Improved Home Blood Pressure Control by CT-guided Ozone-mediated Renal Denervation for Patients with Resistant Hypertension

Summary

CT-guided ozone-mediated renal denervation (RDN) by injecting an O₂-O₃ gas mixture around lumbar ganglia reduces antihypertensive medication burden and achieves an improved home blood pressure control rate. We present a novel, simplified, unilateral, and contrast-free RDN technique that minimizes the renal artery injury in the treatment of patients with resistant hypertension (RH).

Abstract

Accumulating evidence from clinical trials in recent years has consistently supported the blood pressure (BP)-lowering efficacy of renal sympathetic denervation (RDN). However, the most widely used catheter-based RDN technique still has limitations in clinical practice. Therefore, it is necessary to develop an alternative RDN approach for BP control. In our previous clinical trial, we demonstrated that CT-guided ozone-mediated RDN effectively reduced both office and ambulatory BP at 12 weeks post procedure in patients with resistant hypertension (RH). In this study, we further evaluated the efficacy of this technique in home BP control of 15 patients with RH. Based on the reduced use of anti-hypertension drugs following the procedure, the control rates of home BP (<140/90 mmHg) for the overall cohort were 60.0%/93.3%, 80.0%/100%, and 80.0%/100% at weeks 4, 8, 12, respectively, and 57.1%/90.91, 81.8%/100% and 90.9%/100% at weeks 4, 8, 12 for patients with normal baseline renal function. Additionally, 33.3% patients achieved the optimal morning BP target of ≤135/85 mmHg. No complications were reported intra- or post procedure. We present a simplified, unilaterally operated, contrast-free RDN technique that avoids renal artery injury in the management of RH.

Introduction

Resistant hypertension (RH) is diagnosed when individuals do not meet BP targets despite taking three antihypertensive medications, or when individuals achieve the BP target but require four or more antihypertensive medications¹. RH is linked to a significantly higher risk of cardiovascular and renal adverse events². Renal sympathetic denervation (RDN) -- from surgical sympathectomy or the current catheter-based RDN -- was demonstrated to be effective in the treatment of RH^3,4,5.

Due to the invasiveness and severe side effects, surgical sympathectomy has been eliminated. There are still some limitations for catheter-based RDN, including contrast-dependence, potential renal artery injury, relatively lower cost-effectiveness, and the requirement of special catheter assistance⁶. These limitations highlight the need for improved RDN approaches. In recent years, other RDN techniques, such as CT-guided perivascular ethanol-mediated RDN, transurethral laparoscopic-based RDN, and laparoscopic-based perivascular unilateral RDN have been introduced, demonstrating effective BP reduction^7,8,9,10.

The sympathetic ganglion, especially ganglia from T9-L2, are important components of renal sympathetic innervation and are convenient to target under CT guidance^11,12. The smpathetic ganglion was the earliest target for RDN in surgery. A recent animal experiment has shown that the injection of ethanol in the celiac trunk ganglion resulted in significant BP reduction. High concentrations of ozone (18-30 µg/mL) promote an increase in the rates of apoptosis and neuroblast cell death¹³. Our previous trial showed that CT-guided ozone-mediated RDN effectively lowered office and ambulatory BP 12 weeks post procedure in RH patients¹⁴. In this study, we evaluate the changes in anti-hypertensive regimen and the effect of home BP control rate of this approach of RDN.

Protocol

This study was approved by the Guangzhou Red Cross Hospital Ethics Board (No. 2022-145-01), and written informed consent was obtained from all participants prior to enrollment. This single-arm clinical trial was designed and registered in Chictr.org.cn (ChiCTR2300071375).

1. Study design

NOTE: This was a prospective, single-arm clinical study aimed at observing the home BP control rate in patients before and after the procedure.

1. Set the following inclusive criteria: age between 18 and 80 years; hypertensive patients with BP that remains elevated above 140/90 mmHg even with the simultaneous use of three antihypertensive medications from different classes, commonly including a diuretic; or patients whose BP achieves less than 140/90 mmHg on ≥4 antihypertensive medications.
2. Exclude the following patients: diagnosed secondary hypertension; spinal deformities or infective; prior renal artery angioplasty or catheter-based denervation; previous lumbar internal vertebral disc radiofrequency ablation or sympathetic blockage; and a history of myocardial infarction, cerebral vascular accident, or transient ischemic attack within 3 months before enrollment; patients who did not upload the scales in a timely manner as required during the follow-up period.
3. Evaluation of antihypertensive medication burden (AHMB)
   1. Assess the antihypertensive medication burden by counting the number of medication classes, disregarding the doses. When the criteria for medication reduction are met, consider discontinuing one class of medication, regardless of dosage, as reducing one burden. To maintain adherence and prevent unproven medication changes, have the follow-up team verify the medication plan with patients weekly and ensure those eligible for reduction are following the prescribed adjustments.
4. Set the criteria for reducing antihypertensive drugs as systolic blood pressure (SBP) ≤ 110 mmHg on at least two consecutive measurements after the procedure.
5. Home BP monitor
   1. To ensure the accuracy of home BP measurement, train all patients formally to measure their home BP at four different time points each day in a standardized manner: upon waking, at 10:00 AM, at 4:00 PM, and before bedtime. Request that patients log their home BP readings on a record form, which will be collected by the study team every week during follow-up.Define home BP control as SBP of ≤140 mmHg and a diastolic blood pressure (DBP) of ≥90 mmHg.
      NOTE: An electronic automatic device was used to measure brachial artery BP.
6. Safety: Report and record all possible adverse events via phone calls, messaging apps, or in the outpatient clinic. Potential complications include orthostatic hypotension, gastrointestinal dysfunction, dysuria, and male erectile dysfunction.

