TY - JOUR
AU - Calkins, Hugh
AB - Abstract Open in new tabDownload slide Open in new tabDownload slide More than three decades have passed since utilization of radiofrequency (RF) ablation in the treatment of cardiac arrhythmias. Although several limitations and challenges still exist, with improvements in catheter designs and delivery of energy the way we do RF ablation now is much safer and more efficient. This review article aims to give an overview on historical advances on RF ablation and challenges in performing safe and efficient ablation. Radiofrequency ablation, Catheter ablation, Arrhythmias, Technological advances, Trends Introduction Radiofrequency (RF) energy was introduced as an energy source for catheter ablation more than three decades ago. The purpose of this review article is to review the historical timeline of the introduction of RF energy as an ablation energy source, to review the advances that have occurred in understanding how best to create ablation lesions with RF energy, and to look towards the future. Direct current shock catheter ablation Catheters were first used to record intra-cardiac signals in early 1960s and to stimulate the heart in late 1960s and early 1970s.1,2 In 1979, Vedel et al.3 reported an inadvertent case of permanent heart block at the level of His bundle during a electrophysiology study in a patient with ventricular tachycardia requiring cardioversion. They assumed that high-voltage discharge through the His bundle catheter and damage to the surrounding endocardium was the culprit for the atrio-ventricular block. Later in 1981, Gonzales et al.4 successfully tested this hypothesis in dogs by creating complete heart block after passing a direct current (DC) through a catheter located in the bundle of His area. These findings opened the door to several following studies in using catheter ablation by delivering DC shock through intracardiac catheters to achieve complete heart block.5,6 In this technique, a shock was delivered between the distal catheter electrode and a cutaneous surface electrode resulting in tissue destruction from a high-voltage discharge. Later with advances in mapping techniques and operator skills, the application of DC ablation was extended to treat cases of Wolff–Parkinson White, ventricular tachycardia, and atrial tachycardia.7–12 This resulted in gradual replacement of surgery, which was the main non-pharmacological treatment of refractory tachyarrhythmias at that time, by DC ablation. Despite advances over surgical treatment, DC ablation had significant limitations. The high-voltage discharge at the tip of the catheter was difficult to control and was usually associated with extensive tissue damage resulting in serious complications including cardiac perforation, cardiogenic shock, coronary artery spasm, atrioventricular block and late occurrence of ventricular fibrillation.9,13–15 This led to studies in late 1980s to develop an alternative energy source, RF current, to perform catheter ablation safely without requiring anaesthesia.16–19 Biophysics of radiofrequency ablation Huang et al.20 first introduced RF catheter ablation in 1985 as a potentially useful modality in treatment of arrhythmias. RF energy is a form of alternating electrical current with an oscillation frequency of 500–750 kHz (close to the frequency band used for AM radio transmission). The purpose of RF catheter ablation is to transform electromagnetic energy into thermal energy through ohmic (resistive) heating, which was previously utilized by surgeons for cautery. Unlike radio broadcast, the RF electrical current is typically delivered in a unipolar fashion directly to the tissue with completion of the circuit through a ground electrode placed on patient’s body. Resistive heating damages the tissue in direct contact of the catheter.21 Deeper and surrounding tissues are subsequently heated and damaged by conduction from this area (Figure 1).21,22 Resistive heat production is dependent on the current density. The current distributes radially from the source and decreases as the square of distance from the electrode. Therefore, only a narrow rim of tissue in close contact to the catheter is heated directly.21 The heating of the deeper tissue occurs passively through heat conduction. Of note, most of the produced heat is carried away through nearby circulating blood flow in a process known as convective cooling.24 Figure 1 Open in new tabDownload slide Biophysics of heating from radiofrequency ablation. The image shows regions of resistive and conductive heating into the tissue and convection of heat away into the blood pool and epicardial coronary artery. Reproduced with permission from Ref.23 Figure 1 Open in new tabDownload slide Biophysics of heating from radiofrequency ablation. The image shows regions of resistive and conductive heating into the tissue and convection of heat away into the blood pool and epicardial coronary artery. Reproduced with permission from Ref.23 Power control vs. temperature control ablation Resistive heat production and therefore ablation lesion size are proportional to the amount of delivered RF power to the tissue. Thus, in a fixed setting of regional blood flow and the catheter–tissue contact quality, higher power delivery results in larger and deeper lesion formation.21,25 Catheter tip temperature is influenced by convective cooling, electrode–tissue contact, and the location of temperature electrode. However, in the absence of convective cooling, the lesion depth and diameter are dependent on the electrode–tissue interface temperature. Radiofrequency ablation can be performed in either power-control or