Renovascular Disease recognition and management

1. Renovascular Diseaserecognition and management Craig A. Thompson, M.D., MMSc. Cardiac and Vascular Interventional Services Dartmouth Hitchcock Medical Center Lebanon, NH

2. When to • When not to • In whom Renovascular Disease: The Clinical Perspective Old Medical Adage: “Even a monkey can do angioplasty.” Caveat: It takes a real doctor to decide: • What the diagnostic studies do and don’t say • What to do afterward • How to address this problem in the context • of a living, breathing patient

3. Progress in Renovascular Disease • The disease • Clinical diagnosis • Laboratory diagnosis / imaging modalities • Patient selection: who benefits from intervention? • Limiting contrast-induced nephropathy • Atheroembolic protection • Expanding the pool of eligible patients / interventions • Limiting restenosis

4. Progress in Renovascular Disease • The Disease • Clinical diagnosis • Laboratory diagnosis / imaging modalities • Patient selection: who benefits from intervention? • Limiting contrast-induced nephropathy • Atheroembolic protection • Expanding the pool of eligible patients / interventions • Limiting restenosis

5. Etiology of Renal Artery Stenosis • Atherosclerosis • Fibromuscular dysplasia • Polyarteritis Nodosa • Radiation-induced • Takayasu’s arteritis

6. Defining the Problem • RAS is an important cause of secondary hypertension • Renovascular disease under-appreciated as cause of CRF • 23% of malignant hypertension is the result of renovascular causes • Not all patients with RAS are hypertensive as a result

7. What is “medical therapy” for renovascular disease?

8. Natural History of Renal Artery Stenosis • Serial U/S examination of 170 patients with 295 renal arteries • Exclusion for congenitally absent / occluded / prior PCI / poor window • Referred for renal U/S for hypertension or renal insufficiency • Only included in study if not a candidate for immediate revascularization • U/S evaluation every 6 months until time of intervention • Duplex evaluation: Peak Systolic Velocity (PSV) in proximal, middle, and distal RA and AO • Yielding the RAR (Renal-to-Aortic Ratio) Caps et al. Circulation 1998; 98:2866-2872.

9. Natural History of Renal Artery Stenosis Caps et al. Circulation 1998; 98:2866-2872. Role of lipid lowering and Aggressive risk factor modification?

10. L. Gabriel Navar and L. Lee Hamm

11. Mark A. Pohl

12. L. Gabriel Navar and L. Lee Hamm

13. Progress in Renovascular Disease • The Disease • Clinical diagnosis • Laboratory diagnosis / imaging modalities • Patient selection: who benefits from intervention? • Limiting contrast-induced nephropathy • Atheroembolic protection • Expanding the pool of eligible patients / interventions • Limiting restenosis

14. Clinical Clues • Onset of diastolic hypertension after age 55 • Refractory or malignant hypertension • Development of resistant hypertension in a previously well-controlled patient • Progressive increase in Creatinine, even if still “normal” • Presence of atherosclerotic macrovascular disease elsewhere heightens suspicion • Left heart failure out-of-proportion to LV dysfunction or ischemic burden • Clinically silent RAS

15. Progress in Renovascular Disease • The Disease • Clinical diagnosis • Laboratory diagnosis / imaging modalities • Patient selection: who benefits from intervention? • Limiting contrast-induced nephropathy • Atheroembolic protection • Expanding the pool of eligible patients / interventions • Limiting restenosis

16. Screening for Renovascular Disease • Clinical syndrome most important in patient selection • Various diagnostic modalities: • Serologic markers • Duplex ultrasound - in experienced hands can predict with great accuracy the presence or absence of significant RAS • Captopril renal scan - 10-25% false negative • MR angiography - rare false negatives / common false positives. Equipment/experience dependent • Contrast angiography

17. Duplex U/S for Renovascular Disease Olin et al. Ann Intern Med. 1995; 122:833-838. • Prospective Duplex U/S evaluation and Renal Angiography in 102 pts • Goal: Validate renal artery U/S as a viable non-invasive modality • Drawbacks: • Time and labor intensive • Technologist dependent • Not available • NPO • Requires a cooperative patient

18. MRA & Contrast Angiography

19. RN LN Screening Aortography

20. Progress in Renovascular Disease • The Disease • Clinical diagnosis • Laboratory diagnosis / imaging modalities • Patient selection: who benefits from intervention? • Limiting contrast-induced nephropathy • Atheroembolic protection • Expanding the pool of eligible patients / interventions • Limiting restenosis

21. What Are the Goals of Treatment for RAS? • Control hypertension • Aid in medical management • Prevent deterioration in renal function • Forestall need for dialysis • Defer death and disability

22. Hypertension and RAS Among 152 patients with Unilateral or Bilateral RAS undergoing surgical revascularization: • 90% had improvement in BP control • Only 15% had “cure” of hypertension Among 20 published series of PCI for atherosclerotic renal artery disease: • 54% had improvement in hypertension • 9% had “cure” of hypertension Hansen et al. J Vasc Surg 1992;16;319-31.

23. Chronic Renal Insufficiency and RASWho Benefits From Revascularization? Trial of 51 patients with Creat>2.0 before revascularization with >75% Bilateral RAS: • 67% had improvement in renal function • 27% had stabilization in renal function • Only 6% had worsening in renal function • No demonstrated impact upon mortality Novick et al. J Urol 1983; 129:907-12.

24. Experimental Data supporting Stenting for Preservation of Renal Function • 61 vessels in 31 patients with “global” obstructive atherosclerotic renal disease • All with chronic renal insufficiency (Creat 1.5 – 4.0) • Stenting with non-articulated Palmaz stents • Follow-up Renal U/S, Serum Creat , BP measurements: - Improvement in reciprocal slope of serum creatinine - Improved BP control (SBP from 170±21 Pre-stent vs. 148 ±15mmHg Post-stent; p<0.001) - Restenosis (>50%) in only 1 of 61 vessels - Stabilization of pole-to-pole renal dimension Watson et al. Circulation. 2000; 102:1671-1677.

