Huang et al. first introduced radiofrequency (RF) catheter ablation for the disruption of the atrio-ventricular junction in 1987 [1]. Since that time, RF catheter ablation has become one of the most useful and widely accepted therapies in cardiac electrophysiology; modifications of RF energy delivery and improvements in the electrode design have resulted in significant expansion of its cardiac indication. More recently, RF technology has been used for the percutaneous sympathetic denervation of human renal arteries in the treatment of severe drug resistant hypertension [2–5].

RF energy is a form of alternating electrical current that produces a lesion by two distinct physical mechanisms: (1) direct resistive heating of the tissue in contact with the catheter electrode and (2) thermal conduction or passive heat transfer to deeper tissue layers. Resistive heating in regions close to the RF current source is rapid while passive heat transfer into deeper tissue layers is a slower process [6]. The transfer of heat continues after the discontinuation of RF current delivery and results in the lesion expansion. While RF electrical current can be delivered by a bipolar mode (i.e., between two closely placed electrodes), the more frequent use is via a monopolar mode with completion of the electrical circuit via the second electrode placed on the patient’s skin at a distant location (typically the back or thigh). In the case of renal denervation, RF current is delivered to specific sites along the renal artery intimal surface through percutaneous arterial approach.

The effects of RF energy on vascular tissue depends on several factors which include power (wattage), duration of its application, temperature, electrode size, quality of the electrode/tissue contact (impedance), the histological characteristics of the tissue and the blood flow over the electrode/tissue interface which determines the degree of heat dissipation [7, 8]. The RF electrode surface temperature is impacted by the blood flow over the electrode and the temperature of the heated tissue decreases in a hyperbolic manner as the distance from the RF electrode increases, both of which are important factors in the use of the monopolar electrodes in renal denervation [9]. At temperatures above 100 °C, irreversible damage occurs to tissues surrounding the electrode [10]. This results in plasma protein degeneration and coagulation of blood elements resulting in charring or coagulum formation, which are typically noted in cardiac ablation. An important sign indicating charring or coagulant formation is the sudden rise in impedance rather than the gradual decrease that typically accompanies successful RF delivery.

Measuring baseline impedance is used to assess the effectiveness of the contact between the RF electrode and tissue surface. As the tissue is heated, there is a temperature dependent drop in electrical impedance [9]. A positive correlation between the pre-ablation impedance and heating efficacy and a similar association between the decline in impedance during energy delivery and heating efficacy has been established [11]. Therefore, monitoring tissue surface temperature is essential and provides useful information as to the quality of the electrode/tissue interface [12]. Although temperature rise is greater and faster with properly engaged electrodes, a gradual increase in temperature as opposed to an abrupt rise may provide for a more homogeneous RF lesion [9].

The duration of steady state RF energy delivery is also an important variable and typically ranges from between 30 and 45 s in clinical practice. The optimal duration of RF energy application to effect optimal renal denervation remains a topic of debate as it reflects the extent of axonal ablation and the potential clinical effectiveness (i.e., blood pressure reduction) of the procedure and currently ranges from 30 to 120 s. However, the duration of energy application and electrode temperature must be balanced against the potential for renal intimal damage and subsequent renal artery lesion formation [13]. The degree of successfully ablated tissue is also proportional to the applied power of the RF source. In general, energy delivery is regulated by temperature control determined by default target temperatures with adjustment of energy to maintain a specific temperature. The algorithm associating power, temperature, impedance and duration of energy exposure are all specific to individual monopolar renal denervation devices. The Medtronic Ardian renal denervation system uses a non-balloon, non-occlusive design with the initial Arch™ catheter uses a platinum electrode tip, providing adequate renal intimal contact to ensure transfer of adequate energy and impedance. The denervation procedure is performed using non-overlapping ablations spaced in a helical pattern to minimize intimal damage (4–6 ablations/renal artery) with the application of 5–8 W per ablation site while the generator algorithm monitors temperature and impedance and adjusts power to prevent tissue over-heating and potential intimal damage. If the surface temperature exceeds the pre-specified value, the power is terminated; likewise, if the temperature is too low, the system generates an “error code” telling the operator that the surface contact in likely insufficient.