temperature-control mode.26 In power-control mode, a fixed power level of RF delivery is set by the operator which then determines a fixed level of RF current. Temperature-control mode, on the other hand, implements a feedback loop that makes use of a thermistor or thermocouple within the ablation electrode that informs the generator of the instantaneous temperature achieved. The generator dynamically increases and decreases the power level to maintain a fixed electrode temperature. The temperature-control mode attempts to achieve a fixed interface tissue temperature, based on the assumption that electrode temperature reflects tissue temperature.26 Heating tissue by delivery of RF energy results in the denaturation of proteins, and subsequently destruction of the tissue and coagulation of tissue and blood. Irreversible tissue injury occurs at a temperature of ∼50°C.21 However, when the temperature of the electrode–tissue interface exceeds 100°C plasma proteins denature to form a coagulum or char. The development of char results in a smaller electrode surface area available for electrical conduction and therefore manifests as a rapid increase in impedance from ∼100 to 250 Ω or more. If sudden boiling occurs, an audible popping known as ‘steam pop’ may be heard.22 The abrupt increase in impedance leads to significant decrease in the current density and therefore limits the effective lesion formation. Although controlling catheter temperature reduces the risk of coagulum formation and steam pops, it does not eliminate it as the char can still form at temperatures <100°C since tissue temperature is often higher than catheter-tip temperature. Additionally, besides power and electrode temperature, other important determinants of tissue temperature include catheter orientation, electrode size, catheter contact, and convective cooling which are not easy to monitor continuously during ablation.27 Development of irrigation ablation catheters To circumvent the limitations of conventional ablation catheters, in mid 1990s, the effects of convective cooling was exploited advantageously in the design of irrigation ablation catheters.28 Enhancing of the convection heat away from the ablation catheter tip by continuous irrigation results in decreasing the risk of overheating at the electrode–tissue contact point and therefore enables higher magnitude of power delivery while decreasing the chance of coagulum formation at catheter tip.29 As a result of active electrode tip cooling, the region of ohmic heating is driven away from the surface and deeper into the tissue, with conduction carrying the heat even deeper.28,30 Steam pops can still occur despite the absence of markedly elevated tip temperature, and in fact are more prone to occur deep within the myocardium.31,32 Although irrigation of the ablation electrode by itself does not have significant direct effect on lesion size, in several studies use of hypotonic saline was shown to improve actual current delivery to the tissue.33,34 It is hypothesized that due to lower ionic concentration of hypotonic saline, the electrode surface not in contact with the tissue gets partially insulated and therefore the RF delivery to the tissue increases.33 Two types of irrigation catheters have been developed. Closed loop irrigated ablation catheters continuously circulate saline within the electrode which internally cools the electrode tip.32 The second type of irrigated catheters is referred to as ‘open irrigated catheters’. These catheters, which are in wide spread use today, have multiple irrigation holes around the electrode through which saline is flushed into the patient, providing both internal and external cooling (Figure 2). Compared with closed irrigation catheters, open irrigation catheters have similar ablation lesion size, but tend to have lower incidences of thrombus formation and steam pops specially in low blood flow areas.35 This difference is one of the main reasons why closed irrigation catheters are no longer in clinical use, despite having the advantage of not delivering a fluid load to the patient. Figure 2 Open in new tabDownload slide Design of irrigated ablation catheters. (A) Closed-loop irrigation catheter with 4 mm tip electrode, to provide internal cooling, with an internal thermocouple. (B) A 3.5-mm tip electrode with an internal thermocouple and six irrigation holes around the electrode, providing internal and external cooling. Reproduced with permission from Ref.35 Figure 2 Open in new tabDownload slide Design of irrigated ablation catheters. (A) Closed-loop irrigation catheter with 4 mm tip electrode, to provide internal cooling, with an internal thermocouple. (B) A 3.5-mm tip electrode with an internal thermocouple and six irrigation holes around the electrode, providing internal and external cooling. Reproduced with permission from Ref.35 Saline irrigation keeps the tip of ablation catheter relatively cool and therefore precludes the use of electrode temperature for feedback to control the titration of power during RF ablation. To overcome this issue, an irrigation ablation catheter with diamond embedded tip (for rapid cooling) has been designed. The high thermal diffusivity of the tip of this catheter allows using a lower flow rate of the saline irrigation during the ablation. This enables performing the ablation in the temperature control mode while having the advantages of using an irrigation ablation catheter in this type of catheters.36 Ablation catheter size An important factor in determining the ablation lesion size is the diameter of the ablation electrode. In small catheters, the current density at the