Erich Minar Medizinische Universität Wien Präinterventionelle Diagnostik und Indikation zur Behandlung von Nierenarterienstenosen: Stent PTA Erich Minar Medizinische Universität Wien Wiener Gesprächstage, Juni 2013

NAST = Renovaskuläre Hypertonie Renal-Artery Stenosis Safian R and Textor S;N Engl J Med 2001; 344:431-442

Definition der renovaskulären Hypertonie Hämodynamisch signifikante Stenose einer oder beider Nierenarterien, die zur Blutdruckerhöhung führt (Goldblattmechanismus) Derzeitig einziger Beweis für das Vorhandensein einer renovaskulären Ursache der Hypertonie liegt in der Beseitigung der signifikanten Stenose mit darauf einsetzender Normalisierung/ Reduktion des Blutdruckes

NAST im Trend (USA 1992-2004) Atherosclerotic renovascular disease in the United States Kalra et al; Kidney Int 2010;77: 37-43

White CJ et al. Indications for renal arteriography at the time of coronary arteriography: a science advisory from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the Councils on Cardiovascular Radiology and Intervention and on Kidney in Cardiovascular Disease. Circulation 2006; 114:1892– 1895

Circulation 2006; 114:1892– 1895

Unklarer Benefit - Unklare Kosten - Mögliche Komplikationen? Der Oculostenotische Reflex (Reflexangioplastie) [Topol EJ, Nissen SE; Circulation 1995] Unklarer Benefit - Unklare Kosten - Mögliche Komplikationen? Jatrogenosis fulminans Soran O et al. Circulation 2000 Courtesy M.Haumer

Conlon PJ et al, Kidn Int 2001; 60: 1490-97

NAST Prognose (Wien 2004 – 2006; n=487 ) Schlechte Prognose bei NAST oder durch NAST? NAST <30% NAST 30-59% NAST ≥60% Amighi J et al. Eur J Clin Invest 2009;39:784-92

Eur Heart J. 2011 Aug 26. [Epub ahead of print

Screening auf renovaskuläre Hypertonie bei Verdacht * Therapierefraktäre Hypertonie (≥ 3 Antihypertensiva-Klassen) * Schwere Atherosklerose in peripheren Gefäßen, Koronarien, Carotis * Exazerbation einer gut eingestellten Hypertonie * Nierenfunktionsverschlechterung bei ACE-Hemmer, ARB * Rezidivierendes Lungenödem * > 1.5 cm Seitenunterschied der Nierengröße bei der Sonographie

Diagnostic strategies for RAD CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.

Diagnostic strategies for RAD CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.

Diagnostic strategies for RAD CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.

Diagnostic strategies for RAD CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.

Renal Artery Stenosis- Severity Pressure drop & severity of RAS May AG et al. Hemodynamic effects of arterial stenosis. Surgery 1962;53:513-524

RI als Erfolgsprädiktor ? RI = {1-[Vmin/Vmax]} x 100 N Engl J Med 2001;344:410-7

Kumbhani DJ ; Am Heart J 2011;161:622-630 Clinical outcomes after percutaneous revascularization versus medical management in patients with significant renal artery stenosis: A meta-analysis of randomized controlled trials Kumbhani DJ ; Am Heart J 2011;161:622-630 Background We sought to systematically evaluate whether percutaneous revascularization is associated with additional clinical benefit in patients with renal artery stenosis (RAS) as compared with medical management alone. Methods We included randomized controlled trials that compared percutaneous revascularization in addition to medical therapy versus medical management alone in patients with RAS. Six trials with 1,208 patients were included. Results At a mean follow-up of 29 months, there was no change in systolic blood pressure (weighted mean difference [WMD] = 1.20 mm Hg, 95% CI −1.18 to 3.58 mm Hg) or diastolic blood pressure (WMD = −1.60 mm Hg, 95% CI −4.22 to 1.02 mm Hg) from baseline in the percutaneous revascularization arm compared with the medical management arm. There was a reduction in the mean number of antihypertensive medications (WMD = −0.26, 95% CI −0.39 to −0.13, P b .001), but not serum creatinine (WMD = −0.14 mg/dL, 95% CI −0.29 to 0.007 mg/dL), in the percutaneous revascularization arm at the end of follow-up. Percutaneous revascularization was not associated with a significant difference in all-cause mortality (relative risk [RR] = 0.96, 95% CI 0.74-1.25), congestive heart failure (RR = 0.79, 95% CI 0.56-1.13), stroke (RR = 0.86, 95% CI 0.50-1.47), or worsening renal function (RR = 0.91, 95% CI 0.67-1.23) as compared with medical management. Conclusions In patients with RAS, percutaneous renal revascularization in addition to medical therapy may result in a lower requirement for antihypertensive medications, but not with improvements in serum creatinine or clinical outcomes, as compared with medical management over an intermediate period of follow-up. Further studies are needed to identify the appropriate patient population most likely to benefit from its use. (Am Heart J 2011;161:622-630.e1.) Mean FU 29 Mo

