Imaging Of Renal Arteries Research Articles

TCT-481 Renal Artery Imaging Through Long-Term Follow-up Following Radiofrequency Renal Denervation: Results From the SPYRAL Clinical Trial Program

TCT-481 Renal Artery Imaging Through Long-Term Follow-up Following Radiofrequency Renal Denervation: Results From the SPYRAL Clinical Trial Program

Abstract P439: An Uncommon and Missed Diagnosis of Hypertension: Fibromuscular Dysplasia

Introduction: Fibromuscular dysplasia is a noninflammatory vascular disease most commonly affecting carotid and renal arteries, especially in young to middle aged women. Renal artery stenosis may cause refractory and severe hypertension in these patients without traditional risk factors. Case: A 58-year-old woman with uncontrolled hypertension on calcium channel and angiotensin receptor blocker and history of left carotid artery stenosis, and carotid endarterectomy at the age of 48 years, was referred cardiac evaluation. Patient’s twin sister had a diagnosis of fibromuscular dysplasia (FMD). Her blood pressure was 190/90 mmHg at presentation. Computed Tomography Angiography (CTA) of the abdomen/pelvis showed a typical nodular stenosis of the mid renal artery consistent with FMD. Patient underwent renal angiogram and successful percutaneous transluminal angioplasty. She still required medical therapy but her BP significantly improved. Discussion: Our patient had severe hypertension, carotid artery stenosis and even surgery but had missed FMD diagnosis for > 10 years. Physicians should have a high level of clinical suspicion for young and middle aged women with refractory hypertension and/or artery stenosis, aneurysm, or dissection in any vascular bed. CTA should be performed for renal and carotid artery imaging looking for typical “string of beads” appearance. Cerebral artery aneurysm should also be evaluated. The inheritance pattern for FMD such as PHACTR1 is most consistent with an autosomal dominant trait with variable penetrance. Renal artery angioplasty may lessen the degree of refractory or severe hypertension.

Long-term follow-up of patients undergoing renal sympathetic denervation

ObjectivesRenal denervation (RDN) proved to significantly lower blood pressure (BP) at 2–6 months in patients on and off antihypertensive drugs. Given a lack of longer-term follow-up data, our aim was to assess the safety and efficacy of RDN up to five years taking into account antihypertensive drug regimen changes over time.MethodsIn the present single-center study, patients underwent RDN for (therapy resistant) hypertension. Patients underwent protocolized yearly follow-up out to five years. Data were collected on 24-h ambulatory BP and office BP monitoring, renal function, antihypertensive drug regimen, and safety events, including non-invasive renal artery imaging at 6/12 months. Efficacy analyses were performed using linear mixed-effects models.ResultsSeventy-two patients with mean age 63.3 ± 9.5 (SD) years (51% female) were included. Median follow-up time was 3.5 years and Clark’s Completeness Index was 72%. Baseline ambulatory daytime BP was 146.1/83.7 ± 17.4/12.2 mmHg under a mean number of 4.9 ± 2.7 defined daily doses (DDD). At five years, ambulatory daytime systolic BP as calculated from the mixed model was 120.8 (95% CI 114.2–127.5) mmHg and diastolic BP was 73.3 (95% CI 69.4–77.3) mmHg, implying a reduction of -20.9/-8.3 mmHg as compared to baseline estimates (p < 0.0001). The number of DDDs remained stable over time (p = 0.87). No procedure-related major adverse events resulting in long-term consequences were observed.ConclusionsThe BP-lowering effect of RDN was safely maintained at least five years post-procedure as reflected by a significant decrease in ambulatory daytime BP in the absence of escalating antihypertensive drug therapy over time.Graphical abstract

Free‐breathing three‐dimensional isotropic‐resolution MR sequence for simultaneous vessel wall imaging of bilateral renal arteries and abdominal aorta: Feasibility and reproducibility

