Renal Sympathetic Denervation in the Treatment of Resistant Hypertension: Current Clinical Evidence, Patient Selection, Tips and Tricks

Transcription

1 Renal Sympathetic Denervation in the Treatment of Resistant Hypertension: Current Clinical Evidence, Patient Selection, Tips and Tricks Kostadin Kichukov, MD, PhD, Iskren Garvanski MD, Department cardiology, angiology and electrophysiology City Clinic - Sofia

2 In 2014 everyone knows what renal denervation is Symplicity HTN 2

3 Uncontrolled Hypertension is not equal to Resistant Hypertension! What we have to look for? White coat hypertension Secondary hypertension Inaccurate measurement Inappropriate drug combinations Interfering substances Non compliance with drug regimen or lifestyle modification Sleep apnoea

4 Real life data Utrecht registry. Referral for RDN 66% dropouts. Why? Blankestijn, P. J. RHC 2013

5 From theory to practice Symplicity (Medtronic Ardian)

6 Renal Denervation Technologies BSC Vessix MDT Symplicity MDT Spyral STJ EnligHTN COV OneShot ReCor Gen 2 Paradise JNJ ThermoCo ol CE Mark Catheter Design Balloon catheter 4 8 electrodes Catheter with single electrode Pigtail Catheter 4 electrodes Basket with four electrodes Balloon catheter helical electrode and cooling Balloon catheter; internal cooling; Circumferential treatment Pigtail catheter with 5 electrodes and cooling Balloon No No No No Guidewire No No No Energy Bipolar RF Monopolar RF Monopolar RF Monopolar RF Monopolar RF Ultrasound Monopolar RF Power ~1W 8W 8W 6W 25W ~12W 15W Energy Delivery Time Total Treatment Time 30 sec. 2 min. 1 min. 90 sec 2 min. 30 sec. Unknown 2 min min. 2 min. 24 min. 4 min. 3 min. Unknown None of these devices are available for sale in the US. Medtronic Website, March 2013; The New Medtronic Device, Weil, TRENDS Frankfurt 2013; St. Jude Website, May 2013; Papademetriou, TRENDS Frankfort 2013; Covidien (Maya) Presentation; Ormiston et al. EuroIntv The ReCor Device, Weil, TRENDS Frankfurt 2013; Sievert, Live Case, TRENDS, Frankfort 2013; LINC 2013, Live Case ReCor; J&J Thermocool Bertog, TRENDS Frankfurt RF=Radiofrequency; W=Watt

7 RF Energy Devices Consistent Data EnligHTN Change in Office Blood Pressure Month (n=47) 3 Month (n=44) OneShot 6 Month (n=47) SBP DBP Vessix Symplicity HTN 2 RCT p < p = /7 mm Hg n=49 n=47 n=43 n=40 Symplicity Symplicity Symplicity Spyral Krum, H. ESC, 2013; Esler, M. ASH, 2013; Worthley, SG. PCR, Whitbourn R. PCR 2013; Ormiston, J. PCR, 2013; Schofer, J. PCR, 2013 Verheye S, TCT 2013

8 Ultrasound Energy Devices Just the same 0 mm Hg Recor Study: Office Blood Pressure Cardiosonic TIVUS ABPM 3 Month Follow up (n=10) Kona: External Ultrasound Wave 1 study -10 mm Hg 0,0-20 mm Hg -30 mm Hg -40 mm Hg -50 mm Hg Systolic Diastolic BP Mm Hg 5,0 10,0 15,0 20,0 25,0 Systolic Diastolic 11,9 11,8 11,2 23,1 22,2 22,6 24 Hr ABPM Day ABPM Night ABPM Non Focused, High Intensity Ultrasonic Catheter Change from Baseline (mm Hg) External ultrasound energy delivered to renal nerves Ultrasound tranducer inside 6 F balloon Ultrasound creates heat Cooled water in the balloon to protect None of these devices are available for sale in the US. Whitbourn R, WAVE 1; PCR 2013