Clinical outcomes after percutaneous revascularization versus medical management in patients with significant renal artery stenosis: A meta-analysis of randomized controlled trials Kumbhani DJ ; Am Heart J 2011;161:622-630 Conclusions In patients with RAS, percutaneous renal revascularization in addition to medical therapy may result in a lower requirement for antihypertensive medications, but not with improvements in serum creatinine or clinical outcomes, as compared with medical management over an intermediate period of follow-up. Further studies are needed to identify the appropriate patient population most likely to benefit from its use.

Angioplasty and Stenting for Renal Artery Lesions N Engl J Med 2009;361:1953-62 Angioplasty and Stenting for Renal Artery Lesions Conclusions We found substantial risks but no evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease.

ASTRAL Studiendesign Nierenarterienstenose Randomisierung 9/2000 – 10/2007 58 Zentren - 806 Patienten Revaskularisation (N=403) (Angioplastie (7%) oder Stent (93%) und medikamentöse Therapie Keine Revaskularisation (N=403) Nur medikamentöse Therapie 14 Patienten/ Zentrum 2 Patienten/Zentrum/Jahr

Primary Endpoint at 2 years

Stenting versus konservativ N Engl J Med 2009;361:1953-62

ASTRAL – Limitationen/Probleme im Design * Selektions-Bias: wenn der Untersucher sich bezüglich der Therapie sicher war, wurde der Patient nicht randomisiert. Frage: weiß einer von uns wirklich was er bei NAST tun soll? * Primärer Endpunkt war Nierenfunktion: allerdings: bei 25 % war diese normal und bei weiteren 15 % fast normal viele Patienten hatten unilaterale Erkrankung * Es gabe kein Core-Labor zur Adjudizierung der morphologischen Daten. Dies führt erfahrungsgemäß zur Überschätzung des Stenosegrades. * Die Patienten hatten generell eine mäßige Erkrankung, oft sogar unilateral: 40% hatten 50-70% Stenose bzw wahrscheinlich sogar weniger. * Die Studienzentren hatten offensichtlich wenig Erfahrung ( 42% rekrutierten 1-5 Patienten im Verlaufe von 7 Jahren) * Nebenwirkungen viel häufiger als in anderen Studien.

Nierenfunktionsverschlechterung nach Intervention bei 3 – 30% * NAST nicht Ursache der Niereninsuffizienz * KM-induzierte Nephropathie * Distale Atheroembolisation

Das wichtigste Kriterium für eine klinische Verbesserung nach Revaskularisation einer Nierenarterienstenose ist die geeignete Patientenselektion!

Treatment of Renal Artery Fibromuscular Dysplasia with Balloon Angioplasty: a Prospective Follow-up Study M. Birrer et al Eur J Vasc Endovasc Surg 2002; 23: 146

JA !! Sollte man ? RR 196/104 – 3 verschiedene Antihypertensiva Gradient 71 mm Hg