electrode–tissue interface will be high. Therefore, in the absence of irrigation, increasing higher power will result in a quick increase the electrode–tissue interface >100°C, causing char formation and steam pops. Larger electrodes, however, have larger surface area which allows the operator to deliver higher total power without excessive current density which results in a larger ablation lesion.37 With larger electrodes the surface area in contact with blood stream is also increased resulting in augmented convective cooling effects. Similar to the irrigation ablation catheters, a large electrode will result in a bigger lesion formation only if it is accompanied by higher power delivery. The main limitations of a large ablation electrode (8 or 10 mm in length) compared with a conventional 4 mm ablation catheter are decline in flexibility and positioning of the catheter and lower mapping resolution due to damped local electrograms. Development of contact force catheters One important factor in determination of ablation lesion size is the catheter–tissue contact pressure. Increase in contact force improves the efficacy of RF ablation by increasing the surface area in contact with the tissue, and reducing the shunting of current into the blood pool. Therefore, over the past few years many catheters with the ability of real time monitoring of the contact force have been designed. The optimal electrode contact force could be different based on the thickness of the myocardium in the ablation area. In general, a force of <5 g would result in poor lesion formation despite using a high power.38 On the other hand, excessive contact force (e.g. >40 g of force) increases the risk of steam pops and perforation significantly.39 Using contact force catheters show promising results in improving the outcomes of catheter ablation. It also may improve safety of catheter ablation by providing real time feedbacks to the operator to avoid excessive force during catheter manipulation and ablation. Development of real-time ablation metrics The RF lesion is predominantly generated during the first 10 s of RF ablation and it usually reaches its maximum size after 30 s once the thermodynamic equilibrium is achieved. Therefore, ablations for a longer period of time at the same location will not be effective unless the power or force is increased. With recent progress and technical advances in RF catheter ablation, several real-time monitoring methods have been proposed to ensure effective and safe lesion formation during ablation. Titration of energy delivery based on ablation end points such as impedance fall40,41 or reduction in local electrogram amplitude42–44 have been used in a few studies. In animal studies, firm tissue contact was associated with increased baseline impedance and larger initial impedance drop. In general, an impedance drop of >10 Ω is indicative of local tissue heating and durable ablation lesion formation. Monitoring impedance drop also can be used to improve safety of catheter ablation. Large drops in impedance or fast rates of impedance drop (>1 Ω/s) are indicators of excessive tissue heating and steam pops. With development of contact force catheters, other real time metrics such as force time integral (FTI), which multiplies contact force by RF application duration are also developed to ensure an effective RF energy delivery and transmurality of ablation lesions.45 In prospective studies, achieving a minimum FTI target of 400 and a target contact force of 20 g for each ablation application improved rates of enduring pulmonary vein isolation.46 Although FTI-guided ablation resulted in a reduction of pulmonary vein reconnection, 15% of the pulmonary veins were still found to be reconnected in follow-up electrophysiology study.46 Ablation index (AI) which is another novel metric incorporating contact force, time and power in a weighted formula is also proposed with different minimum values based on the ablation site to prevent reconnection of pulmonary veins.47 In a prospective study in patients with persistent atrial fibrillation undergoing pulmonary vein isolation, AI-guided ablation with a target AI of 550 for anterior and roof and 400 for posterior and inferior left atrial segments were associated with high rate of durable pulmonary vein isolation.48 In another study on patients with idiopathic outflow tract premature ventricular complexes undergoing catheter ablation, higher AI was a predictor of long-term success.49 High power short duration: what is the best recipe? Using RF energy with high power and short duration has been proposed as an alternative strategy to improve lesion formation and decrease collateral damages during pulmonary vein isolation. In this method, high power (50–90 W) for a short duration (from 15 s to as short as 4 s) is delivered. The results of high power energy are a larger zone that is heated directly by the catheter with resistive heating.50 However, because the ablation duration is very brief, temperature decay is significantly shorter, resulting in restriction of heat conduction to the deeper tissues.50 This strategy potentially results in less oedema formation at ablation site and decreases the chances of collateral damage while allows the operator to perform faster point-by-point ablation.51–53 Despite reported benefits, one of the main challenges for high power with short duration ablation has been the inability to adequately assess temperature and lesion formation in real time. Additionally, this strategy might not be as effective when ablation is performed in thicker areas of the atrium. Further randomized clinical trials are required to