Abstract
Objective
The aim of this study was to understand the role of accessory renal arteries in resistant hypertension, and to establish their role in nonresponse to radiofrequency renal denervation (RDN) procedures.
Background
Prior studies suggest a role for accessory renal arteries in hypertensive syndromes, and recent clinical trials of renal denervation report that these anomalies are highly prevalent in resistant hypertension. This study evaluated the relationships among resistant hypertension, accessory renal arteries, and the response to radiofrequency (RF) renal denervation.
Methods
Computed Tomography Angiography (CTA) and magnetic resonance imaging (MRI) scans from 58 patients with resistant hypertension undergoing RF renal denervation (RDN) were evaluated. Results were compared with CT scans in 57 healthy, normotensive subjects undergoing screening as possible renal transplant donors. All scans were carefully studied for accessory renal arteries, and were correlated with long term blood pressure reduction.
Results
Accessory renal arteries were markedly more prevalent in the hypertensive patients than normotensive renal donors (59% vs 32% respectively, p = 0.004). RDN had an overall nonresponse rate of 29% (response rate 71%). Patients without accessory vessels had a borderline higher response rate to RDN than those with at least one accessory vessel (83% vs 62% respectively, p = 0.076) and a higher RDN response than patients with untreated accessory arteries (83% vs 55%; p = 0.040). For accessory renal arteries and nonresponse, the sensitivity was 76%, specificity 49%, with positive and negative predictive values 38% and 83% respectively.
Conclusions
Accessory renal arteries were markedly over-represented in resistant hypertensives compared with healthy controls. While not all patients with accessory arteries were nonresponders, nonresponse was related to both the presence and non-treatment of accessory arteries. Addressing accessory renal arteries in future clinical trials may improve RDN therapeutic efficacy.
Highlights
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This paper advances the hypothesis that accessory renal arteries have an important role in non-response to renal denervation.
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In this paper systematic review of cases from the REDUCE-HTN study found that accessory renal arteries are a highly significant risk for renal denervation nonresponse.
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Accessory renal arteries were markedly over-represented in resistant hypertensives compared with healthy controls.
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Addressing accessory renal arteries in future clinical trials may improve RDN therapeutic efficacy.
1
Introduction
Radiofrequency renal denervation (RDN) for resistant hypertension has been recently questioned after pivotal trial data showed no differences in 6 month office blood pressure change compared to sham . Reasons for failure are unclear in view of earlier successful uncontrolled studies , but include inadequate ablations per artery, inadequate radio frequency (RF) energy delivery to all arterial quadrants, medication changes within the trial , and patient selection. Another reason for RDN nonresponse may be untreated accessory renal arteries . This study sought to clarify the role of accessory renal arteries in RDN nonresponse.
2
Methods
2.1
Study populations: the REDUCE-HTN trial and healthy controls
This study retrospectively analyzed data from the REDUCE-HTN trial. All patients signed informed consent for study enrollment and data analysis. This study was an open label single arm evaluation of 146 patients who received RDN for resistant hypertension (Vessix-Boston Scientific) where 6-month office systolic blood pressure was reduced by 24.7 mmHg. Accessory renal arteries, when identified during study procedures, were treated at operator discretion.
2.2
Accessory renal artery identification and analysis
High resolution computed tomographic (CT) or magnetic resonance (MR) angiography was performed prior to treatment in a subset of patients in this study. All available images were retrospectively reviewed to identify accessory renal arteries. Both imaging modalities are validated as accurate, sensitive, and specific for detecting these anomalies . Scans were examined by 2 expert observers blinded to RDN treatment and response status. Each kidney was reviewed separately for renal arteries with special attention to anatomy, location, and presence/absence of accessory renal arteries. Accessory artery presence was defined on a per-patient basis, i.e. as any accessory artery in either kidney of subject patients.
Office systolic blood pressure (SBP) pre-procedure was recorded and systolic blood pressure at 2, 4, 12, 18 and 24 months was averaged over these time points for all patients where available. RDN response was defined as ≥10 mmHg difference between baseline and mean follow-up systolic blood pressures. The RDN patient cohort was compared with a control set of healthy individuals undergoing renal CTA for clinical evaluation prior to kidney transplant donation. These patients were non-hypertensive, non-diabetic, and free of apparent clinical disease.