Kein Update der Sektion “Nierenarterien” bei Fassung 2011

NAST Angioplastie und Überleben RCT: PTRA + BMT vs. BMT n=1.080 Einschlusskriterien 1) aNAST ≥60% und 20 mmHg Gradsyst oder ≥ 80% 2) Systolische Hypertonie 155 mmHg trotz ≥2 Antihypertensiva 1°EP Tod (CV oder renal) / MI / Hosp.(CHF), Insult / S-Krea x 2 / Dialyse 2°EP Tod (gesamt) / Nierenfunktion / Offenheitsrate / Blutdruck Bitte warten bis 2014 Stent revascularization for the prevention of cardiovascular and renal events among patients with renal artery stenosis and systolic hypertension: Rationale and design of the CORAL trial Christopher J. Cooper, MD,a Timothy P. Murphy, MD,b Alan Matsumoto, MD,c Michael Steffes, MD,d David J. Cohen, MD,e Michael Jaff, DO,f Richard Kuntz, MD,g Kenneth Jamerson, MD,h Diane Reid, MD,i Kenneth Rosenfield, MD,f John Rundback, MD,j Ralph DTAgostino, MD,k William Henrich, MD,l and Lance Dworkin, MDb Toledo, OH; Providence, RI; Charlottesville, VA; Minneapolis, MN; Boston, MA; Ann Arbor, MI; Bethesda and Baltimore MD; and Teaneck, NJ Background Atherosclerotic renal artery stenosis is a problem with no consensus on diagnosis or therapy. The consequences of renal ischemia are neuroendocrine activation, hypertension, and renal insufficiency that can potentially result in acceleration of atherosclerosis, further renal dysfunction, myocardial infarction, heart failure, stroke, and death. Whether revascularization improves clinical outcomes when compared with optimum medical therapy is unknown. Methods CORAL is a randomized clinical trial contrasting optimum medical therapy alone to stenting with optimum medical therapy on a composite cardiovascular and renal end point: cardiovascular or renal death, myocardial infarction, hospitalization for congestive heart failure, stroke, doubling of serum creatinine, and need for renal replacement therapy. The secondary end points evaluate the effectiveness of revascularization in important subgroups of patients and with respect to all-cause mortality, kidney function, renal artery patency, microvascular renal function, and blood pressure control. We will also correlate stenosis severity with longitudinal renal function and determine the value of stenting from the perspectives of quality of life and cost-effectiveness. The primary entry criteria are (1) an atherosclerotic renal stenosis of z60% with a 20 mm Hg systolic pressure gradient or z80% with no gradient necessary and (2) systolic hypertension of z155 mm Hg on z2 antihypertensive medications. Randomization will occur in 1080 subjects. The study has 90% power to detect a 28% reduction in primary end point hazard rate. Conclusions CORAL represents a unique opportunity to determine the incremental value of stent revascularization, in addition to optimal medical therapy, for the treatment of atherosclerotic renal artery stenosis. (Am Heart J 2006;152:59- 66.)

Medical Therapy vs. Stent-Angioplasty Survival Multivariate Cox regression analysis for mortality risk Relative risk for death (CI) P-value Revascularization 0,55 (0,34-0,88) 0,013 Age 1,03 (1,0-1,1) 0,04 CKD stage 1/ 2 1 CKD stage 3 3,00 (1,49- 6,03) 0,002 CKD stage 4/ 5 4,30 (2,06- 8,97) <0,0001 Parameter included into multivariate analysis: Age, intermittent dialysis, diabetes mellitus, ACE-inhibitor- or AT1-RB, statin therapy, CKD stage, pulse pressure. Kalra PA, Zeller T et al. The benefit of renal artery stenting in patients with atheromatous renovascular disease and advanced chronic kidney disease. Cath Cardiovasc Intervent 2010;75:1-10.

Zusammenfassung Es gibt eine Gruppe von Patienten , die von einer Intervention der NAST maximal profitiert. Es gibt allerdings derzeit keine Methode, die mit absoluter Sicherheit vorhersagen kann, welcher Patient von der Intervention profitiert.

Nephrologe Interventionist Resistente HTN NAST ja  PTA/Stent ?? Courtesy M.Haumer

Nephrologe Interventionist Resistente HTN NAST nein  RDN Courtesy M.Haumer

Nephrologe Interventionist Resistente HTN NAST ja  PTA/Stent ?? NAST nein  RDN Courtesy M.Haumer

Treatment strategies for RAD (1) Medical therapy Recommendations Class Level ACE inhibitors, angiotensin II receptor blockers, and calcium channel blockers are effective medications for treatment of hypertension associated with unilateral RAS. I B ACE inhibitors and angiotensin II receptor blockers are contraindicated in bilateral severe RAS and in case of RAS in a single functional kidney. III ACE = angiotensin-converting enzyme; RAS = renal artery stenosis.