2. Preparation before the procedure (prone position training for patients in the ward)

1. Have the patient assume a prone position on the bed, extending their arms parallel above the head.
2. Place a pillow beneath the lower abdomen to flatten the lumbar curve, ensuring the back and buttocks are on the same level.
   NOTE: Pillow placement may vary according to individual body types.
3. Carry out this exercise twice a day for 2-3 days with the aim of keeping the position stationary for at least 20 min.

3. Ozone-mediated renal denervation (in CT laboratory)

1. Remove the patient's upper garment to expose the torso.
2. Attach the electrodes and connect to an electrocardiogram monitor.
3. Measure the supine blood pressure.
4. Have the patient switch to a prone position, ensuring comfort and stability.
5. For reference points on the body surface, place a metal wire on the midline of the torso (approximately at T12-L3 level) to act as a reference for the deviation distance from the midline of the body surface puncture point under CT guidance (Point C in Figure 1).
6. Identify the puncture target
   1. Use a CT scanner to get anteroposterior and lateral images of the lumbar spine (range: S2 to T11) for vertebral counting and transitional vertebrae assessment.
   2. On the transverse images, identify the left renal artery origin level and determine the injection target point (Point A in Figure 1) at the anterolateral third of the vertebral right edge at this level.
      NOTE: If the renal artery is directly below the transverse process at the same level, adjust the injection level to avoid the transverse process.
   3. Record the corresponding transverse plane position.
7. CT-guided puncture parameter measurement
   1. On the selected transverse image in step 3.6.2, identify injection target point A (Figure 1) at the anterolateral third of the vertebral side.
      NOTE: The target point should be below the fascia of the ipsilateral psoas major muscle, ~2-3 mm away from the left renal artery.
   2. Draw a line from A along the outer lateral border of the left psoas major. The intersection of this line with the body surface is the skin puncture point B, with the metal wire on the lumbar body surface corresponding to point C. Measure the length of AB (needle insertion depth), the angle between AB and BC (puncture angle Q), and the length of BC (lateral distance of the body surface puncture point from the midline (Figure 1)).
      NOTE: Ensure that the needle remains entirely within the psoas major throughout its trajectory.
8. Surface puncture point positioning
   1. Adjust the bed to the recorded position in step 3.6.2. Activate the laser positioning line and mark two lines using a marker: one along the projection line (A line) and the other along the preplaced metal line on the body surface midline (B line). The intersection of these two lines is point C in step 3.5.
   2. Remove the metal wire and mark the puncture point B on line A according to the BC segment length measured in step 3.7.
9. Puncture protocol
   1. Insert a 21 G needle with length markers at point B, puncturing at the predetermined angle to the predicted depth. Perform continuous 2 mm slice thickness scans around the puncture point ± 0.4-0.8 cm to confirm the needle tip.
      NOTE: If resistance is encountered, indicating an excessive puncture angle and needle-vertebra contact, retract and readjust the puncture angle under CT guidance.
   2. Connect a 10 mL syringe, ensure no blood or gas is aspirated, and then inject 2 mL of 10% ropivacaine. Use a 20 mL syringe to draw 10 mL of O₂-O₃ gas mixture from a medical ozone generator and inject slowly along the needle. Repeat the CT scan to show ozone distribution.
      NOTE: The ozone concentration is 30 µg/mL.
10. After the procedure, ask the patient to lie in a supine position, and measure cuff BP every 5 min. Ensure that the monitoring in the CT room lasts for at least 20 min.

Results

Baseline characteristics:
Initially, 20 patients were selected. Two patients diagnosed with renal artery stenosis and one with sleep apnea syndrome were excluded, resulting in 17 patients eligible for inclusion. Of these 17 patients, two were unable to continue in the follow-up. Finally, 15 patients were included in this clinical observation, with an age of 65.1 ± 10.8 years. Six patients (6/15; 40.0%) had chronic kidney dysfunction and one (1/15; 5.9%) was on dialysis at the time of enrollment. Elev...

Discussion

Our previous study demonstrated that ozone-mediated RDN significantly reduced in-hospital, office, and ambulatory BP, as well as antihypertensive medication use. The BP reduction was rapid and persisted through the 12 weeks follow-up. Additionally, we observed that the BP-lowering effect was particularly noteworthy in patients with normal baseline renal function¹⁴. In this study, CT-guided ozone-mediated RDN showed the effect of improved home BP control for patients with RH.

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
CT scanner	General Electrics, Hi Speed ZX/I. USA
Graduated measuring tape	no specified brand
Marker pen	no specified brand
Medical ozone generator	Medozon compact, Herrmann Apparatebau GmbH. Germany
Metal wire	no specified brand
Peit needle	Hakko Co., Ltd. JAPAN	21 G x 150 mm
Ropivacaine Hydrochloride Injection	AstraZeneca AB	100 mg/10 mL
Single-use puncture pack	no specified brand		containing sterile cotton swabs, sterile gauze, sterile surgical drape, a 5 mL syringe, and a 20 mL syringe.