compare safety and efficacy of high-power short-duration ablation with conventional ablation strategies. Multi-electrode radiofrequency catheters RF catheter ablation for pulmonary vein isolation is usually performed by linear point-by-point ablation. However, creating contiguous lesions can be time consuming and requires advanced three-dimensional mapping systems. To overcome these limitations, multi-electrode ablation systems are designed. Phased RF ablation system uses ablation catheters with different morphology and multiple electrodes (usually between 9 and 12 electrodes). Each electrode has a thermocouple and is capable of delivering bipolar (between contiguous electrodes) or unipolar (from the electrode to the ground pad) independent of other electrodes. Power regulation is achieved through cycling RF energy through the electrodes. The time with no RF energy delivery through the electrode allows them to cool between the RF bursts, and accurately measure the temperature.54,55 The outcomes of pulmonary vein isolation using phased RF systems have been comparable with conventional point-by-point RF ablation. However, there were higher incidents of reported ischaemic stroke, silent cerebral ischaemia and atrioesophageal fistula after the procedure.54–56 In recent years, RF ablation balloons are also developed (Figure 3). In the available form of this catheter, 10 flat and flexible electrodes with irrigation holes are mounted with equal space on a compliant balloon. Due to insulation of back side of the electrodes with the balloon and also as a result of favourable thermal interaction between the electrodes relatively low RF powers (10 W) are required to achieve transmural ablation lesions.57 The advantage of this system is simultaneous application of RF energy across the electrodes with intention of creating contiguous lesions. In addition, multi-electrode catheters allow selective mapping and ablation through any of electrodes if required. Initial studies using balloon RF technologies revealed a short procedure time with acceptable clinical outcomes.58 Additionally, multi-electrode catheters with simultaneous high definition mapping and single-shot ablation capabilities have been designed and successfully tested for pulmonary vein isolation.59 Figure 3 Open in new tabDownload slide Novel multi-polar electrode ablation catheters. (A) The pulmonary vein ablation catheter (courtesy of Medtronic, Minneapolis, MN, USA) capable of map and ablate pulmonary veins using Duty-Cycled Radiofrequency; (B) Multi-Array Ablation Catheter (courtesy of Medtronic, Minneapolis, MN, USA) designed to map and ablate complex fractionated electrograms in the atrium; (C) Multi-Array Septal Catheter (Medtronic, Minneapolis, MN, USA) designed to map and ablate complex fractionated atrial signals within left atrial septum; (D) Globe® mapping and ablation catheter containing 122 electrodes enabling high definition mapping and performing single-shot PVI using the same electrode. (courtesy of Kardium®; Burnaby, BC, Canada); (E) HELIOSTAR™ multi-electrode balloon catheter with LASSOSTAR™ mapping catheter (©BIOSENSE WEBSTER, INC. 2020. All rights reserved) using 10 independent open irrigation electrodes designed for pulmonary vein isolation. (F) The LUMINIZE™ multi-electrode RF balloon catheter with built in camera to visualize tissue contact (Image provided courtesy of Boston Scientific. ©2020 Boston Scientific Corporation or its affiliates. All rights reserved. The LUMINIZE™ RF Balloon Catheter is in development and not available for use or sale. Figure 3 Open in new tabDownload slide Novel multi-polar electrode ablation catheters. (A) The pulmonary vein ablation catheter (courtesy of Medtronic, Minneapolis, MN, USA) capable of map and ablate pulmonary veins using Duty-Cycled Radiofrequency; (B) Multi-Array Ablation Catheter (courtesy of Medtronic, Minneapolis, MN, USA) designed to map and ablate complex fractionated electrograms in the atrium; (C) Multi-Array Septal Catheter (Medtronic, Minneapolis, MN, USA) designed to map and ablate complex fractionated atrial signals within left atrial septum; (D) Globe® mapping and ablation catheter containing 122 electrodes enabling high definition mapping and performing single-shot PVI using the same electrode. (courtesy of Kardium®; Burnaby, BC, Canada); (E) HELIOSTAR™ multi-electrode balloon catheter with LASSOSTAR™ mapping catheter (©BIOSENSE WEBSTER, INC. 2020. All rights reserved) using 10 independent open irrigation electrodes designed for pulmonary vein isolation. (F) The LUMINIZE™ multi-electrode RF balloon catheter with built in camera to visualize tissue contact (Image provided courtesy of Boston Scientific. ©2020 Boston Scientific Corporation or its affiliates. All rights reserved. The LUMINIZE™ RF Balloon Catheter is in development and not available for use or sale. Other energy sources for catheter ablation Along with advances in RF ablation technologies over the past 40 years, several other ablation modalities have been also developed. The most commonly used energy source as an alternative to RF energy is cryoablation. The mechanism of cellular injury from cryoablation is extracellular ice formation, causing intracellular fluid to shift to the extracellular space and damage to the plasma membrane.60 Clinical use of cryoablation catheters for the management of arrhythmias was first started in early 2000s.61 Cryoballoon catheters were used for pulmonary vein isolation in mid 2000s.62 With improvements in safety and efficacy of the second-generation cryoballoon catheters, they became a popular tool for pulmonary vein isolation in patients with paroxysmal