as hypokalemia, an abdominal bruit, the absence of a family history of essential hypertension, a duration of hypertension of less than one year, and the onset of hypertension before the age of 50 years, are more suggestive of renovascular hypertension than of other types of hypertension,11 but none have strong predictive value. In fact, the majority of patients with renal-artery stenosis who have hypertension have essential hypertension, as suggested by the fact that the hypertension usually persists despite successful revascularization

Aktuelle Metaanalysen? Angioplastie der Nierenarterien bringt Nichts zur Verbesserung der RR-Einstellung Verbesserung der Nierenfunktion Verbesserung der Prognose . Lehrer Lämpel in einer kolorierten Fassung des Max und Moritz Do device characteristics impact outcome in carotid artery stenting? Joseph P. Hart, MD,a,c Patrick Peeters, MD,b Jurgen Verbist, MD,b Koen Deloose, MD,a and Marc Bosiers, MD,a Dendermonde and Bonheiden, Belgium; and Rochester, NY Objectives: The study was conducted to identify patient and procedural parameters that negatively impact the 30-day rates for stroke, death and transient ischemic attack (TIA) after carotid artery stenting (CAS) and that might be modified or further studied in future efforts to improve CAS. Methods: This was a retrospective investigation of a dual-center CAS database of 701 consecutive CAS patients (414 men; mean age, 72.4 8.4). A subset of patient-related, lesion-related, or procedure-related variables (age >80, left sided lesion, symptomatic, nicotine abuse, hypertension, diabetes mellitus, other peripheral vascular disease, hypercholesterolemia, embolic protection devices usage, predilation, ulcerated lesion, echolucent plaque, restenosis after surgery) were analyzed for association with occurrence of stroke, death, or TIA <30 days after CAS. The odds ratio (OR) and 95% confidence interval (CI) and P value were calculated for each variable to predict adverse outcome. Results: The overall combined rate of stroke, death, and TIA within this database was 3.7% at 30 days. In the total population of 701 patients, only the OR of 2.7 for hypercholesterolemia (95% CI, 1.0 to 7.3; P .041) was found to be significant. Subgroup analysis of the 304 symptomatic patients (43%) showed that open-cell stent designs and concentric EPD designs yielded an OR of 4.1 (95% CI, 1.4 to 12, P .0136) and 3.3 (95% CI, 1.016 to 10, P .0525), respectively, for 30-day stroke/death/TIA within this database. Analysis of open-cell stent designs and concentric EPD designs in patients with echolucent lesions yielded an OR of 3.1 (95% CI,1.2 to 8.2, P .0343) and 3.7 (95% CI, 1.3 to 10, P .0174), respectively, for 30-day stroke/death/TIA. Conclusions: We conclude that increased analysis of device design variables may be necessary. Particularly in symptomatic patients or with echolucent lesions, closed-cell design and eccentric filters seem superior. Prospective investigation comparing open-cell vs closed-cell stents and eccentric vs concentric filter devices may be warranted. ( J Vasc Surg 2006; 44:725-30.)

NAST - Angioplastie und Blutdruck Prädiktor für Erfolg Hyperämischer systolischer Druckgradient[Papaverin] ≥21mmHg Globale Testgenauigkeit [AUCROC] 0.87 Background We sought to systematically evaluate whether percutaneous revascularization is associated with additional clinical benefit in patients with renal artery stenosis (RAS) as compared with medical management alone. Methods We included randomized controlled trials that compared percutaneous revascularization in addition to medical therapy versus medical management alone in patients with RAS. Six trials with 1,208 patients were included. Results At a mean follow-up of 29 months, there was no change in systolic blood pressure (weighted mean difference [WMD] = 1.20 mm Hg, 95% CI −1.18 to 3.58 mm Hg) or diastolic blood pressure (WMD = −1.60 mm Hg, 95% CI −4.22 to 1.02 mm Hg) from baseline in the percutaneous revascularization arm compared with the medical management arm. There was a reduction in the mean number of antihypertensive medications (WMD = −0.26, 95% CI −0.39 to −0.13, P b .001), but not serum creatinine (WMD = −0.14 mg/dL, 95% CI −0.29 to 0.007 mg/dL), in the percutaneous revascularization arm at the end of follow-up. Percutaneous revascularization was not associated with a significant difference in all-cause mortality (relative risk [RR] = 0.96, 95% CI 0.74-1.25), congestive heart failure (RR = 0.79, 95% CI 0.56-1.13), stroke (RR = 0.86, 95% CI 0.50-1.47), or worsening renal function (RR = 0.91, 95% CI 0.67-1.23) as compared with medical management. Conclusions In patients with RAS, percutaneous renal revascularization in addition to medical therapy may result in a lower requirement for antihypertensive medications, but not with improvements in serum creatinine or clinical outcomes, as compared with medical management over an intermediate period of follow-up. Further studies are needed to identify the appropriate patient population most likely to benefit from its use. (Am Heart J 2011;161:622-630.e1.) Lesaar MA et al. JACC 2009;53:2363-71.

