Renal Denervation Current evidence and new

technical developments OA Dr. med Massimiliano Fusaro

fusaro@dhm.mhn.de

Deutsches Herzzentrum and 1. Medizinische Klinik, Klinikum rechts der Isar Technische Universität - Munich, GERMANY

SITE 2013 Barcelona, 9 May 2013

75M Patients with HTN

Diagnosed HTN

Treated HTN

Uncontrolled HTN

US Patients with HTN 75M

Diagnosed HTN 78%

Treated HTN 68%

Uncontrolled HTN 38%

Resistant HTN 9%

Lloyd-Jones D: Circulation 2010;121:e46 – e215 Persell SD: Hypertension 2011;57:1076-1080

 •  Blood pressure >140/90 mmHg •  Diabetes mellitus >130-139/85 •  Chronic renal disease >130/80

In the presence of three or more antihypertensive drugs of different classes (including diuretic) at

maximal or highest tolerated dose

(European society of hypertension and ESC Guidelines)

 

1Chobanian et al. Hypertension 2003;42:1206-1252 2Lancet 2002;360:1903-1913

1940s 1950s 1960s 1970s 1980s 1990s 2000s

Peripheral Sympatholytics

Ganglion Blockers

Veratrum Alkaloids

Direct Vasodilators

Thiazide Diuretics

Central Alpha2

Agonists

Beta Blockers

Alpha Blockers

DHP CCBs

ACE Inhibitors

ARBs DRIs

38% of HTN population remain Uncontrolled

9% of HTN population remain resistant

0

Effec&veness  

Side  Effects  

90.5%  of  all  nerves  existed  within  2.0  mm  of  the  renal  artery  lumen  

Denerva&on  Sites  

• Catheter-­‐based  delivery  of  low-­‐power  RF  energy  administered  at  mul&ple  site,  ensures  denerva&on  

• Bilateral  denerva&on  required  • Asa  required  during  and  aKer  4  weeks  • Seda&on  and  analgesia  mandatory  

-19 -21 -22

-26

-33 -33

-9 -10 -10

-13 -15

-19

1M (n=143) 3M (n=148) 6M (n=144) 12M (n=130) 24M (n=59) 36M (n=24)

BP

chan

ge (m

m H

g)

Systolic BP Diastolic BP

Lancet. 2010. published electronically on November 17, 2010

Symplicity HTN-2 Investigators. The Lancet. 2010.

•  Purpose: To demonstrate the effectiveness of catheter-based renal denervation for reducing blood pressure in patients with uncontrolled hypertension in a prospective, randomized, controlled, clinical trial

•  Patients: 106 patients randomized 1:1 to treatment with renal denervation vs. control

•  Clinical Sites: 24 centers in Europe, Australia, & New Zealand (67% were designated hypertension centers of excellence)

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Inclusion Criteria: –  Office SBP ≥ 160 mmHg (≥ 150 mmHg with type II diabetes mellitus) –  Stable drug regimen of 3+ more anti-HTN medications –  Age 18-85 years

Exclusion Criteria: –  Hemodynamically or anatomically significant renal artery abnormalities or prior renal

artery intervention –  eGFR < 45 mL/min/1.73m2 (MDRD formula) –  Type 1 diabetes mellitus –  Contraindication to MRI –  Stenotic valvular heart disease for which reduction of BP would be hazardous –  MI, unstable angina, or CVA in the prior 6 months

Symplicity HTN-2 Investigators. The Lancet. 2010. 12

Symplicity HTN-2 Investigators. The Lancet. 2010.