atrial fibrillation.63 A recent clinical trial showed cryoballoon ablation to be safe and effective in patients with persistent atrial fibrillation with AF duration of <6 months.64 Catheters with ability of delivering microwave energy causing thermal damage by dielectric effect have been also designed. Microwave energy is not absorbed by the blood and can penetrate deeply into the tissue creating a large lesion with higher risk of collateral damage compared with RF or cryoablation.65,66 Use of microwave ablation has not been popular, however, catheters using this modality are still under clinical investigation. Catheters utilizing highly energetic ultrasound waves have been also tested. Ultrasound can generate tissue damage by thermal energy and also by non-thermal mechanisms through ultrasonic cavitation, and mechanical stress.67 Ultrasound energy transits through blood, therefore, the catheter does not require direct contact with the tissue for ablation.67 Although pulmonary vein isolation using ultrasound ablation is effective, due to atrioesophageal fistula occurrence and phrenic nerve palsy, it did not pass the safety criteria for clinical use.68,69 Infrared light emitted by a laser has been utilized in some ablation systems. Infrared light heats tissue via electromagnetic radiation. However, infrared light cannot penetrate through blood and thus requires direct tissue contact or transmission through a transparent balloon placed against the target tissue so blood is pushed out of the way.70 Fibreoptics have been used in catheter designs to deliver the infrared light and can be used for visual inspection of the tissue at optical light wavelengths as well.70 Non-invasive ablation for treatment of ventricular tachycardia has gained significant attention recently. In this method, the suspicious location of the ventricular tachycardia circuit is localized using cardiac magnetic resonance imaging, cardiac single-photon emission computed tomography, 12-lead ECG during the ventricular tachycardia, and electrocardiographic imaging. Then using stereotactic body radiotherapy, the suspected area is targeted non-invasively. Initial studies reveal promising short-term outcomes of this non-invasive approach in reducing ventricular tachycardia burden. However, further studies are required to assess long-term safety and efficacy of radioablation.71,72 Finally, pulsed field ablation (PFA) has recently emerged as a very promising technology for ablation. It is a recent adaptation of low-energy DC catheter ablation using large electrodes to reduce current density.73 In distinct contrast to RF ablation and cryoablation, which are thermal ablation energy sources, PFA is a tool for non-thermal ablation. This modality involves application of trains of high-voltage electrical pulses in very short duration to injure tissue by the mechanism of irreversible electroporation of the cellular membrane, rather than through thermal injury.74 Based on recent studies, myocardium is more susceptible to the effects of PFA compared with other tissues, particularly the oesophagus and nerves. Therefore, PFA is less likely to produce collateral damage than RF ablation during pulmonary vein isolation procedures (Figure 4). Clinical studies performing pulmonary vein isolation using this modality have been promising with durable pulmonary vein isolation with sparing of oesophagus and phrenic nerve.75,76 The results of ongoing clinical trials on long-term efficacy of PFA in the treatment of cardiac arrhythmias are pending. Figure 4 Open in new tabDownload slide Comparison of radiofrequency, cryoballoon, and pulsed field ablation. Thermal ablation using radiofrequency or cryoballoon catheters damages all tissue types indiscriminately, potentially damaging adjacent structures such as the phrenic nerve and oesophagus. Conversely, pulsed field ablation was shown to preferentially affect myocardial tissue, thus sparing these adjacent structures. Reproduced with permission from Ref.75 Figure 4 Open in new tabDownload slide Comparison of radiofrequency, cryoballoon, and pulsed field ablation. Thermal ablation using radiofrequency or cryoballoon catheters damages all tissue types indiscriminately, potentially damaging adjacent structures such as the phrenic nerve and oesophagus. Conversely, pulsed field ablation was shown to preferentially affect myocardial tissue, thus sparing these adjacent structures. Reproduced with permission from Ref.75 Conclusion Approximately 40 years have passed since RF energy was first used as an energy source for catheter ablation. During this period of time, much has been learned concerning how best to deliver RF ablation lesions to accomplish an effective and safe ablation procedure (central illustration). But despite all of the efforts that have been expended on RF energy, it is recognized as imperfect. The limitations of RF energy include inadequate lesion size for targets deep within the myocardium, which prevents creation of lesions with sufficient depth for some targets for VT ablation. Another limitation is the ever present risk of developing a steam pop. And a third risk is that of collateral injury to structures such as the phrenic nerve and oesophagus. It is sobering that despite more than three decades of research, there is still uncertainly how best to deliver RF energy. A good example of this is the debates among skilled investigators on the relative merits of a high-power short duration strategy vs. a lower power energy delivery with a specific lesion index target based on power, time, and contact force. Today, we have high hopes that electroporation will be the ‘perfect’ energy