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. 2012 Sep 11;14(12):861–870. doi: 10.1111/j.1751-7176.2012.00704.x

Catheter‐Based Renal Sympathetic Denervation Improves Central Hemodynamics and Arterial Stiffness: A Pilot Study

Kai Mortensen 1, Klaas Franzen 1, Frank Himmel 1, Frank Bode 1, Heribert Schunkert 1, Joachim Weil 1, Michael Reppel 1
PMCID: PMC8108752  PMID: 23205753

Abstract

J Clin Hypertens (Greenwich). 2012;14:861–870. ©2012 Wiley Periodicals, Inc.

Renal sympathetic denervation (RDN) is a novel treatment strategy for patients with resistant arterial hypertension. Recently, the Symplicity trials demonstrated significant peripheral blood pressure (BP) reduction. The present study aimed at measuring central aortic pressures and arterial stiffness as better predictors for cardiovascular risk in patients undergoing RDN. RDN was performed in 21 patients (systolic peripheral BP ≥150 mm Hg) with an Ardian/Medtronic (Mountain View, CA) ablation system. Data were recorded with an Arteriograph. After 6 months, peripheral systolic BP was reduced by 6.1% (P<.05) while central systolic pressure was reduced by 7.0% (P<.05). Subgroup analysis showed that in responders, peripheral systolic BP was reduced by 16.1% (P<.01) while central systolic pressure was reduced by 18.3% (P<.01). Arterial stiffness improved significantly. Aortic augmentation index (AIx) improved by 9.5% (P<.05). In responders, AIx improved by 19.2% (P<.02). Pulse wave velocity (PWV) was high at baseline (10.8 m/s) and improved by 10.4% (P<.05). In responders, PWV improved by 13.7% (P<.05). Multivariate analysis showed that short‐term effects on PWV were BP‐related, whereas during follow‐up, improvement of PWV becomes BP‐unrelated. RDN improves peripheral and central blood pressure as well as arterial stiffness and, thus, may improve cardiovascular outcome.

Arterial hypertension is typically treated with medication and lifestyle changes to reduce cardiovascular events such as stroke, myocardial infarction, and death. 1 , 2 , 3 Despite these intensive efforts in controlling blood pressure (BP) in some patients with so called resistant arterial hypertension, therapeutic targets are not met. 4 , 5 Both hypertension and atherosclerosis cause aortic stiffness. 6 , 7 , 8 , 9

In daily practice, individual cardiovascular risk assessment is mainly based on measurements of peripheral BP. However, the Strong Heart Study indicated that central aortic pressures correlate better with vascular disease and outcome than peripheral pressures. 10 , 11 Parameters such as central systolic BP and diastolic aortic BP as well as aortic pulse pressure (PP) together with measurements of pulse wave velocity (PWV) more precisely determine underlying hemodynamics such as cardiac afterload, coronary perfusion pressure, and arterial stiffness. As a consequence, end‐organ damage, ie, left ventricular hypertrophy and cardiovascular events, were shown to be better correlated with central than peripheral pressures and hemodynamics. 10 The two leading causes of death, myocardial infarction and stroke, are a direct consequence of this pathophysiologic process.

Due to hypertension and atherosclerosis, the aorta stiffens. 12 Finally, the pulse wave is faster and early reflecting aortic pulse waves from the periphery reach the heart early during systole leading to higher systolic and lower diastolic central BP. Both, the former leading to increased systolic pressure load and the latter leading to decreased coronary blood flow may serve in part as an explanation for the fact that stiffer arteries are related to the increased number of cardiac events. PWV and aortic augmentation index (AIx) are both widely used and well‐accepted direct and indirect parameters that measure arterial stiffness. 13 , 14

Efferent and afferent renal sympathetic nerves communicate with the central nervous system and thereby control BP. They contribute to the development and perpetuation of hypertension. Recently, a novel percutaneous interventional approach using radiofrequency energy was developed to disrupt renal sympathetic nerves. This catheter‐based ablation, called catheter‐based renal sympathetic denervation (RDN), led to a significant reduction in both systolic and diastolic BP for up to 24 months. 15 , 16 The first randomized controlled study in humans, the Symplicity HTN‐2 trial, was recently published confirming these observations. 17

In the present study we addressed whether RDN and subsequent reduction in peripheral BPs may influence central aortic pressure and arterial stiffness, both each better evaluating potential end‐organ damage and later clinical events in humans.