Many diseases can simultaneously involve renal arteries and the adjacent abdominal aorta. This study proposed a free-breathing three-dimensional (3D) isotropic-resolution magnetic resonance sequence for simultaneous vessel wall imaging (VWI) of bilateral renal arteries and adjacent abdominal aorta. A respiratory-triggered isotropic-resolution sequence that combined the improved motion-sensitized driven-equilibrium (iMSDE) preparation with the spoiled gradient recalled (SPGR) readout (iMSDE-SPGR) was proposed for simultaneous VWI of renal arteries and abdominal aorta. The proposed iMSDE-SPGR sequence was optimized by positioning spatial saturation pulses (i.e., REST slabs) elaborately to further alleviate respiratory and gastrointestinal motion artifacts and selecting appropriate first-order gradient moment (m1 ) of the iMSDE preparation. Thirteen healthy subjects and 13 patients with renal artery stenosis underwent simultaneous VWI with the optimized iMSDE-SPGR sequence at 3.0 T. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and morphology of renal arterial wall and aortic wall were measured. Reproducibility of intra-observer, inter-observer, and scan-rescan (n=13 healthy subjects) in measuring SNR, CNR, and morphology was evaluated. For the reproducibility test, the agreement was determined using intraclass correlation coefficients (ICC), and the differences were compared using paired t-test or nonparametric Wilcoxon test when appropriate. Bland-Altman plots were used to calculate the bias between observers and between scans. The proposed iMSDE-SPGR sequence was feasible for simultaneous VWI both in the healthy subjects and the patients. The sequence showed good to excellent inter-observer (ICC: 0.615-0.999), excellent intra-observer (ICC: 0.801-0.998), and scan-rescan (ICC: 0.768-0.998) reproducibility in measuring morphology, SNR, and CNR. There were no significant differences in SNR, CNR, and morphology measurements between observers and between scans (all p>0.05). Bland-Altman plots showed small bias in assessing SNR, CNR, and morphology. The proposed free-breathing 3D isotropic-resolution iMSDE-SPGR technique is feasible and reproducible for simultaneous VWI of bilateral renal arteries and adjacent abdominal aorta.

Comparison of axial and coronal acquisitions by non-contrast-enhanced renal 3D MR angiography using flow-in time-spatial labeling inversion pulse

ObjectiveWe evaluated image quality differences between axial and coronal non-contrast-enhanced renal three-dimensional (3D) magnetic resonance angiography (MRA) acquisitions, using time-spatial labeling inversion pulse (Time-SLIP) with flow-in balanced steady-state free precession (bSSFP).Materials and methodsAxial and coronal images were acquired in 128 subjects using non-contrast-enhanced 3D-MRA with Time-SLIP flow-in bSSFP on a clinical 1.5-T MRI system. Visualization of source and maximum intensity projection (MIP) images of renal arteries were compared between the axial and coronal acquisitions using a four-point scale. For quantitative analysis, vessel-to-background contrast ratios of aorta and renal arteries were calculated.ResultsBoth acquisitions yielded similarly excellent quality. In source image evaluation, coronal acquisitions showed significantly more motion degradation (p < 0.01) than did axial acquisitions. In MIP image evaluation, coronal acquisitions yielded superior image quality, less motion degradation, and better visualization of the number of renal branches than did axial acquisition. The renal artery to background signal contrast was greater in coronal than in axial acquisitions (p < 0.01).ConclusionCoronal acquisition provides superior contrast between the renal arteries and background and allows more persistent visualization than axial acquisitions in non-contrast-enhanced MRA using flow-in bSSFP with Time-SLIP. First-line screening of renal non-contrast-enhanced MRA should involve coronal acquisition.

Abstract P2051: Incidence of Renal Artery Damage Following Percutaneous Renal Denervation With Radio Frequency Renal Artery Ablation Systems

