1. Renovascular Hypertension and Renal Artery Ultrasounds Amajd AlMahameed, MD, MPH Division of Cardiology Beth Israel Deaconess Medical Center Boston

2. Moderate RAS: visually estimated 50-69% w 10 mm Hg mean or 20 mm Hg systolic translesional gradient Severe RAS: visually estimated diameter stenosis of > 70% (Rundback et al Circulation 2002;106:1572–1585) Necropsy Studies: Luminal stenosis > 50% was found: Overall 27-53% of autopsies Age > 70 y/o: 74% (Holley et al Am J Med. 1964;37:14 –22) (Schwartz et al BMJ. 1964;5422:1415 –1421) CHS: significant RAS (>60%) in 6.8%, M:F ratio 2:1, W = B (Hansen et al J Vasc Surg 2002;36:443-51) Patients with PAD: Significant RAS in 22% to 59% (Olin et al Am J Med. 1990;88:46N–51N, Valentine et al Ann Vasc Surg. 1993;7:220 –224.) Patients with proven history of MI: 12% had RAS > 75% (Uzu et al Am J Kidney Dis 1997;29:733-8) Bilateral RAS: is not uncommon, found in 44% of RAS patients (Rimmer et al Ann Intern Med 1993;118:712-9) Patients with 1 or more clinical clues to the presence of RAS, significant RAS can be found in up to 70% (Olin et al Am J Med. 1990;88:46N–51N) How Common is Renal Artery Stenosis White CJ. Circulation. 2006;113:1464-1473. Hirsch AT et al. Circulation 2006;113;463-654

3. Incidence of Renal Artery Stenosis at Cardiac Catheterization White CJ. Circulation. 2006;113:1464-1473.

4. Clues to RAS: Must Evaluate Such Patients White CJ. Circulation. 2006;113:1464-1473.

5. 29% of patients progressed, 11% developed total occlusion (mean f/u of 28 months) (Dean et al Arch Surg 1981;116:1408-15) 48% progressed from 60% stenosis (within 3 years) (Zierler Am J Hypertens 1996;9:1055-61) Progression occurred at an average rate of approximately 7% per year (Zierler Am J Hypertens 1996;9:1055-61) Disease progression, based on sonographic determination, was 35% at 3 years and 51% at 5 years Caps et al Circulation 1998;98:2866-72 Randomized trial, med Rx vs. PTA for RAS, over a 1-year, progression to RA occlusion occurred in 16% of the med Rx group compared with none in the angioplasty group (van Jaarsveld et al N Engl J Med. 2000;342:1007– 1014) Progressive worsening of RAS occurs despite medical therapy that effectively controls blood pressure (Crowley et al Am Heart J. 1998;136:913–918, Dean et al Arch Surg. 1981;116:1408 –1415) RAS is the cause of ESRD in 15% of patients over age 50 beginning dialysis each year (Rimmer Ann Intern Med. 1993;118:712–719, Scoble et al Clin Nephrol. 1989;31:119 –122) Renal Artery Stenosis is a PROGRESSIVE Disease White CJ. Circulation. 2006;113:1464-1473. Hirsch AT et al. Circulation 2006;113;463-654

6. RAS: An Ominous Diagnosis to Make RAS (50%): Stronger independent predictor of 4- yr all-cause mortality (RR 2.9) than CHF (RR 2.3), dec LVEF (RR 1.7), or dec renal function (RR 1.3) Conlon et al J Am Soc Nephrol. 1998;9:252– 256 mild-to-moderate (50%) RAS was associated with a 30% 4-year mortality rate, which almost doubled (52%) with severe (95%) RAS (incremental effect) Conlon Kidney Int. 2001;60:1490 –1497. independent predictor of death regardless of the presence, severity, or method of revascularization of coronary artery disease Kennedy et al Am J Kidney Dis. 2003;42:926 –935, Conlon et al J Am Soc Nephrol. 1998;9:252–256, Conlon Kidney Int. 2001;60:1490 –1497. White CJ. Circulation. 2006;113:1464-1473. Hirsch AT et al. Circulation 2006;113;463-654

7. Indications for Revascularization Hemodynamically significant renal artery stenosis associated with: - HTN (accelerated, resistant, malignant, with a unilaterally small kidney, and/or with intolerance to medication) - Renal insufficiency - Recurrent CHF or “flash” pulmonary edema, refractory heart failure, or refractory angina pectoris● White CJ. Circulation. 2006;113:1464-1473. Hirsch AT et al. Circulation 2006;113;463-654

8. Patient Selection for Renal Revascularization: Prediction of Success Fractional flow reserve BNP Resistive Index White CJ. Circulation. 2006;113:1464-1473. Hirsch AT et al. Circulation 2006;113;463-654

9. Duplex scanning was introduced in 1974 First applied to the carotid arteries Major advances since included: ◘ Improved B-mode imaging ◘ Better low-frequency transducers (deeper penetration) ◘ Improved microprocessor software, and ◘ The addition of color to B-mode image. The History of Peripheral US

10. Principles of Peripheral US

11. Provides information about native anatomy and grafts Localizes and measures stenoses Peripheral US

12. Identifies occlusion with reconstitution Peripheral US

13. Flow in a cylinder with concentric layers Friction created between layers Velocity is slowest near the walls and fastest in the center Laminar Flow

14. A product of FFT analysis (displays all velocities within the Doppler signal) Spectral broadening is the term used to describe turbulent flow filling the Doppler spectral window Turbulent Flow

15. Chaotic blood flow with different directions and speeds within the signal Identified after an area of disruption of flow (severe stenosis) Turbulent Flow Turbulant flow has a shape similar to Bart Simpson’s hair!