9 SYMPLICITY HTN 3 Complicated the future of renal denervation. All onging similar trials were stopped. WHY?

10 Still we have only assumptions But look at Eurointervention Vol.9 Num.9! we need to wait until the peer-reviewed publication of clinical data, most likely around the end of March 2014, to have further information rather than speculating on a technical level, the cannulation of the catheter is relatively straightforward, however, the renal nerves are widely distributed and perhaps catheter orientation issues appeared. As in all new therapies, a learning curve exists, perhaps this was a contributing factor. The majority of the first studies, and the Symplicity HTN-1 and 2, were performed at selected sites in Europe and Australia, whereas the Symplicity HTN-3 trial was performed at selected sites in the United States and Australia. Patrick W. Serruys, Editor in Chief EuroIntervention

11 Still we have only assumptions, but look at Eurointervention Vol.9 Num.9! Despite the strict inclusion/exclusion criteria in HTN-3, did the patients truly have resistant hypertension? How did the investigators confirm medication adherence when a recent publication recently reported that 43 to 65.5% of patients with presumed resistant hypertension are nonadherent? Was the HTN-3 primary efficacy endpoint of a 10 mmhg systolic pressure difference between the two groups overly ambitious? Some experts explain that a long-term sustainable 5 mmhg decrease in systolic pressure is still beneficial for the patient group, suggesting that this decrease is the equivalent of adding one additional tablet. Is the outcome of Symplicity HTN-3 related to the first generation device that has been used? What about the other investigational devices with different design and energy sources? Patrick W. Serruys, Editor in Chief EuroIntervention

12 Renal denervation success is not in the believing, but in doing it right The non-responder hypotheses emerged nearly an year ago

13 A Non responding patient Hypothesis 1 for Non Response The Patient You did a good technical but clinically ineffective job because in some patients: Overactivation of sympathetic system trough the kidneys is not involved in the pathophysiology of resistant hypertension Anatomical variations of the splanchnic sympathetic fibers are able to bypass the renal plexus through other circuits (independently of vascularization) Masked presence of multiple renal arteries is able to maintain some sympathetic connections despite main renal artery denervation

14 A Non responding patient Hypothesis 2 for Non Response The Technique You did an ineffective job because you don t know the temperature at the adventitia/nerves level and in some patients : Atheromatous disease and renal artery thickness are limiting temperature rise/transduction A significant proportion of nerves are at more than 4 mm from the intima which distance may be out of the efficacy perimeter of the electrode Some surrounding anatomical structures (renal veins, IVC) may limit temperature rise / transduction

15 A Non responding patient Hypothesis 3 for Non Response The Doctor You did an ineffective job because you don t follow current recommendations of use of the device : Diameter/lenght of the target vessels Inappropriate value of impedance (tissue contact) To limited number of ablations (only 4) per artery or unilateral procedure Inappropriate duration of ablation (repeated automatic interruption from generator for technical reasons) Inappropriate anticoagulation (fibrin deposit) Other mistakes

16 Vascular Safety? Prospective observational study, 32 renal arteries of patients with treatment-resistant hypertension underwent OCT pre & post RDN Vasospasm in 10 renal arteries (42%) after RDN (no vasospasm before the procedure) (P < 0.001) Await Similar studies with other RF & balloon based technologies Templin C et al, Eur Heart J 2013

17 Intraluminal thrombus formation from 18% to 67% EnligHTN multi-electrode induces a different tissue response (with a higher amount of thrombus formation measured by OCT per renal artery than the Simplicity catheter) Templin C et al, Eur Heart J 2013

18 Pioneers in Bulgaria Ivo Petrov MD, PhD and team: Kostadin Kichukov MD, PhD Christo Dimitrov, MD Lora Nikolova, MD Currently three active RDN centres in Bulgaria City Clinic, Lozenetz, Sv. Anna (Pat. N>100) All treated with Symplicity system

