Catheter-based ablation of nerves in the adventitia of renal arteries (renal artery denervation [RAD]) using radiofrequency energy can reduce blood pressure (BP) in patients with resistant arterial hypertension (RAH). Occurrence of renal artery stenosis after RAD is still an important concern. We systematically investigated the renal artery anatomy using magnetic resonance imaging (MRI) or computed tomography (CT) angiography in a consecutive series of patients 6 months after RAD. Patients with RAH were treated by RAD after exclusion of secondary causes of hypertension. RAH was defined by a mean systolic office BP >160 mm Hg. Renal artery imaging was performed 6 months after RAD by MRI angiography. In case of any contraindication for MRI, a CT angiography was performed. The primary end point was the incidence of significant renal artery stenosis (≥70% lumen diameter reduction). RAD was performed in 76 patients, and evaluation of renal artery anatomy by MRI (n = 66; 87%) or CT angiography (n = 10; 13%) was performed in all patients 6 months after RAD. We found no renal artery stenosis but 2 cases of new nonsignificant stenosis (50% TO 69% lumen diameter reduction). In responders, mean systolic office BP reduction was −30 mm Hg (p <0.001) and mean systolic 24-hour BP reduction was −18 mm Hg (p <0.001). In conclusion, the incidence of significant renal artery stenosis 6 months after RAD seems to be very low. However, late-onset development of nonsignificant renal artery narrowing cannot be excluded in some patients and should be anticipated in the case of RAH relapse or worsening of renal function after successful RAD.
During the last years, overactivity of the sympathetic nervous system was in the focus of research in pathogenesis of resistant arterial hypertension (RAH). Catheter-based renal artery denervation (RAD) of nerves in the adventitia of the renal arteries can contribute to blood pressure (BP) lowering in patients with RAH. With regard to the ongoing discussion on the efficacy of RAD, systematic evaluation of the benefit/risk ratio is necessary for the evaluation process. One important concern over RAD is the possible development of focal renal artery stenosis because of fibrotic scarring in the vessel’s wall after radiofrequency (RF) ablation. In the Symplicity-1 and Symplicity-2 trial, only 14 of 45 (31%) and 43 of 49 (88%) treated patients have been evaluated by renal artery imaging (mainly by renal duplex ultrasound and only partially by computed tomography (CT) or magnetic resonance imaging [MRI] angiogram) 6 months after RAD, respectively. Thereby, 1 patient with a new atherosclerotic lesion, which was not clearly associated with the RAD procedure, was detected. However, the number of published case reports on patients with renal artery stenosis after RAD is increasing. We systematically investigated renal artery morphology using MRI or CT angiography 6 months after RAD in a consecutive series of patients with RAH.
Methods
Patients with RAH were treated by RAD after exclusion of secondary causes of hypertension. RAH was defined by a mean systolic office BP >160 mm Hg (>150 mm Hg in patients with diabetes) after 3 BP measurements. All patients had to be on at least 3 antihypertensive drugs including 1 diuretic. Exclusion criteria included age <18 years, pregnancy, and an estimated glomerular filtration rate <45 ml/min/1.73 m 2 . Eligibility criteria for renal artery anatomy, as evaluated by MRI angiography before the procedure, were a diameter of >4 mm, a length of >20 mm, and the absence of renal artery stenosis (≥50% lumen diameter reduction).
Before RAD, the absence of a renal artery stenosis ≥50% was excluded by selective angiography through a transfemoral access and the guiding catheter used for the ablation. Images were acquired with cine fluoroscopy at a rate of 15 frames/second. Injection of 10 ml of nonionic iodinated contrast medium was performed by hand. Images were obtained in an anterior-to-posterior direction with the guiding catheter in place. The percentage of a lumen diameter reduction, if present, was assessed using quantitative angiography performed with a semiautomated device (Quantcor, version 4.0; Pie Medical Imaging, Maastricht, The Netherlands). All lumen diameter reductions between 20% and 49% were documented in the RAD database. Lumen diameter reductions <20% were interpreted as vessel wall irregularities and not documented. RAD was performed in both renal arteries using the Symplicity RAD Catheter System (Medtronic Inc., Minneapolis, Minnesota) for point-to-point RF ablation. RF was delivered at each ablation point with a maximum of 8 Watts and 120 seconds, respectively. In case of fluctuations in temperature or resistance, energy delivery was automatically stopped for safety reasons by the system. Depending on renal artery anatomy, a maximum of 8 ablation points was performed in each renal artery. The distance (mm) from each ablation site to the ostium of the renal artery was documented. All patients received antiplatelet therapy for 4 weeks after RAD (aspirin 100 mg or clopidogrel 75 mg everyday). In case of necessity of dual antiplatelet therapy because of previous cardiac stent revascularization, this treatment was continued. Patients with ongoing anticoagulation treatment received no additional antiplatelet therapy.
