Renal sympathetic denervation lowers systemic vascular resistance in true treatment-resistant hypertension

Figures & data

Figure 1. Trial design. RDN: renal sympathetic denervation.

Table 1. Baseline characteristics.

	RDN (n = 9)	Control (n = 9)
Clinical characteristics
Age, y	57 [49–67]	63 [58–69]
Gender (women)	22% (2)	0% (0)
Body mass index, kg/m^2	27 [26–35]	31 [26–35]
Hypercholesterolemia	22% (2)	33% (3)
Diabetes mellitus	22% (2)	33% (3)
Microalbuminuria	33% (3)	44% (4)
Left ventricular hypertrophy	56% (5)	67% (6)
Peripheral arteriosclerosis	0% (0)	0% (0)
Coronary artery disease	11% (1)	56% (5)
Previous stroke	11% (1)	11% (1)
Biological characteristics
eGFR, mL/min per 1.73 m^2	80 [68–91]	82 [67–93]
Hemodynamic measurements
Office systolic BP, mmHg	153 [146–169]	157 [144–172]
Office diastolic BP, mmHg	94 [78–106]	84 [79–93]
Ambulatory daytime systolic BP, mmHg	147 [144–163]	149 [144–159]
Ambulatory daytime diastolic BP, mmHg	92 [88–100]	90 [82–95]
Supine systolic BP, mmHg	152 [142–171]*	149 [139–164]
Supine diastolic BP, mmHg	89 [83–98]*	85 [74–95]
Supine MAP, mmHg	106 [103–122]*	103 [99–119]
Office heart rate, bpm^†	64 [57–80]	55 [48–58]
Supine heart rate, bpm	66 [59–70]*	54 [49–60]
Cardiac index, L/min/m^2	3.0 [2.1–3.7]*	3.0 [2.2–3.6]
Stroke index, mL/m^2	45.5 [33.8–53.8]*	59.0 [32.5–69.5]
Systemic vascular resistance index, dyn*s*m^2/cm^5	3,100 [2,112–4,122]*	2,773 [2,234–3,984]
Antihypertensive treatment
No. of antihypertensive drugs	5.0 [3.5–6.5]	5.0 [4.0–6.0]
ACE-i/ARBs	100% (9)	100% (9)
Calcium channel blockers	89% (8)	78% (7)
Potassium losing diuretics	100% (9)	89% (8)
Aldosterone antagonists	33% (3)	56% (5)
β-blockers	56% (5)	89% (8)
Direct renin inhibitors	22% (2)	0% (0)
α-1 blockers	56% (5)	22% (2)
Centrally acting sympathicolytics	56% (5)	33% (3)
Vasodilators	0% (0)	22% (2)

Data presented as medians [IQR] or % (n). Comparisons between groups are performed with Mann-Whitney U test for continuous variables and Fisher’s exact probability test for categorical variables. *n = 8. ^†p = 0.04 for difference between groups.

ACE-i: angiotensin-converting enzyme inhibitors; ARB: angiotensin II receptor 1-blocker; BP: blood pressure; eGFR: estimated glomerular filtration rate calculated by the CKD-EPI equation; MAP: mean arterial pressure; RDN: renal sympathetic denervation.

Figure 2. Individual changes in systemic vascular resistance index in the RDN group. Panel A shows the SVRI levels for each individual at each time point in the RDN group (n = 9). The other panels show the change in SVRI for each individual from baseline to three months follow-up (panel B, n = 8), from three to six months follow-up (panel C, n = 9) and from baseline to six months follow-up (panel D, n = 8), the median is marked with a horizontal line. *p < 0.01 on Wilcoxon signed rank test (n = 9). RDN: renal sympathetic denervation; SVRI: systemic vascular resistance index.

Table 2. Changes in hemodynamic variables in the RDN group.