19 Patient Selection o Office SBP 160 mmhg ( 150 mmhg with type II diabetes mellitus) o ABPM above thresholds for day/night; 24H BP o Stable drug regimen of 3+ more anti-htn medications o Age >18 years o Suitable renal vessels - Length>20mm, Diameter>4mm. o Without hemodynamically or anatomically significant renal artery abnormalities or prior renal artery intervention o egfr > 45 ml/min/1.73m 2 (MDRD formula)

20 Renal denervation is not a procedure it is a program Started on March 15, 2012 (FIB) patients urdergone the procedure patients up to All procedures performed with the Medtronic Symplicity system A dedicated team for patient management

21 PRE PROCEDURE AND IN HOSPITAL ASSESSMENT All patients are well KNOWN with initial ABPM readings 100%. Clinical physical exam ECG EchoCG Doppler ultrasound of renal arteries Baseline laboratory panel Careful observation (BP) after procedure Control doppler and creatinine before discharge

22 Follow up scheme? You need a team! Tailored for individual patient s needs, e.g. associated morbidities treated Control physical exams at M1, M3, M6, M12 Control ABPM M1, M3, M6, M12 Control Lab screa, suric Acid, sk, sna, Control cardiac Echo M12 Control Doppler of the renal arteries M1, M3.

23 PRE PROCEDURE ANTIHYPERTENSIVE TREATMENT Average number of drug classes 4,7 (3 7) % usage ACE I 34% ARB 66% CCB 71% Duiretic 100% Aldosterone antagonist 27% Centrally acting sympatholytics 57% DRI 11% Beta blockers 92% Alfa blockers 43%

24 Results over office BP City clinic data 180 P<0, SBP 80 DBP MO M1 M3 M6 P<0,05

25 Other variables during FU egfr Without significant change between BL, M01, M03, M06. o With 2 exclusions. 1 Pt with early CIN (72h), successfully treated. 1 patient with CKD had dialysis on the day of procedure and the day after. After that case all patients with ESRD have planned dialysis the same manner. o 2 patients had gradual deterioration of kindey function at M06 Consulted with nephrologist+biopsy (Both with DM type 2>15years). Dg: Diabetic Nephropathy. Heart Rate Without significant change between BL, M01, M03, M06 o Explanation: First type of medication withdrawn are usually centrally acting sympaticolytics Responder rate by the Symplicity HTN criteria: o At M03 67%, at M06 82%

26 Other variables during FU Antihypertensive Medication o Average No. of antihypertensive classes dropped from 4,7 (3-7) to 3,8 (2-6) at M03. There were exclusions. Exclusions o Three patients (6,81%) were non-responders ( 2 without any change in BP; 1 with insignificant elevation of BP. Two retreated after M06 one with good result. Off-Label Use o RDN in 4 patients with CKD on dialysis with malignant hypertension with perfect outcome during FU More than 25mm drop in SBP, 14mmDrop in DBP. Safe and sound! Responder vs non-responder o Up to now we do not have predictors of success. Optimal response in unilateral RDN vs poor response in bilateral x6-7.

27 We cautiously change therapy at Mo 3 following this advice Plouin, RHC 2013

28 The Renal Denervation Procedure Itself Data and tips from our Experience

29 INVASIVE PROCEDURE (1) Femoral / Brachial artery access 6/5 Fr Up to 08/02/14 5 patients had RDN via Brachial Renal angiogram o Absence of flow limiting stenoses o Diameter >4mm in target vessel o Length >20mm o Guide catheter selection RDC, IMA, MP o Areas to avoid Atherosclerosis, calcification, FMD

30 INVASIVE PROCEDURE (2) Remember Treat all suitable vessels! Never rely on 4 ablations per artery! Conscious sedation and analgesia o Midazolam uptitration to 5mg; Fentanyl up to 6ml o Tip: Lidocaine mg ia in the renal artery before/during ablation session Careful monitoring of pulse oxymetry Anticoagulation Heparine IU All patients pretreated with mg ASA

