Transradial Renal Denervation for the Treatment of Resistant Hypertension

Abstract: Objective. As a novel device-based approach targeting the renal sympathetic nerves, renal denervation has been shown to be effective and safe in reducing blood pressure. The femoral artery is currently the most common access site for this procedure due to catheter profile and length limitations that restrict the use of radial access. The purpose of this study was to evaluate technical feasibility and short-term outcomes of transradial renal denervation by a longer radiofrequency ablation catheter (155 cm; AngioCare). Methods. Five patients (mean age, 46 ± 15 years; 3 male) with resistant hypertension underwent successful transradial renal denervation (3 right, 2 left) at our institution from April to June, 2013. In this group, 3 patients were excluded from femoral access due to an acute aorto-renal angle, or severe tortuosity of the abdominal aorta and iliac arteries. All 5 patients were followed at 1 month and 3 months post procedure. Blood pressure, use of antihypertensive agents, renal function, and complications were investigated. Results. The mean reduction of 24-hour ambulatory blood pressure was -13/-8 mm Hg at 1-month and -20/-12 mm Hg at 3-month follow-up exam (P<.05, compared with baseline) with unchanged antihypertensive drugs. There was no significant change of renal function at 3-month follow-up exam (P>.05, compared with baseline). No complications were observed in this patient group. Conclusions. Our preliminary results revealed that transradial renal denervation is technically feasible, relatively safe, and effective for the treatment of resistant hypertension, especially where a femoral approach may not be possible. 

J INVASIVE CARDIOL 2014;26(7):322-327

Key words: transradial, renal denervation, drug-resistant hypertension

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Renal sympathetic hyperactivity plays a crucial pathogenetic role in the maintenance and progression of arterial hypertension.^1,2 As a novel device-based approach targeting the renal sympathetic nerves, renal denervation (RDN) has been shown to be effective and safe in reducing sympathetic nerve activity, norepinephrine spillover, and blood pressure.^3,4 Currently, the femoral artery is the most widely used access site for RDN. However, this approach may be difficult or impossible in certain patients with aorto-iliac occlusive disease, an acute angle between the infrarenal aorta and the renal arteries, or severe tortuosity of the abdominal aorta and/or iliac arteries.^5,6 

In a case report, de Araújo Gonçalves et al reported the feasibility of transradial RDN in a short female guided by a “customized” Judkins right catheter.⁷ However, due to the unavailability of longer radiofrequency ablation catheter, RDN via radial access has not been possible in most patients. Here, we describe 5 successful cases using a new radiofrequency ablation catheter designed for transradial RDN (155 cm Iberis catheter; AngioCare) to evaluate technical feasibility and short-term outcomes of transradial RDN. The Iberis renal sympathetic denervation system includes a generator and a 4 Fr compatible catheter with single-use radiofrequency probe. Energy is delivered to the renal arterial wall from a monopolar platinum electrode located at the distal tip of the catheter. The system received CE-mark approval in March 2013 (Table 1).⁸ All 5 patients were enrolled in the ongoing first-in-man study. In addition, the pivotal trial has been designed to evaluate the effectiveness of the device in a multicenter randomized trial in China.

Methods 

Patients. Between April and June 2013, a total of 5 consecutive patients with resistant hypertension underwent transradial RDN at our institution. Three patients had been precluded from femoral access due to an acute angle between the infrarenal aorta and the renal arteries (Figure 1A), or severe tortuosity of abdominal aorta and iliac arteries (Figure 1B). The other two patients with no ineligible anatomy for femoral access also underwent transradial RDN to test the feasibility of this new approach. Patients 18-65 years with a mean 24-hour ambulatory systolic blood pressure of 140 mm Hg or more, despite compliance with three or more antihypertensive drugs, were eligible for inclusion. Exclusion criteria included: (1) impaired renal function with an estimated glomerular filtration rate (eGFR, based on the Modification of Diet in Renal Disease criteria) of less than 45 mL/min per 1.73 m²;⁹ (2) ineligible renal arteries, including main renal arteries of <4 mm in diameter or <20 mm in length, polar or accessory arteries, severe renal artery stenosis, and prior renal revascularization; (3) known secondary hypertension; (4) type 1 diabetes; (5) severe comorbidity in patients not tolerable to RDN, such as new myocardial infarction (≤30 days), unstable angina, or cerebrovascular accident in the previous 6 months. Before the procedure, informed written consent was obtained from each patient.