source for ablation. As noted above, early research has suggested that this form of ablation energy prevents collateral damage to the oesophagus and phrenic nerve, while achieving large permanent ablation lesions in seconds. Whether our hopes will be realized will play out over the next 5 years. Until then RF energy remains the longest standing and dominant energy source for catheter ablation. Conflict of interest: none declared. References 1 Durrer D Schoo L Schuilenburg RM Wellens HJ. The role of premature beats in the initiation and the termination of supraventricular tachycardia in the Wolff-Parkinson-White syndrome . Circulation 1967 ; 36 : 644 – 62 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Wellens HJ Schuilenburg RM Durrer D. Electrical stimulation of heart in study of patients with the Wolff-Parkinson-White syndrome type A . Br Heart J 1971 ; 33 : 147 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Vedel J Frank R Fontaine G Fournial JF Grosgogeat Y. Permanent intra-hisian atrioventricular block induced during right intraventricular exploration . Arch Mal Coeur Vaiss 1979 ; 72 : 107 – 12 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 4 Gonzalez R Scheinman M Margaretten W Rubinstein M. Closed-chest electrode-catheter technique for His bundle ablation in dogs . Am J Physiol 1981 ; 241 : H283 – 7 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 5 Gallagher JJ Svenson RH Kasell JH German LD Bardy GH Broughton A et al. Catheter technique for closed-chest ablation of the atrioventricular conduction system . N Engl J Med 1982 ; 306 : 194 – 200 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Scheinman MM Morady F Hess DS Gonzalez R. Catheter-induced ablation of the atrioventricular junction to control refractory supraventricular arrhythmias . JAMA 1982 ; 248 : 851 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Haissaguerre M Warin JF Lemetayer P Saoudi N Guillem JP Blanchot P. Closed-chest ablation of retrograde conduction in patients with atrioventricular nodal reentrant tachycardia . N Engl J Med 1989 ; 320 : 426 – 33 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Hartzler GO. Electrode catheter ablation of refractory focal ventricular tachycardia . J Am Coll Cardiol 1983 ; 2 : 1107 – 13 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Morady F Sgheinman MM. Transvenous catheter ablation of a posteroseptal accessory pathway in a patient with the Wolff-Parkinson-White syndrome . N Engl J Med 1984 ; 310 : 705 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Weber H Schmitz L. Catheter technique for closed-chest ablation of an accessory atrioventricular pathway . N Engl J Med 1983 ; 308 : 653 – 4 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 11 Jackman WM Friday KJ Scherlag BJ Dehning MM Schechter E Reynolds DW et al. Direct endocardial recording from an accessory atrioventricular pathway: localization of the site of block, effect of antiarrhythmic drugs, and attempt at nonsurgical ablation . Circulation 1983 ; 68 : 906 – 16 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Gang ES Oseran D Rosenthal M Mandel WJ Deng ZW Meesmann M et al. Closed chest catheter ablation of an accessory pathway in a patient with permanent junctional reciprocating tachycardia . J Am Coll Cardiol 1985 ; 6 : 1167 – 71 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Morady F Scheinman MM Kou WH Griffin JC Dick M 2nd Herre J et al. Long-term results of catheter ablation of a posteroseptal accessory atrioventricular connection in 48 patients . Circulation 1989 ; 79 : 1160 – 70 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Hartzler GO Giorgi LV Diehl AM Hamaker WR. Right coronary spasm complicating electrode catheter ablation of a right lateral accessory pathway . J Am Coll Cardiol 1985 ; 6 : 250 – 3 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Sebag C Lavergne T Millat B Belhassen B Davy JM Bedossa P et al. Rupture of the stomach and the esophagus after attempted transcatheter ablation of an accessory pathway by direct current shock . Am J Cardiol 1989 ; 63 : 890 – 1 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Huang SK. Radio-frequency catheter ablation of cardiac arrhythmias: appraisal of an evolving therapeutic modality . Am Heart J 1989 ; 118 : 1317 – 23 . Google Scholar Crossref Search ADS PubMed WorldCat 17 Huang SK Graham AR Bharati S Lee MA Gorman G Lev M. Short- and long-term effects of transcatheter ablation of the coronary sinus by radiofrequency energy . Circulation 1988 ; 78 : 416 – 27 . Google Scholar Crossref Search ADS PubMed WorldCat 18 Jackman WM Kuck KH Naccarelli GV Carmen L Pitha J. Radiofrequency current directed across the mitral anulus with a bipolar epicardial-endocardial catheter electrode configuration in dogs . Circulation 1988 ; 78 : 1288 – 98 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Jackman WM Wang XZ Friday KJ Roman CA Moulton KP Beckman KJ et al. Catheter ablation of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome) by radiofrequency current . N Engl J Med 1991 ; 324 : 1605 – 11 . Google Scholar Crossref Search ADS PubMed WorldCat 20 Huang SK Bharati S Graham AR Lev M Marcus FI Odell RC. Closed chest catheter desiccation of the atrioventricular junction using radiofrequency energy – a new method of catheter ablation . J Am Coll Cardiol 1987 ; 9 : 349 – 58 . Google Scholar Crossref Search ADS PubMed WorldCat 21 Haines DE. The biophysics of radiofrequency catheter ablation in the heart: the importance of temperature monitoring . Pacing Clin Electrophysiol 1993 ; 16 : 586 – 91 . Google Scholar Crossref Search ADS PubMed WorldCat 22 Haines DE Verow AF. Observations