31 Procedure specific details City Clinic data (up to sep/2013) Renal ablation procedural details Procedural success 100% Procedure time 69±35 min X ray time 16 min Number of ablations per artery 5.8 Bilateral ablation 94,5% Combined with coronary intervention Combined with renal intervention Contrast volume 23% 6,8% 145 ± 67 ml GC used IMA RDC 2 Guiding sheath 5/6Fr Double GW use Telescopic technique 38% 58% 4% 18% 12%

32 Procedural safety City Clinic Data 73 patients treated Minor bleeding at puncture site - 2 pt 1 pt transient haematuria with on D1 with full resolution 3 pt with hypotension within hospital period 1 case of renal artery dissection, successfully stented No cases of renal artery blood flow compromise (assessed by doppler)during FU

33 Some brief clinical cases (If we still have time)

34 The Easy renal arteries Telescopic technique for accessory vessel/ FMD

35 The Easy Renal arteries Brachial approach could help (Guiding sheath 5F, MP Curve)

36 Case 1 KTK History (FIB) 53 YO Male History of severe uncontrolled hypertension since 2005 Dyslipidemia on statin therapy Hyperurikaemia Evidence of Target organ Damage: o LV Hypertrophy - ECG and Echo criteria o No evidence of angina at effort Drug regimen o Lercanidipine - 2x10mg o HCTZ - 25mg o Candesartan - 32mg o Metoprolol Succinate - 150mg o Doxazosine - 4mg o Moxonidine - 0,4mg

37 Case 1 KTK ABPM readings 09 10/03/2012

38 Case 1 KTK Clinical and lab findings 13/03/12 Physical exam - unremarkable; BP - 180/100 ECG - sinus rhythm, criteria for LVH Cardiac Echo: Preserved LV systolic function - EF-65% LVH - IVS/LVPW - 14/14mm; LVd Mass A-L 191g Impaired LV relaxation; E/e - 10,660 Peripheral Echo Doppler: No evidence of carotid, mesenteric or renal stenoses. Renal arteries - solitary bilaterally, with diameter 6mm, lenght >30mm. Lab - CrCl - 112,77ml/min

39 KTK Procedure

40 KTK 18M FU Lercanidipine - 2x10mg HCTZ - 25mg Candesartan - 32mg Metoprolol Succinate - 150mg Doxazosine - 4mg Moxonidine - 0,4mg

41 Expanding indications Heart failure LV Hypertrophy Sleep apnoea Insulin resistance Chronic kidney disease/esrd Atrial fibrillation

42 Case VPS History 62 YO Male History of severe uncontrolled hypertension since ESRD: on dialysis since SBP at home 260 systematically; during dialysis. Type 2 Diabetes since Hard evidence of Target organ Damage Drug regimen o o o o o Nifedipine - 6x10mg Zofenopril - 15mg Prazosine 4x2mg Moxonidine 2x0,4mg Clonidine up to 6x0,150mg

43 Case VPS Clinical and lab findings Physical exam HR - 53; BP 210/80 ECG - sinus rhythm, criteria for LVH Cardiac Echo: Preserved LV systolic function EF-73% LVH - IVS/LVPW - 17/15mm; Impaired LV relaxation; E/e 16,2 Peripheral Echo Doppler: No evidence of carotid, mesenteric or renal stenoses. Renal arteries - solitary bilaterally, with diameter 6mm, lenght >30mm. Lab Hb 114; Cr 457; NT-pro BNP > 35000

44 Case VPS Challenging, state of the art procedure

45 Case VPS Challenging, state of the art procedure

46 Case VPS Compelling evidence of effect on M01 Mean 24h SAP 196,4 178 (Drop 18,4) Mean 24h DAP 88,6 79 (Drop 9,6) Home BP Drop of SAP 40-50mm!

47 Take home messages Careful selection of candidates for RDN is essential Inform patients not to expect immediate results and be patient up to M06. But be prepared for immediate drops in BP! Expect results in most of the cases around M03 Never miss to control s Creatinine, e.g. GFR soon after procedure and during FU Try to keep BP-lowering therapy unchanged until M03, except in cases of hypotension. You never know who will be responder of the procedure, because we do not have reliable predictors of success. That s why do your best!

48 Thank you for your attention!