Electrode size influences the volume of the ablation lesion and may also impact the clinical effectiveness of ablation. In general, larger electrodes result in larger lesions, which may produce greater ablative efficacy [13, 14]. However, in the case of renal denervation, the ideal relationship between lesion size, treatment efficacy and safety is yet to be fully understood and reported.

The blood supply and proximity to major blood vessels determines the degree of heat dissipation (i.e., the “heat sink”) and represents another important factor that influences optimal ablative lesion formation. Convective heat dissipation through blood flow occurs at the tissue level and at the electrode tip [14]. At the tissue level, convective heat dissipation removes heat from the tissue limiting the penetration depth of the RF current. In the case of renal denervation, an appropriately sized renal artery and adequate renal artery blood flow is essential in delivering the appropriate amount of energy to affect renal denervation. In the case of accessory renal arteries and patients with end-stage renal disease (ESRD) with small renal arteries, the reduction in the caliber of the renal artery diameter and blood flow is an important factor which reduces the effectiveness of the monopolar technology.

During the application of RF energy for renal denervation, duration of energy application and impedance are typically the only parameters available for direct observation by the operator. Newer iterations of the monitoring systems may provide feedback regarding the rate of rise of temperature and provide the operator with feedback if an ideal combination of impedance drop and temperature rise has not been achieved, which in the case of the Medtronic Ardian Flex™ Catheter monitor system, an “error 50” may be recorded. Beyond this limited procedural feedback, the application of RF energy to the renal intima may cause substantial visceral pain with the ablation of afferent sympathetic nerves and type A and C nerve fibers that mediate pain via the dorsal root ganglia of the central nervous system.

Both efferent and afferent nerves are ablated during RF denervation; however, the effectiveness of the RF ablative lesion relates to the depth and distribution of these nerve fibers along the renal artery. In postmortem studies of nine renal arteries, over 90 % of the sympathetic nerves were located within 2 mm of the renal lumen [15]. The methodology of this study by Atherton et al., has centered on the fixation process involved in assessing renal nerves. In these nine specimens, nerves were distributed equally around the artery but tended to arborize and become more superficial when analyzed proximal in the renal artery through its distal segment. Thus, the optimal procedure is to perform treatment at the proximal through the distal part of the renal artery. Additionally, the depth of the ablative RF energy and the resultant death of renal sympathetic nerves and its potential influence on subsequent near and long-term blood pressure effect has been a point of speculation [16, 17].

In another assessment of renal denervation, Steigerwald performed renal artery ablation in seven pigs [18]. These pigs were followed up by repeat angiography, optical coherence tomography (OCT) and complete histological examination of both kidneys. This evaluation demonstrated that renal denervation leads to loss of renal artery endothelium but this is almost completely reversed by 10 days without having detrimental effect on renal parameters (renal function). The ablated segments of the renal artery demonstrate transmural tissue coagulation; ablation caused an immediate reduction in the number of autonomic nerve fascicles in the adventitia of these arteries and declined further through 10 days. OCT of the artery performed immediately pre- and post- ablation revealed evidence of thrombus. Similar observations have been noted in human renal arteries treated with another RF monopolar catheter [19]. This has prompted a European expert panel to suggest the potential use of antiplatelet therapy during the procedure and for 4 weeks follow-up [20].

Finally, the potential negative impact on the effectiveness of the RF ablation by unapparent atherosclerosis and/or vessel wall calcification has caused some controversy with regards to the relevance of RF parameters drawn from normal renal arteries in pigs. Nevertheless, the appropriate balance of RF energy induced tissue temperature, duration of applied power and the resulting lesion depth may influence the subsequent blood pressure response; however, this is balanced by potential safety concerns of RF induced renal intimal lesions.

The first generation Ardian renal denervation catheter, the Arch™ catheter (Fig. 7.1), had a uni-electrode configuration that required a point-by-point application of RF energy to the renal artery wall by the operator. This allowed for greater operator flexibility as to the number and location of applied ablations (minimum 4–6 ablation sites per renal artery) and allowed the operator to avoid sites of obvious fluoroscopically evident calcium and/or atheroma. It is not recommended that a complete circumferential ablation be performed in a single plane due to the potential risk of inducing a renal artery stenosis. The second generation Flex™ catheter (Fig. 7.2) is also uni-electrode, but with a smaller shaft size and markedly improved flexibility, providing greater catheter maneuverability, which is particularly helpful in complex or tortuous renal anatomies.