Methods

Study Design and Patients

We included in our single‐center study patients aged 31 to 82 years with peripheral office systolic BP of at least 150 mm Hg, treated with ≥3 antihypertensive drugs of different classes, including diuretics. All patients with an estimated glomerular filtration rate (GFR) <45 mL/min/1.73 m2, substantial valvular heart disease, pregnancy or planned pregnancy during the study, history of myocardial infarction, unstable angina, or cerebral vascular accident in the previous 6 months, or significant renal artery stenosis and/or previous renal artery intervention were excluded. A total of 23 patients fulfilled the inclusion criteria. One patient in the treatment group was excluded because of low systolic BP before treatment and one patient withdrew consent during follow‐up (Figure 1). During the screening process, patients were asked to record home BP measurements, at least twice daily, and to document drug compliance for 14 days. The screening visit was 2 weeks before RDN and defined as −14 days. Validation of hypertensive BP values was performed 2 days before treatment (−2 days) and was taken for statistical reference of BP follow‐ups (baseline). On the day of RDN (day 0), measurements were performed before intervention started. Routine follow‐up visits were at day 1 (+1 day), 1 month (+30 days), 3 months (+90 days), and 6 months (+180 days) after RDN. The protocol was approved by the local ethics committee (AZ 10‐211) and all patients provided written informed consent.

Figure 1.

Figure 1

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 Patient enrollment.

Procedures

For patients undergoing RDN, a femoral artery access with a standard endovascular technique was chosen. The ablation catheter was advanced into the renal artery and connected to a radiofrequency generator. Three to six ablation points (maximum 8 W) were applied from the distal to proximal part of both renal arteries. All patients were treated with unfractionated heparin to achieve an activated clotting time >250 seconds. Intravenous analgesics and narcotics were applied to manage diffuse visceral pain that was restricted to the duration of energy delivery. Changes to baseline doses of antihypertensive treatment were not allowed. When judged medically necessary because of relevant changes in BP in association with signs or symptoms of hypotension or hypertension, specific drugs could be added or withdrawn selected at the discretion of the investigators. Outpatient follow‐up visits were planned at 1, 3, and 6 months after the procedure, with assessment of adverse events and drugs and measurements of office‐based BP and ambulatory BP monitoring. Office‐based peripheral BP was taken with an automatic oscillometric Omron HEM‐705 monitor (Omron Healthcare, Vernon Hills, IL). BP was measured in a lying position according to protocol‐specified guidelines according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, European Society of Cardiology, and European Society of Hypertension recommendations. 1

Endpoints

Endpoints were defined as (1) changes in office‐based measurements of peripheral BPs from baseline to follow‐up, (2) changes in central aortic pressures, and (3) changes in arterial stiffness. The correct definition of response to RDN is still a matter of debate. Therefore, rate of response was studied using different definitions of response, ie, 10 mm Hg, ≥5%, and ≥10% lowering of peripheral BP 6 months after RDN (Figure 2). For statistical analysis of RDN effects on central hemodynamics and stiffness in order to distinguish between responders and non responders, ≥10% lowering of peripheral BP was chosen. 18

Figure 2.

Figure 2

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 Renal sympathetic denervation (RDN) improves peripheral blood pressure. Effects of RDN on peripheral systolic blood pressure (SBP) (A) and on peripheral diastolic blood pressure (DBP) (B). Measurements were performed with an Omron device (HEM‐705 monitor; Omron Healthcare, Vernon Hills, IL) with the patient in the sitting position. The solid line represents development of blood pressure of the total RDN group during follow‐up while the dotted lines represent responders (dark grey line) and nonresponders (light grey line). *, #Significant reduction of blood pressure values as compared with baseline. Data are expressed as mean±standard error of the mean.

