Bioplar RF Energy

Bipolar systems, such as the Vessix V2, deliver energy using the electrical phenomena of ohmic resistive heating to the adjacent tissue and deliver electrical energy between two electrodes, which in the case of the V2 catheter are within a few millimetres of each other.  The V2 confines its energy delivery to an area very close to the two electrodes and moreover, thermistors mounted at each electrode pair allow for precise monitoring and temperature control at each independent electrode pair.  This delivery of energy causes thermal heat to perfuse through the artery wall into the adventitia layer of the artery and results in denervation of the target renal sympathetic nerves. The RF energy treatment, in effect, denervates the renal sympathetic nerves surrounding the renal artery without creating any flow limiting stenosis or any other deleterious effects to the renal artery. Bipolar systems do not unnecessary dissipate energy into areas further away from the electrode, and thus use energy very efficiently.  Accordingly, the V2 bipolar System uses lower voltages and power (approximately 2 watts) to achieve necessary depth of penetration.  Moreover, unlike monopolar RF systems, the lesion or footprint formed at the contact points inside the artery using bipolar RF are well defined in the immediate region of the electrode pair.

Key benefits of the Vessix approach to renal denervation include:

• Employing a balloon catheter that is quite familiar to interventionists thereby increasing the safety profile of the device

• Ability to deliver RF treatment that lasts only thirty (30) seconds per artery which, in turn, significantly reduces discomfort for the patient

• Fast RF treatment time greatly increasing the efficiency of the procedure and provides the benefit of lower exposure to radiation, lower amount of contrast dye and therefore lower renal toxicity to the patient.

Pre-Clinical Summary 

A program of in vitro and in vivo testing has been carried out to verify that the product meets appropriate standards and that the performance of the device meets the design parameters necessary to achieve the level of clinical effect associated with the desired therapeutic result.

Following a series of bench tests, pre-clinical animal studies were undertaken by Vessix Vascular to determine the safety and efficacy of radiofrequency renal denervation in juvenile pigs following treatment employing the V2 System. 

Healthy juvenile swine were chosen as the species for these studies because of the clinically relevant size and anatomy of their cardiovascular system. To date, over one hundred and ten male Yorkshire swine were evaluated.

The efficacy of the RF renal denervation procedure was compared with surgical denervation, which served as a positive control. Untreated animals served as negative controls. Efficacy studies were conducted by treating one renal artery (kidney) and using the contralateral kidney as a control to compare treated to untreated kidney as well as treating bilaterally.

Safety was examined by daily clinical observations; measurements of body weights and body condition score, blood sample collection for clinical pathology, histology of kidneys and renal arteries at follow up and analysis of angiography images immediately post treatment and at follow up intervals.

During all RF renal denervation treatments no complications occurred and all animals remained healthy for the study durations. There was no angiographic evidence of acute dissection, perforation or thrombus immediately post RF treatment, or prior to necropsy at any of the time points.

Renal artery stenosis was determined as luminal gain or loss calculated by quantitative angiographic analysis. No stenosis developed inside the renal arteries due to the RF treatments at any of the follow up periods. 

There were no significant changes in body weight, body condition or clinical pathology parameters in any animal over the course of the study. There were no macroscopic findings at necropsy of any animal treated with RF renal denervation. Histology of the renal arteries also verified the safety of the RF renal denervation treatments. All RF treated renal arteries remained intact (i.e., no dissections and/or perforations) with no disruption of wall layers (i.e., internal elastic lamina [IEL], tunica media, and external elastic lamina [EEL]). In addition, the lumen of all treated arteries remained open with minimal neointima formation and no evidence of luminal thrombosis.

For efficacy, a decrease in norepinephrine (NEPI – noradrenaline is a synonym) kidney tissue concentration was utilized as a surrogate marker of efficacy following renal denervation. A highly specific and highly sensitive HPLC-MS/MS was employed as the primary analytical tool for the determination of NEPI concentration (ng/g) in kidney tissue. The assessment of the effectiveness of bilateral renal RF denervation was measured through comparison of the NEPI level in kidneys of untreated control animals and in kidneys of surgical denervation animals. Each kidney sample was sectioned bilaterally and triplicate samples were analyzed for NEPI concentration. 

• Following the RF treatment, the percent of NEPI reduction ranged from approximately 70-96% when compared to untreated contralateral control kidney (or as compared to endogenous levels when a bilateral treatment was performed). The reduction in NEPI levels following V2 RF treatment was similar to the NEPI reduction observed following surgical denervation, which served as positive control for renal denervation in animals.

• Regardless of the RF treatment dose (temperature, duration, length of electrode and treatment zone) the lumens of all treated arteries remained open with no flow limiting stenosis and no evidence of luminal thrombosis.

In summary, these studies demonstrated that the V2 System RF treatment in porcine renal arteries was safe and efficacious across all treatment groups and time points.