Study procedure. To assure suitability for RDN, all 5 patients underwent baseline evaluations, including physical examination, serum biochemical analysis, controlled administration of antihypertensive drugs, 24-hour ambulatory blood pressure monitoring, and computed tomography renal angiography. Allen’s tests were normal in both radial arteries of all patients and the puncture side was selected by the operator based on preference.¹⁰

Under local anesthesia, using a modified Seldinger technique, a 6 Fr introducer sheath (Cordis Corporation) was inserted into the radial artery. A heparin bolus of 3000 units was administered intravenously and a continuous infusion of fentanyl and midazolam was started (5 µg and 0.2 mg/kg/h, respectively) and maintained until completion of RDN. In each case, the operator could easily advance a 6 Fr MPA1 guiding catheter (125 cm; Cordis Corporation) to the orifice of the renal arteries over a 0.035˝ HiWire angled hydrophilic guidewire (Cook Medical) (Figure 2). Renal angiography was first performed to further assess renal anatomy and dimensions (Figures 3A and 4A). Then, a 155 cm Iberis ablation catheter (AngioCare) was inserted and its tip was positioned proximal to the bifurcation of the renal artery. As previously described,^3,4 4-8 ablations of 8 W or less and lasting up to 120 s each were performed along the length of the renal artery, separated both longitudinally and rotationally (Figures 3B, 3C, 4B, 4C). The procedure was repeated in the contralateral artery. Supplementary doses of fentanyl or midazolam were given at the discretion of the anesthetist and guided by the clinical and hemodynamic responses. After the procedure, renal angiography was performed to evaluate changes in the renal arteries (Figures 3D, 4D). The access-site sheath was removed immediately after the procedure, and a single tourniquet was pulled tight over the radial puncture site. Pressure was maintained on the puncture site for approximately 6 hours. Patients were typically discharged the day after the procedure.

At 1 month and 3 months post RDN, office blood pressure, 24-hour ambulatory monitored blood pressure, use of antihypertensive agents, renal function indexes including serum creatinine and eGFR, and complications were assessed.

Statistical analysis. Continuous variables were presented as mean ± standard deviation (SD). Differences in blood pressure between baseline and follow-up were analyzed using the paired Student’s t-test. All probability values were 2-sided, and a P-value <.05 was considered to indicate statistical significance. All analyses were performed using the software SPSS 17.0 (SPSS, Inc).

Results

Patient and procedural characteristics. Patient ages ranged from 26-60 years (46 ± 15 years). Three patients were male and 2 were female. Disease duration (the time between onset of hypertension to RDN) was 2-20 years (10.0 ± 7.7 years). Two patients has type-2 diabetes mellitus, 3 patients suffered from hyperlipemia, and 2 patients were cigarette smokers. Two patients exhibited left ventricular hypertrophy. Two exhibited microalbuminuria. The mean office and 24-hour ambulatory blood pressure measurements before RDN were 166.4 ± 11.8/107.2 ± 9 mm Hg and 160.8 ± 11.7/104.4 ± 8.8 mm Hg respectively, despite the administration of 4 antihypertensive medications, 1 of which is a diuretic. 

The puncture site was the right radial artery in 3 patients and the left radial artery in 2 patients. The mean time of the procedure (from puncture of the radial artery to closure) was 41.8 ± 4.0 minutes, mean fluoroscopy time was 9.2 ± 1.9 minutes, and the mean use of contrast was 78.0 ± 16.0 mL. In total, an average of 5.8 ± 0.4 ablations and 6.2 ± 0.8 ablations were applied in the right and left renal artery, respectively. There were no adverse events in the perioperative period. 

Follow-up. With unchanged antihypertensive drugs in all 5 patients, the office-based blood pressure decreased from 166.4 ± 11.8/107.2 ± 9.8 mm Hg at baseline to 149.0 ± 10.8/97.2 ± 5.6 mm Hg at 1 month and 143.0 ± 9.7/93.6 ± 3.5 mm Hg at 3 months with a mean decrease of -17/-10 mm Hg and -23/-14 mm Hg, respectively (all P<.05). Similarly, the 24-hour ambulatory blood pressure changed from 160.8 ± 11.7/104.4 ± 8.8 mm Hg to 147.6 ± 12.7/96.6 ± 6.2 mm Hg at 1 month and 140.6 ± 10.5/92.2 ± 3.6 at 3 months, with a mean decrease of -13/-8 mm Hg and -20/-12 mm Hg, respectively (all P<.05). The plasma concentration of noradrenaline decreased slightly at 3 months after RDN compared with baseline, but there was no statistical significance (306.5 ± 58.7 ng/L vs 332.6 ± 52.5 ng/L; P>.05). Real function did not significantly change at 3 month follow-up exam (serum creatinine, 87.8 ± 11.8 µmol/L vs 93.6 ± 16.5 µmol/L; eGFR, 82.4 ± 16.2 mL/min/1.73 m² vs 77.1 ± 16.3 mL/min/1.73 m²; both P>.05) (Table 2). No clinical complications were observed at 3-month follow-up exam. 

