Abstract
Radiofrequency (RF) is the most frequently used mode of ablation energy for most atrial and ventricular arrhythmias. A major limitation of standard RF ablation is the relatively small depth of tissue injury produced, which can potentially limit the success of the ablation procedure. Larger ablation lesions can be obtained by increasing the size and surface area of the ablation electrode, using an electrode material with high thermal conductivity, active or passive cooling of the electrode-tissue interface, and the use of pulsed energy. Furthermore, real-time measurement of tissue contact and contact force can help to optimize catheter-tissue contact and improve lesion formation.
Alternative ablation energy sources include cryoenergy, laser, microwave, and ultrasound. Currently, two different types of cryoablation catheters are available: traditional-tip ablation catheters and balloon catheters. The cryoballoon catheter is specifically designed for pulmonary vein (PV) isolation. Catheter-based cryoablation can have specific advantages over RF energy in certain patient populations; however, it is unlikely that cryoablation will replace standard RF ablation in unselected cases. Laser energy has been used with balloon technology for PV isolation. Microwave ablation has been increasingly used intraoperatively (epicardially or endocardially) during surgical maze procedures for atrial fibrillation (AF). Currently, transvenous microwave catheter ablation is available only for investigational use. Although PV isolation with high-intensity focused ultrasound had proven to be successful, it did not meet the safety standards required for treatment of AF, and this led to a halt of its clinical use.
Keywords
ablation, radiofrequency, microwave, cryoenergy, laser, high-intensity ultrasound
Outline
Radiofrequency Ablation, 206
Biophysics of Radiofrequency Energy, 206
Biophysics of Cooled Radiofrequency Ablation, 210
Pathophysiology of Radiofrequency Lesion Formation, 211
Determinants of Radiofrequency Lesion Size, 212
Monitoring Radiofrequency Lesion Formation, 215
Titration of Standard Radiofrequency Energy, 217
Titration of Cooled Radiofrequency Energy, 217
Optimizing Catheter-Tissue Contact, 218
Prevention of Steam Pops, 221
Clinical Applications of Standard Radiofrequency Ablation, 222
Clinical Applications of Cooled Radiofrequency Ablation, 222
Phased Radiofrequency Ablation, 223
nMARQ Ablation System, 225
Cryoablation, 225
Biophysics of Cryothermal Energy, 225
Pathophysiology of Lesion Formation by Cryoablation, 226
Determinants of Cryogenic Lesion Size, 228
Technical Aspects of Cryoablation, 229
Clinical Advantages of Cryoablation, 230
Clinical Applications of Cryoablation, 230
Laser Energy, 231
Ultrasound Energy, 232
Biophysics of Ultrasound Energy, 232
Pathophysiology of Lesion Formation by Ultrasound Energy, 232
Clinical Applications of Ultrasound Energy, 233
Microwave Ablation, 233
Biophysics of Microwave Energy, 233
Pathophysiology of Lesion Formation by Microwave Ablation, 234
Clinical Applications of Microwave Ablation, 234
Electroporation, 235
Radiofrequency Ablation
Biophysics of Radiofrequency Energy
Radiofrequency (RF) refers to the portion of the electromagnetic spectrum in which electromagnetic waves can be generated by alternating current (AC) fed to an antenna. Electrosurgery (coagulation, cauterization, and ablation) currently uses hectomeric wavelengths found in band 6 (300 to 3000 kHz), which are similar to those used for broadcast radio. However, the RF energy is electrically conducted, not radiated, during catheter ablation. The RF current is similar to low-frequency AC or direct current (DC) with regard to its ability to heat tissue and create a lesion, but it oscillates so rapidly that cardiac and skeletal muscles are not stimulated, thereby avoiding induction of arrhythmias and decreasing the pain perceived by the patient. RF current rarely induces rapid polymorphic arrhythmias; such arrhythmias can, however, be observed in response to low-frequency (60-Hz) stimulation. Frequencies higher than 1000 kHz are also effective in generating tissue heating; however, such high frequencies are associated with considerable energy loss along the transmission line. Therefore frequencies of the RF current commonly used are in the range of 300 to 1000 kHz, a range that optimizes efficacy and safety.
Radiofrequency Energy Delivery
Delivery of RF energy depends on the establishment of an electrical circuit involving the human body as one of its in-series elements. The RF current is applied to the tissue via a metal electrode at the tip of the ablation catheter and is generally delivered in a unipolar fashion between the tip electrode and a ground pad applied to the patient’s skin. Bipolar RF systems also exist, in which the current flows between two closely apposed small electrodes, thus limiting the current flow to small tissue volumes interposed between the metal conductors. Bipolar systems, partly because of their relative safety, are now the preferred tools in electrosurgery (oncology, plastic surgery, and ophthalmology), and have been increasingly utilized for catheter ablation of cardiac arrhythmias.
Unipolar RF systems.
Unipolar systems apply RF energy between the ablation catheter tip electrode and a large dispersive electrode (indifferent electrode, or ground pad) applied to the patient’s skin. The polarity of connections from the electrodes to the generator is not important because the RF current is an AC. The system impedance comprises the impedance of the generator, transmission lines, catheter, electrode-tissue interface, dispersive electrode-skin interface, and interposed tissues. As electricity flows through a circuit, every point of that circuit represents a drop in voltage, and some energy is dissipated as heat. The point of greatest drop in line voltage represents the area of highest impedance and is where most of the electrical energy becomes dissipated as heat. Therefore with excessive electrical resistance in the transmission line, the line actually warms up and power is lost. Currently used electrical conductors from the generator all the way through to the patient and from the dispersive electrode back to the generator have low impedance, to minimize power loss.
Flow of the RF current from the ablation electrode through the myocardium to the indifferent electrode results in resistive tissue heating and lesion formation. With normal electrode-tissue contact, only a fraction of all power is effectively applied to the tissue. The rest is dissipated in the blood pool and elsewhere in the patient. With an ablation electrode in contact with the endocardial wall, part of the electrode contacts tissue and the rest contacts blood, and the RF current flows through both the myocardium and the blood pool surrounding the electrode. The distribution between both depends on the impedance of both routes and also on how much electrode surface contacts blood versus endocardial wall. Whereas tissue heating is the goal of power delivery, the blood pool is the most attractive route for RF current because blood is a better conductor and has significantly lower impedance than tissue and because the contact between electrode and blood is often better than with tissue. Therefore with normal electrode-tissue contact, much more power is generally delivered to blood than to cardiac tissue.
After leaving the electrode-blood-tissue interface, the current flows through the thorax to the ground pad. Part of the RF power is lost in the patient’s body, including the area near the ground pad. However, because the surface area of the ablation electrode (approximately 12 mm 2 ) is much smaller than that of the dispersive electrode (approximately 100 to 250 cm 2 ), the current density is higher in the immediate vicinity of the ablation electrode, and heating occurs preferentially at that site, with no significant heating occurring at the dispersive electrode. Nonetheless, when RF energy delivery is power-limited, dissipation of energy can occur at the dispersive electrode site (at the contact point between the ground pad and the skin) to a degree that can limit lesion formation at the ablation electrode.
The dispersive electrode may be placed on any convenient skin surface. The geometry of the RF current field is defined by the geometry of the ablation electrode and is relatively uniform in the region of volume heating. Thus, the position of the dispersive electrode (on the patient’s back or thigh) has little effect on impedance, voltage, current delivery, catheter tip temperature, or geometry of the resulting lesion. The size of the dispersive electrode, however, is important. Sometimes it is advantageous to increase the surface area of the dispersive electrode. This increase leads to lower impedance, higher current delivery, increased catheter tip temperatures, and more effective tissue heating. This is especially true in patients with baseline system impedance greater than 100 Ω. Moreover, when the system is power limited, as with a 50-W generator, heat production at the catheter tip varies with the proportion of the local electrode-tissue interface impedance to the overall system impedance. If the impedance at the skin-dispersive electrode interface is high, then a smaller amount of energy is available for tissue heating at the electrode tip. Therefore when ablating certain sites, adding a second dispersive electrode or optimizing the contact between the dispersive electrode and skin should result in relatively more power delivery to the target tissue. In addition, meticulous skin preparation is imperative to optimize skin-patch contact and minimize impedance at the skin interface with the dispersive electrode.
A large surface area, and good skin contact, is required at the indifferent electrode patch not only to effectively dissipate heat but also to prevent skin burns. The skin temperature beneath the patch is inversely proportional to patch surface area in contact with the skin and the distance between the patch and the active electrode. If ablation is performed with a high-amplitude current (more than 50 W) and skin contact by the dispersive electrode is poor, skin temperatures can potentially rise above 45°C which, even when short lasting, can result in significant skin burns, especially at the “leading edge” of the patch (the side closest to the RF catheter electrode) ( eFig. 7.1 ).