NAST Angioplastie und Blutdruck 3 randomisierte Studien Limitation STAR ASTRAL CORAL N 140 806 1080 Indikation CRI Stenosegrad ≤70% 33% 40% NA Ischämienachweis nein ja/nein eGFR [mL/min/1.73m2] 45 40 (25% >50) ? S-Krea [mg/dL] 1.7 2.0 <3.0 1°EP eGFR 20% 1/S-Krea S-Krea x2 Inclusion Bias! STAR Ann Intern Med 2009;150:840-8; ASTRAL NEJM 2009;361:1953-62; CORAL Am Heart J 2006;59-66.

NAST Angioplastie und Nierenfunktion 4 randomisierte Studien Background We sought to systematically evaluate whether percutaneous revascularization is associated with additional clinical benefit in patients with renal artery stenosis (RAS) as compared with medical management alone. Methods We included randomized controlled trials that compared percutaneous revascularization in addition to medical therapy versus medical management alone in patients with RAS. Six trials with 1,208 patients were included. Results At a mean follow-up of 29 months, there was no change in systolic blood pressure (weighted mean difference [WMD] = 1.20 mm Hg, 95% CI −1.18 to 3.58 mm Hg) or diastolic blood pressure (WMD = −1.60 mm Hg, 95% CI −4.22 to 1.02 mm Hg) from baseline in the percutaneous revascularization arm compared with the medical management arm. There was a reduction in the mean number of antihypertensive medications (WMD = −0.26, 95% CI −0.39 to −0.13, P b .001), but not serum creatinine (WMD = −0.14 mg/dL, 95% CI −0.29 to 0.007 mg/dL), in the percutaneous revascularization arm at the end of follow-up. Percutaneous revascularization was not associated with a significant difference in all-cause mortality (relative risk [RR] = 0.96, 95% CI 0.74-1.25), congestive heart failure (RR = 0.79, 95% CI 0.56-1.13), stroke (RR = 0.86, 95% CI 0.50-1.47), or worsening renal function (RR = 0.91, 95% CI 0.67-1.23) as compared with medical management. Conclusions In patients with RAS, percutaneous renal revascularization in addition to medical therapy may result in a lower requirement for antihypertensive medications, but not with improvements in serum creatinine or clinical outcomes, as compared with medical management over an intermediate period of follow-up. Further studies are needed to identify the appropriate patient population most likely to benefit from its use. (Am Heart J 2011;161:622-630.e1.) Mean FU 29 Mo Kumbhani DJ et al. Am Heart J 2011;161:622-30.

NAST Angioplastie und Nierenfunktion 6 randomisierte Studien Background We sought to systematically evaluate whether percutaneous revascularization is associated with additional clinical benefit in patients with renal artery stenosis (RAS) as compared with medical management alone. Methods We included randomized controlled trials that compared percutaneous revascularization in addition to medical therapy versus medical management alone in patients with RAS. Six trials with 1,208 patients were included. Results At a mean follow-up of 29 months, there was no change in systolic blood pressure (weighted mean difference [WMD] = 1.20 mm Hg, 95% CI −1.18 to 3.58 mm Hg) or diastolic blood pressure (WMD = −1.60 mm Hg, 95% CI −4.22 to 1.02 mm Hg) from baseline in the percutaneous revascularization arm compared with the medical management arm. There was a reduction in the mean number of antihypertensive medications (WMD = −0.26, 95% CI −0.39 to −0.13, P b .001), but not serum creatinine (WMD = −0.14 mg/dL, 95% CI −0.29 to 0.007 mg/dL), in the percutaneous revascularization arm at the end of follow-up. Percutaneous revascularization was not associated with a significant difference in all-cause mortality (relative risk [RR] = 0.96, 95% CI 0.74-1.25), congestive heart failure (RR = 0.79, 95% CI 0.56-1.13), stroke (RR = 0.86, 95% CI 0.50-1.47), or worsening renal function (RR = 0.91, 95% CI 0.67-1.23) as compared with medical management. Conclusions In patients with RAS, percutaneous renal revascularization in addition to medical therapy may result in a lower requirement for antihypertensive medications, but not with improvements in serum creatinine or clinical outcomes, as compared with medical management over an intermediate period of follow-up. Further studies are needed to identify the appropriate patient population most likely to benefit from its use. (Am Heart J 2011;161:622-630.e1.) Kumbhani DJ et al. Am Heart J 2011;161:622-30.