Recent prospective randomized clinical trials have demonstrated blood pressure lowering following renal denervation (RDN) with radiofrequency (RF) ablation systems and minimal adverse events in relatively small populations with short follow up duration. The current analysis estimates the rate of renal artery adverse events based on a comprehensive review of published reports. An online database search was performed to identify trials, registries and case reports that employed either the SYMPLICITY Flex or Spyral RF denervation systems (Medtronic, Santa Rosa, CA). Updated reviews of the SYMPLICITY HTN-3 trial and the Global SYMPLICITY Registry were also included. Renal artery stenoses classified as “significant”, greater than 50%, resulted in stent implant or if not specified were counted. The pooled incidence rate of stent implantation was determined by fixed-effects meta-analysis of the study-level incidence rates. Review of 45 published RDN trials reporting on procedural safety with 10,130 patient-years of follow up identified 0.44% of patients (25 of 5,657) with reported renal artery stenosis or dissection and 0.39% of patients (22 of 5,657) with required renal artery stenting. Meta-analysis of all reports indicated an 0.20% pooled annual incidence rate of stent implantation (95% CI: 0.11 to 0.29 % per patient-year). This result was consistent with a fixed effects Poisson regression model (0.22%; 95% CI: 0.14 to 0.32%). An additional 10 case reports including 11 patients with renal artery stenosis resulting in at least one stent implant were identified, with most cases diagnosed after recurrent hypertension, occasionally with concomitant symptoms. Median time from RDN procedure to all renal artery interventions, including both case reports and clinical trials, was 5.5 months (range: 0 to 33 months). A separate review of 14 clinical trials reporting on prospective follow up high resolution imaging of main renal arteries or branches using either MRI, CT or angiography following RDN found a new significant stenosis rate of 0.20% (one event out of 511 patients). Renal artery stenosis and re-intervention following renal denervation with the most commonly applied RF renal denervation system are rare.

Optical coherence tomography in varying aetiologies of renal artery stenosis: a case series.

BackgroundRenal artery stenosis (RAS) is a common cause of secondary hypertension. The most common aetiology is atherosclerosis; however, other causes like fibromuscular dysplasia (FMD) and Takayasu arteritis (TA) are also frequently encountered. The lesion characteristics and its response to percutaneous intervention depend upon the aetiology of RAS. Optical coherence tomography (OCT) is an excellent imaging modality to analyse coronary lesions during percutaneous coronary interventions. The data regarding the utility of OCT in renal artery imaging is limited, consisting of a few case reports.Case summaryWe hereby report four cases of RAS, each of different aetiology (atherosclerotic, FMD, post-transplant, and TA), who underwent OCT imaging of the renal artery along with percutaneous renal angioplasty.DiscussionThe advantages of OCT imaging include demonstration of the arterial wall, pathological features of the disease, and to guide percutaneous interventions. The major limitation of OCT is its lower imaging depth, which may render imaging of large vessels difficult.

Serial changes in vessel walls of renal arteries after catheter-based renal artery denervation: insights from volumetric computed tomography analysis.

AimRadiofrequency ablation of peri-arterial renal autonomic nerves has been studied as a potential therapeutic option for resistant hypertension. While recent clinical trials have reported its efficacy, there is paucity of data addressing the effects of the procedure on renal arteries, such as changes in vessel and lumen areas. Herein, the effect of atheroma burden on renal arteries after renal denervation was assessed using computed tomography (CT) imaging.Materials and methodsSerial renal artery CT imaging was conducted in 38 patients from the EnligHTN™ I study, a prospective, multicenter study evaluating the efficacy of the EnligHTN multi-electrode radiofrequency ablation catheter in resistant hypertensive subjects. Cross-sectional images of renal arteries at 1 mm intervals were acquired using commercially available software (3mensio Structural Heart version 5.1). Vessel and lumen areas were manually traced in each image. Vessel wall volume (VWV) and percent vessel wall volume (P-VWV) were calculated. The measurements within the ablation (first 30 mm segments) and the non-ablation (subsequent 30 mm segment after the first bifurcation of renal arteries) zones were compared.ResultsOn serial evaluation, greater increase in P-VWV and VWV was observed in the ablation zone (change in P-VWV, 6.7%±5.1% vs 3.6%±2.8%, P=0.001; change in VWV, 106.3±87.4 vs 23.0±18.2 mm3, P=0.001). Receiver-operating characteristic analysis demonstrated baseline P-VWV in the ablation zone >37.1% as an optimal cutoff value to predict its substantial progression after the procedure (area under the curve=0.88, sensitivity 89.8%, specificity 79.1%).ConclusionChange in vessel wall was greater within the segments receiving renal artery denervation. Baseline VWV predicted its substantial increase after the procedure. These observations suggest that atheroma burden within the renal arteries is a potential contributing factor to vascular changes after renal sympathetic denervation.