25. Renal Artery Stenting pre post

26. Global Renal Revascularization

27. Watson et al. Circulation. 2000; 102:1671-1677.

28. Watson et al. Circulation. 2000; 102:1671-1677.

29. Dutch Renal Artery Stenosis Intervention Cooperative Study N Engl J Med 2000; 342:1007-14 Results: • BP same in both groups • Fewer meds (2.1 vs. 3.2) in the PTA vs. Medical group • Renal function similar between groups • Study Design: • 106 hypertensive patients with RAS (>50%) and Creat<2.3 mg/dl • PTA vs. Medical rx with follow-up of BP/meds/ renal fxn • at 3&12 mths • Shortcomings: • Crossover of patients from medical-to-PTA • No stents • Is 50% stenosis physiologically significant? • Pts with elevated creatinine excluded • Is the goal of renal artery revascularization improvement in BP control?

30. ( ) PSV - MEDV = PSV Resistive Index Predicts Fate of Renal Function Radermacher et al. NEJM 2001 344: 410-17 Resistive Index

31. Factors That Predict Failure Radermacher et al. NEJM 2001; 344: 410-417.

32. Progress in Renovascular Disease • The Disease • Clinical diagnosis • Laboratory diagnosis / imaging modalities • Patient selection: who benefits from intervention? • Limiting contrast-induced nephropathy • Atheroembolic protection • Expanding the pool of eligible patients / interventions • Limiting restenosis

33. HOCM may increase cellular injury when potentiated by hypoxemia c/t LOCM Useful for localization > Anatomic definition -Gadopentatate dimeglumine -Renally cleared by GF -Not nephrotoxic to 0.4mmol/kg -Changing kV may improve image quality AC and hydration reduce Creatinine > hydration alone in CT with CRI (2% vs 21%) May decrease incidence of RCN vs. historical controls (4.7% vs 18.8%) Options: Contrast minimizing maneuvers Use of low-osmolar, non-iodinated contrast CO2 Angiography Gadolinium contrast Mucomyst (Acetylcysteine) Selective DA-1 agonists

34. Progress in Renovascular Disease • The Disease • Clinical diagnosis • Laboratory diagnosis / imaging modalities • Patient selection: who benefits from intervention? • Limiting contrast-induced nephropathy • Atheroembolic protection • Expanding the pool of eligible patients / interventions • Limiting restenosis

35. Guarding Against Atheroembolism • Meticulous “no touch” technique • Use of low profile, atraumatic catheters • Limited catheter manipulation • Primary stenting when feasible • GP 2b3a Antagonists • Distal protection devices

36. Distal Atheroembolic Protection: The Ideal Capture all debris Continued renal perfusion during procedure Limitless reservoir Atraumatic to vessel wall Technically easy to use Low profile Trackable

37. Pathology of Atheroembolism • Plaque / cholesterol • Endothelial cells • Platelet-Fibrin Thrombi • Calcified tissue

38. Evolution of Distal Protection Devices • Initially used in the treatment of patients with coronary bypass graft disease • These interventions commonly plagued by angiographic “No Reflow” phenomenon • Cardiac enzyme leak • Clinical myocardial infarction • Long attributed to RBC lysis and platelet activation with resultant microvascular spasm

39. Initial Reports: Atheroembolic Protection “Percusurge Guardwire” 47% of patients with SVG intervention had gross, macroscopic evidence of red-yellow debris An additional 20% of patients had evidence of microscopic debris Carlino et al.Circulation 1999; 99: 3221-3223

40. SAFER Trial • Randomized comparison of SVG lesions treated +/- PercuSurge Guardwire • Improved outcomes: 42% decrease MACE • Lower laboratory MI’s • Safe • High procedural success Baim et al. Circulation 2002.

41. Distal Protection in Renovascular Disease: An Opportunity • Most RAS caused by atheromatous disease • Ostial / proximal segments of disease are common • Kidney will tolerate longer balloon occlusion time than coronary / cerebral circulation • Atheroembolism has long been viewed as a major risk / complication of percutaneous intervention of the renal arteries.

42. FILTER DEVICES OCCLUSION DEVICES + Preserve flow Limit Ischemic Time More complete capture - Small debris Vascular Injury No antegrade flow Prolonged Ischemic Time Vascular Injury Shoulder Regions

43. FILTER DEVICES Cordis

44. OCCLUSION DEVICES

45. Atheroembolization Protection • Percusurge Guardwire • Traverse • Inflate • Intervene • Embolectomize

46. Early Experience: Distal Protection in Renovascular Intervention Henry et al.J Endovasc Ther 2001; 8(3): 227-37. 28 patients with 32 renal arteries 29 Lesions ostial location 100% Technical success with GuardWire Visible debris aspirated: 100% cases Mean RA occlusion time: 6.55 min (2.29-13.21 min) Creatinine post-procedure and at follow-up stable or improved in all cases. Conclusion: Distal protection against atheroembolism is feasible and safe But is it effective?

47. Characterization of Debris Characterize debris in carotid intervention Can we extrapolate to renal artery intervention? Both atheromatous Similar patient population Tuber et al.Circulation 2001; 104: 2791-6.

48. Characterization of Debris Why did complications still occur? What type of debris was not captured? Tuber et al.Circulation 2001; 104: 2791-6.

49. Characterization of Debris Tuber et al.Circulation 2001; 104: 2791-6.

50. Splenic A RRA LRA CO2 Aortogram