Bipolar RF systems.
Bipolar RF ablation uses two adjacent ablation electrodes between which the RF flows, leading to lesion formation between electrodes. Although used in cardiac surgery, bipolar RF ablation has not been widely adopted as a catheter-based treatment for clinical arrhythmias.
Recent studies have demonstrated that bipolar RF ablation using two ablation catheter tips (at opposite sides of the myocardial wall) as the active and ground poles, can potentially create deeper, transmural lesions ( Fig. 7.1 ). Simultaneous tissue heating and increased current density result in the concentration of thermal injury within the zone between the two closely spaced ablation electrodes and improve efficacy of ablation, as compared with sequential or even simultaneous unipolar RF ablation. In one report, transmurality with bipolar RF ablation could be realized in tissues as thick as 25 mm, in contrast to sequential unipolar RF, which was unable to achieve transmurality when thicknesses are greater than 15 mm. This can offer a significant advantage for ablation of septal atrial tachycardia (AT) or ventricular tachycardia (VT) circuits (with one ablation catheter positioned at one side of the septum and the second catheter positioned at the opposite side, Fig. 7.2 ) or intramural free wall VT circuits (with one ablation catheter positioned endocardially and the second catheter positioned epicardially).
In another design, bipolar RF ablation is used to create contiguous lesions between adjacent electrodes mounted on a multielectrode ablation catheter positioned at one side of the myocardial wall. A multichannel duty-cycled RF ablation generator (GENius MultiChannel RF Generator, Medtronic, Minneapolis, MN, United States) contains 12 independently controlled RF generators, and is capable of delivering RF energy to each electrode independently. RF energy can be delivered in either bipolar (between the electrodes) and unipolar (from the electrode to the ground pad) current by a phase difference between the channels (thus the term, “phased RF”). During unipolar ablation, current flow is provided between the electrodes and an indifferent electrode attached to the patient’s skin, while in the bipolar energy mode, current flows between adjacent electrodes. In this design, bipolar RF ablation lesions are longer, but shallower than unipolar RF lesions. To improve lesion depth, RF energy can also be delivered in a unipolar mode from each electrode to a dispersive electrode.
A second atrial fibrillation (AF) ablation system (nMARQ, Biosense Webster, Diamond Bar, CA, United States) employs a multichannel RF generator capable of independently delivering unipolar or bipolar RF energy to a maximum of 10 electrodes simultaneously. The nMARQ catheter is a decapolar mapping and ablation catheter with individually irrigated platinum electrodes. Each electrode possesses a thermocouple and holes for irrigation. RF energy is applied in a temperature-controlled mode and energy delivery can be individually arranged over each combination of the 10 electrodes in unipolar mode or bipolar mode between two adjacent electrodes.
Tissue Heating
While free electrons serve as charge carriers inside the RF generator, cables, and RF electrode, the electric current inside tissue is carried by charged ions (such as Na + , K + , and Cl − ). During AC flow, charged carriers in tissue (ions) attempt to follow the changes in the direction of the AC. For a typical frequency of 500 kHz, the direction of the current (and ion movement) changes a million times per second. Ion oscillations generate heat due to friction, thus converting electromagnetic (current) energy into molecular mechanical energy or heat. This type of electric current-mediated heating is known as ohmic (resistive) heating. Using Ohm’s law, with resistive heating, the amount of power (= heat) per unit volume equals the square of current density times the specific impedance of the tissue. With a spherical ablation electrode, the current flows outward radially, and current density therefore decreases with the square of distance from the center of the electrode. As a consequence, power dissipation per unit volume decreases with the fourth power of distance. The thickness of the electrode eliminates the first steepest part of this curve, however, and the decrease in dissipated power with distance is therefore somewhat less dramatic.
Approximately 90% of all RF power that is delivered to the tissue is absorbed within the first 1 to 1.5 mm from the ablation electrode surface. Therefore only a thin rim of tissue in immediate contact with the RF electrode is directly heated (within the first 2 mm of depth from the electrode). The remainder of tissue heating occurs as a result of heat conduction from this rim to the surrounding tissues. On initiation of fixed-level energy application, the temperature at the electrode-tissue interface rises monoexponentially to reach steady state within 7 to 10 seconds, and the steady state is usually maintained between 80°C and 90°C. However, whereas resistive heating starts immediately with the delivery of RF current, conduction of heat to deeper tissue sites is relatively slow and requires 1 to 2 minutes to equilibrate (thermal equilibrium). Therefore the rate of tissue temperature rise beyond the immediate vicinity of the RF electrode is much slower, resulting in a steep radial temperature gradient as tissue temperature decreases radially in proportion to the distance from the ablation electrode, and deep tissue temperatures continue to rise for several seconds after interruption of RF delivery (the so-called thermal latency phenomenon). Therefore RF ablation requires at least 30 to 60 seconds to create full-grown lesions. In addition, when temperature differences between adjacent areas develop because of differences in local current density or local heat capacity, heat conducts from hotter to colder areas, thus causing the temperature of the former to decrease and that of the latter to increase. Furthermore, heat loss to the blood pool at the surface and to intramyocardial blood vessels determines the temperature profile within the tissue.
At steady state, the lesion size is proportional to the temperature measured at the interface between the tissue and the electrode, as well as to the RF power amplitude. By using higher powers and achieving higher tissue temperatures, the lesion size can be increased. Tissue temperatures of up to 110°C can be achieved. Above this temperature, tissue vaporization ensures and prevents any further heating by RF current due to the electrically insulating properties of vapor. Also, boiling of the plasma at the electrode-tissue interface can cause tissue carbonization (“charring”) at the site of very high RF current densities (typically very close to the RF electrode), producing an electrically insulating coagulum, which is accompanied by a sudden increase in electrical impedance that prevents further current flow into the tissue and further heating.
The range of desired tissue temperatures during RF ablation is 50°C to 90°C. Within this range, relatively uniform desiccation of tissue can be expected. If the temperature is lower than 50°C, no or only minimal tissue necrosis results. Temperatures above 100°C are associated with tissue vaporization, including steam pops, and charring. Because the rate of temperature rise at deeper sites within the myocardium is slow, a continuous energy delivery of at least 60 seconds is often warranted to maximize depth of lesion formation.
Convective Cooling
At the site of endocardial ablation, tissues heated directly by RF energy start losing heat into deeper layers of myocardium as well as into the circulating blood pool and the metal ablation electrode ( Fig. 7.3 ). Heat conduction into deeper myocardial layers helps increase the size of the ablation lesion. Heat conduction to the ablation electrode helps indirect monitoring of tissue temperature via the embedded temperature sensors. On the other hand, convective heat loss from the endocardium at the site of ablation into the circulating blood pool results in cooling of the endocardial surface, and constitutes the dominant factor opposing effective myocardial heating and lesion formation. Because the tissue surface is cooled by the blood flow, the highest temperature during RF delivery occurs slightly below the endocardial surface. Consequently, the width of the endocardial lesion matures earlier than the intramural lesion width (20 seconds vs. 90 to 120 seconds). Hence, the maximum lesion width is usually located intramurally, and the resultant lesion is usually teardrop shaped, with less necrosis of the superficial tissue.
As the magnitude of convective cooling increases (e.g., unstable catheter position, poor catheter-tissue contact, or high blood flow in the region of catheter position), there is decreased efficiency of heating as more energy is carried away in the blood and less energy is delivered to the tissue. When RF power is limited and insufficient to overcome the heat lost by convection, lesion size is reduced. On the other hand, when RF power delivery is not limited, convective cooling allows for more power to be delivered into the tissue (as long as adequate electrode-tissue contact is maintained), increasing the depth of direct resistive heating and intramural tissue temperatures (and hence larger ablation lesion size), while avoiding very high endocardial surface temperatures (and temperatures measured by the catheter tip sensors) that can otherwise result in blood boiling and coagulum formation at the electrode tip, with consequent sudden rise in electrical impedance and reduction of further power delivery.
The concept of convective cooling can explain why there are few coronary arterial complications with conventional RF ablation. Coronary arteries act as a heat sink; substantive heating of vascular endothelium is generally prevented by heat dissipation in the high-velocity coronary blood flow, even when the catheter is positioned close to the vessel. Although this is advantageous, because coronary arteries are being protected, it can limit success of the ablation lesion if a large perforating artery is close to the ablation target and can protect the target tissue from ablation by transferring heat away from it.