Abstract P431: Renal Artery Stenosis Caused by a Bcr-Abl Tyrosine Kinase Inhibitor: Blood Pressure Response to Revascularization

Introduction: Bcr-Abl tyrosine kinase inhibitors (TKI) are first line agents for management of chronic myelogenous leukemia (CML). Amongst the second generation TKIs, which have less resistance and improved side effect profile, nilotinib and ponatinib have also been reported to be associated with vascular adverse events (VAEs), including systemic and peripheral arterial stenosis. We report on a patient with CML treated with ponatinib, who developed bilateral renal artery stenoses, difficult to control hypertension, and responded to revascularization. Case: A 55 year old man, with CML due to a Bcr-Abl truncating mutation diagnosed in 2007, was treated with ponatinib 45 mg daily starting in 2011, which induced a complete remission. He subsequently developed hypertension. Hypertension appeared angiotensin II-dependent as BP normalized on combination of candesartan 32 mg once daily and hydrochlorothiazide 25 mg once daily. This treatment was however associated with an increase in serum creatinine from 1.4 to 2.6 mg/dL. Consistent with our clinical suspicion, a computed tomography angiogram revealed bilateral renal artery stenosis. He eventually required bilateral renal artery angioplasty and stenting as the BP could not be controlled without renin-angiotensin system blockers despite using up 5 classes of BP lowering drugs. Furthermore, follow up imaging of renal arteries showed progressive renal artery stenosis bilaterally. He underwent angioplasty and stenting in the left renal artery and angioplasty of both the branches of the right main renal artery, which could not be stented because of the early branching. After 6 months, BP is within target with 8 mg candesartan, amlodipine 10 mg and bisoprolol 2.5 mg daily, and the renal function is stable (creatinine 1.1 mg/dL). Overall, in this case, renal artery angioplasty and stenting stabilized renal function and improved control of hypertension. Discussion: Second generation TKIs are associated with VAEs, including renal artery stenosis. Renal artery angioplasty and stenting stabilized renal function and improved control of hypertension in this case. Future research should clarify the mechanisms of VAEs with TKIs, natural history, and long term response to revascularization in this setting.

Renal Artery Fibromuscular Dysplasia: Clinical Aspects and Ultrasound Diagnostics

Fibromuscular dysplasia (FMD) is a noninflammatory and nonatherosclerotic type of vascular stenosis that affects mainly the renal and carotid arteries. The most common type of FMD is the media fibroplasia with the characteristic “string of beads” appearance. The disease must be suspected in young people, commonly women, with arterial hypertension, in the resistant hypertension and in the hypertension associated with a decrease of renal mass. Considering that the string of beads appearance generally isn't seen on duplex imaging of renal arteries, a peak systolic velocity of 285 cm/sec or a renal aortic ratio of 3.5 alone can be used in detecting >60% of renal artery stenosis. Duplex ultrasound visualization of middle third of renal arteries may be very difficult in some cases, particularly on the left side as a result of gas artifact from the colon. In these cases comparing spectral waveforms and resistive index at the renal hilum can be helpful. Catheter based angiography remains the most accurate imaging to diagnose and evaluate FMD. Balloon angioplasty alone of the renal arteries is the treatment of choice of hypertension due to FMD and should be considered in patients with a recent onset of hypertension in whom the goal is the cure of hypertension, in those in whom blood pressure control is difficult to achieve and in those who have lost renal volume because of ischemic nephropathy.

Displasia Fibromuscolare Delle Arterie Renali: Aspetti Clinici e Diagnostica Ultrasonografica

Abstract non disponibile

Altered plasma fibrin clot properties in hypertensive patients with obstructive sleep apnoea are improved by continuous positive airway pressure treatment.