Measurements of Central Hemodynamics and Arterial Stiffness

To determine aortic pressures and arterial stiffness parameters, an Arteriograph device (TensioMed, Budapest, Hungary) was used to measure arterial stiffness using the oscillometric technique with a regular BP cuff. 19 , 20 Measurements were performed according to current recommendations. 13 , 21 , 22

Statistical Analysis

Two approaches were used for analysis. First, all treated patients were analyzed during follow‐up. For within‐group paired data, a paired t test was used unless otherwise specified. Second, a subgroup analysis of responders and nonresponders was performed (see above). Baseline values were used as the reference point. Analysis of variance on ranks was applied where applicable. For determination of BP‐unrelated effects of RDN on PWV a multivariate analysis of variance (MANOVA) was performed correcting for age, mean arterial pressure (MAP), and sex. During MANOVA, a mean MAP was calculated for each individual patient. Data are expressed as mean±standard deviation if not otherwise stated. A P value of <.05 was considered significant. All statistical analyses were performed with SPSS statistical version 19 software (SPSS Inc, Chicago, IL). All graphics were edited by SigmaPlot 8.0 (Systat Software Inc, San Jose, CA) and CorelDraw 11.0 (Corel Inc, Mountain View, CA).

Results

Baseline Characteristics

Baseline characteristics for the RDN group are shown in Table I. Regarding age, smoking status, height, and cardiovascular diseases, responders and nonresponders did not differ significantly. The rate of response was 52%, 62%, and 38% after 3 months and 52%, 57%, and 33% for lowering of peripheral systolic BP by 10 mm Hg, ≥5%, and ≥10% 6 months after RDN, respectively (Figure 3). Detailed data and statistics for all parameters are given in Table III–V.

Table I.

 Baseline Characteristics

Renal Sympathetic Denervation Group (n=21)
Sex 61.9% men and 38.1% women
Age, y 64.4±12.3
Height, m 1.76±0.11
Weight, kg 86.9±19
Body mass index, kg/m2; 27.9±4.1
Diabetes, % 24
Respiratory disease, % 19
Vascular disease, % 24
Cardiac disease, % 33
Drugs, No. 7.3±2.5
Antihypertensives, No. 5.4±1.3
More than 5 antihypertensives, % 81
Serum creatinine, μmol/L 73.6±15.3
Ablation points in right renal artery 4.6±1.1
Ablation points in left renal artery 4.6±1
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Data are expressed as mean±standard deviation.

Figure 3.

Figure 3

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 Rate of peripheral systolic blood pressure (SBP) according to different response criteria and different devices. (A) Different rates of response presented for the Omron device (HEM‐705 monitor; Omron Healthcare, Vernon Hills, IL) with patients in the sitting position. (B) Rate of response presented for the Arteriograph with patients in the lying position. Data are expressed as mean±standard error of the mean.

RDN and Peripheral Systolic and Diastolic BP

Systolic BP was 157.2±12.9 mm Hg in the RDN group at baseline and was reduced by 7.7% (P<.05) after 3 months and by 6.1% (P<.05) after 6 months (Table II). At baseline, responders and nonresponders did not significantly differ (Table III). Systolic BP in the responder group declined significantly by 8.0% after three months and by 16.1% (P<.01) after 6 months (Figure 4A). The nonresponder group showed a temporary slight reduction after 3 months (7.5%, P>.05) that recurred to baseline levels 6 months after RDN (1.3%, P>.05).

Table II.

 Statistical Analysis of RDN Patients (n = 21) at Baseline and During Follow‐Up

Baseline Follow‐Up – 1 Mo P Values (Baseline vs 1 Mo) Follow‐Up – 3 Mo P Values (Baseline vs 3 Mo) Follow‐Up – 6 Mo P Values (Baseline vs 6 Mo)
Omron
 SBP 168.8±15.0 156.5±19.2 .013 149.0±21.2 .003 150.6±19.2 .001
 DBP 92.8±11.5 88.5±10.8 .053 84.7±14.0 .012 84.9±11.0 .012
Arteriograph
 SBP 157.2±12.9 149.9±20.1 .097 145.1±13.5 .009 147.6±17.3 .009
 DBP 93.9±10.1 88.4±11.8 .025 87.7±11.2 .021 87.1±13.8 .028
 HR 61.4±6.7 59.9±7.4 .234 61.8±9.4 .927 60.1±7.6 .132
 MAP 115.0±9.5 108.9±13.7 .035 106.9±11.2 .011 107.3±14.5 .014
 PP 63.3±12.1 61.6±13.2 .592 57.4±9.4 .039 60.5±8.6 .147
 AIxbra 20.9±30.8 14.2±32.4 .145 5.7±33.7 .038 11.9±35.5 .047
 AIxao 48.2±15.6 44.8±16.4 .144 38.7±19.2 .045 43.6±18.0 .047
 SBPao 162.2±15.7 153.8±24.2 .088 139.7±36.5 .026 150.8±22.1 .019
 DBPao 93.9±10.1 88.4±11.8 .025 83.1±22.0 .055 87.2±13.8 .031
 PPao 67.6±14.2 65.4±17.3 .568 56.6±19.1 .024 63.6±12.4 .111
 PWVao 10.8±1.7 10.6±2.1 .408 8.9±2.4 .010 9.7±1.8 .006
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Abbreviations: AIxbra, augmentation index on brachial artery; AIxao, aortic augmentation index; DBP, diastolic blood pressure; DBPao, aortic diastolic blood pressure; HR, heart rate; MAP, mean arterial pressure; PP, pulse pressure; PPao, aortic pulse pressure; PWVao, aortic pulse wave velocity; SBP, systolic blood pressure; SBPao, aortic systolic blood pressure. Omron HEM‐705 monitor; Omron Healthcare, Vernon Hills, IL. Arteriograph, Tensiomed, Budapest, Hungary. Data are expressed as mean±standard deviation.