The effects of convective cooling have been exploited to increase the size of catheter ablative lesions. Active electrode cooling by ablation electrode irrigation is currently used to largely eliminate the risk of overheating at the electrode-tissue contact point and increase the magnitude of power delivery and the depth of volume heating.
Of note, standard RF ablation is not as effective when delivered to the epicardium compared with lesions delivered to the endocardium for a number of reasons, one of which is the lack of convective cooling (by the circulating blood) of the ablation electrode in the epicardial space. This results in high electrode temperatures at low-power settings (≤10 W), limiting power delivery in the pericardial space and hindering lesion formation. Therefore active electrode cooling is required in this setting.
Catheter Tip Temperature
Ablation catheter tip temperature depends on tissue temperature, tissue contact of the ablation electrode, convective cooling by the surrounding blood, heat capacity of the electrode material, and type and location of the temperature sensor.
Catheter tip temperature is measured by a sensor located in the ablation electrode. There are two different types of temperature sensors: thermistors and thermocouples. Thermistors require a driving current, and the electrical resistance changes as the temperature of the electrical conductor changes. More frequently used are thermocouples, which consist of copper and constantan wires and are incorporated in the center of the ablation electrode. Thermocouples are based on the so-called “Seebeck effect”; when two different metals are connected (sensing junction), a voltage can be measured at the reference junction that is proportional to the temperature difference between the two metals.
The electrode temperature rise is an indirect process—the ablation electrode is not heated by RF energy, but it heats up because it happens to touch heated tissue. Consequently, the catheter tip temperature is always lower than, or ideally equal to, the superficial tissue temperature. Conventional electrode catheters with temperature monitoring report the temperature only from the center of the electrode mass with one design, or from the apex of the tip of the catheter with another design. It is likely that the measured temperature underestimates the peak tissue temperature (which occurs slightly below the endocardial surface).
Several other factors can increase the disparity between catheter tip temperature and tissue temperature, including catheter tip irrigation, large ablation electrode size, and poor electrode-tissue contact. Catheter tip irrigation increases the disparity between tissue temperature and electrode temperature because it results in cooling of the ablation electrode, but not the tissue. With a large electrode tip, a larger area of the electrode tip is exposed to the cooling effects of the blood flow than with standard tip lengths, thus resulting in lower electrode temperatures. Similarly, with poor electrode-tissue contact, less electrode material is in contact with the tissue, and heating of the tip by the tissue occurs at a lower rate, resulting in relatively low tip temperatures.
Biophysics of Cooled Radiofrequency Ablation
There are two methods of active electrode cooling by irrigation: internal and external ( Fig. 7.4 ). With the internal (closed-loop) system (Chilli, Boston Scientific, Natick, MA), cooling of the ablation electrode is achieved by circulating fluid within the electrode. In contrast, with the external (open-loop) system (Celsius or Navistar ThermoCool, Biosense Webster, Diamond Bar, CA, United States; and Therapy Cool Path, St. Jude Medical, St. Paul, MN, United States), electrode cooling is performed by flushing saline through openings in the porous-tipped electrode (showerhead-type system). Another cooling system is sheath-based open irrigation, which uses a long sheath around the ablation catheter for open irrigation. The latter system was found to provide the best results, but this type of catheter tip cooling is not clinically available.
Active electrode cooling by irrigation can produce higher tissue temperatures and create larger lesions, compared with standard RF ablation catheters, because of a reduction in overheating at the tissue-electrode interface, even at sites with low blood flow. This allows the delivery of higher amounts of RF power for a longer duration to create relatively large lesions with greater depth but without the risk of coagulum and char formation. Unlike with standard RF ablation, the area of maximum temperature with cooled ablation is within the myocardium, rather than at or just below the electrode-myocardial interface. Higher power results in greater depth of volume heating, but if the ablation is power limited, power dissipation into the circulating blood pool can actually result in decreased lesion depth ( Fig. 7.5 ). Compared with large-tip catheters, active cooling has been shown to produce equivalent lesions with energy delivery via smaller irrigated electrodes, with less dependence on catheter tip orientation and extrinsic cooling, whereas larger electrodes have significant variability in their electrode-tissue interface, depending on catheter orientation (see Fig. 7.5 ). For the nonirrigated catheter, greater lesion volumes are observed with a horizontal orientation of the RF electrode compared with a vertical orientation. In contrast, for irrigated catheters, lesion volume increased with a perpendicular electrode orientation compared with the horizontal orientation.
Lesion depth seems to be similar between closed-loop and open-irrigation electrodes. However, open irrigation is more effective in cooling the electrode-tissue interface, as reflected by lower interface temperature, lower incidence of thrombus, and smaller lesion diameter at the surface (with the maximum diameter produced deeper in the tissue). These differences between the two electrodes are greater in low blood flow, presumably because the flow of saline irrigation out of the electrode provides additional cooling of the electrode-tissue interface (external cooling). Ablation with internal electrode cooling in low blood flow regions frequently results in high electrode-tissue interface temperature (despite low electrode temperature) and coagulum formation.
When maximum power and temperature parameters that did not result in any evidence of excessive heating (including popping, boiling, or impedance rise) for each catheter type were selected, closed-irrigation catheters resulted in slightly larger lesion volumes and greater lesion depths than the open-irrigation catheters. Both cooled catheters fared better than the standard 4-mm-tip and large 10-mm-tip catheters with larger lesions achieved within the range of safe energy delivery.
Pathophysiology of Radiofrequency Lesion Formation
Cellular Effects of Radiofrequency Ablation
The primary mechanism of tissue injury by RF ablation is likely to be thermally mediated. Hyperthermic injury to the myocyte is both time- and temperature-dependent, and it is likely the result of changes in the cell membrane, protein inactivation, cytoskeletal disruption, nuclear degeneration, as well as other potential mechanisms. The cell membrane, in particular, is very sensitive to thermal injury. Hyperthermia results in potential phase change in membrane fluidity, kinetic and structural changes in membrane ion channels and ion pumps, inhibition of transport proteins, and formation of nonspecific ionic membrane pores.
Experimentally, the resting membrane depolarization is related to temperature. In the low hyperthermic range (37°C to 45°C), little tissue injury occurs, and a minor change can be observed in the resting membrane potential and action potential amplitude. However, action potential duration shortens significantly, and conduction velocity becomes greater than at baseline. In the intermediate hyperthermic range (45°C to 50°C), progressive depolarization of the resting membrane potential occurs, and action potential amplitude decreases. In addition, abnormal automaticity is observed, reversible loss of excitability develops, and conduction velocity progressively decreases. In the high temperature ranges (higher than 50°C), marked depolarization of the resting membrane potential occurs, and permanent loss of excitability is observed. Temporary (at temperatures of 49.5°C to 51.5°C) and then permanent (at 51.7°C to 54.4°C) conduction block develops, and fairly reliable irreversible myocardial injury occurs with a short hyperthermic exposure.
In the clinical setting, the success of ablation is related to the mean temperature measured at the electrode-tissue interface. Block of conduction in an atrioventricular (AV) bypass tract (BT) usually occurs at 62°C ± 15°C. During ablation of the AV junction, an accelerated junctional rhythm, which is probably caused by thermally or electrically induced cellular automaticity or triggered activity, is observed at temperatures of 51°C ± 4°C, whereas reversible complete AV block occurs at 58°C ± 6°C, and irreversible complete AV block occurs at 60°C ± 7°C.
RF ablation typically results in high temperatures (70°C to 90°C) for a short time (up to 60 seconds) at the electrode-tissue interface, but significantly lower temperatures at deeper tissue sites. This leads to rapid tissue injury within the immediate vicinity of the RF electrode but relatively delayed myocardial injury with increasing distance from the RF electrode. Therefore, although irreversible loss of electrophysiological (EP) function can usually be demonstrated immediately after successful RF ablation, this finding can be delayed because tissue temperatures continue to rise somewhat after cessation of RF energy delivery (thermal latency phenomenon). This effect can account for the observation that patients undergoing atrioventricular node (AVN) modification procedures who demonstrate transient heart block during RF energy delivery can progress to persisting complete heart block, even if RF energy delivery is terminated immediately. Reversible loss of conduction can be demonstrated within seconds of initiating the RF application, which can be caused by an acute electrotonic effect. On the other hand, there can be late recovery of EP function after an initial successful ablation.
