The TIVUS™ System uses high intensity US to induce thermal effect to target nerves, and is intended for renal denervation. US is a widely accepted energy source for hyperthermia therapy in various organs [2]. The TIVUS™ System, comprised of a catheter-mounted ultrasonic transducer and a console, generates high intensity, non-focused ultrasonic energy which can be delivered percutaneously to tissues adjacent to blood vessels of varying diameters (Fig. 10.3a).

In contrast to low intensity US applied for imaging, where tissue heating is negligible, the US energy generated by the TIVUS™ System is absorbed into the tissue and transformed into heat, thus resulting in a thermal effect on the target tissue and nerves. The other ultrasonic effects on tissue (such as cavitation or streaming) are insignificant. Figure 10.4 illustrates the intensity and frequency range of the TIVUS™ system in comparison to other ultrasonic medical modalities. It is noteworthy that while Cardiosonic’s US element frequency is at a higher range similar to imaging modalities, the intensity is somewhat higher than physical therapy devices and significantly lower than High Intensity Focused Ultrasound (HIFU) products, mostly used in oncological therapies. During treatment, the catheter is placed at a distance from the artery wall, therefore preventing mechanical damage to the artery wall and allowing cooling of the ultrasonic transducer as well as vascular intima by renal blood flow. The ultrasonic energy is absorbed by the tissues adjacent to the artery, which is heated to 50–80 °C. Heating a tissue beyond 50 °C causes irreversible denaturation of protein (eg. collagen) and other thermal effects, resulting in remote damage to the outer artery wall layers and perivascular tissue, while avoiding damage to the vessel’s intimal layer. Thermal damage to the media, if present, is negligible. When US is applied to nerves located in the adventitial and perivascular layers, heating of nerve cells and their supporting tissue results in axonal degeneration and cell death (Fig. 10.3c) [2, 6, 11]. Heating causes irreversible damage and blockage of unmyelinated nerve fibres above 47 °C and of myelinated nerve fibres above 58 °C [11]. The depth of penetration and hence absorption of US energy, depends on the beam frequency; as the frequency rises, the depth of penetration decreases (Fig. 10.3d).

TIVUS I is a First-In-Man (FIM) multicenter study conducted across centres in Australia, Europe and Israel in order to evaluate the TIVUS™ System safety and performance. The study included patients with essential hypertension with Office Systolic Blood Pressure (OSBP) ≥160 mmHg, despite treatment with more than three antihypertensive medications, including a diuretic. In addition, the clinical experience includes patients treated under a compassionate use program for severe resistant hypertension associated with impaired renal function or previously implanted renal artery stent. Overall a total of 18 patients were successfully treated at six investigational sites worldwide. Safety and feasibility have been demonstrated by virtue of absence of device related complications and reduction in blood pressure measurements.