Discussion

RDN is a promising device-based intervention for resistant hypertension. In the non-randomized Simplicity HTN-1 trial and the randomized HTN-2 trial, a decrease in office-based blood pressure by more than 20/10 mm Hg at 6 months was recorded, with no radiofrequency-related adverse sequelae visible by imaging examination 6 months after the procedure.^3,4,11 Currently, the femoral artery is the most widely used access site for RDN and most reported complications have been access-site related. Femoral artery pseudoaneurysm and hematoma formation have been reported in several trials.^11,12 Compared to femoral access, the advantages of radial access include substantial reduction in access-site related vascular complications, shorter bed confinement and hospital stay, and lower health-care costs.^5,6,10 In addition, access to the renal artery from a proximal approach is often easier since the most common course of the renal artery is inferior.⁶ In a cadaveric study, Wozniak found that the right and left renal artery usually originated from the aorta at an angle of <75° and 85°, respectively.¹³ Therefore, renal artery interventions including RDN and renal artery stenting appear particularly suitable for a transradial approach. However, transradial access for RDN has rarely been attempted due to the length limitations of ablation catheters.⁷

To the best of our knowledge, this is the first report of successful transradial RDN for treatment of resistant hypertension using a 155 cm radiofrequency ablation catheter. In our report, 3 patients had ineligible anatomy for femoral access due to an acute aorto-renal angle or severe tortuosity of abdominal aorta and iliac arteries. All 5 patients underwent transradial RDN successfully. No complications were observed in the perioperative period or at 3-month follow-up exam. Compared with baseline, the mean reduction of 24-hour ambulatory blood pressure was -13/-8 mm Hg at 1 month and -20/-12 mm Hg at 3 months post RDN, respectively, with no change in antihypertensive drugs. Our results compare favorably with findings from the Simplicity HTN-1 and HTN-2 trials.^3,4 Transradial RDN was technically feasible, relatively safe, and effective for these patients with resistant hypertension. A transradial approach to RDN offers numerous potential benefits to interventionists and patients, especially patients with anatomy that renders the transfemoral approach impracticable. These initial patients treated with transradial RDN were hospitalized for 1 day post procedure. We expect that subsequent patients undergoing RDN via transradial approach can be discharged the same day.

Compared with traditional transfemoral access, the main concern for radial access is distance from the access site to the renal arteries. In addition to the availability of longer ablation catheter with well flexibility, we believe the following points are critical to successful transradial RDN. First, good coaxiality between the guiding catheter and the renal artery is required to improve the steerability of the ablation catheter.⁵ Second, it is critical to maintain the “curved-tip” of the ablation catheter to reduce catheter movement from the respiratory cycle. With strict implementation of these two points, we maintained good wall contact between the catheter electrode and the renal arterial wall during the ablation in every case. Another argument against the radial approach is derived from current device limitations of multi-electrode ablation catheter, including relative stiffness due to catheter tip components and large catheter profile requiring sheath sizes up to 8 Fr or guiding catheter sizes up to 9 Fr.¹⁴ Therefore, a single-electrode ablation catheter may be feasible for transradial RDN. In our study, using a longer single-electrode ablation catheter, the catheter tip in every case could reach up to target ablation sites readily through a 6 Fr guiding catheter via radial approach. 

Study limitations. Limitations of this initial report include the limited sample size and short follow-up time. Further trials with larger patient populations and long-term follow-up are needed. Due to the absence of a control group (eg, transfemoral RDN), results can only be compared to data from the literature. Hospital costs were also not evaluated.

Conclusion

In conclusion, the transradial access is a technically feasible, relatively safe, and effective alternative for RDN in patients with resistant hypertension. This approach is especially attractive for patients where vascular anatomy poses a challenge for femoral access to the renal arteries. The availability of a novel 155 cm catheter makes the radial approach possible in many patients. Future trials with larger patient populations and long-term follow-up are needed to investigate the safety and efficacy of RDN via the radial approach.

Acknowledgments. We thank AngioCare Medical, Inc for donating the 155 cm Iberis ablation catheter for use in these cases. 

References

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From the Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted October 21, 2013, provisional acceptance given November 26, 2013, final version accepted January 9, 2014.

Address for correspondence: Xiongjing Jiang, MD, Department of Cardiology, Fuwai Hospital, 167 Beilishilu, Xicheng District, Beijing 100037, China. Email: jxj103@hotmail.com