In addition to the dominant thermal effects of RF ablation, some of the cellular injury has been hypothesized to be caused by a direct electrical effect, which can result in dielectric breakdown of the sarcolemmal membrane with creation of transmembrane pores (electroporation), resulting in nonspecific ion transit, cellular depolarization, calcium overload, and cell death. Such an effect has been demonstrated with the use of high-voltage electrical current. However, it is difficult to examine the purely electrical effects in isolation of the dominant thermal injury.
Tissue Effects of Radiofrequency Ablation
Changes in myocardial tissue are apparent immediately on completion of the RF lesion. Pallor of the central zone of the lesion is attributable to denaturation of myocyte proteins (principally myoglobin) and subsequent loss of the red pigmentation. Slight deformation, indicating volume loss, occurs at the point of catheter contact in the central region of lesion formation. The endocardial surface is usually covered with a thin fibrin layer and, occasionally, if a temperature of 100°C has been exceeded, with char and thrombus ( eFig. 7.2 ). In addition, a coagulum (an accumulation of fibrin, platelets, and other blood and tissue components) can form at the ablation electrode because of the boiling of blood and tissue serum.
On sectioning, the central portion of the RF ablation lesion shows desiccation, with a surrounding region of hemorrhagic tissue and then normal-appearing tissue. Histological examination of an acute lesion shows typical coagulation necrosis with basophilic stippling consistent with intracellular calcium overload. Immediately surrounding the central lesion is a region of hemorrhage and acute monocellular and neutrophilic inflammation.
The progressive changes seen in the evolution of an RF lesion are typical of healing after any acute injury. Within 2 months of the ablation, the lesion shows fibrosis, granulation tissue, chronic inflammatory infiltrates, and significant volume contraction. The lesion border is well demarcated from the surrounding viable myocardium without evidence of a transitional zone. This likely accounts for the absence of proarrhythmic side effects of RF catheter ablation. As noted, because of the high-velocity blood flow within the epicardial coronary arteries, these vessels are continuously cooled and are typically spared from injury, despite nearby delivery of RF energy. Nonetheless, high RF power delivery in small hearts, such as in pediatric patients, or in direct contact with the vessel can potentially cause coronary arterial injury.
The border zone around the acute pathological RF lesion accounts for several phenomena observed clinically. The border zone is characterized by marked ultrastructural abnormalities of the microvasculature and myocytes acutely, as well as a typical inflammatory response later. The most thermally sensitive structures appear to be the plasma membrane and gap junctions, which show morphological changes as far as 6 mm from the edge of the pathological lesion. The border zone accounts for documented effects of RF lesion formation well beyond the acute pathological lesion. The progression of the EP effects after completion of the ablation procedure can be caused by further inflammatory injury and necrosis in the border zone region that result in late progression of physiological block and a delayed cure in some cases. On the other hand, initial stunning and then early or late recovery of function can be demonstrated in the border zone, thus accounting for the recovery of EP function after successful catheter ablation in the clinical setting, which can be caused by healing of the damaged, but surviving, myocardium.
Coagulum Formation
Excessive tissue heating can lead to high temperatures at the electrode-tissue interface. Once the peak tissue temperature exceeds the threshold of 100°C, boiling of blood and tissue serum at the electrode-tissue interface can ensue. When boiling occurs, denatured serum proteins and charred tissue form a thin film that adheres to the electrode, thus producing an electrically insulating coagulum (an accumulation of fibrin, platelets, and other blood and tissue components). The coagulum can detach and embolize. Of note, unlike typical thrombi, a coagulum is not formed by activation of clotting factors, and its formation is not prevented by anticoagulation.
In temperature-controlled RF ablation, electrode temperature does not reach the boiling point. Nonetheless, the true tissue temperature can be significantly higher than the measured electrode temperature. In addition, serum proteins denature at temperatures well below the interfacial boiling temperature. Therefore coagulum can still form even when the electrode temperature is limited to 65°C with a 4-mm ablation electrode, and 55°C with an 8-mm electrode. Open irrigation cools the electrode and its direct environment (blood, and catheter-tissue interface), reducing (but not eliminating) the risk of interfacial boiling and coagulum formation. Also, the irrigant helps wash away denatured proteins as it forms.
Usually, coagulum adheres to the electrode tip, which is accompanied by a sudden increase in electrical impedance that prevents further current flow into the tissue and further heating, at which point the ablation catheter needs to be withdrawn from the body and cleaned to remove the adhering coagulum. However, when the coagulum attaches to the tissue surface rather than to the electrode tip, electrode temperature or impedance may not be affected, and coagulum formation can continue unnoticed. Therefore the absence of impedance rise during ablation does not guarantee the absence of coagulum formation on the tissue contact site.
Steam Pop
High RF power application (especially in the setting of cooled RF ablation) can cause superheating within the tissue (with subendocardial tissue temperatures exceeding 100°C), which can result in boiling of water within the tissue under the electrode. Consequently, evaporation and rapid steam expansion can occur intramurally, and a gas bubble can develop in the tissue under the ablation electrode. Continued application of RF energy causes the bubble to expand and its pressure to increase, which can lead to eruption of the gas bubble (causing a popping sound) through the path with the least mechanical resistance that can leave behind a gaping hole (the so-called “steam pop”). This often occurs toward the heat-damaged endocardial surface (leading to crater formation) or, infrequently, across the myocardial wall (resulting in myocardial perforation).
The consequence of a steam pop depends on the area of the heart being ablated. The risk of cardiac perforation is low in areas of dense ventricular scar. The risk of perforation and cardiac tamponade is likely to be higher for ablation in the thin-walled right ventricular outflow tract (RVOT) and in the atria. Therefore it is reasonable to take a more conservative approach to power application in these areas.
Steam pops are often associated with a sudden, although small (less than 10 Ω) impedance rise and a sudden drop in electrode temperature. When steam pops burst toward the endocardial surface, a shower of microbubbles is often detected on intracardiac echocardiography (ICE).
The risk of steam pops is relatively low with temperature-controlled standard 4-mm-tip RF catheter ablation, since the electrode temperature, which approximates tissue temperature, is limited to a safe level. However, when there is significant discrepancy between tissue and electrode temperature, due to passive or active electrode cooling, tissue temperature can reach the boiling point without being detected by the monitoring electrode temperature.
Electrode orientation also seems to affect the significance of steam pops; pops that occur when the electrode tip is perpendicular to the tissue are more likely to cause cardiac perforation than those that occur when the electrode is lying horizontally on the tissue. Therefore one should try to avoid high-pressure perpendicular tissue contact, especially at higher RF power outputs. RF applications preceding steam pops have a greater and more rapid decrease in impedance and occur at a higher maximum RF power than applications without pops. Because of the considerable overlap of impedance changes in lesions with and without steam pops, it is not possible to advocate a general limit for impedance decrease for all RF lesions. However, when ablation is performed in areas at risk for perforation (i.e., especially in thin-walled structures), reducing power to achieve an impedance decrease of less than 18 Ω is a reasonable strategy to reduce the chance of a pop.
Determinants of Radiofrequency Lesion Size
It is axiomatic that successful ablation occurs when an adequate amount of ablation energy is delivered for an adequate amount of time, with adequate electrode-tissue contact, at an appropriate target site. Many of the elements of this statement relate to formation of an effective ablation lesion. Lesion size is defined as the total volume or dimensions (width and depth) of the lesion. The size of the lesion created by RF power is determined by the amount of tissue heated to more than the critical temperature for producing irreversible myocardial damage (50°C). Tissue heating is a function of the magnitude of RF power that is converted into heat in the tissues. As noted, only a thin rim (1 to 2 mm) of tissue immediately under the ablating electrode is directly heated. This heat then radiates to adjacent tissue; however, conduction of heat to deeper tissue sites is relatively slow and very inefficient. The distance at which temperature drops to less than 50°C delimits the depth of lesion formation. The use of higher power output to achieve higher tissue temperatures results in larger lesions by raising the temperature of the rim of resistively heated tissue to substantially more than 50°C for deeper tissue to reach the 50°C threshold required for tissue necrosis. However, the rim of heated tissue in direct contact with the ablating electrode conducts not only to deeper tissue but also to the electrode tip itself. Higher electrode temperatures either limit further energy delivery (in temperature-controlled power delivery mode) or increase electrode impedance as a result of coagulum formation; these effects potentially limit lesion size. Furthermore, tissue temperatures higher than 100°C are unsafe because they are associated with a higher risk of steam pops. Cooling of the ablating electrode (passively by using a larger electrode length or actively by using catheter irrigation) can help diminish electrode heating, allowing for greater power delivery and creation of larger lesions. Several other factors can influence RF lesion size ( Table 7.1 ).