Table III.

 Statistical Comparison Between Nonresponders and Responders as Well as Between Different Response Criteria at Baseline

  Baseline
Subgroup 10% Subgroup 10 mm Hg
RSs NRs P Values (Between Subgroups) RSs NRs P Values (Between Subgroups) P Values – RSs (10% vs 10 mm Hg) P Values – NRs (10% vs 10 mm Hg)
Omron
 SBP 168.3±15.4 169.4±15.4 .872 168.8±14.8 168.9±16.3 .988 .413 .626
 DBP 89.6±10.0 97.0±12.5 .149 90.2±9.9 96.9±13.4 .207 .995 .934
Arteriograph
 SBP 155.7±13.7 158.0±12.9 .711 160.4±13.6 153.3±11.5 .230 .795 .732
 DBP 89.4±12.9 96.3±7.8 .146 92.6±12.4 95.4±6.9 .552 .616 .995
 HR 62.4±9.1 60.8±5.4 .639 61.3±7.8 61.4±5.6 .972 .818 .528
 MAP 111.4±10.7 116.9±8.6 .224 115.2±11.3 114.7±7.4 .912 .783 .881
 PP 66.4±16.1 61.7±9.8 .427 67.8±12.8 57.9±9.3 .069 .513 .612
 AIxbra 7.0±38.7 28.4±24.1 .142 15.7±32.8 27.2±28.7 .419 .807 .950
 AIxao 41.2±19.6 52.0±12.2 .143 45.6±16.6 51.4±14.6 .418 .808 .951
 SBPao 158.3±16.7 164.3±15.4 .431 165.1±17.0 158.6±14.1 .370 .962 .774
 DBPao 89.4±12.9 96.3±7.8 .146 92.6±12.4 95.4±6.9 .552 .616 .995
 PPao 67.0±17.3 67.9±13.1 .893 71.2±14.7 63.1±13.0 .214 .645 .689
 PWVao 9.7±1.4 11.3±1.5 .034 10.1±1.6 11.6±1.4 .046 .397 .880
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Abbreviations: AIxbra, augmentation index on brachial artery; AIxao, aortic augmentation index; DBP, diastolic blood pressure; DBPao, aortic diastolic blood pressure; HR, heart rate; MAP, mean arterial pressure; PP, pulse pressure; PPao, aortic pulse pressure; PWVao, aortic pulse wave velocity; SBP, systolic blood pressure; SBPao, aortic systolic blood pressure. 10% and 10 mm Hg blood pressure reduction, measured with the Arteriograph, were compared. The Table shows the statistical comparison between responders (RSs) and nonresponders (NRs) in the 10% subgroup (left panel) and 10 mm Hg subgroup (middle panel). The right panel depicts the statistical analysis between 10% and 10 mm Hg blood pressure reduction. Omron HEM‐705 monitor; Omron Healthcare, Vernon Hills, IL. Arteriograph, Tensiomed, Budapest, Hungary. Data are expressed as mean±standard deviation.

Figure 4.

Figure 4

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 Renal sympathetic denervation (RDN) improves peripheral blood pressure (Arteriograph). Effects of RDN on peripheral systolic blood pressure (SBP) (A) and on peripheral diastolic blood pressure (DBP) (B), measured with the patient in lying position. *,#Significant reduction of blood pressure values as compared with baseline. For SBP and DBP, significant differences between responders and nonresponders were found 6 months after RDN (P=.001). Data are expressed as mean±standard error of the mean.