16. Aliasing Aliasing corrected by dropping the baseline or increasing the scale

17. True Aliasing secondary to very high velocities “wrap around”

18. Velocity Criteria in Peripheral Ultrasounography Proximal Lesions Low Cardiac Output Cardiac Arrhythmia Compensatory Flow Long Lesions Tortuosity Necessary for Standardization Same Criteria for Stents Several Limitations/Pitfalls Doppler Angle

19. Hints to Proximal Stenotic Lesions –Delayed acceleration time to peak systole –Velocities alone not reliable as they may be normal, slightly elevated, or even low –Turbulence should be documented distal to the lesion –Occasionally, collateral vessels may be identified by abnormal flow patterns (retrograde) Normal Doppler signal Abnormal Doppler signal (turbulant)

20. High Resistive Low Resistive

21. Renal Artery US as the diagnostic test of choice for RAS

22. The Normal Anatomy of the Renal Arteries.

23. Direct Assessment of RAS Velocity Criteria (+ Turbulance)Renal/Aortic Ratio Supportive findings White CJ. Circulation. 2006;113:1464-1473. Hirsch AT et al. Circulation 2006;113;463-654

24. 0-59% stenosis (No clinically significant stenosis) –PSV<200cm/sec. 60-99% stenosis (Clinically significant stenosis) –PSV>200cm/sec –Post-stenotic turbulence present Occlusion –Artery visualized without flow Velocity Criteria for RAS White CJ. Circulation. 2006;113:1464-1473. Hirsch AT et al. Circulation 2006;113;463-654

25. RAR < 3.5: Non-significant stenosis (0-59%) RAR > 3.5: Significant stenosis (60-99%) (Sensitivity 84-88%, Specificity 97-99%, PPV 94-98%) EDV > 150 cm/sec may indicate > 80% stenosis Aorta velocities must be between 40 and 100cm/sec for above criteria! If not go back to PSV > 200cm/sec (and the presence of post-stenotic turbulance). Renal/Aortic Ratio Normal Renal Artery: RAR < 3.5 and PSV < 200 200 but RAR < 3.5 (Note, AO PSV should be 40-100) 60-99% stenosis: RAR > 3.5, regardless of PSV White CJ. Circulation. 2006;113:1464-1473. Hirsch AT et al. Circulation 2006;113;463-654

26. Resistive Index – Normal: 0.53 to 0.70 – > 0.70: suggests intrinsic kidney disease – < 0.53: suggests renal artery stenosis Acceleration time – Normal < 100m/sec Tardus/parvus waveform (delayed upstroke) Small kidney ( 1.5 cm discrepancy from other kidney) PSV-EDV PSV Supportive Data (Indirect Assessment) White CJ. Circulation. 2006;113:1464-1473. Hirsch AT et al. Circulation 2006;113;463-654

27. RA US showing the whole course of the R renal artery Aorta R Kidney

28. RRA stenosis at origin. Note turbulent flow And increased velocities

29. Normal flow at RRA origin

30. Normal flow at RRA proximal segment

31. Increased velocities at mid renal artery segment: Typical of non-atherosclerotic RAS (such as FMD)

33. RA US can evaluate the parenchymal flow as well

34. RI 0.53 AT 140 m/s RA US can evaluate the parenchymal flow as well Note increased acceleration time (AT) and borderline resistive index (RI)

36. Another example of the common form of RAS (atherosclerotic) Lesion is typically at the origin of the vessel

37. RI 1.00 Example of increased resistive index (indicative Of intrinsic kidney disease)

38. US can also detect renal stents

39. Documentation of floe within the renal vein is part of RA US exam

40. Prediction of Clinical Response to Revascularization: RFFR The renal fractional flow reserve (FFR) is an assessment of the severity of the RAS by using maximal vasodilation with papaverine Patients with an abnormal baseline renal FFR (0.8) had a higher rate of blood pressure improvement (86%) compared with only 30% in those with a normal baseline FFR White CJ. Circulation. 2006;113:1464-1473. Mitchell J, et al. Catheter Cardiovasc Interv. 2005;65:135. Abstract.

41. Prediction of Clinical Response to Revascularization: BNP Hemodynamically significant RAS activates renin- angiotensin system, leading to increased levels of angiotensin II. In animal experiments, angiotensin II induces synthesis and release of BNP, and the BNP mRNA is upregulated in the setting of RAS. BNP is increased in patients with refractory hypertension and renal artery stenosis An elevated baseline BNP 80 pg/mL strongly correlated with hypertension improvement after 3.5 months of follow- up. White CJ. Circulation. 2006;113:1464-1473. Silva JA et al. Circulation. 2005;111:328 –333.

42. Prediction of Clinical Response to Revascularization: BNP Mean (±SE) Changes in Creatinine Clearance post PTA, According to the Resistive-Index Value before Revascularization Asterisks indicate a significant difference (P<0.05) between the two groups with use of an unpaired t-test with Bonferroni's adjustment. Radermacher et al. NEJM;344 (6): 410

43. Mean BP in patients without nephrosclerosis (RI 0.8) P >0.0001 P >0.05 RI < 0.7RI 0.7- 0.8RI > 0.8 BaselineOne Year Mean BP 84 88 92 96 100 104 108 White CJ. Circulation. 2006;113:1464-1473. Zelelr T et al. Circulation. 2003;108:2244 –2249.

44. Serum Cr in patients without nephrosclerosis (RI 0.8) P = NS P < 0.05 One YearBaseline Serum Cr RI < 0.7RI 0.7-0.8RI > 0.8 White CJ. Circulation. 2006;113:1464-1473. Zelelr T et al. Circulation. 2003;108:2244 –2249.