2.3
Statistical analysis
Descriptive statistics were expressed as mean and SD for continuous variables with number and percentage given for categorical variables. Continuous variables were analyzed using Student’s t-test and Pearson’s chi-square or Fisher’s exact test in categorical variable analysis. Binary classifications for sensitivity, specificity, positive/negative predictive values, and accuracy were calculated using standard definitions. A p-value ≤0.05 was considered significant, and two-sided p-values were used where possible. All statistical analyses were performed using Stata 11.2 (StataCorp, College Station, TX).
2
Methods
2.1
Study populations: the REDUCE-HTN trial and healthy controls
This study retrospectively analyzed data from the REDUCE-HTN trial. All patients signed informed consent for study enrollment and data analysis. This study was an open label single arm evaluation of 146 patients who received RDN for resistant hypertension (Vessix-Boston Scientific) where 6-month office systolic blood pressure was reduced by 24.7 mmHg. Accessory renal arteries, when identified during study procedures, were treated at operator discretion.
2.2
Accessory renal artery identification and analysis
High resolution computed tomographic (CT) or magnetic resonance (MR) angiography was performed prior to treatment in a subset of patients in this study. All available images were retrospectively reviewed to identify accessory renal arteries. Both imaging modalities are validated as accurate, sensitive, and specific for detecting these anomalies . Scans were examined by 2 expert observers blinded to RDN treatment and response status. Each kidney was reviewed separately for renal arteries with special attention to anatomy, location, and presence/absence of accessory renal arteries. Accessory artery presence was defined on a per-patient basis, i.e. as any accessory artery in either kidney of subject patients.
Office systolic blood pressure (SBP) pre-procedure was recorded and systolic blood pressure at 2, 4, 12, 18 and 24 months was averaged over these time points for all patients where available. RDN response was defined as ≥10 mmHg difference between baseline and mean follow-up systolic blood pressures. The RDN patient cohort was compared with a control set of healthy individuals undergoing renal CTA for clinical evaluation prior to kidney transplant donation. These patients were non-hypertensive, non-diabetic, and free of apparent clinical disease.
2.3
Statistical analysis
Descriptive statistics were expressed as mean and SD for continuous variables with number and percentage given for categorical variables. Continuous variables were analyzed using Student’s t-test and Pearson’s chi-square or Fisher’s exact test in categorical variable analysis. Binary classifications for sensitivity, specificity, positive/negative predictive values, and accuracy were calculated using standard definitions. A p-value ≤0.05 was considered significant, and two-sided p-values were used where possible. All statistical analyses were performed using Stata 11.2 (StataCorp, College Station, TX).
3
Results
Scans were available and of sufficient diagnostic quality in 58 of 146 REDUCE-HTN resistant hypertensive patients and from 57 healthy pre-transplant donors. Table 1 shows demographics, risk factors, and office blood pressure for the RDN and healthy donor patients. RDN patients were older (61 vs 46 years; p < 0.001), more often male (71% vs 42%; p = 0.002), and weighed more (94 vs 77 kg; p < 0.001). As the donor population had no recognized morbidities, dyslipidemia, diabetes, and coronary artery disease were all lower in donors than in RDN patients, and estimated glomerular filtration rate was higher in the donor population.
| Reduce HTN Patients (n = 58) | Renal Transplant Donors (n = 57) | P-Value | |
|---|---|---|---|
| Age (years), mean (SD) | 60.8 ± 10.6 | 45.6 ± 12.5 | <0.001 |
| Male, (%) | 41 (71.0) | 24 (42.0) | 0.002 |
| Height (cm), mean (SD) | 170.5 ± 10.1 | 170.9 ± 8.9 | 0.82 |
| Weight (kg), mean (SD) | 93.8 ± 19.6 | 77.2 ± 16.0 | <0.001 |
| Diabetes, (%) | 21 (36.0) | 0 (0) | <0.001 |
| Coronary Artery Disease, (%) | 26 (45.0) | 0 (0) | <0.001 |
| Congestive Heart Failure, (%) | 1 (1.7) | 0 (0) | 1.00 |
| Dyslipidemia, (%) | 37 (67.0) | 0 (0) | <0.001 |
| eGFR (ml/min), mean (SD) | 80.0 ± 16.3 | 86.2 ± 13.5 | 0.029 |
| Systolic Blood Pressure, mean (SD) | 181.6 ± 17.5 | 117.7 ± 12.2 | <0.001 |
| Diastolic Blood Pressure, mean (SD) | 99.2 ± 14.2 | 72.2 ± 10.1 | <0.001 |
| Renal Accessory Artery, (%) | 34 (58.6) | 18 (31.6) | 0.004 |
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