on electrode-tissue interface temperature and effect on electrical impedance during radiofrequency ablation of ventricular myocardium . Circulation 1990 ; 82 : 1034 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 23 Nath S Haines DE. Biophysics and pathology of catheter energy delivery systems . Prog Cardiovasc Dis 1995 ; 37 : 185 – 204 . Google Scholar Crossref Search ADS PubMed WorldCat 24 Haines DE Watson DD. Tissue heating during radiofrequency catheter ablation: a thermodynamic model and observations in isolated perfused and superfused canine right ventricular free wall . Pacing Clin Electrophysiol 1989 ; 12 : 962 – 76 . Google Scholar Crossref Search ADS PubMed WorldCat 25 Wittkampf FH Hauer RN Robles de Medina EO. Control of radiofrequency lesion size by power regulation . Circulation 1989 ; 80 : 962 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 26 Calkins H Prystowsky E Carlson M Klein LS Saul JP Gillette P. Temperature monitoring during radiofrequency catheter ablation procedures using closed loop control. Atakr Multicenter Investigators Group . Circulation 1994 ; 90 : 1279 – 86 . Google Scholar Crossref Search ADS PubMed WorldCat 27 Kongsgaard E Steen T Jensen O Aass H Amlie JP. Temperature guided radiofrequency catheter ablation of myocardium: comparison of catheter tip and tissue temperatures in vitro . Pacing Clin Electrophysiol 1997 ; 20 : 1252 – 60 . Google Scholar Crossref Search ADS PubMed WorldCat 28 Nakagawa H Yamanashi WS Pitha JV Arruda M Wang X Ohtomo K et al. Comparison of in vivo tissue temperature profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus temperature control in a canine thigh muscle preparation . Circulation 1995 ; 91 : 2264 – 73 . Google Scholar Crossref Search ADS PubMed WorldCat 29 Otomo K Yamanashi WS Tondo C Antz M Bussey J Pitha JV et al. Why a large tip electrode makes a deeper radiofrequency lesion: effects of increase in electrode cooling and electrode-tissue interface area . J Cardiovasc Electrophysiol 1998 ; 9 : 47 – 54 . Google Scholar Crossref Search ADS PubMed WorldCat 30 Dorwarth U Fiek M Remp T Reithmann C Dugas M Steinbeck G et al. Radiofrequency catheter ablation: different cooled and noncooled electrode systems induce specific lesion geometries and adverse effects profiles . Pacing Clin Electrophysiol 2003 ; 26 : 1438 – 45 . Google Scholar Crossref Search ADS PubMed WorldCat 31 Bruce GK Bunch TJ Milton MA Sarabanda A Johnson SB Packer DL. Discrepancies between catheter tip and tissue temperature in cooled-tip ablation: relevance to guiding left atrial ablation . Circulation 2005 ; 112 : 954 – 60 . Google Scholar Crossref Search ADS PubMed WorldCat 32 Cooper JM Sapp JL Tedrow U Pellegrini CP Robinson D Epstein LM et al. Ablation with an internally irrigated radiofrequency catheter: learning how to avoid steam pops . Heart Rhythm 2004 ; 1 : 329 – 33 . Google Scholar Crossref Search ADS PubMed WorldCat 33 Nguyen DT Olson M Zheng L Barham W Moss JD Sauer WH. Effect of irrigant characteristics on lesion formation after radiofrequency energy delivery using ablation catheters with actively cooled tips . J Cardiovasc Electrophysiol 2015 ; 26 : 792 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 34 Nguyen DT Gerstenfeld EP Tzou WS Jurgens PT Zheng L Schuller J et al. Radiofrequency ablation using an open irrigated electrode cooled with half-normal saline . JACC Clin Electrophysiol 2017 ; 3 : 1103 – 10 . Google Scholar Crossref Search ADS PubMed WorldCat 35 Yokoyama K Nakagawa H Wittkampf FH Pitha JV Lazzara R Jackman WM. Comparison of electrode cooling between internal and open irrigation in radiofrequency ablation lesion depth and incidence of thrombus and steam pop . Circulation 2006 ; 113 : 11 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 36 Iwasawa J Koruth JS Petru J Dujka L Kralovec S Mzourkova K et al. Temperature-controlled radiofrequency ablation for pulmonary vein isolation in patients with atrial fibrillation . J Am Coll Cardiol 2017 ; 70 : 542 – 53 . Google Scholar Crossref Search ADS PubMed WorldCat 37 Haines DE Watson DD Verow AF. Electrode radius predicts lesion radius during radiofrequency energy heating. Validation of a proposed thermodynamic model . Circ Res 1990 ; 67 : 124 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 38 Afzal MR Chatta J Samanta A Waheed S Mahmoudi M Vukas R et al. Use of contact force sensing technology during radiofrequency ablation reduces recurrence of atrial fibrillation: a systematic review and meta-analysis . Heart Rhythm 2015 ; 12 : 1990 – 6 . Google Scholar Crossref Search ADS PubMed WorldCat 39 Reddy VY Shah D Kautzner J Schmidt B Saoudi N Herrera C et al. The relationship between contact force and clinical outcome during radiofrequency catheter ablation of atrial fibrillation in the TOCCATA study . Heart Rhythm 2012 ; 9 : 1789 – 95 . Google Scholar Crossref Search ADS PubMed WorldCat 40 Strickberger S Weiss RAUL Knight BP Baju M Bogun F Brinkman K et al. Randomized comparison of two techniques for titrating power during radiofrequency ablation of accessory pathways . J Cardiovasc Electrophysiol 1996 ; 7 : 795 – 801 . Google Scholar Crossref Search ADS PubMed WorldCat 41 Reichlin T Knecht S Lane C Kuhne M Nof E Chopra N et al. Initial impedance decrease as an indicator of good catheter contact: insights from radiofrequency ablation with force sensing catheters . Heart Rhythm 2014 ; 11 : 194 – 201 . Google Scholar Crossref Search ADS PubMed WorldCat 42 Schwartzman D Michele JJ Trankiem CT Ren JF. Electrogram-guided radiofrequency catheter ablation of atrial tissue comparison with thermometry-guide ablation: comparison with thermometry-guide