Electrode temperature | Lesion size increases with higher electrode temperature unless a coagulum is formed or power output is limited |
RF power amplitude | Lesion size increases with higher RF power delivery given adequate tissue contact |
Duration of RF application | Lesion size increases with increasing duration of RF application (up to 30–60 s for 4-mm tip standard RF, or up to 60–120 s for large or irrigated RF electrodes) |
Electrode-tissue contact | Lesion size increases with improved tissue contract, unless RF power output is limited by increasing electrode temperatures and lack of electrode cooling |
Electrode length | Lesion size increases with larger electrode length, unless RF power output is limited |
Electrode orientation | With the same total power, perpendicular electrode orientation yields larger lesion volumes than parallel electrode orientation. When RF power level is unrestricted and is increased to maintain a constant current density, lesion size will increase proportionally to the electrode-tissue contact area, which is larger with parallel tip orientation |
Electrode material | Gold electrodes have greater thermal conductivity than platinum, allowing for more RF power to be applied at constant temperature |
Reference patch electrode size | Lesion size increases with increasing ground pad size and optimizing skin contact |
Convective cooling | At any given power output (with no temperature restriction), RF lesion size decreases with increasing passive or active convective cooling At any given electrode temperature (with no power restriction), RF lesion size increases with increasing convective cooling |
RF system polarity | Unipolar RF ablation produces narrower but deeper lesions. Bipolar RF ablation produces longer but shallower lesions |
Electrode flexibility | Electrode flexibility improves tissue contract and can increase lesion size, unless RF power output is limited by increasing electrode temperatures and lack of electrode cooling |
Ablation Electrode Temperature
The relationship between lesion size and the recorded catheter tip temperature is complex and subject to several confounding factors. When electrode tip temperature closely resembles tissue temperature (the main determinant of lesion formation), lesion size appears to increase directly with electrode temperature up until the point of coagulum formation at the electrode-tissue interface, when further power delivery becomes limited. However, with good contact between catheter tip and tissue and low cooling of the catheter tip, the target temperature can be reached with little power, thus resulting in fairly small lesions although a high catheter tip temperature is being measured.
Furthermore, catheter tip temperature is not a reliable measure of tissue temperature, as it is also influenced by convective cooling, electrode-tissue contact, and type and location of the temperature sensor. A low catheter tip temperature can be caused by a high level of convective cooling, which allows a higher amount of RF power to be delivered to the tissue (because it is no longer limited by temperature rise of the ablation electrode) and yields relatively large lesions. This is best illustrated with active cooling of the ablation electrode using irrigation during RF energy delivery; the tip temperature is usually less than 40°C, which allows the application of high-power output for longer durations.
Radiofrequency Power Amplitude
Lesion size is proportional to the amount of RF power delivered effectively into the tissue. Higher RF power delivery increases the amount of directly heated tissue as well as tissue temperatures, resulting in greater depth of thermal injury and larger lesion size. However, the mere amplitude of RF power application does not necessarily translate to a larger amount of power delivered into the tissue, since RF power can be wasted into the surrounding blood pool due to poor electrode-tissue contact.
Duration of Radiofrequency Application
The RF lesion is predominantly generated within the first 10 seconds of target energy delivery and tissue temperatures, and it reaches a maximum after 30 seconds. Extension of RF application beyond 45 to 60 seconds during power-controlled RF delivery does not generally seem to increase lesion size further. However, lesions created using large or irrigated RF electrodes have a longer half time of lesion growth, and extended ablation (60 to 120 seconds) can potentially help create larger lesions.
Electrode-Tissue Contact
Catheter electrode-tissue contact pressure is a major determinant of lesion size. Data indicate that increasing the firmness of contact (contact force) is comparable to increasing RF power; that is, the same tissue temperatures and lesion size can be reached at a much lower power level when tissue contact is optimized.
The efficiency of energy transfer to the myocardium (i.e., temperature rise per watt of applied power) largely depends on the electrode-tissue contact. Increasing contact force can improve the efficiency of RF lesion formation by several mechanisms: (1) expanding the area of the contact footprint of the electrode on myocardial tissue by embedding it deeper within the soft myocardium, which leads to a higher amount of RF power that can be effectively delivered to the tissue; (2) reducing the electrode surface exposed to surrounding blood pool and, hence, reducing RF current shunting into the low-impedance blood pool; (3) improving stability of the electrode-tissue contact and reducing catheter sliding with cardiac motion, which improves the efficiency of lesion formation; and (4) stretching of the myocardium, bringing the epicardium closer to the ablation electrode and, hence, improving transmurality of the RF lesion.
However, at a certain moderate contact force, further increase in contact firmness results in progressively smaller lesions because a lesser amount of RF power is required to reach target temperature. The temperature rise of the ablation electrode signals excessive tissue heating and limits power delivery in a temperature-controlled system. Reduced convective cooling of the ablation electrode (because of lesser interface with the blood pool) results in higher electrode temperatures and can further reduce RF current delivery.
Electrode Length
Ablation catheters have tip electrodes that are conventionally 4 mm long and are available in sizes up to 10 mm long ( see eFig. 4.3 ). An increased electrode size reduces the interface impedance with blood and tissue, but the impedance through the rest of the patient remains the same. Hence, the ratio between interface impedance and the impedance through the rest of the patient is lower with an 8-mm electrode than with a 4-mm electrode, which reduces the efficiency of power transfer to the tissue. Therefore with the same total power, lesions created with a larger electrode are always smaller than lesions created with a smaller electrode ( Fig. 7.6 ). A larger electrode size also creates a greater variability in power transfer to the tissue because of greater variability of tissue contact, and tissue contact becomes much more dependent on catheter orientation with longer electrodes. Consequently, an 8-mm electrode may require a 1.5 to 4 times higher power level than a 4-mm electrode to create the same lesion size.
On the other hand, when the power is not limited, catheters with large distal electrodes create larger lesions, both by increasing the ablation electrode surface area in contact with the bloodstream (resulting in an augmented convective cooling effect) and by increasing the volume of tissue directly heated because of an increased surface area at the electrode-tissue interface (see Fig. 7.6 ). However, this assumes that the electrode-tissue contact, tissue heat dissipation, and blood flow are uniform throughout the electrode-tissue interface. As the electrode size increases, the likelihood that these assumptions are true diminishes because of variability in cardiac chamber trabeculations and curvature, tissue perfusion, and intracardiac blood flow, which affect the heat dissipation and tissue contact. These factors result in unpredictable lesion size and uniformity for electrodes more than 8 mm long.
There is a potential safety concern with the use of long ablation electrodes because of nonuniform heating, with maximal heating occurring at the electrode edges. Thus, large electrode-tipped catheters with only a single thermistor can underestimate maximal temperature and allow char formation and potential thromboembolic complications. Catheter tips with multiple temperature sensors at the electrode edges are preferable for temperature feedback. In addition, the greater variation in power delivered to the tissue and the greater discrepancy between electrode and tissue temperature make it difficult to avoid steam pops and char formation. Another point of concern is that the formation of char may only minimally affect electrode impedance by covering a much smaller part of the electrode surface. Therefore the lower electrode temperature and the absence of any impedance rise may erroneously suggest a safer ablation process.
The principal limitations of a large ablation electrode (8 to 10 mm in length) are the reduction in mobility and the flexibility of the catheter (which can impair positioning of the ablation electrode) and a reduction in the resolution of recordings from the ablation electrode, thus making it more difficult to identify the optimal ablation site. A larger electrode dampens the local electrogram, especially that of the distal electrode. With an 8- or 10-mm long distal and a 1-mm short proximal ring electrode, the proximal electrode can be the main source for the bipolar electrogram; this then confuses localization of the optimal ablation site. In contrast, a smaller electrode improves mapping accuracy and feedback of tissue heating; its only drawback is the limited power level that can be applied to the tissue.
Electrode Orientation
The effect of catheter orientation on lesion size depends on the presence of passive or active cooling, whether or not power delivery is restricted, the length of the ablation electrode, as well as the placement of the temperature sensors relative to the portion of the electrode in contact with tissue. Lesion size is only slightly affected by catheter tip orientation using 4- or 5-mm-long tip catheters; the effects of catheter orientation become more pronounced for larger ablation electrodes.