Diastolic BP declined by about 6.6% (P<.05) after 3 months and 7.2% (P<.05) after 6 months in the RDN group (Figure 4B). In responders, a significant reduction of diastolic pressure occurred by 17.0% (P<.05) after 6 months (Figure 4B).

MAP showed a significant reduction of 5.3% (P<.05), 7.0% (P<.05), and 6.7% (P<.05) after 1, 3, and 6 months, respectively. Within the responder group, an improvement of 8.5%±6.5% (P<.05) and 16.5%±10.0% (P<.01) after 1 month and 6 months, respectively, was observed (Figure 5A).

Figure 5.

Figure 5

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 Renal sympathetic denervation (RDN) improves mean arterial blood pressure (MAP). Effects of RDN on peripheral MAP (A) and heart rate (HR) (B). *, #Significant reduction of individual values as compared with baseline. For MAP, a significant difference between responders and nonresponders was found at 6‐month follow‐up (P<.001). There was a trend toward reduction of HR that failed to reach significance. Data are expressed as mean±standard error of the mean.

RDN and Heart Rate

There was no significant effect of RDN on heart rate in the total RDN group, neither in nonresponders, nor responders (Figure 5B). The mean heart rate at baseline was 61.4±6.7 beats per minute (bpm) and did not significantly change after 6 months (60.1±7.6 bpm, P>.05). Also, when responders and nonresponders were studied and compared we did not observe significant changes during follow‐up (Table III). In the responder group, heart rate was 62.4±9.1 bpm compared with 60.8±5.4 bpm in the nonresponder group at baseline (P>.05) and after 6 months 58.8±9.4 bpm in the responder group and 60.8±6.8 bpm in the nonresponder group (P>.05).

RDN and Peripheral PP

The treatment group showed a reduction of PP by 9.3% (P<.05) after 3 months and by 4.5% (P>.05) after 6 months. Subgroup analysis showed a significant improvement in the responder group during follow‐up with its maximum 6 months after RDN (14.9%; P<.05) (Figure 6A). The nonresponders did not show significant effects over time (1.2%) 6 months after RDN.

Figure 6.

Figure 6

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 Renal sympathetic denervation (RDN) improves pulse pressure (PP) and aortic augmentation index (AIxao). Effects on peripheral PP (A) and AIxao (B). *, #Significant reduction of respective values as compared with baseline. No significant differences were found between responders and nonresponders. Data are expressed as mean±standard error of the mean.

RDN and AIx

In the total RDN group, aortic AIx decreased from 48.2%±15.6% at baseline to 38.7%±19.2% (P<.05) after 3 months and to 43.6%±18.0% (P<.05) after 6 months. Aortic AIx declined significantly from 41.2%±19.6% at baseline to 33.3%±21.2% (P<.05) after 6 months in the responder group whereas aortic AIx did not reveal any changes over time in the nonresponder group (Figure 6B).

RDN and Central Aortic Pressures

Central aortic pressures were reduced by 13.9% after 3 months (P<.01) and by 7% after 6 months (P<.05). In the responder group, a sustained reduction was observed by 9.7% (P<.05) and 18.3% (P<.01) after 3 and 6 months, respectively (Figure 7A). In the nonresponder group, a significant reduction by 16% (P<.05) after 3 months was observed that recovered to baseline values after 6 months (1.7%, P>.05).

Figure 7.

Figure 7

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 Renal sympathetic denervation (RDN) improves central blood pressures. Effects on aortic systolic blood pressure (SBPao) (A) and aortic diastolic blood pressure (DBPao) (B). *, #Significant reduction of blood pressure values as compared with baseline. For SBPao and for DBPao, significant differences between responders and nonresponders were found 6 months after RDN (P<.001). Data are expressed as mean±standard error of the mean.

For aortic diastolic pressure, a reduction by 11.5% (P<.05) after 3 months and 7.2% (P<.05) after 6 months was observed in the RDN group. In nonresponders, we observed a reduction by 13% (P<.05) after 3 months that diminished after 6 months (2.8%, P>.05). In the responder group, we observed a significant and preserved decline by 7.1% (P<.05) after 3 months and by 17.0% (P<.05) after 6 months (Figure 7B).

