1. Harvard Medical School Duane S. Pinto, M.D. Director Peripheral Angiographic Core Laboratory, TIMI Data Coordinating Center Director, Cardiology Fellowship Training Program Interventional Cardiologist Beth Israel Deaconess Medical Center Assistant Professor of Medicine, Harvard Medical School Renal Artery Stenosis: Diagnosis and Indications for Revascularization

2. Harvard Medical School Clinical Clues for RAS  Onset of HTN after 55 yrs  Exacerbation of well-controlled HTN  Malignant or resistant HTN  Epigastric bruit  Unexplained azotemia  Azotemia while on ACE or ARB  Atrophic kidney or size discrepancy  Recurrent CHF or “flash” pulmonary edema  Atheroscerosis elsewhere

3. Harvard Medical School Making the Diagnosis of RAS: Imaging Requirements 1.Identify main and accessory renal arteries 2.Localize site of stenosis or disease 3.Provide hemodynamic significance of disease 4.Identify associated pathology

4. Harvard Medical School Making the Diagnosis of RAS: Imaging Options  Renal arteriography  Duplex ultrasound  MRA  CTA  Nuclear Perfusion  Renal Vein Renin Sampling

5. Harvard Medical School Renal Arteriography  Advantages  Meets all 4 criteria  Can size RA and intervene at the same time of diagnosis  Sensitivity and Specificity are Gold Standard  Disadvantages  Expense  Risks: Atheroembolis, CIN  Oculostenotic

6. Harvard Medical School Renal Arteriography Can Distinguish Integrity of Main, Accessory, and Branch Vessels  Nonatherosclerotic forms of Renovascular Disease  FMD  Misc: Spontaneous dissection, aneurysmal disease, William’s Syndrome, neurofibromatosis, trauma  Atherosclerotic Disease  Unilateral or Bilateral ostial disease (75%)  Nonostial disease (<20%)  Isolated branch disease or segmental disease (5%)

7. Harvard Medical School Hemodynamic Assessment  Hemodynamic Assesment confirms visual estimate  60% stenosis diameter stenosis correlates with 84% CSA reduction to create a pressure drop  Magic number is 20 mm Hg Gross, et al. Radiology 2001. 220:751-756 Haimovici, et al. J Cardiovasc Surg. 1962; 3: 259-62

8. Harvard Medical School Duplex Ultrasound  Meets 3 or 4 criteria  Least expensive  Predict whether stenting will be effective  Sensitivity 84-88%  Specificity 62-99%  Accessory arteries missed  Limited imaging in obese, gaseous patients  Technician dependent

9. Harvard Medical School Renal Resistive Index  Offers prognosis for intervention  Avoid Compression and Valsalva which increase RI  RI= PSV-EDV/PSV  RI=(1-[Vmin/Vmax])  Multiply by 100 Radermacher J., et al. Hypertension. 2002; 39: 699-703)

10. Harvard Medical School RRI: Prognosis  RI >80 is a strong predictor of death, dialysis or progressive disease  Seen with or without RAS  Found to be similar with GFR <40 and Proteinuria  However, data only based on 25 patients with RI >80 Radermacher J., et al. Hypertension. 2002; 39: 699-703)

11. Harvard Medical School Outcomes: 215 patients with ≥70% RAS treated with stenting  In 52% (99/191) of the patients, Cr decreased during 1-year follow-up  1.21 mg/dL (quartiles: 0.92, 1.60 mg/dL) to 1.10 mg/dL (quartiles: 0.88, 1.50 mg/dL) (P=0.047)  MAP decreased from 102±12 mm Hg (mean±SD) at baseline to 92±10 mm Hg (P<0.001)  Independent predictors of improved renal function were:  Baseline serum Cr (odds ratio [95% CI], 2.58 [1.35 to 4.94], P=0.004)  LV function (OR 1.51 [1.04 to 2.21], P=0.032) Zeller. Circulation. 2003;108:2244.

12. Harvard Medical School Outcomes: 215 patients with ≥70% RAS treated with stenting  Female sex, high baseline mean blood pressure, and normal renal parenchymal thickness were independent predictors for decreased mean blood pressure.  1yr mortality was approximately 7.5%  CHF or MI (73%)  Stroke (13.5%)  7 patients hospitalized with flash pulmonary edema and/or acute renal failure requiring acute hemodialysis could be withdrawn from the chronic hemodialysis program Zeller. Circulation. 2003;108:2244.

13. Harvard Medical School MRA of the Renals  3 of the 4 requirements  No radiation or nephrotoxins  Short duration scans  Sensitivity 90-100%  Specificity 76-94%  Expensive  Claustrophobia  May miss FMD  Overcalls Stenoses  Stent Artificact

14. Harvard Medical School CTA of the Renals  3 of the 4 requirements  Widely available  Visualize stents  No Flow Artifact  Short duration scans  Sensitivity 89-100%  Specificity 82-100%  Expensive  Radiation  Contrast  Claustrophobia

15. Harvard Medical School Indications for Continued Medical Treatment  Mild HTN  Controlled BP on Meds  Stable and Good renal function  Advanced Age  Anatomic/Technical Considerations

16. Harvard Medical School Indications for Renal Revascularization  Hypertensive Control  Reasonable Likelihood of Improvement  Recent escalation on top of essential HTN  Refractory, accelerated or malignant HTN  Renal Salvage  Unexplained Azotemia or ACE induced  Loss of renal mass over time  Progression of RAS  Cardiac disturbance  USA, “Flash Pulmonary Edema”, CHF

17. Harvard Medical School Predictors of Success  Female Gender (p=0.032)  MAP at baseline (p<0.001)  Renal Failure  More improvement if moderate dysfunction (1.5 mg/dl) vs. severe (p=0.025)  LV function normal (p=0.032)  Neutral: DM an nephrosclerosis

18. Harvard Medical School Case Selection: Should You ?  BP 148/94  2 Antihypertensive Meds  12 mm Hg gradient

19. Harvard Medical School Case Selection: Should You ?  “Drive-by Aortogram”  BP 148/94  Atenolol only  Creatinine 1.9 NO!

20. Harvard Medical School Case Selection: Should You ?  28 y/o nurse  BP 209/119 mm Hg  Meds: None  Creat 0.9  LRA normal YES!

21. Harvard Medical School Case Selection: Should You ? YES!!! BP 196/104 Prinivil, HCTZ, Metoprolol 71 mm gradient

22. Harvard Medical School What about the incidentalomas? Normal BP, No Meds, Normal GFR Pro  Prevent renal injury  Treat before it occludes Con  ?Data  Complications  Cost I say, No.

23. Harvard Medical School SummarySummary  Evaluate patient for clues suggesting RAS  Perform imaging if patient is a candidate for revascularization  Combine imaging studies if necessary  Intervene on those who have reasonable life expectancy and potential to benefit from revascularization