Renal artery imaging was performed in all patients 6 months after RAD by MRI angiography. In case of any contraindication for MRI, CT angiography was performed. For evaluation of the MRI and CT images, direct axial images, multiplanar reformations, and curved multiplanar reformations in the axial and coronal planes were used. Postprocessing and evaluation were performed with separate workstations by an independent radiologist. The percentage of renal artery stenosis, if present, was assessed by measuring the diameter lumen with digital calipers at its narrowest section and comparing it with the reference diameter of the vessel.
In addition to office BP measurements, 24-hour BP was measured at baseline and after 6 months by ambulatory blood pressure measurement (ABPM). ABPM was performed using the “Del Mar Reynolds Medical ABPM System” (version 2.08.005). Devices were preset from 6 a.m . to 9:45 p.m . defined as daytime (readings every 15 minutes) and from 10 p.m . to 5:30 a.m . as night-time (readings every 30 minutes), and patients were told to follow their usual activities during the monitoring. The arm cuff was placed on the nondominant upper arm, and patients were instructed to steady their arm during each measurement. Written informed consent was obtained from all patients, and the local ethic committee approved the study. The investigation was performed in accordance with the Declaration of Helsinki.
The primary end point was the incidence of significant renal artery stenosis 6 months after RAD. A significant renal artery stenosis was defined by a lumen diameter reduction of ≥70%. A lumen diameter reduction between 50% and 69% was defined as nonsignificant stenosis. Secondary end points were the mean office and 24-hour BP reductions 6 months after RAD. Derived from the documented BP reductions, responder-to-RAD status was defined by a mean systolic BP reduction of ≥10 mm Hg in office BP and of ≥5 mm Hg in 24-hour BP.
Data are presented as mean ± SD. For comparisons of variables between the groups and for comparison of BP measurements at each visit, a paired t test was performed. A 2-sided alpha level of 0.05 was considered as statistically significant. All analyses were performed using the SPSS 17.0 software (SPSS Inc., Chicago, Illinois).
Results
From June 2010 to November 2011, 76 patients were enrolled in the study. RAD was successfully performed in all patients without periprocedural complications. Selective renal artery angiography immediately before RAD revealed a lumen diameter reduction of 20% to 49% in 13 vessels (9%) in 9 patients (12%). Patients’ characteristics and drugs are listed in Table 1 . Patients were taking 4.8 ± 1.1 antihypertensive drugs at baseline and 4.7 ± 1.2 after 6 months without statistical differences between responders and nonresponders. During the RAD procedure, a mean of 5.3 ± 1.1 ablation points were performed in the left renal artery and 5.6 ± 1.1 ablation points in the right renal artery, respectively.
| Baseline characteristics | |||||||
|---|---|---|---|---|---|---|---|
| Age | Female | CAD | DM | PAD | Stroke/TIA | Hyperlipidemia | |
| All patients | 64±10 | 33 (43%) | 29 (38%) | 23 (30%) | 3 (4%) | 9 (12%) | 47 (62%) |
| Antihypertensive drug treatment | |||||
|---|---|---|---|---|---|
| RAAS Blocker | Diuretics | Ca ++ Blocker | Alpha Blocker | Beta Blocker | |
| Baseline | 73 (96%) | 68 (89%) | 36 (47%) | 15 (20%) | 58 (76%) |
| 6 Months | 68 (89%) | 65 (86%) | 37 (49%) | 14 (18%) | 57 (75%) |
| Antiplatelet therapy and anticoagulation | ||||
|---|---|---|---|---|
| Aspirin 100mg q.d. | Clopidogrel 75mg q.d. | Dual antiplatelet therapy | Oral anticoagulation | |
| Baseline | 53 (70%) | 8 (11%) | 11 (14%) | 4 (5%) |
| 4 weeks | 53 (70%) | 8 (11%) | 11 (14%) | 4 (5%) |
| ongoing | 29 (38%) | 1 (1%) | 11 (14%) | 4 (5%) |
Renal artery imaging was performed in all patients 6 months after intervention. In 66 patients (87%), MRI angiography was performed. In all other patients (n = 10, 13%), CT angiography was performed. No case of significant renal artery stenosis was detected in any patient. In 2 patients, we found a new nonsignificant renal artery stenosis through MRI angiography.
In the first of these cases, an atherosclerotic formation (20% to 49% lumen diameter reduction) in the middle of the right renal artery, which was documented by renal artery angiography before RAD, progressed to a nonsignificant stenosis (50% to 69%). RF delivery had been performed very close to the site of the atherosclerotic lesion. The second nonsignificant stenosis was detected also in a right renal artery but at a site where no ablations had been performed during RAD. In addition, no local spasms or other abnormalities like dissections had been documented at the location of the later nonsignificant stenosis during the RAD procedure in both patients. We found no correlation between the number of ablation points and lesion development or progression.
In 49 patients (65%), we found a BP reduction ≥10 mm Hg. In these responders, mean systolic BP reduction was −30 mm Hg 6 months after RAD. Using the 24-hour BP date, we found a BP reduction ≥5 mm Hg in 40 patients (53%) and a mean systolic 24-hour BP reduction of −18 mm Hg in these patients (p <0.001, all BP data are depicted in Table 2 ).