When the catheter tip is perpendicular to the tissue surface, a much smaller surface area is in contact with the tissue (resulting in increased current density at the electrode-tissue interface) and larger area exposed to the circulating blood pool (resulting in augmented convective cooling) than when the catheter electrode tip is lying on its side. On the other hand, parallel tip orientation provides larger electrode-tissue contact area (resulting in less power waste into the blood stream and less current density at the electrode-tissue interface). Therefore with the same total power, perpendicular electrode orientation yields larger lesion volumes than parallel electrode orientation. However, if the RF power level is unrestricted and is increased to maintain a constant current density, lesion size will increase proportionally to the electrode-tissue contact area, which is larger with parallel tip orientation.
Furthermore, the character of the lesion created with temperature control depends on the placement of the temperature sensors relative to the portion of the electrode in contact with tissue. Thus, the orientation of the electrode and its temperature sensors determines the appropriate target temperature required to create maximal lesions while avoiding coagulum formation caused by overheating at any location within the electrode-tissue interface.
Electrode Material
Although platinum-iridium electrodes have been the standard for most RF ablation catheters, gold exhibits excellent electrical conductive properties, as well as a more than four times greater thermal conductivity than platinum (300 vs. 70 W/m K), although both materials have similar heat capacities (130 and 135 J/kg K). The higher thermal conductivity of gold can potentially lead to a higher mean rate of power delivery because of better heat conduction at the tissue-electrode interface and to enhanced cooling as a result of heat loss to the surrounding blood with this electrode material. Therefore gold electrodes allow for greater power delivery to create deeper lesions at a given electrode temperature without impedance increases. Enhanced electrode cooling allows for more RF power to be applied at constant temperature, before the temperature limit is reached or before the impedance of the electrode rises. However, the higher thermal conductivity of gold electrodes is no longer an advantage in areas of low blood flow (e.g., between myocardial trabeculae), where convective cooling at the electrode tip is minimal. Under these circumstances, electrode materials with a low thermal conductivity can produce larger lesions.
Conflicting results were observed in clinical studies comparing 8-mm gold-tip with platinum-iridium–tip catheters for ablation of the cavotricuspid isthmus (CTI). During catheter ablation of the slow AVN pathway in patients with atrioventricular nodal reentry tachycardia (AVNRT), no significant differences were observed between 4-mm gold-tip and platinum-iridium–tip catheters in the primary endpoint or in the increases of power or temperature at any of the measured time points. However, ablation with gold electrodes seemed to be safe and well tolerated and specifically did not increase the risk of AV block. Interestingly, a significant reduction of charring on gold tips was observed, compared with platinum-iridium material, a finding suggesting a possible advantage of this material beyond its better conduction properties.
An irrigated gold-tip ablation catheter was recently tested and found to allow for improved energy delivery at lower catheter-tip temperatures and at lower irrigation flow rate compared to irrigated platinum–iridium-tip catheters.
Reference Patch Electrode Location and Size
The RF current path and skin reference electrode interface present significant impedance for the ablation current flow, thereby dissipating part of the power. Increasing patch size (or using two patches) and optimizing skin contact reduce electrical impedance at skin-patch interface (and minimize power dissipation) and provide for increased heating at the electrode-endocardium interface and thus increase ablation efficiency and increase lesion size. On the other hand, the position of the dispersive electrode (on the patient’s back or thigh) has little effect on the size of the resulting lesion.
Convective Cooling
The ablation electrode temperature is dependent on the opposing effects of heating from the tissue and cooling by the blood flowing around the electrode. Because ablation lesion size is primarily dependent on the RF power delivered to the tissue, lesion size varies with the magnitude of convective cooling of the ablation electrode. Electrode cooling can be achieved passively (by local blood flow) or actively (by electrode irrigation).
At any given electrode temperature, the RF power delivered to the tissue is significantly reduced in areas of low local blood flow (e.g., deep pouch in the CTI, dilated and poorly contracting atria, between myocardial trabeculae). The reduced cooling associated with low blood flow causes the electrode to reach the target temperature at lower power levels, and if the ablation lesion is temperature-controlled, power delivery will be limited. In these locations, increasing electrode temperature to 65°C or 70°C only minimally increases RF power but it does increase the risk of thrombus formation and impedance rise. Conversely, increasing local blood flow is associated with increased convective cooling of the ablation electrode. Passive electrode cooling can be promoted by using large electrode length or electrode material with high thermal conductivity. Convective cooling can also be achieved by internal or external saline irrigation of the ablation electrode.
With enhanced convective cooling, more power is delivered to the tissue to reach and maintain target temperature, thus resulting in larger lesion volumes. However, when RF power output is limited, increased convective cooling curtails tissue heating due to increased heat loss into the blood pool. Therefore at any given power output (with no temperature restriction), RF lesion size decreases with increasing convective cooling. Conversely, at any given electrode temperature (with no power restriction), RF lesion size increases with increasing convective cooling.
Radiofrequency System Polarity
Most RF lesions are created by applying energy in a unipolar fashion between an ablating electrode touching the myocardium and a grounded reference patch electrode placed externally on the skin. Bipolar energy delivery produces larger lesions than unipolar delivery. In general, the unipolar configuration creates a highly localized lesion, with the least amount of surface injury (i.e., narrower but deeper lesions), while bipolar RF ablation produces longer but shallower lesions.
Electrode Flexibility
An irrigated catheter with a flexible tip design (Cool Flex, St. Jude Medical) allows the ablation tip to flex and provide more uniform distribution of force and a larger, more stable tissue-contact (nonperpendicular orientations) in beating hearts, regardless of catheter orientation relative to targeted tissue ( eFig. 7.3 ). This design also enhances cooling of the catheter-tissue interface through open irrigation with numerous slits that are uniformly spread throughout the electrode for radial cooling, which also creates preferential flow toward the tissue when the catheter tip is flexed, as in a drag lesion. Four additional ports are built into the distal tip for cooling of the target tissue when the catheter is in a perpendicular orientation.
In one report, the Cool Flex flexible-tip catheter was associated with larger ablation lesions at similar depths compared to the rigid-tip catheter. This was mainly related to enhanced cooling of the catheter tip-tissue interface which allowed more power delivery to targeted tissue, especially in nonperpendicular catheter orientation which would also result in a larger contact area during RF applications with the flexible tip. The performance of the rigid-tip catheter seemed to be significantly affected by catheter orientation which was not the case with the flexible-tip catheter.
Monitoring Radiofrequency Lesion Formation
The goal of optimizing RF ablation is to create an adequate-sized lesion while minimizing the chance of coagulum formation at the electrode itself and steam formation within the tissue. As discussed previously, for ablation to be effective, RF power must be increased sufficiently to achieve temperatures substantially higher than 50°C at the tissue directly in contact with the ablating electrode in order to achieve tissue necrosis. At the same time, for ablation to be safe, the highest tissue temperature must be maintained at less than 100°C to prevent steam pops and coagulum formation. Monitoring of RF energy delivery is therefore very important to help achieve successful as well as safe ablation.
RF lesion creation is influenced by many factors, some of which can be controlled, whereas others are variable and can be unpredictable. With standard RF ablation, power delivery is titrated to electrode temperature, typically at 55°C to 65°C. Higher temperatures can increase the chance of reaching 100°C at edges of the ablation electrode (away from the temperature sensor), thus resulting in coagulum formation. An increase in tissue temperature is accompanied by a decrease in impedance, also a reliable marker of tissue heating. Impedance reduction and temperature rise correlate with both lesion width and depth; maximum temperature rise is best correlated with lesion width, and maximum impedance reduction is best correlated with lesion depth.
The efficiency of tissue heating (i.e., the temperature per watt of applied power) is dependent on several variables, including catheter stability, electrode-tissue contact pressure, electrode orientation relative to the endocardium, effective electrode contact area, convective heat loss into the blood pool, and target location. Thus, applied energy, power, and current are poor indicators of the extent of lesion formation, and the actual electrode-tissue interface temperature remains the only predictor of the actual lesion size. Currently, although less than ideal, monitoring temperature and impedance are used to help ensure adequate but not excessive heating at the electrode-tissue interface. Newer technologies may be implemented in the future to monitor tissue temperatures during RF delivery, including infrared sensors and ultrasound transducers.
Impedance Monitoring
The magnitude of the current delivered by the RF generator used in ablation is largely determined by the impedance between the ablation catheter and the dispersive electrode. This impedance is influenced by several factors, including intrinsic tissue properties, catheter contact pressure, catheter electrode size, dispersive electrode size, presence of coagulum, and body surface area. Impedance measurement does not require any specific catheter-based sensor circuitry and can be performed with any catheter designed for RF ablation.
