SHA24/081003

Resistant Hypertension Percutaneous Renal Interventions Shaiful Azmi Yahaya, MD, FNHAM Consultant Cardiologist, Kuala Lumpur, Malaysia Your Heart‌Our Passion

Disclosure Slide I have no conflict of interest in the context of this presentation

Resistant Hypertension Definition: Blood Pressure > target goals >140/90 mmHg,  despite taking 3 anti-hypertensive medications, or 

requiring > 4 anti-hypertensives to control.

These  patients are at risk for:  stroke  heart disease kidney failure.

Resistant Hypertension  The exact prevalence of Resistant Hypertension is unknown  A few large trials have indicated that it can be relatively common, between 16-27% of study population.  Control & Treatment of Hypertension is important.  Current treatment options: Lifestyle modification Pharmacotherapy  After ruling out secondary or reversible causes of elevated BP, the only options until recently have been to add more medications and diet regimes like DASH.

ďƒž These patients may benefit from special diagnostic and therapeutic considerations.

Percutaneous Renal Interventions 1) Renal Revascularization PTA

Pre

2) Renal Denervation RDN

Post

Percutaneous Renal Interventions 1) Renal Revascularization PTA

Pre

2) Renal Denervation RDN

Post

1) Renal Revascularization PTA • A retrospective review of patients who underwent renal artery revascularization at Institut Jantung Negara (National Heart Institute), Kuala Lumpur between October 1999 and February 2012. (n = 203) • Data at baseline and follow-up were compared using paired t-test or McNemar’s test • A p<0.05 was considered as statistical significant Age: Mean: 59.3 + 15.9 years Gender: Male: 119 (59%); Female: 84 (41%)

Associated Clinical Conditions: ď&#x201A;Ż

ď&#x201A;Ż

Percentage % of patients

Number of cases by year:

year

Number of cases by year: Initial enthusiasm with increasing number was

contributed by routine renal angiogram [with JR catheter], at end of procedure for patients with BP >160/90 mmHg and patients with multivessel disease.

 As literature showed debatable results of renal

stenting, coupled by increasing number of radial procedures, enthusiasm for the ‘drive-by shooting’ of renal arteries declined and numbers decreased

Clinical disease conditions:

Percentage % of patients

Clinical Indications for Revascularization:

Renal artery PTA

Location

Lesions Total number of lesions

238

Mean, % stenosis

80 ± 13

Stents Total number of stents

251

Mean, length, (mm)

15.1 ± 2.5 (5-24)

Mean, diameter size (mm)

5.5 ± 1.2 (2.5-8)

Direct stenting

116 (46.2%)

Mean, deployment pressure

12 ± 3 (6-22)

Mean stents per patient

1.2

Procedural success

Complications

n

Dissection Perforation Stent dislodgement Vascular access Complications Death Others

4 0 0 0 0 0 3

Systolic BP [Office BP] Significant reduction in SBP p=0.02

p<0.05

155±26

155±26 144±25

p=0.023

155±26 143±22

p=0.015

155±26 148±24

147±12

Diastolic BP [Office BP] No change in DBP p=0.527

80±16

79±11

p=0.611

80±16

78±14

p=0.831

80±16

79±12

p=0.737

80±16 78±12

No. of anti-hypertensive drugs Reduction in number of antihypertensives in first 12 months p=0.074

2.8±1.2

p=0.008

2.8±1.2 2.5±1.0

p=0.013

2.8±1.2 2.4±0.9

p=0.612

2.8±1.2 2.5±0.9

2.6±0.9

Creatinine No change in serum creatinine level p=0.620

147±108 150±86

p=0.172

147±108 147±120

p=0.608

147±108 153±137

p=0.329

147±108 154±142

Cumulative survivors (freedom from Death)

Month 0 12 24 36 48 60 72

No. at risk 181 138 121 107 90 69 47

Prob.

100% 95.2% 95.2% 93.6% 93.6% 93.6% 93.6%

Event Free Survival (freedom from Death, TLR, stroke)

Month 0 12 24 36 48 60 72

No. at risk 181 136 118 104 88 67 45

Prob.

100% 92.8% 92.8% 89.5% 87.7% 87.8% 87.7%

Renal Artery Revascularization: Conclusions: Limitations: single centre, small number [n=203],

ď&#x192;&#x2DC; The debate on the value of Percutaneous Renal Artery Revascularisation continues among nephrologists and interventionalists despite recent prospective randomized trial data. ď&#x192;&#x2DC; In our single centre experience, for patients with Renal Artery stenosis, percutaneous renal revascularization in addition to medical therapy, resulted in a lower Systolic Blood Pressure and transient reduction in number of antihypertensive medications.

Renal Artery Revascularization: Conclusions: Limitations: single centre, small number [n=203],

 However, Renal revascularization did not result in improvements in serum creatinine and Diastolic Blood Pressure.  More “definitive” studies on the long-term outcomes are needed to answer if:  renal PTA would have added benefits over medical therapy  who are the appropriate patients with RAS (if not all) who will benefit.

Percutaneous Renal Interventions 1) Renal Revascularization PTA

Pre

2) Renal Denervation RDN

Post

Following results of:  Symplicity HTN-1  Symplicity HTN-2: randomized 106 patients with Resistant Hypertension from 24 centres in Australia, Europe and New Zealand to either medical therapy or RDN from 2009-2010.