Aortic PP improved significantly in the RDN group after 3 months by 16.3% (P<.05) whereas no significant improvement could be found after 6 months. A significant reduction was observed in the nonresponder group only after 3 months (19.1%, P<.01). In responders, aortic PP became significantly different after 3 months (10.6%, P<.05) and 6 months (17.5%, P<.01) (Figure 8A).

Figure 8.

Figure 8

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 Renal sympathetic denervation (RDN) improves arterial stiffness. Improvement of aortic pulse pressure (PPao) (A) and aortic pulse wave velocity (PWVao) (B). *, #Significant reduction of individual values as compared with baseline. For PPao and for PWVao, significant differences between responders and nonresponders were found 6 months after RDN (P=.024 and P=.015, respectively). Data are expressed as mean±standard error of the mean.

RDN and Aortic PWV

In the RDN group, a significant improvement in PWV was observed after 3 months (17.3%, P<.05) and after 6 months (10.4%, P<.05). Furthermore, we noticed a significant improvement after 3 months in the nonresponder group (to 22.7%, P<.01) followed by a partial recovery of the effect 6 months after RDN (9.3%, P = .054). In the responder group, an improvement was observed 3 months after RDN (5.4%, P>.05) that further improved 6 months after RDN (13.7%, P = .056) (Figure 8B).

Multivariate analysis of PWV changes in the RDN group showed that short‐term effects on PWV (within 1‐month follow‐up) are BP‐related, whereas improvement of PWV becomes, at least in part, BP‐unrelated during further follow‐up.

Discussion

In patients with arterial hypertension, central aortic pressures and arterial stiffness serve as better predictors for cardiovascular risk and end‐organ damage than peripheral brachial pressures. 8 , 10 , 11 , 23 , 24 , 25 We therefore wondered whether RDN with its reported reduction of peripheral BP may be accompanied by an improvement in central aortic pressures and aortic stiffness. We found that RDN improves peripheral and central BPs as well as aortic stiffness. Systolic, diastolic, and mean arterial pressures improved significantly, almost to normal values according to the World Health Organization definition. In more detail, we observed a significant improvement in (1) aortic pressures, (2) aortic PP, (3) AIx, and (4) PWV. Thus, since in all these parameters independent prognostic value has been previously demonstrated, 13 , 24 , 26 , 27 RDN might also improve prognosis in patients with therapy‐resistant arterial hypertension. Long‐term follow‐up should address this issue.

PWV serves as an excellent and well‐accepted predictor for cardiovascular mortality. 27 , 28 The mean age in our cohort was 64 years. In a recent publication, PWV values in an all comer, besides arterial hypertension otherwise healthy cohort (60–69 years) measured on the basis of different platforms, were for optimal peripheral BP (≤120/80 mm Hg) 9.1 m/s, for normal (>120–129/80–84 mm Hg) 9.7 m/s, high normal (≥130–139/85–89 mm Hg) 10.3 m/s, grade I hypertension (≥140–160/90–100 mm Hg) 11.1 m/s, and grade II/III hypertension (≥160/100 mm Hg) 12.2 m/s, respectively. 14 At the time point of RDN, our patients were classified as having grade I hypertension. Thus, as compared with the data published by Boutouryie and Vermeersch, 14 our responder cohort was characterized by better PWVs, pointing to less end organ damage. The significant improvement in PWV during follow‐up, moreover, indicates a reversible level of arterial stiffness and argues against apparent irreversible arteriosclerosis.

The study by Boutouryie and Vermeersch showed that PWV is BP‐dependent. To clarify whether our finding of PWV improvement is mainly BP‐related, we adjusted PWV to MAP. 14 These data show that short‐term improvement of PWV is related to the reduction of BPs, whereas during follow‐up, improvement of PWV indeed also becomes BP‐independent. We assume that reversible mechanisms, such as RDN‐induced reduction of vasoconstrictive and/or inflammatory factors leading to improvement of endothelial dysfunction, might have contributed to our observations. Since endothelial dysfunction contributes to cardiovascular diseases and morbidity, 29 , 30 , 31 one could hypothesize that RDN might improve morbidity and mortality in patients with resistant arterial hypertension. Intramural vascular remodeling processes may have additionally contributed to our findings. 32 , 33