As tissue temperature rises during RF energy application, ions within the tissue being heated become more mobile, resulting in a decrease in impedance to current flow. Hence a drop in impedance resulting from RF ablation can serve as a real-time marker of tissue heating. Although the impedance drop during RF ablation occurs mainly because of a reversible phenomenon, rather than from an irreversible myocardial tissue damage secondary to ablation, lesion diameter and depth have been shown to correlate well with impedance decrease, with an even more direct relationship than measured temperature.
Typically, the impedance associated with firm catheter contact (before tissue heating has occurred) is 90 to 120 Ω. When catheter contact is poor, the initial impedance is 20% to 50% less, because of the lower resistivity of blood. Moreover, larger electrodes have larger contact area and consequently lower impedance. A 5- to 10-Ω reduction in impedance is usually observed in clinically successful RF applications, it correlates with a tissue temperature of 55°C to 60°C, and it is rarely associated with coagulum formation. Larger decrements in impedance reflect excessive tissue heating and are noted when coagulum formation is imminent. Once a coagulum is formed, an abrupt rise in impedance to more than 250 Ω is usually observed.
To titrate RF energy using impedance monitoring alone, the initial power output is set at 20 to 30 W and is then gradually increased to target a 5- to 10-Ω decrement in impedance. When target impedance is reached, power output should be manually adjusted throughout the RF application to maintain the impedance in the target range. A larger decrement of impedance should prompt reduction in power output. Lack of impedance drop during RF energy application can reflect inefficient energy delivery to the tissue due to poor catheter–tissue or catheter instability, and should prompt catheter repositioning and verification of adequate tissue contact.
The drop in impedance as a monitoring tool has several limitations. When blood flow rates are low, blood can also be heated, and electrode impedance drops accordingly. Moreover, a large rise in tissue temperature at a small contact area and a smaller rise with better tissue contact can result in a similar drop in impedance. Inversely, similar tissue heating with different tissue contact can result in a different change in impedance. In addition, resistive heating nearby is fast, whereas conductive heating to deeper layers is relatively slow. The former, at close distance, has a much greater effect on impedance than the latter, which occurs at greater distance. Therefore the drop in impedance during RF application is not a reliable parameter for estimating deep tissue heating and lesion growth.
Although coagulum formation is usually accompanied by an abrupt rise in impedance, the absence of impedance rise during ablation does not guarantee the absence of coagulum formation on the tissue contact site, which can unnoticeably be created on the tissue surface rather than on the ablation electrode. In addition, with large ablation electrodes, formation of blood clots may only minimally affect electrode impedance by covering a much smaller part of the electrode surface. Any increase in impedance during RF application can, however, indicate the beginning of coagulum formation or unintended catheter movement; in either case, RF application is discontinued.
Electrode Temperature Monitoring
Temperature monitoring utilizes dedicated sensors within the catheter tip. Two types of sensors are available: thermistor and thermocouple. No catheter or thermometry technology has been demonstrated to be superior in clinical use. Conventional electrode catheters with temperature monitoring report the temperature only from the center of the electrode mass with one design or from the apex of the tip of the catheter with another design, and it is likely that the measured temperature underestimates the peak tissue temperature. Therefore it is best if target temperatures no higher than 70°C are selected in the clinical setting.
Monitoring of catheter tip temperature and closed-loop control of power output are useful to accomplish effective heating at the target area while avoiding excessive heating at the tissue surface that can lead to coagulum formation. However, catheter tip temperature is influenced by cooling effects and electrode-tissue contact and, thus, correlates poorly with lesion size. Tissue temperature can be markedly higher than catheter tip temperature; a higher target temperature can increase the incidence of tissue overheating associated with coagulum formation and steam pops. High-flow areas are associated with more efficient cooling of the ablation electrode; hence, more RF power is delivered to the tissue to reach target temperature, thus resulting in relatively large lesions and vice versa.
The discrepancy between monitored electrode temperature and tissue temperature is significantly exaggerated by active cooling of the ablation electrode. The thermal effects on the electrode temperature are dependent on electrode heating from the tissue, internal cooling by the irrigation fluid, and external cooling from blood flow or open irrigation. With high irrigation flow rates, catheter tip temperature is no longer representative of tissue temperature, and therefore feedback cannot be used to guide power output. The difference between the electrode temperature and tissue-electrode interface temperature is greater with the closed-loop electrode than with the open-irrigation electrode. The discrepancy is likely to be increased in areas of high blood flow, by increasing the irrigation flow rate, or by cooling the irrigant. Saline-irrigated catheters result in peak tissue heating several millimeters from the electrode-tissue interface. Because maximum tissue heating does not occur at the electrode-tissue interface, the value of temperature and impedance monitoring is limited with this type of catheter.
Therefore monitoring lesion formation and optimizing power delivery during cooled RF ablation remain challenging. Appropriate energy titration is important to allow greater power application and to produce large lesions while avoiding overheating of tissue with steam formation leading to pops. Moreover, the inability to assess tissue heating, and hence to titrate power to an objective endpoint, prevents the operator from determining whether unsuccessful applications are caused by inadequate mapping or inadequate heating. In general, temperatures exceeding 42°C to 45°C with power greater than 30 W during open-irrigation RF ablation can be associated with a greater risk of steam pops and impedance rises, particularly during long RF applications, exceeding 60 seconds. Steam pops are often, but not always, audible. A sudden decrease in temperature, sudden catheter movement (as a consequence of the pop blowing the catheter out of position), and a sudden change in impedance are all potential indications that a pop has occurred.
Electrophysiological Effects of Ablation
In addition to impedance and catheter tip temperature monitoring, effects of tissue heating on recorded electrograms or the arrhythmia are important indicators for monitoring lesion formation. Interruption of tachycardia (VT, atrial flutter [AFL], supraventricular tachycardia) or block in conduction over a pathway (AVN or BT) during the process of ablation provide immediate feedback about the disruption of tissue integrity. In addition, an increase in pacing threshold and a decrease in electrogram amplitude can indicate tissue damage. These factors, however, are not easily monitored during the RF application, particularly the change in pacing threshold. Moreover, the decrease in electrogram amplitude is often not visible during RF application because of superimposed electrical artifact.
Of note, reductions in amplitude and steepness of the local electrogram as indicators of tissue heating apply only to the unipolar distal electrogram. With a bipolar recording, the signal from the ring electrode may dominate the electrogram, and the bipolar amplitude can theoretically even rise during ablation because of a greater difference between the signals from both electrodes.
Tissue Temperature Monitoring
Technologies to directly measure tissue temperature during RF ablation (which is the primary determinant of lesion formation) are currently not available for clinical use. Novel technologies are being evaluated, including microwave radiometry, near-field ultrasound thermal strain imaging, and magnetic resonance thermometry
Direct monitoring of tissue temperature enables titration of RF power output, duration of energy application, and active cooling to optimize lesion formation. Maintaining temperatures during ablation in a “safe and effective” zone (50°C to 80°C) helps achieve adequate RF lesion and prevent steam pops.
Titration of Standard Radiofrequency Energy
Monitoring catheter tip temperature and closed-loop control of power output are useful to accomplish effective heating at the target area while avoiding excessive heating at the tissue surface that can lead to coagulum formation. However, catheter tip temperature is influenced by cooling effects and electrode-tissue contact and, thus, correlates poorly with lesion size.
Titration of RF energy using temperature monitoring is usually done automatically by a closed-loop temperature monitoring system. When manual power titration is directed by temperature monitoring, the power initially is set to 20 to 30 W and then is gradually increased until the target temperature is achieved. With both manual and automatic power titration, a change in power output is frequently required throughout the RF application to maintain the target temperature. Application of RF energy is continued if the desired clinical effect is observed within 5 to 10 seconds after the target temperature or impedance is achieved. If the desired endpoint does not occur within this time, the failed application is probably because of inadequate mapping. If the target temperature or impedance is not achieved with maximum generator output within 20 seconds (the time it takes to achieve subendocardial steady-state temperature), the RF application can be terminated, and catheter adjustment should be considered to obtain better tissue contact.
The target ablation electrode temperature varies according to the arrhythmia substrate. For AVNRT, target temperature is usually 50°C to 55°C. For BT, AV junction, AT, and VT, higher temperatures (55°C to 60°C) are usually targeted.
When using 4-mm-tip catheters, the target temperature should be lower than 80°C. In high-flow areas in the heart, the disparity between tip temperature and tissue temperature is large and a lower cutoff temperature (e.g., 60°C) should be considered. Conversely, in low flow areas tissue temperature is much better reflected by tip temperature and a higher target temperature can be considered (e.g., 70°C to 80°C). The duration of RF application is usually limited to 30 to 60 seconds for nonirrigated 4-mm-tip electrodes. The lesion is predominantly formed within the first 30 seconds. A longer duration does not create larger lesions.