At 6 months follow up, the mean blood pressure reduced by 32/12mmHg in patients who underwent RDN.13 No serious procedural complications occurred and renal function remained the same at follow up.  Another bigger randomized trial using this system, the Symplicity HTN-3 trial had just been approved by the US FDA and is due to start soon

In May 2011,  Funding from IJN foundation  Started Resistant Hypertension clinic: to screen and review [referred] patients with uncontrolled hypertension.  Patients were reviewed, secondary or reversible causes of elevated BP ruled out.  Underwent Ambulatory BP monitoring ABPM  Those with true Resistant Hypertension, meeting a set of criteria, would be offered RDN.

Renal Denervation RDN

 On 14th September 2011, Institut Jantung Negara performed renal artery denervation for patients with Resistant Hypertension, using the Symplicity® Catheter system (Ardian).

 The following reports the early results of the first 15 patients from our Registry, concentrating only on BP response Note that in Symplicity HTN-2, the BP reduction of 32/12mmHg was seen at 12 months follow up.

Procedure:

 Access into the femoral artery  Guiding catheter advanced to engage the renal artery ostium.  Angiogram performed to determine the anatomical suitability.  The ablation catheter introduced into the renal artery The tip positioned to achieve good contact with the artery wall.

Ablation catheter

Procedure:  Radiofrequency energy ablationapplied for 2 minutes.  Catheter tip is repositioned at another site to achieve ideally between 4-6 ablations within each artery.  A “dimple” of the artery wall can often times be seen after each ablation.  The same is repeated in the contralateral artery

 As there is no immediate change in BP immediate post procedure, current endpoint is achieving 4-6 “good” ablations in each artery.  It is a relatively simple procedure.  The total procedure time is usually less than 1 hour.  As the ablation can be painful and uncomfortable, we routinely administer opioid intraprocedurally.

Baseline characteristics Number of cases

15

Mean age, years

65.6 Âą 9.5

BMI, kg/m2

29.0 Âą 3.6

Clinical data

Percentage

Clinical data

Percentage

Baseline data

ABPM - Systolic BP, mmHg - Diastolic BP. mmHg

154.8 ± 17.8 83.1 ± 14.2

BP Office - Systolic BP, mmHg - Diastolic BP. mmHg

182.5 ± 14.6 86.6 ± 9.6

eGFR

69.3 ± 16.4

Creatinine, mg/dl

93.9 ± 24.3

Procedure data

No. of ablation -Right -Left

5.1± 1.6 4.6 ± 1.5

Mean procedure time, mins

63.9 ± 13.6

Mean fluoro time, mins

17.8 ± 6.3

Mean contrast used, ml

171.5 ± 39.8

No. of medications Mean, 4.4 Âą 0.9 Median, 4 Min-Max, 3-6

No. of drugs

Medications

No. of patients

ABPM-Systolic BP

No significant change in ABPM SBP

154.8+17.8 vs.50.88+16.97,p=0.54 154.8+17.8 vs.142.7+14.1,p=0.321

154.8+17.8 vs.142.1+19.8, p=0.126 154.8+17.8 vs.140.6+15.1, p=0.088 154.8+17.8 vs.135.6+25.6, p=0.148

ABPM-Diastolic BP No change in ABPM DBP 83.1+14.2 vs.84.3+15.4,p=0.606 83.1+14.2 vs.81.1+14.4,p=0.316 83.1+14.2 vs.79.0+13.3,p=0.798

83.1+14.2 vs.83.8+20.6,p=0.824

83.1+14.2 vs.71.3+15.0,p=0.081

Office- Systolic BP Significant reduction in office SBP 182.5+14.6 vs.165.6+27.8,p=0.148

182.5+14.6 vs.172.0+17.2,p=0.061

182.5+14.6 vs.161.5+27.4,p=0.002

182.5+14.6 vs.160.1+22.0,p=0.001

182.5+14.6 vs.146.4+21.9,p=0.013

Office-Diastolic BP

No change in office DBP 86.6+9.6 vs.86.0+11.5,p=0.336

86.6+9.6 vs.81.7+11.1,p=0.133

86.6+9.6 vs.79.5+14.87,p=0.015

86.6+9.6 vs.83.8+16.2,p=0.259 86.6+9.6 vs.79.6+11.3,p=0.88

e GFR No change in eGFR 69.3+16.4 vs.56.1+23.6,p=0.436 69.3+16.4 vs.65.1+18.3,p=0.44

69.3+16.4 vs.68.6+19.7,p=0.369

Serum Creatinine No significant change in serum creatinine 93.9+24.3 vs.103.8+40.5,p=0.199

93.9+24.3 vs.97.1+27.4,p=0.360

93.9+24.3 vs.94.0+28.8,p=0.280

93.9+24.3 vs.95.0+28.0,p=0.233 93.9+24.3 vs.94.7+25.5,p=0.152

Renal Denervation: Conclusions: Limitations: single centre, small number [n=15], follow-up [12 months] ď&#x192;&#x2DC; In our experience, Catheter-based Renal Artery denervation with Radiofrequency Energy resulted in a reduction of Systolic blood pressure of Resistant Hypertension patients during short term follow up. ď&#x192;&#x2DC; We await our intermediate and longer term results.

Renal Denervation: Conclusions: Limitations: single centre, small number [n=15], follow-up [12 months] ď&#x192;&#x2DC; Catheter-based Renal Artery denervation appeared to be a safe procedure and did not result in significant change in renal function. ď&#x192;&#x2DC; Future larger trials with longer- term clinical outcomes and larger study populations with milder hypertension may expand the indications/acceptance of this procedure.

Thank You