-32

1

-12

0

-50

-40

-30

-20

-10

0

10 RDN (n=49) Control (n=51)

∆ from Baseline

to 6 Months (mmHg)

33/11 mmHg difference between RDN and Control

(p<0.0001)

•  84% of RDN patients had ≥ 10 mmHg reduction in SBP •  10% of RDN patients had no reduction in SBP

13

Systolic

Diastolic

Systolic Diastolic

•  No serious device or procedure related adverse events (n=52) •  Minor adverse events •  1 femoral artery pseudoaneurysm treated with manual compression

•  1 post-procedural drop in BP resulting in a reduction in medication

•  1 urinary tract infection

•  1 prolonged hospitalization for evaluation of paraesthesias

•  1 back pain treated with pain medications & resolved after one month

•  6-month renal imaging (n=43) •  No vascular abnormality at any RF treatment site •  1 MRA indicates possible progression of a pre-existing stenosis unrelated to

RF treatment (no further therapy warranted)

Symplicity HTN-2 Investigators. The Lancet. 2010. 14

Mahfoud F et al. Eur Heart J 2013

1.  Office-based systolic BP ≥ 160 mmHg (≥150 mmHg diabetes type 2) 2.  ≥3 antihypertensive drugs in adequate dosage and combination

(incl. diuretic) 3.  Lifestyle modification 4.  Exclusion of secondary hypertension 5.  Exclusion of pseudo-resistance using ABPM (average BP > 130

mmHg or mean daytime BP > 135 mmHg) 6.  Preserved renal function (GFR ≥45 ml/min/1.73 m2) 7.  Eligible renal arteries: no polar or accessory arteries, no renal artery

stenosis, no prior revascularization

BP, blood pressure; ABPM, ambulatory blood pressure monitoring;

GFR, glomerular filtration rate.

Baseline 3 Mo 6 Mo 12 Mo 24 Mo 36 Mo 48 Mo 60 Mo Office BP X X X X X X X X

ABPM X X X X X X X X

Heart rate X X X X X X X X

Body weight X X X X X X X X

Review medications X X X X X X X X

Blood tests, including GFR determination X X X X X X X X

ECG X X X X X X X

Renal artery imaging (duplex ultrasound, MRI/CT with contrast or angiogram)

X X X X X X X

Oral glucose tolerance test (where appropriate) X X X X X X X

Echocardiography in patients with heart failure or left ventricular hypertrophy X X X X X X X

UACR in patients with albuminuria X X X X X X X X

BP, blood pressure; ABPM, ambulatory blood pressure monitoring;

GFR, glomerular filtration rate UACR, urine albumin to creatinine ratio.

•  Long-lasting effect of renal denervation beyond currently documented 36 months is uncertain

•  Repeated intervention for patients with inadequate response to a first RDN procedure has been raised. with present knowledge, this could not be recommended.

•  In contrast to some antihypertensive drug regimen, renal denervation has not been shown to affect cardiovascular morbidity and mortality. The multicentre, prospective, single-blinded, randomized, placebo-controlled

(NCT01418261) is recruiting patients in the USA, which will hopefully answer the question.

•  Diabetes mellitus and insulin resistance In a pilot study renal denervation positively influenced glucose metabolism in patients with resistant hypertension (Mahfoud F et al. Circulation 2011;123:1940-1946) •  Cardiac effects One published study investigated the effects of renal denervation on left ventricular mass and diastolic filling pattern in 46 patients with resistant hypertension. Renal denervation was associated with substantial reductions in blood pressure and significantly reduced left ventricular mass. Diastolic function was also improved (Brandt MC et al. J Am Coll Cardiol 2012;59:901-909) •  Chronic kidney disease In 15 patients with moderate-to-severe chronic kidney renal denervation was effective in terms of blood pressure lowering and there was no evidence of a further decline in GFR or effective renal plasma flow 6 months after the procedure. (Hering D et al J Am Soc Nephrol 2012;23:1250-1257) •  Antiarrhythmic effects 27 patients were randomized to pulmonary vein isolation alone or pulmonary vein isolation plus renal denervation. Besides significant reductions in blood pressure, patients in the pulmonary vein isolation plus renal denervation group experienced significantly fewer episodes of atrial fibrillation at follow-up. (Pokushalov E. et al. J Am Coll Cardiol 2012;60:1163-1170)

•  Catheter-based radiofrequency ablation of renal nerves reduces blood pressure and improves blood pressure control in patients with drug-treated resistant hypertension, with data now extending out to 36 months

•  In patients with resistant hypertension, whose blood

pressure cannot be controlled by a combination of lifestyle modification and pharmacological therapy according to current Guidelines

•  Renal denervation may also be beneficial in other clinical

states characterized by sympathetic nervous system activation