weeks of this treatment Referred to Interventional Radiology for Trellis treatment

17. LEFT RIGHT

19. Case 2 57 year old construction worker Never sick in his life Right leg felt heavy Went to doctor, sent for Ultrasound scan “Negative for DVT” 2 days later right leg felt worse Came to ER Referred directly to Interventional Radiology

20. One of the worst cases of DVT I have seen- straight to IR lab

21. 24 hours later……… Back to work in one week

22. Summary Largest prospective database of DVT intervention Isolated pharmaco-mechanical thrombolysis removes thrombus to restore vessel patency –97% Grade II & III Lysis achieved Clot removal tallies with clinical improvement Isolated pharmaco-mechanical thrombolysis substantially reduces lytic dose and time to restore venous patency compared to CDT –Completed in a single setting in the majority of cases in less than 2 hours No reported bleeding complications in acute follow up

23. Take home points Interventional Radiologists are experts in management of Deep Vein Thrombosis IR doctors can help primary physicians determine the best course of action for particular patients If leg is tense or blue IMMEDIATE referral is mandatory Treatment using the Trellis isolated thrombolysis catheter is QUICK, SAFE and EFFECTIVE DVT patients across America deserve better!!