When using 8-mm-tip catheters, a larger portion of the ablation electrode is exposed to the blood and thus cooled by blood flow, and a relatively large difference between catheter tip temperature and tissue temperature can be expected. Consequently, a moderate target temperature (e.g., 60°C) should be chosen; the RF power may be limited to 50 to 60 W to avoid tissue overheating and coagulum formation.
It is important to recognize that prevention of coagulum formation is difficult, even with temperature and impedance monitoring. The clot first adheres to the tissue because that is the site with the highest temperature and may only loosely attach to the cooler electrode. The denaturized proteins probably have higher electrical impedance than blood, but the contact area with the electrode can be small, and RF impedance may not rise noticeably. The absence of flow inside the coagulum and its presumed higher impedance accelerate local heating and, because of some contact with the electrode, also accelerate heating of the electrode. Desiccation and adherence to the electrode then lead to coagulum formation on the metal electrode and impedance rise. Automatic power reduction by temperature-controlled RF ablation compensates for the reduction of electrode cooling and may prevent desiccation and impedance rise. The coagulum, however, can still be formed as demonstrated by experimental in vivo studies, and this can remain unnoticeable until it detaches from the tissue. Therefore the absence of thermal and electrical phenomena does not imply that the ablation has been performed safely.
Titration of Cooled Radiofrequency Energy
Active cooling of the ablation electrodes makes lesion formation more difficult to monitor and control. As noted, the discrepancy between monitored electrode temperature and tissue temperature is significantly exaggerated by active electrode cooling; as a result, electrode temperature is no longer a reliable predictor of lesion formation. Several other indicators of tissue heating can be monitored, including impedance and EP effects of ablation. Adjustment of RF power output, duration of RF application, and irrigant flow rate help modulate lesion formation.
The most easily controllable factors are the power output and duration of RF application. Although the optimal method for adjusting power during saline-irrigated RF ablation is not yet clearly defined, some useful guidelines have emerged. The most commonly recommended approach is to perform ablation in a power-controlled mode, typically starting at 20 to 30 W and gradually increasing power to achieve evidence of tissue heating or damage. An impedance fall likely indicates tissue heating, similar to that observed with conventional RF ablation. When catheter temperature is between 28°C and 31°C, power can be ramped up, watching for a 5- to 10-Ω impedance fall. Measured electrode temperature will generally increase, and electrode temperatures of 37°C to 40°C are commonly achieved. Power levels typically used during open-irrigation ablation depend on the site of ablation: 25 to 30 W in the left and right atrial free wall, 35 to 40 W for CTI and mitral isthmus ablation, 50 W in the LV, and 20 W in the coronary sinus (CS).
Also, instead of increasing the power (which increases the likelihood of steam pops) to achieve the desired EP effect, the duration of energy application may be increased. A moderate power of 20 to 35 W with a relatively long RF duration of 60 to 300 seconds may be considered to achieve relatively large lesions, with a limited risk of crater formation.
The flow rate of the irrigant determines the degree of cooling. Faster flow rates likely allow greater power application without impedance rises, increase the difference between tissue and electrode temperature, and thereby potentially increase the risk of steam pops if temperature is used to guide ablation. With the internally irrigated ablation system, the approved flow rate is fixed at 36 mL/min and is not currently manipulated. With the externally irrigated ablation system, an irrigation flow rate of 10 to 17 mL/min during RF application (and 2 mL/min during all other times to maintain patency of the pores in the electrode) may be selected in a power-controlled mode with a delivered power of up to 30 W. The irrigation flow rate should be increased to 20 to 30 mL/min with delivery of more than 30 W, to avoid excessive heating of the superficial tissue layers. Using a lower irrigation flow rate (10 mL/min) in the left atrium (LA) can help maintain some temperature feedback, with a cutoff temperature of 43°C. The temperature is usually set at 40°C to 45°C. If the temperature at the tip is lower than 40°C, the flow rate may be reduced. If the desired power is not met because the target temperature is reached at a lower power, the irrigation flow rate may be increased to a maximum of 60 mL/min. Parameters for epicardial ablation are similar to those used for endocardial ablation. New catheter designs employing lower irrigation flow rates (e.g., ThermoCool SF, Biosense Webster), in order to maintain adequate electrode cooling but with less total fluid load during long procedures, are also available.
In addition, the temperature of the irrigant can be manipulated. Cooling the irrigant can potentially allow power delivery to be increased without coagulum formation. However, the cooled irrigant is warmed as it passes through the tubing to reach the catheter and through the length of the catheter, and the impact of cooling the irrigant has not been well studied. In most studies, the irrigant that enters the catheter is at room temperature.
Temperatures exceeding 42°C to 45°C with power greater than 30 W during open-irrigation RF ablation can be associated with a greater risk of steam pops and impedance rises, particularly during long RF applications, exceeding 60 seconds. Steam pops are often, but not always, audible. A sudden decrease in temperature, a sudden catheter movement (as a consequence of the pop blowing the catheter out of position), and a sudden change in impedance are all potential indications that a pop has occurred. Whether the catheter is maintained in a stable position, as opposed to dragging it across the tissue during linear ablation, also likely influences tissue heating. High power can be applied continuously during dragging with little risk of excessive heating, although the duration of time to spend at each site to create an effective lesion may be difficult to ascertain. As a rule, the lowest effective power setting, shortest duration, and fewest applications should be employed whenever possible.
During open-irrigation RF ablation, initiation of irrigation results in a drop of electrode temperature by several degrees. Failure of electrode temperature to decrease indicates a lack of irrigant flow. When power delivery begins, catheter tip temperature should rise to 36°C to 42°C (the presence of rising temperature, not the magnitude, reflects tissue heating). Temperatures higher than 40°C achieved with low power (less than 20 W) can indicate that the electrode is in a location with little or no cooling from the surrounding circulating blood, or that there is a failure of the catheter cooling system that requires attention. In contrast, the absence of any increase in tip temperature should raise the possibility of poor catheter contact.
With the internally irrigated system, the room temperature irrigant flowing at 36 mL/min typically cools the measured electrode temperature to 28°C to 30°C. During RF application, the electrode temperature increases; temperatures of 50°C can indicate that cooling is inadequate or has stopped, which warrants termination of RF application. The measured impedance typically decreases during cooled RF ablation by 5 to 10 Ω, in a manner similar to that observed during standard RF ablation.
Optimizing Catheter-Tissue Contact
Optimizing catheter-tissue contact and minimizing catheter motion are critical for achieving safe and effective lesion formation. Poor or unstable contact leads to ineffective tissue heating and lesion formation as well as potential collateral injury to adjacent structures. Suboptimal contact can also result in partially successful ablation lesions, which can transiently interrupt the arrhythmia or eliminate its inducibility but without permanent destruction of the arrhythmogenic substrate. This outcome hinders further mapping and ablation efforts and predicts higher risk of arrhythmia recurrence. In addition, repetitive RF applications with inconsistent contact can result in tissue edema that can prevent effective lesion formation during later RF energy applications (even with optimized tissue contact). Therefore stable catheter contact should be ensured before each and every ablation lesion.
On the other hand, excess catheter pressure against the cardiac wall during RF ablation can cause tissue compression and thinning and, as a result, increase the risk of steam pop and cardiac perforation. Excessive contact force can also result in stretching and potential disruption of the chamber wall, even without RF ablation. Tenting of the chamber wall can potentially bring the tip of the ablation catheter in closer proximity to adjacent extracardiac structures (e.g., esophagus, phrenic nerve), increasing the risk of collateral damage during RF ablation.
Several methods to both optimize catheter contact and minimize catheter motion have been developed. General anesthesia and high-frequency jet ventilation have been used to optimize catheter stability and minimize the degree of respiratory effects on catheter contact during AF ablation. In addition, the use of steerable sheaths facilitates achieving stable and firm tissue contact, at least partly by increasing the column rigidity of the catheter-sheath combination. Furthermore, several approaches have been employed to ensure adequate catheter-tissue contact during RF ablation ( Table 7.2 ). Most of those approaches utilize indirect measures that represent imperfect surrogate of catheter-tissue contact. In addition, while those methods can potentially suggest inadequate tissue contact, they are far less reliable in estimating the force applied by the catheter tip on the chamber wall. More recently, real-time measurement of tissue contact and contact force has become available in several irrigated ablation catheters, and can potentially improve RF ablation efficacy and safety.