NAST Angioplastie und Nierenfunktion Beobachtungs-Studien Background We sought to systematically evaluate whether percutaneous revascularization is associated with additional clinical benefit in patients with renal artery stenosis (RAS) as compared with medical management alone. Methods We included randomized controlled trials that compared percutaneous revascularization in addition to medical therapy versus medical management alone in patients with RAS. Six trials with 1,208 patients were included. Results At a mean follow-up of 29 months, there was no change in systolic blood pressure (weighted mean difference [WMD] = 1.20 mm Hg, 95% CI −1.18 to 3.58 mm Hg) or diastolic blood pressure (WMD = −1.60 mm Hg, 95% CI −4.22 to 1.02 mm Hg) from baseline in the percutaneous revascularization arm compared with the medical management arm. There was a reduction in the mean number of antihypertensive medications (WMD = −0.26, 95% CI −0.39 to −0.13, P b .001), but not serum creatinine (WMD = −0.14 mg/dL, 95% CI −0.29 to 0.007 mg/dL), in the percutaneous revascularization arm at the end of follow-up. Percutaneous revascularization was not associated with a significant difference in all-cause mortality (relative risk [RR] = 0.96, 95% CI 0.74-1.25), congestive heart failure (RR = 0.79, 95% CI 0.56-1.13), stroke (RR = 0.86, 95% CI 0.50-1.47), or worsening renal function (RR = 0.91, 95% CI 0.67-1.23) as compared with medical management. Conclusions In patients with RAS, percutaneous renal revascularization in addition to medical therapy may result in a lower requirement for antihypertensive medications, but not with improvements in serum creatinine or clinical outcomes, as compared with medical management over an intermediate period of follow-up. Further studies are needed to identify the appropriate patient population most likely to benefit from its use. (Am Heart J 2011;161:622-630.e1.) Holden A et al. Kidney Int 2006;70:948-55.

Mögliche Indikationen für PTRA nach Garovic VD, Textor SC Circulation 2005;112:1362-74.

NEJM 2001

Klinische Anhaltspunkte für NAST Onset HTN nach 55 Jahren Exacerbation einer gut eingestellten HTN Maligne or refraktäre HTN Epigastrisches Geräusch (systolic/diastolic) Unerklärte Azotämie Azotämie während ACEI, ARB Atrophe Nieren, Diskrepanz in Grösse Rekurrente CHF or ‘flash’ Lungenödem Atherosklerose irgendwo

RI als Erfolgsprädiktor nach PTA RI = {1-[Vmin/Vmax]} x 100 Radermacher J, et al. Hypertension. 2002;39:699-703.

Treatment strategies for RAD (2) Endovascular and surgical therapy Recommendations Class Level Endovascular therapy Angioplasty, preferably with stenting, may be considered in the case of >60% symptomatic RAS secondary to atherosclerosis. IIb A In the case of indication for angioplasty, stenting is recommended in ostial atherosclerotic RAS. I B Endovascular treatment of RAS may be considered in patients with impaired renal function. Treatment of RAS, by balloon angioplasty with or without stenting, may be considered for patients with RAS and unexplained recurrent congestive heart failure or sudden pulmonary oedema and preserved systolic left ventricular function. C Surgical therapy Surgical revascularization may be considered for patients undergoing surgical repair of the aorta, patients with complex anatomy of the renal arteries, or after a failed endovascular procedure. RAS = renal artery stenosis.