We investigated plasma fibrin clot properties in high-risk hypertensive patients with obstructive sleep apnoea (OSA) and assessed the impact of continuous positive airway pressure (CPAP) treatment on clot phenotype. We studied 50 hypertensive patients with clinically significant OSA (age 50.0 ± 8.8 years, 39 M, 11 F). In total, 38 hypertensive patients without OSA balanced for age, sex, blood pressure, cardiovascular risk factors, and metabolic status served as controls. Plasma fibrin clot properties, including clot permeability coefficient, clot lysis time (CLT), and turbidimetric parameters of clot formation were determined. Patients underwent transthoracic echocardiography, carotid ultrasonography, evaluation of endothelial function and calcium score index of coronary arteries, and Doppler imaging of renal arteries. Compared with controls, OSA patients were characterized by more compact fibrin structure (lower median clot permeability coefficient, 6.00 vs. 7.25 10 cm; P < 0.001), impaired fibrinolysis (longer median CLT, 108.00 vs. 92.50 min; P < 0.001), and by faster clot formation (shorter median lag phase, 40.50 vs. 42.50 s; P = 0.041), and higher median maximum clot absorbency indicating denser fibrin networks (0.87 vs. 0.81; P = 0.028). Clot permeability coefficient and CLT correlated with apnoea-hypopnoea index (r = -0.46; P < 0.001 and r = 0.44; P < 0.001, respectively) as well with mean (r = 0.31; P = 0.003; r = -0.36; P = 0.001, respectively) and minimal oxygen saturation (r = 0.46; P < 0.001; r = -0.49; P < 0.001, respectively). After 3 months of CPAP treatment we observed an increase in clot permeability coefficient (5.95 vs. 7.60 10 cm; P = 0,001), shortened CLT (107.00 vs. 87.00; P = 0.006), a longer lag phase of fibrin formation (40.00 vs. 43.50 s; P = 0.013), and a trend toward lower maximum clot absorbency (0.86 vs. 0.81; P = 0.058). In hypertensive patients at high cardiovascular risk, OSA was associated with unfavourable prothrombotic fibrin clot characteristics, including hypofibrinolysis, which significantly improve as early as after 3 months of CPAP treatment.

Renal Artery Stenosis in Patients with Peripheral Artery Disease: Prevalence, Risk Factors and Long-term Prognosis

The objective was to determine the prevalence and clinical determinants of renal artery stenosis (RAS) in patients undergoing digital subtraction angiography (DSA) for the assessment of peripheral artery disease (PAD), and to evaluate its prognostic significance. All DSAs performed from January 2000 to January 2006 were retrospectively reviewed for assessment of PAD in patients naive for any prior revascularisation of lower-limb arteries. All DSA studies were read by two senior physicians blinded to outcome, and consensus was reached in cases of disagreement. RAS was defined as the presence of ≥50% stenosis in either renal artery. Patients' electronic medical files were systematically reviewed and follow-up was completed by contact with family physicians until January 2014. The primary outcome was composite, including death, peripheral revascularisation, or any limb amputation. Secondary outcomes were all-cause mortality, and another composite, including death and non-fatal myocardial infarction or stroke or coronary or carotid revascularisation. In total, 400 consecutive patients having a first DSA of lower extremities, two thirds of whom were for critical limb ischaemia, were studied. Thirteen patients were excluded owing to poor renal artery imaging. RAS was detected in 57 patients (14%). Only two factors were independently and significantly associated with RAS in multivariate analysis: diffuse PAD (involving both proximal and distal segments [odds ratio {OR} 3.50, 95% confidence interval {CI} 1.16-10.54; p=.026]) and decreased glomerular filtration rate (OR 0.55 per 30 mL/minute/1.73m2, 95% CI 0.41-0.75; p<.001). During follow-up (mean±SD 62±47 months), 25% experienced limb amputation and 54% died. In multivariate analysis, no significant association was found between RAS and primary outcome (hazard ratio 0.80; 95% CI 0.57-1.10). No significant association was found with secondary outcomes. Incidental RAS is frequent (14%) among patients with PAD undergoing lower extremity imaging. No difference in outcome in patients with RAS versus those without RAS was seen. Larger studies are necessary to draw definite conclusions.

Preoperative evaluation of renal artery in patients with renal tumor

To investigate the feasibility of the noncontrast-enhanced magnetic resonance angiography (NCE-MRA) to evaluate renal arteries before partial nephrectomy (PN).Retrospective analyzed 479 patients who underwent renal surgery between January 2013 and December 2015 with NCE-MRA or computed tomographic angiography (CTA) renal artery image reconstruction preoperative in our department. The renal artery reconstruction score (RARS) was based on the level of artery visualization in a 4-class criterion, and the R.E.N.A.L nephrometry score (R.E.N.A.L), arterial based complexity (ABC) were also analyzed.Of the 479 patients, the overall-lever RARS was 3.62, and the average in 2 groups was no significant difference (NCE-MRA vs CTA, P = 0.072). The performance of NCE-MRA in PN group was similar with CTA. Further comparison demonstrated that the efficiency of NCE-MRA in moderate- or low-degree tumor according to the R.E.N.A.L and ABC complexity less than 3S was equal to CTA. However, high degree (P < 0.001), 3S (P = 0.027), or 3H (P < 0.001) would affect the imaging of renal artery. Intragroup analysis showed that tumor complexity such as max tumor size (r = −o.351, P < 0.001), R.E.N.A.L (r = −0.439, P < 0.001), and ABC (r = −0.619, P < 0.001) were closely correlated with the NCE-MRA performance. The images of 2 sides of the kidney were compared in single person as well, which was meaningful for NCE-MRA patients only (NCE-MRA, P < 0.001; CTA, P = 0.182).The renal artery reconstruction performed by NCE-MRA is feasible and has a similar achievement in the PN potential recipients, with a lower side effect, and meets the requirements for making surgical decision. It has a broad application prospect in clinical practice; however, it still needs to further improve the ability in more complex tumors.