Limitations

We found, with inclusion of systolic BP >150 mm Hg, 10 mm Hg lower than in the Symplicity trials, a slightly lower response to RDN. Taking 10 mm Hg as the reference value used in the Symplicity trials (HTN1), we found after 3 and 6 months a response that was 16.2% and 19.7% lower as compared with those found in Symplicity. We did not find significant differences between responders and nonresponders regarding ablation points or periprocedural impedance as an indication for insufficient sympathetic nerve ablation. One might speculate that the less restrictive inclusion criteria of ≥150 mm Hg and/or a reduction of medication during follow‐up, which was documented in approximately 19% of patients, might account for our findings. Additionally, there is some evidence that patients might also be “slow responders,” with a significant BP reduction after years. 34 Thus, we might have missed these slow responders during short‐term follow‐up. Nevertheless, as some patients had to be classified as nonresponders after 6 months that would have been responders after 3 months, we cannot exclude that a recovery of sympathetic nerve fibers might have occurred in some patients during follow‐up. Comparability, however, is limited since arterial stiffness, recorded with the Arteriograph, has to be measured with the patients in a lying position. Besides the relatively short follow‐up period of 6 months, further limitations of our study are that inclusion was not based on 24‐hour BP measurements and that the number of patients was lower as compared with the Symplicity trials.

Table IV.

 Statistical Comparison Between Nonresponders and Responders as Well as Between Different Response Criteria at 3‐Month Follow‐Up

  Follow‐Up – 3 Mo
Subgroup 10% Subgroup 10 mm Hg P Values – RSs (10% vs 10 mm Hg) P Values – NRs (10% vs 10 mm Hg)
RSs P Values (Baseline vs 3 Mo)e NRs P Values (Baseline vs 3 Mo) P Values (Between Subgroups) RSs P Values (Baseline vs 3 Mo)e NRs P Values (Baseline vs 3 Mo)e P Values (Between Subgroups)
Omron
 SBP 143.8±26.1 .020 156.1±9.7 .079 .194 144.5±25.1 .013 156.5±10.3 .140 .216 .963 .606
 DBP 80.6±14.3 .029 90.2±12.3 .221 .122 80.2±13.8 .013 92.1±11.6 .401 .055 .724 .733
Arteriograph
 SBP 143.2±19.1 .261 146.1±10.4 .009 .651 146.7±15.9 .055 143.4±10.8 .097 .587 .676 .542
 DBP 83.0±12.3 .221 90.1±10.3 .061 .183 85.9±10.8 .046 89.7±11.9 .242 .457 .406 .444
 HR 59.8±5.4 .472 62.8±10.9 .770 .497 60.0±4.5 .556 63.8±12.8 .832 .366 .791 .945
 MAP 103.0±13.7 .215 108.9±9.7 .026 .270 106.3±11.9 .040 107.7±11.0 .163 .777 .462 .443
 PP 60.1±11.8 .415 56.0±8.1 .017 .357 60.8±9.2 .148 53.7±8.4 .132 .084 .742 .897
 AIxbra −2.7±44.2 .449 9.8±28.2 .043 .439 7.9±39.7 .354 3.2±27.8 .048 .762 .798 .914
 AIxao 36.3±22.4 .447 39.9±18.3 .070 .694 41.6±20.1 .353 35.5±18.8 .083 .482 .797 .913
 SBPao 143.0±26.2 .229 138.1±41.5 .070 .780 149.3±22.3 .050 129.2±46.5 .153 .216 .750 .696
 DBPao 83.0±12.3 .221 83.1±26.0 .115 .993 85.9±10.8 .046 80.0±30.4 .199 .550 .499 .536
 PPao 59.9±20.3 .368 54.9±19.0 .043 .584 63.3±16.5 .114 49.2±19.7 .123 .090 .942 .917
 PWVao 9.2±1.8 .355 8.8±2.6 .016 .710 9.5±1.6 .150 8.3±3.0 .026 .285 .950 .945
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Abbreviations: AIxbra, augmentation index on brachial artery; AIxao, aortic augmentation index; DBP, diastolic blood pressure; DBPao, aortic diastolic blood pressure; HR, heart rate; MAP, mean arterial pressure; PP, pulse pressure; PPao, aortic pulse pressure; PWVao, aortic pulse wave velocity; SBP, systolic blood pressure; SBPao, aortic systolic blood pressure. 10% and 10 mm Hg blood pressure reduction, measured with arteriography, were compared. The left panel shows the comparison between responders (RSs) and nonresponders (NRs) in the 10% blood pressure reduction subgroup. The middle panel shows the same statistical approach for 10 mm Hg as response criteria. The right panel depicts statistical comparison between the two different response criteria. Omron HEM‐705 monitor; Omron Healthcare, Vernon Hills, IL. Arteriograph, Tensiomed, Budapest, Hungary. Data are expressed as mean±standard deviation.