NAST – PTA-Indikationen klinische Situation Empfehlung Evidenzgrad vorher unbekannt plötzlich auftretendes Lungenödem + hypertensive Entgleisung I B nein akzeleriert, therapierefraktäre oder maligne Hypertonie mit Endorganschäden IIa Niereninsuffizienz + bilaterale NAST oder funktionelle Einzelniere instabile Angina pectoris ja Asymptomatische bilaterale NAST oder funktionelle Einzelniere IIb C Unilaterale Stenose ± Niereninsuffizienz

Renovaskuläre Hypertonie wer soll getestet werden Schwere, therapierefraktäre Hypertonie Neuauftreten oder akute Verschlechterung Akuter Kreatininanstieg (ev. unter ACEI) pAVK und unilateral kleine Niere (<9 cm) Rezidivierende Lungenödeme ACEI-sensible Patienten

Indikationen für Revaskularisation Bilaterale Stenose >60% oder Einzelniere + eingeschränkte Nierenfunktion Bilaterale Stenose>60% oder Einzelniere + therapierefraktäre Hypertension Uni oder bilaterale Stenose > 60% + flush Lungenödem Uni oder bilaterale Stenose >60% + Hypertension oder inzipiente Nephropathie + RI <80 Uni oder bilaterale Stenose >60% + Hypertonie + FMD Uni oder bilaterale Stenose >60% + eingeschränkte Nierenfunktion + FMD

Courtesy A.Rosenkranz

ASTRAL Course of Blood Pressure N Engl J Med 2009;361:1953-62. 68

Patients were enrolled in the trial only if their own physician was uncertain as to whether revascularization would provide a worthwhile clinical benefit.

What is a “significant” renal artery stenosis? After Stenting: Graded Renal Stenoses Inflation of the balloon (1 mm smaller than the stent) to produce a Controlled Gradient Pd / Pa of .... 1 0.9 0.8 0.7 0.6 0.5 10 min 10 min 10 min 10 min 10 min 10 min Dosage of renin Controlled Unilateral RAS B. De Bruyne et al JACC 2006

Prediction of Hypertension Improvement After Stenting of Renal Artery Stenosis Comparative Accuracy of Translesional Pressure Gradients, Intravascular Ultrasound, and Angiography Lesaar MA et al. J Am Coll Cardiol 2009;53: 2363–71 Conclusions An HSG ≥ 21 mm Hg provided the highest accuracy in predicting hypertension improvement after stenting of RAS, suggesting that an HSG ≥ 21 mm Hg is indicative of significant RAS

NAST Angioplastie und Blutdruck 3 randomisierte Studien Nordmann AJ et al. Am J Med 2003;114:44-50.

Nordman et al., Am J Med 2003;114:44-50 Revascularization of RAD Blood Pressure Control – RCT‘s prior to ASTRAL Nordman et al., Am J Med 2003;114:44-50

ASTRAL - PLOT OF SCr OVER TIME Primary Endpoint at 2 years 30% & 46% lost for follow-up! N Engl J Med 2009;361:1953-62

ANGIOGRAPHIC DATA BY RANDOMIZED TREATMENT Revasc. Medical P-value % Stenosis 76% (40 – 100%) 75% (20 – 100%) 0.3 Renal length 9.7cm (6 – 14) 9.7cm (6 – 20) 0.5 Location of ostial/distal ARVD lesion Left kidney 24% 20% 0.2 Right kidney 18% 17% Both 50% 57% Missing data 8% 6% Derriford Hosp, Plymouth Medical Left 100 Yes Yes 90 Yes Yes Hull Royal Inf Revascularisation Left 100 Yes Yes 0 No No Arrowe Park Hosp, Wirral Medical Left 100 Yes Yes 60 Yes Yes 635 Gosford Hospital, Australia Revascularisation Right 80 Yes Yes 100 Yes Yes The method of diagnosis for these patients were unknown (n=1), MRA (n=1) and CT (n=2). 49% of patients < 70% diameter stenosis by visual estimation N Engl J Med 2009;361:1953-62

RAD and Hypertension Summary of data of uncontrolled studies Fibromuscular dysplasia Atherosclerotic RAD cured cured & improved 50 – 85% 85 - 100% 5 – 15% 50 – 70% Zeller T. Renal artery stenosis. Current Treatment Options in Cardiovascular Medicine 2007:9:90

After Stenting: Graded Renal Stenoses What is a “significant” renal artery stenosis? After Stenting: Graded Renal Stenoses B. De Bruyne et al JACC 2006