	Baseline (n = 8)	3 months (n = 8)	6 months (n = 8)	Median change			Friedman test p Value	Wilcoxon signed rank test p Value
				Baseline to 3 months	3 months to 6 months	Baseline to 6 months		Baseline vs 3 months	3 months vs 6 months	Baseline vs 6 months
Supine BP, mmHg
Systolic BP	152 [142–171]	151 [147–164]	138 [120–153]	7 [−22 to 8]	−15 [−24 to 2]	−10 [−45 to 10]	n.s.	–	–	–
Diastolic BP	89 [83–98]	90 [83–94]	78 [71–88]	2 [−7 to 9]	−9 [−18 to −3]	−7 [−28 to 5]	n.s.	–	–	–
MAP	106 [103–122]	111 [104–115]	98 [88–109]	5 [−11 to 9]	−11 [−22 to −2]	−6 [−33 to 6]	n.s.	–	–	–
Supine heart rate, bpm	66 [59–70]	58 [50–61]	62 [57–68]	−9 [−12 to −4]	8 [2 to 9]	−3 [−4 to 0]	<0.01	0.01	0.02	n.s.
Cardiac index, L/min/m^2	3.0 [2.1–3.7]	2.8 [2.4–3.0]	3.2 [2.6–3.4]	−0.3 [−0.8 to 0.1]	0.2 [−0.1 to 0.7]	0.0 [−0.3 to 0.3]	n.s.	–	–	–
Stroke index, mL/m^2	45.5 [33.8–53.8]	47.5 [43.3–55.5]	49.5 [37.8–51.0]	0.5 [−4.3 to 10.0]	−0.5 [−6.3 to 6.8]	2.0 [−0.8 to 6.8]	n.s.	–	–	–

Data are presented as medians [IQR]. BP: blood pressure; MAP: mean arterial pressure; n.s.: not significant. RDN: renal sympathetic denervation.

Figure 3. Individual changes in systemic vascular resistance index in the control group. Panel A shows the SVRI levels for each individual at each time point in the control group (n = 10). Ticked line represents the participant with a deviant SVRI pattern, i.e. large changes that diverge strongly in opposite directions from the general pattern. The other panels (n = 9) show the change in SVRI for each individual from baseline to three months follow-up (panel B), from three to six months follow-up (panel C) and from baseline to six months follow-up (panel D), the median is marked with a horizontal line. *p = 0.01, †p < 0.01 on Wilcoxon signed rank test (n = 9). SVRI: systemic vascular resistance index.

Table 3. Changes in hemodynamic parameters in the control group.

	Baseline (n = 9)	3 months (n = 9)	6 months (n = 9)	Median change			Friedman test p Value	Wilcoxon signed rank test p Value
				Baseline to 3 months	3 months to 6 months	Baseline to 6 months		Baseline vs 3 months	3 months vs 6 months	Baseline vs 6 months
Supine BP, mmHg
Systolic BP	149 [139–164]	147 [136–170]	134 [118–140]	2 [−17 to 12]	−19 [−32 to 1]	−23 [−29 to −4]	n.s.	–	–	–
Diastolic BP	85 [74–95]	87 [77–95]	67 [64–78]	4 [−5 to 6]	−12 [−24 to −8]	−17 [−22 to −7]	<0.01	n.s.	<0.01	<0.01
MAP	103 [99–119]	107 [102–116]	91 [83–97]	5 [−10 to 7]	−15 [−29 to −6]	−20 [−23 to −6]	<0.01	n.s.	0.01	<0.01
Supine heart rate, bpm	54 [49–60]	49 [43–59]	56 [49–63]	−3 [−8 to 0]	8 [4 to 9]	2 [−3 to 7]	0.01	n.s.	0.01	n.s.
Cardiac index, L/min/m^2	3.0 [2.2–3.6]	2.6 [2.0–2.9]	2.9 [1.8–3.3]	−0.5 [−0.9 to −0.1]	0.2 [0.1 to 0.5]	−0.3 [−0.6 to 0.1]	<0.01	0.01	n.s.	n.s.
Stroke index, mL/m^2	59.0 [32.5–69.5]	52.0 [32.5–62.5]	57.0 [28.5–60.5]	−2.0 [−12.0 to 2.0]	−1.0 [−4.0 to 2.0]	−6.0 [−11.5 to −0.5]	n.s.	–	–	–

Data are presented as medians [IQR]. BP: blood pressure; MAP: mean arterial pressure; n.s.: not significant.