EP08.09: Pulsed Doppler imaging of renal artery and vein is useful for diagnosis of fetal arrhythmia

EP08.09: Pulsed Doppler imaging of renal artery and vein is useful for diagnosis of fetal arrhythmia

Two-photon imaging of endothelin-1-mediated intracellular Ca2 + handling in smooth muscle cells of rat renal resistance arteries

AimsEndothelin-1 (ET-1) is a potent vasoconstrictor which regulates the physiology of cardiorenal system. The aim of this study was to evaluate ET-1-mediated elevation of intracellular Ca2+ in smooth muscle cells (SMC) of renal resistance arteries. Main methodsIn in vitro studies of primary SMC, which were isolated from rat renal microvessels, the levels of intracellular Ca2+ were calculated from the ratio of emissions at 340 and 380nm after loading cells with Fura 2-AM dye. In ex vivo studies we used two-photon imaging of renal resistance arteries excised from rat kidneys and loaded with fluorescent Ca2+ indicator Fluo-4 AM. Key findingsThe two-photon imaging demonstrates that treatment of isolated rat renal resistance arteries with ET-1 causes a rapid increase of intracellular Ca2+ concentration in smooth muscle vasculature of these vessels. These ex vivo observations are in accordance with in vitro findings indicating that ET-1 mediates activation of TRPC channels and increases the level of intracellular Ca2+ in cultured SMC to 510±83nM. SignificanceET-1-mediated elevation of intracellular Ca2+ is strongly linked to renal microvascular contraction and is crucial for ET-1-induced contraction of SMC. The two-photon imaging of intracellular Ca2+ in intact SMC of rat renal resistance arteries is a powerful technique which allows the detailed ex vivo analysis of intracellular Ca2+ handling by ET-1, an important player in hypertension-related kidney diseases.

Smaller caliber renal arteries are a novel feature of uromodulin-associated kidney disease

Hyperuricemia is very common in industrialized countries and known to promote vascular smooth muscle cell proliferation. Juvenile hyperuricemia is a hallmark of uromodulin-associated kidney disease characterized by progressive interstitial renal fibrosis leading to end-stage renal disease within decades. Here we describe a member of a Polish-German family with a history of familial background of chronic kidney disease, hyperuricemia, and gout. This patient had hypertension because of bilateral small renal arteries, hyperuricemia, and chronic kidney disease. Clinical and molecular studies were subsequently performed in 39 family members, which included a physical examination, Duplex ultrasound of the kidneys, laboratory tests for renal function, and urine analysis. In eight family members contrast-enhanced renal artery imaging by computed tomography-angiography or magnetic resonance imaging was conducted and showed that bilateral non-arteriosclerotic small caliber renal arteries were associated with hyperuricemia and chronic kidney disease. Of the 26 family members who underwent genotyping, 11 possessed the P236R mutation (c.707C>G) of the uromodulin gene. All family members with a small caliber renal artery carried the uromodulin P236R mutation. Statistical analysis showed a strong correlation between reduced renal artery lumen and decreased estimated glomerular filtration rate. Thus, bilateral small caliber renal arteries are a new clinical phenotype associated with an uromodulin mutation.

Incidence of renal artery stenosis after renal denervation in patients with resistant arterial hypertension

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 L30 mm Hg (p <0.001) and mean systolic 24-hour BP reduction was L18 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

Frequency of Renal Artery Stenosis After Renal Denervation in Patients With Resistant Arterial Hypertension

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 6months 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 >160mm Hg. Renal artery imaging was performed 6months 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 6months 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-30mm Hg (p <0.001) and mean systolic 24-hour BP reduction was-18mm Hg (p <0.001). In conclusion, the incidence of significant renal artery stenosis 6months 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.