Table V.

 Statistical Comparison Between Nonresponders and Responders as Well as Between Different Response Criteria at 6‐Month Follow‐Up

  Follow‐Up – 6 Mo
Subgroup 10% Subgroup 10 mm Hg P Values – RSs (10% vs 10 mm Hg) P Values – NRs (10% vs 10 mm Hg)
RSs P Values (Baseline vs 6 Mo) NRs P Values (Baseline vs 6 Mo) P Values (Between Subgroups) RSs P Values (Baseline vs 6 Mo) NRs P Values (Baseline vs 6 Mo) P Values (Between Subgroups)
Omron
 SBP 143.8±18.0 .001 159.6±17.9 .022 .062 142.8±17.7 <.001 163.3±15.0 .510 .014 .684 .981
 DBP 81.7±9.1 .038 89.1±12.3 .171 .127 81.0±9.1 .018 91.1±11.4 .323 .036 .789 .500
Arteriography
 SBP 130.6±15.5 <.001 156.1±10.8 .664 <.001 139.8±18.6 <.001 156.1±11.1 .236 .026 .251 .753
 DBP 74.1±12.4 .041 93.6±9.4 .364 .001 80.5±14.2 .012 94.3±9.5 .830 .018 .241 .508
 HR 58.8±9.4 .011 60.8±6.8 .761 .580 59.5±7.8 .249 60.8±7.7 .379 .722 .530 .404
 MAP 93.0±13.0 .008 114.4±9.0 .456 <.001 100.3±15.3 .001 114.9±9.0 .496 .017 .236 .548
 PP 56.5±8.1 .047 62.5±8.4 .847 .137 59.3±7.4 .007 61.8±9.9 .153 .515 .719 .798
 AIxbra −8.6±41.9 .025 22.1±28.1 .554 .059 0.6±35.4 .001 24.3±32.9 .456 .130 .542 .943
 AIxao 33.3±21.2 .024 48.8±14.2 .553 .059 37.9±17.9 .001 49.9±16.7 .460 .130 .542 .171
 SBPao 129.4±19.6 .002 161.5±14.2 .795 <.001 141.6±23.7 <.001 160.9±15.6 .173 .042 .242 .758
 DBPao 74.1±12.4 .041 93.7±9.3 .399 .001 80.5±14.2 .012 94.5±9.5 .772 .017 .241 .515
 PPao 55.2±10.5 .007 67.8±11.3 .757 .024 61.1±11.6 <.001 66.5±13.3 .094 .335 .418 .934
 PWVao 8.4±1.4 .056 10.3±1.6 .054 .015 8.8±1.3 .019 10.6±1.8 .160 .015 .479 .889
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Abbreviations: AIxbra, augmentation index on brachial artery; AIxao, aortic augmentation index; DBP, diastolic blood pressure; DBPao, aortic diastolic blood pressure; HR, heart rate; MAP, mean arterial pressure; PP, pulse pressure; PPao, aortic pulse pressure; PWVao, aortic pulse wave velocity; SBP, systolic blood pressure; SBPao, aortic systolic blood pressure. 10% and 10 mm Hg blood pressure reduction, measured with arteriography, were compared. The Table shows the statistical comparison between responders (RSs) and nonresponders (NRs) in the 10% (left panel) and 10 mm Hg (middle panel) blood pressure reduction subgroups. The right panel shows the statistical comparison between the two different response criteria. Omron HEM‐705 monitor; Omron Healthcare, Vernon Hills, IL. Arteriograph, Tensiomed, Budapest, Hungary. Data are expressed as mean±standard deviation.

Conclusions

RDN not only improved peripheral but also central BPs and arterial stiffness and might therefore be of prognostic value. We therefore recommend routine assessment of central hemodynamics and arterial stiffness in RDN patients.

Acknowledgments

Acknowledgments and disclosures:  The authors thank R. Sharp for carefully reading and commenting on the manuscript. The authors report no specific funding in relation to this research and no conflicts of interest to disclose. Drs Mortensen and Franzen contributed equally to this manuscript.

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