E. Minar

Report
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
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 )
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
Recommendations
Class Level
DUS is recommended as the first-line imaging test to establish
the diagnosis of RAS.
CTA (in patients with creatinine clearance >60 mL/min) is
recommended to establish the diagnosis of RAS.
MRA (in patients with creatinine clearance >30 mL/min) is
recommended to establish the diagnosis of RAS.
When the clinical index of suspicion is high and the results of
non-invasive tests are inconclusive, DSA is recommended as a
diagnostic test (prepared for intervention) to establish the
diagnosis of RAS.
Captopril renal scintigraphy, selective renal vein renin
measurements, plasma renin activity, and the captopril test are
not recommended as useful screening tests to establish the
diagnosis of RAS.
I
B
I
B
I
B
I
C
III
B
1
CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex
ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.
Diagnostic strategies for RAD
Recommendations
Class Level
DUS is recommended as the first-line imaging test to establish
the diagnosis of RAS.
CTA (in patients with creatinine clearance >60 mL/min) is
recommended to establish the diagnosis of RAS.
MRA (in patients with creatinine clearance >30 mL/min) is
recommended to establish the diagnosis of RAS.
When the clinical index of suspicion is high and the results of
non-invasive tests are inconclusive, DSA is recommended as a
diagnostic test (prepared for intervention) to establish the
diagnosis of RAS.
Captopril renal scintigraphy, selective renal vein renin
measurements, plasma renin activity, and the captopril test are
not recommended as useful screening tests to establish the
diagnosis of RAS.
I
B
I
B
I
B
I
C
III
B
1
CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex
ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.
Diagnostic strategies for RAD
Recommendations
Class Level
DUS is recommended as the first-line imaging test to establish
the diagnosis of RAS.
CTA (in patients with creatinine clearance >60 mL/min) is
recommended to establish the diagnosis of RAS.
MRA (in patients with creatinine clearance >30 mL/min) is
recommended to establish the diagnosis of RAS.
When the clinical index of suspicion is high and the results of
non-invasive tests are inconclusive, DSA is recommended as a
diagnostic test (prepared for intervention) to establish the
diagnosis of RAS.
Captopril renal scintigraphy, selective renal vein renin
measurements, plasma renin activity, and the captopril test are
not recommended as useful screening tests to establish the
diagnosis of RAS.
I
B
I
B
I
B
I
C
III
B
1
CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex
ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.
Diagnostic strategies for RAD
Recommendations
Class Level
DUS is recommended as the first-line imaging test to establish
the diagnosis of RAS.
CTA (in patients with creatinine clearance >60 mL/min) is
recommended to establish the diagnosis of RAS.
MRA (in patients with creatinine clearance >30 mL/min) is
recommended to establish the diagnosis of RAS.
When the clinical index of suspicion is high and the results of
non-invasive tests are inconclusive, DSA is recommended as a
diagnostic test (prepared for intervention) to establish the
diagnosis of RAS.
Captopril renal scintigraphy, selective renal vein renin
measurements, plasma renin activity, and the captopril test are
not recommended as useful screening tests to establish the
diagnosis of RAS.
I
B
I
B
I
B
I
C
III
B
1
CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex
ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.
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
Clinical outcomes after percutaneous revascularization versus medical
management in patients with significant renal artery stenosis: A metaanalysis of randomized controlled trials
Kumbhani DJ ; Am Heart J 2011;161:622-630
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.
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
Sollte man ?
RR 196/104 –
3 verschiedene Antihypertensiva
JA !!
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
Medical Therapy vs. Stent-Angioplasty Survival
Multivariate Cox regression analysis for mortality risk
Revascularization
Age
CKD stage 1/ 2
Relative risk for death (CI)
P-value
0,55 (0,34-0,88)
0,013
1,03 (1,0-1,1)
0,04
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.
Interventionist
NAST ja
 PTA/Stent ??
Nephrologe
Resistente HTN
Courtesy
M.Haumer
Interventionist
NAST nein  RDN
Nephrologe
Resistente HTN
Courtesy
M.Haumer
Interventionist
Nephrologe
Resistente HTN
NAST ja
 PTA/Stent ??
NAST nein  RDN
Courtesy
M.Haumer
Treatment strategies for RAD (1)
Medical therapy
Recommendations
Class
ACE inhibitors, angiotensin II receptor blockers, and I
calcium channel blockers are effective medications
for treatment of hypertension associated with
unilateral RAS.
ACE inhibitors and angiotensin II receptor blockers III
are contraindicated in bilateral severe RAS and in
case of RAS in a single functional kidney.
ACE = angiotensin-converting enzyme; RAS = renal artery stenosis.
Level
B
B
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
.
NAST - Angioplastie und Blutdruck
Prädiktor für Erfolg
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
CRI
CRI
Stenosegrad ≤70%
33%
40%
NA
Ischämienachweis
nein
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
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
Mean FU 29 Mo
Kumbhani DJ et al. Am Heart J 2011;161:622-30.
NAST Angioplastie und Nierenfunktion
6 randomisierte Studien
Kumbhani DJ et al. Am Heart J 2011;161:622-30.
NAST Angioplastie und Nierenfunktion
Beobachtungs-Studien
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
Endovascular therapy
Angioplasty, preferably with stenting, may be considered in the case
of >60% symptomatic RAS secondary to atherosclerosis.
In the case of indication for angioplasty, stenting is recommended in
ostial atherosclerotic RAS.
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.
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.
Class Level
IIb
A
I
B
IIb
B
IIb
C
IIb
C
NAST – PTA-Indikationen
klinische Situation
Empfehlung
Evidenzgrad
vorher
unbekannt
I
B
nein
akzeleriert, therapierefraktäre oder
maligne Hypertonie mit Endorganschäden
IIa
B
nein
Niereninsuffizienz + bilaterale NAST oder
funktionelle Einzelniere
IIa
B
nein
instabile Angina pectoris
IIa
B
ja
Asymptomatische bilaterale NAST oder
funktionelle Einzelniere
IIb
C
ja
Unilaterale Stenose ± Niereninsuffizienz
IIb
C
ja
plötzlich auftretendes Lungenödem +
hypertensive Entgleisung
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.
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
10 min
0.9
10 min
0.8
10 min
0.7
10 min
0.6
10 min
0.5
10 min
Controlled Unilateral RAS
1
Dosage of renin
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.
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
P = 0.06
30%
&
46% lost for follow-up!
N Engl J Med 2009;361:1953-62
ANGIOGRAPHIC DATA BY RANDOMIZED TREATMENT
% Stenosis
Renal length
Revasc.
Medical
P-value
76% (40 – 100%)
75% (20 – 100%)
0.3
9.7cm (6 – 14)
9.7cm (6 – 20)
0.5
0.2
Location of ostial/distal ARVD lesion
Left kidney
24%
20%
Right kidney
18%
17%
Both
50%
57%
Missing data
8%
6%
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
What is a “significant” renal artery stenosis?
After Stenting: Graded Renal Stenoses
500
P er cen t In cr ease in R en in
400
300
200
100
0
1(BL1)
1 (BL 2)
0.9
0.8
0.7
0.6
D eg r ee o f S ten o sis (P d /P a )
B. De Bruyne et al JACC 2006
0.5
1 (End)

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