Preliminary results of RETREAT renal denervation study go against the grain

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Horst Sievert, CardioVascular Center, Frankfurt, Germany reported “interesting, but inconclusive observations” from a small cohort of patients enrolled in the RETREAT (Renal denervation with ultrasound after failed radiofrequency denervation) study.

The findings were presented at the Leipzig Interventional Course (LINC, 27–30 January, Leipzig, Germany).

“Renal denervation with ultrasound after performed after prior denervation with radiofrequency seems to be safe. After an initial decrease of blood pressure after one month, we observed an increase in blood pressure in this small number of patients, a finding which has not been seen in other denervation studies,” said Sievert.

RETREAT is a physician-initiated prospective, multicentre study with no industry funding in which 30 patients will be enrolled.  Its purpose is to evaluate the effect of renal denervation using ultrasound energy (with Recor’s Paradise system) after failed denervation with radiofrequency (with Medtronic’s Symplicity system).

Sievert said: “Enrolment in the RETREAT study coincided with the publication of the SYMPLICITY HTN-3 study results following which the reimbursement for renal denervation was stopped in Germany. There was a decline in referrals for renal denervation and new treatment modalities for hypertension began to be explored. This resulted in enrolment becoming very slow and almost stopping.”

At the outset, Sievert identified the many potential reasons why renal denervation could fail as a therapy including that renal denervation may not work at all; changes in medication (either before the procedure or in the follow-up period); patient specific factors such as type of medication or race; or technical issues with the procedure (such as incomplete ablation, or ablation that is not circumferential.) “It might also be that the technology is not good enough to destroy all renal nerves in all patients,” Sievert explained.

Renal denervation with ultrasound

As with radiofrequency, renal denervation is achieved with ultrasound by inducing thermal necrosis. “Ultrasound energy passes through fluids and generates frictional heating in soft tissues. Unlike radiofrequency, no direct tissue contact is required and therefore stability of the catheter is less of an issue,” he said.

The paradise system is an ultrasound transducer that is mounted inside a low pressure balloon. Cooled water in the balloon protects the endothelium against heat. The procedure involves 30 seconds of circumferential heating independent of the positioning of the device.

RETREAT study

Patients were included in RETREAT if they had had a first renal denervation treatment with the Symplicity catheter at any time in the previous year and had been classified as a non-responder, defined in this study as those who either experienced a blood pressure drop of less than 10mmHg or because their blood pressure was still high (above 160mmHg). Patients also had to have a systolic office blood pressure of 140mmHg and be on optimal medical therapy consisting of three or more antihypertensive drugs including one diuretic, all at the maximum tolerated dose in order to be eligible. Secondary hypertension also had to be ruled out for these patients before the first procedure was performed.

The primary endpoints of RETREAT were a change in office and ambulatory blood pressure 12 months after the procedure, or a change in antihypertensive medications. The secondary endpoint was freedom from adverse events.

At baseline, examinations included measurement of office-based blood pressure and 24-hr ambulatory blood pressure, a blood test to determine creatinine levels, and MRI/ angiographic evaluation to rule out renal artery abnormalities including stenosis from the first procedure. Follow-up was scheduled at one, three, six and 12 months for measurement of office-based pressure, and ambulatory blood pressure, changes in medication, and adverse events. A renal duplex ultrasound was performed after six months and a blood test for creatinine was done after six and 12 months.

In the first renal denervation procedure with radiofrequency, both renal arteries were treated in each patient. Circumferential ablation was performed with 10–20 ablations per patient. There were no adverse events seen during the procedure. After six months, if there was an office-based blood pressure decrease of less than 10mmHg and/or office-based blood pressure of >160mmHg, the patient was enrolled in the trial and second renal denervation with ultrasound was performed.

RETREAT procedure

Eight patients were treated with the Paradise system with 2–3 ablations per artery being performed. “There was technical success in all patients and no device-related adverse events occurred. There was one false aneurysm seen. We observed a decrease in office-blood pressure in the first month and then this decrease actually disappeared over time. (See table 1) We have not seen this in other trials. Similarly, when we looked at the ambulatory blood pressure, there was a large decrease initially and then a diminishing effect over time. There were no changes in creatinine levels,” Sievert concluded.

 

Table 1:

 

Follow-up point

Mean office-based blood pressure

Number of patients

Baseline

171/87mmHg

9

One month

150/80mmHg

3

Three months

154/84mmHg

6

Six months

175/89mmHg

7

12 months

171/94mmHg

1