Renal denervation therapy: The 1st Malaysia experience

INSTITUT JANTUNG NEGARA

DR. ROBAAYAH ZAMBAHARI DR. AZLAN HUSSEIN DR. SHAIFUL AZMI YAHAYA

Date JANUARY 2012

Catheter-based treatment for renal symphatetic denervation

Treatment using the Symplicity Catheter

Transcatheter renal denervation trials: Chronology

The burden of hypertension in Malaysia

The prevalence of hypertension in Malaysians aged 30 years and above was 42.6% in 2006 4.8 million individuals with hypertension in Malaysia 3rd National health and morbidity survey in 2006 revealed 2/3 of individuals in Malaysia with hypertension were unaware that they have hypertension Only 26% of Malaysian patients achieved blood pressure control while on treatment
Source: MOH/P/PAK/158/Malaysia clinical practice guidelines for the management of hypertension 2008 (3rd edition)

Transcathether renal denervation for the treatment of resistant hypertension: The first IJN experience
Setting up resistant hypertension clinic IJN (Malaysian National Heart Institute) is the first centre in Asia to perform the renal denervation on the 11th September 2010. Performed using the Symplicity Cathether system (Ardian Medtronic) Presence of a proctor- Dr. Justin Davies (Interventional cardiologist and Walport clinical lecturer at Imperial College, London)

IJN resistant hypertension clinic website and facebook page

Methods
Patients referred to IJN resistant hypertension clinic Stratified based on inclusion and exclusion criteria Medication compliance assessment Ambulatory blood pressure monitoring/investigations Screening for secondary hypertension Consented for renal denervation therapy Follow up

Inclusion criterias
Based on the SYMPLICITY-HTN 2 trial Systolic BP of more than 160 mmHg based on average 3 office BP reading previously measured (more than 150 mmHg for type 2 DM) Patient is adhering to a stable 3 or more antihypertensive medications Patient is 18-85 years of age

Exclusion criterias
Renal artery abnormalities ( Renal artery stenosis, diameter less than 4mm or 20mm in length) EGFR of less than (45ml/min/1.73m2) based on MDRD calculation criteria Type 1 diabetes mellitus Recent MI, Unstable angina and CVA within the last 6 months or scheduled or planned surgery in the next 6 months Haemodynamically significant valvular heart disease Pregnant, nursing or planning to be pregnant

Patient group
43 patients referred to the IJN resistant hypertension clinic
(N=4) excluded due to not meeting initial inclusion criteria (N=25) Resistant Hypertension (N=14) White coat hypertension

(N=10) consented for renal denervation therapy

(N=12) declined to participate and withdrew consent

(N=3) excluded due to renal impairment

Period between August 2010 January 2012

Patient Age distribution

Ethnic group and sex

Cardiovascular risk factors

Antihypertensive medications

N= 39 Resistant Hypertension=25 White coat HTN=14

*4 patients excluded

Classes of anti hypertensive medications

Average baseline office BP based on 3 previous outpatient clinic visits prior to referral

Patient is on 4 antihypertensive medications

Ambulatory BP results pre procedure

Results
Blood pressure changes from baseline and at follow up (2 weeks, 1 month, 3 month, 6 month and 12 month) Acute procedural safety and chronic procedural safety EGFR and renal profile at 2 weeks, 1 month and 3 month follow up Fasting sugar and HBAIC at 6 month follow up Composite cardiovascular endpoints (MACE)

Procedural analysis
Right renal artery ablation Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 2 5 5 3 2 Left renal artery ablation 4 5 5 4 0 Immediate procedural complications no no no no BP dropped to systolic 60 requiring inotrope and iv fluid no no Back pain resolved after 2 weeks no

Patient 6 Patient 7 Patient 8 Patient 9

6 6 6 6

5 4 5 5

EGFR at follow up post procedure

Transient drop in one of the patient EGFR is preserved of at least more than 45 mls/min/1.73m2 during follow up

On average, the EGFR did not show any significant change

Results of ABPM at follow up: Average 24 hour ABPM

Pre RDN ABPM Patient 1 Patient 2 Patient 3 133/64 148/87 144/75 ABPM at 2 weeks 171/87 150/96 178/85 ABPM at 1 month 156/83 147/95 138/72 ABPM at 3 month 118/55 154/109 175/85

Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9

146/82 154/91 137/58 188/93 157/104 157/75

141/65 127/79 147/66 177/88 156/108 118/57

148/77 150/81 122/63 147/95 195/125

140/81

138/65

Pre RDN
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 160 182 167 165 189 170 226 186 203

Follow up at 2 week
198 169 198 172 153 179 226 191 145

Results: Systolic BP (max)

Follow up at 1 month
189 170 167 171 186 148 168 150 182 197 168

Follow up at 3 month

232

Result: Diastolic BP (max)

Pre RDN Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 73 104 85 98 109 72 109 120 Follow up at 2 weeks Follow up at 1 month Follow up at 3 month 98 108 92 76 94 73 109 132 145 99 109 85 98 101 71 80 66 121 94 94

Patient 9

88

65

Result: Mean BP
Pre RDN Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 105 126 113 133 134 105 Follow up at 2 weeks Follow up at 1 month Follow up at 3 month 129 130 130 117 115 112 129 130 114 140 129 100 109 94 143 130 122

Patient 7
Patient 8 Patient 9

149
144 126

150
152 89 176

Results: Average 24 hour Systolic difference at F/U

Result: Average 24 hour Diastolic difference at F/U

SYMPLICITY HTN-2: Results

Average office-based BP in the renal-denervation group was reduced 32/12 mm Hg (average baseline 178/96 mm Hg) six months after the ablation
Between-group differences in BP at six months were 33/11 mm Hg (p<0.0001) Of the patients in the ablation arm, 84% had a 10-mm-Hg or greater drop in SBP vs 35% of controls (p<0.0001)

There did not appear to be any adverse events:

Imaging of renal arteries for damage showed no evidence of renal artery stenosis or aneurysmal dilatation during the six-month followup . There were no changes in renal function, even in those with mild to moderate renal failure

Conclusions
Percutaneous catheter-based theraputic renal denervation is safe and simple Symplicity 2 study has shown that there is BP lowering benefit with no significant decline in renal function Longer follow up is necessary to observe further response to BP stabilization in our small cohort