What is the true incidence of renal artery stenosis after sympathetic denervation?

Renal denervation (RDN), a recently developed therapy for resistant hypertension, is generally regarded as a safe procedure (Krum et al., 2009; Esler et al., 2010; Bhatt et al., 2014). The Symplicity HTN trials reported that the rate of renal artery stenosis after RDN was low. For example, the Symplicity HTN-1 trial showed that 1 of 45 (2.2%) denervated patients developed a non-obstructive renal artery stenosis in an untreated area at 6 months after RDN (Krum et al., 2009). This low rate of renal artery stenosis after RDN was confirmed by the 6-month report of the Symplicity HTN-2 trial (N = 106) (Esler et al., 2010) and the recently published 6-month report of the Symplicity HTN-3 trial (N = 535) (Bhatt et al., 2014), which was 1.9 and 0.3%, respectively. In these Symplicity HTN trials, renal artery stenosis occurred at a low rate (0.3–2.2%) and was not reported to cause further complications. However, some studies reported that renal artery stenosis occurred at a higher rate. For example, the EnligHTN I study (Worthley et al., 2013) reported that 2 of 46 (4.3%) patients showed progression of a pre-existing renal artery stenosis; a study from 10 European expert centers (Persu et al., 2014) reported that 3 of 109 (2.8%) patients showed progression of a non-significant (<30%) renal artery stenosis; and Versaci et al. (2014a) reported that 2 of 11 (18.2%) patients developed severe renal artery stenosis. It is worthwhile to point out that the sample size of 11 in Versaci et al.'s report is relatively small (Versaci et al., 2014a). In 2012, Vonend et al. reported that a patient developed a 75% stenosis near the ostium of the right renal artery, which caused recurrent hypertension (Vonend et al., 2012). Subsequently, another 3 case reports reported that renal artery stenosis after RDN caused recurrent hypertension (Kaltenbach et al., 2012; Aguila et al., 2014; Pucci et al., 2014). The causal role of RDN in promoting renal artery stenosis is currently speculative. However, given that (1) renal artery stenosis causes recurrent hypertension in denervated patients (Kaltenbach et al., 2012; Vonend et al., 2012; Aguila et al., 2014; Pucci et al., 2014) and (2) treatment of renal artery stenosis is not always safe and sometimes leads to death (Soriano-Perez et al., 2012), it is important to thoroughly investigate the effect of RDN on renal artery stenosis (Mahfoud and Kjeldsen, 2013; Wang, 2014a,b,c,d). To do this, the following three points need to be emphasized in future clinical trials on RDN: Long-term randomized trials are needed. Two major randomized trials on RDN, i.e., the Symplicity HTN-2 and HTN-3 trials (Esler et al., 2012; Kandzari et al., 2012), allowed patients in the randomized control group to receive RDN after completion of the 6-month study. This crossover design makes it difficult to investigate possible long-term side effects of RDN, e.g., promoting renal artery stenosis. Therefore, long-term randomized trials without a short-term crossover design are needed to investigate the effect of RDN on renal artery stenosis. Imaging methods monitoring renal artery stenosis need to be standardized. Symplicity HTN trials did not standardize renal artery imaging methods during follow ups. Ultrasonography, magnetic resonance angiography, and computerized tomographic angiography were used (Krum et al., 2009; Esler et al., 2010). The computerized tomographic angiography, the gold standard method to detect renal artery stenosis (Persu et al., 2012), was not the major imaging method in these trials. It is known that ultrasonography has limited visualization on renal artery stenosis because (1) the imaging is interfered by overlying adipose tissue and bowel gas (Zhang et al., 2009); and (2) the entire length of the renal artery or an accessory renal artery can be overlooked (Lao et al., 2011). Therefore, it is worthwhile to use computerized tomographic angiography as the standardized method during follow ups in future trials to investigate the effect of RDN on renal artery stenosis. It is likely that improved catheters for RDN using lower power radiofrequency over a shorter time will reduce the local tissue injury at the ablation site compared with that caused by the first generation RDN systems (Versaci et al., 2014b). However data regarding the vascular injury induced by these new devices are lacking.