ablation . J Interv Cardiac Electrophysiol 2001 ; 5 : 253 – 66 . Google Scholar Crossref Search ADS WorldCat 43 Gepstein L Hayam G Shpun S Cohen D Ben-Haim SA. Atrial linear ablations in pigs. Chronic effects on atrial electrophysiology and pathology . Circulation 1999 ; 100 : 419 – 26 . Google Scholar Crossref Search ADS PubMed WorldCat 44 Otomo K Uno K Fujiwara H Isobe M Iesaka Y. Local unipolar and bipolar electrogram criteria for evaluating the transmurality of atrial ablation lesions at different catheter orientations relative to the endocardial surface . Heart Rhythm 2010 ; 7 : 1291 – 300 . Google Scholar Crossref Search ADS PubMed WorldCat 45 Squara F Latcu DG Massaad Y Mahjoub M Bun SS Saoudi N. Contact force and force-time integral in atrial radiofrequency ablation predict transmurality of lesions . Europace 2014 ; 16 : 660 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 46 Kautzner J Neuzil P Lambert H Peichl P Petru J Cihak R et al. EFFICAS II: optimization of catheter contact force improves outcome of pulmonary vein isolation for paroxysmal atrial fibrillation . Europace 2015 ; 17 : 1229 – 35 . Google Scholar Crossref Search ADS PubMed WorldCat 47 Das M Loveday JJ Wynn GJ Gomes S Saeed Y Bonnett LJ et al. Ablation index, a novel marker of ablation lesion quality: prediction of pulmonary vein reconnection at repeat electrophysiology study and regional differences in target values . Europace 2017 ; 19 : 775 – 83 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 48 Hussein A Das M Riva S Morgan M Ronayne C Sahni A et al. Use of ablation index-guided ablation results in high rates of durable pulmonary vein isolation and freedom from arrhythmia in persistent atrial fibrillation patients: the PRAISE study results . Circ Arrhythm Electrophysiol 2018 ; 11 : e006576 . Google Scholar Crossref Search ADS PubMed WorldCat 49 Casella M Gasperetti A Gianni C Zucchelli G Notarstefano P Al-Ahmad A et al. Ablation Index as a predictor of long-term efficacy in premature ventricular complex ablation: a regional target value analysis . Heart Rhythm 2019 ; 16 : 888 – 95 . Google Scholar Crossref Search ADS PubMed WorldCat 50 Leshem E Zilberman I Tschabrunn CM Barkagan M Contreras-Valdes FM Govari A et al. High-power and short-duration ablation for pulmonary vein isolation: biophysical characterization . JACC Clin Electrophysiol 2018 ; 4 : 467 – 79 . Google Scholar Crossref Search ADS PubMed WorldCat 51 Reddy VY Grimaldi M De Potter T Vijgen JM Bulava A Duytschaever MF et al. Pulmonary vein isolation with very high power, short duration, temperature-controlled lesions: the QDOT-FAST Trial . JACC Clin Electrophysiol 2019 ; 5 : 778 – 86 . Google Scholar Crossref Search ADS PubMed WorldCat 52 Barkagan M Contreras-Valdes FM Leshem E Buxton AE Nakagawa H Anter E. High-power and short-duration ablation for pulmonary vein isolation: safety, efficacy, and long-term durability . J Cardiovasc Electrophysiol 2018 ; 29 : 1287 – 96 . Google Scholar Crossref Search ADS PubMed WorldCat 53 Kottmaier M Popa M Bourier F Reents T Cifuentes J Semmler V et al. Safety and outcome of very high-power short-duration ablation using 70 W for pulmonary vein isolation in patients with paroxysmal atrial fibrillation . Europace 2020 ; 22 : 388 – 93 . Google Scholar Crossref Search ADS PubMed WorldCat 54 Rosso R Halkin A Michowitz Y Belhassen B Glick A Viskin S. Radiofrequency ablation of paroxysmal atrial fibrillation with the new irrigated multipolar nMARQ ablation catheter: verification of intracardiac signals with a second circular mapping catheter . Heart Rhythm 2014 ; 11 : 559 – 65 . Google Scholar Crossref Search ADS PubMed WorldCat 55 Boersma LV van der Voort P Debruyne P Dekker L Simmers T Rossenbacker T et al. Multielectrode pulmonary vein isolation versus single tip wide area catheter ablation for paroxysmal atrial fibrillation: a multinational multicenter randomized clinical trial . Circ Arrhythm Electrophysiol 2016 ; 9 : e003151 . Google Scholar Crossref Search ADS PubMed WorldCat 56 Burri H Park CI Poku N Giraudet P Stettler C Zimmermann M. Pulmonary vein isolation for paroxysmal atrial fibrillation using a circular multipolar ablation catheter: safety and efficacy using low-power settings . J Cardiovasc Electrophysiol 2016 ; 27 : 170 – 4 . Google Scholar Crossref Search ADS PubMed WorldCat 57 Reddy VY Schilling R Grimaldi M Horton R Natale A Riva S et al. Pulmonary vein isolation with a novel multielectrode radiofrequency balloon catheter that allows directionally tailored energy delivery: short-term outcomes from a multicenter first-in-human study (RADIANCE) . Circ Arrhythm Electrophysiol 2019 ; 12 : e007541 . Google Scholar Crossref Search ADS PubMed WorldCat 58 Dhillon GS Honarbakhsh S Di Monaco A Coling AE Lenka K Pizzamiglio F et al. Use of a multi-electrode radiofrequency balloon catheter to achieve pulmonary vein isolation in patients with paroxysmal atrial fibrillation: 12-month outcomes of the RADIANCE study . J Cardiovasc Electrophysiol 2020 ; 31 : 1259 – 69 . Google Scholar Crossref Search ADS PubMed WorldCat 59 Kottkamp H Hindricks G Ponisch C Bertagnolli L Moser F Hilbert S et al. Global multielectrode contact-mapping plus ablation with a single catheter in patients with atrial fibrillation: global AF study . J Cardiovasc Electrophysiol 2019 ; 30 : 2248 – 55 . Google Scholar Crossref Search ADS PubMed WorldCat 60 Wood MA Parvez B Ellenbogen AL Shaffer KM Goldberg SM Gaspar MP et al. Determinants of lesion sizes and tissue temperatures during catheter cryoablation . Pacing Clin Electrophysiol 2007 ; 30 : 644 – 54 . Google Scholar Crossref Search ADS PubMed WorldCat 61 Dubuc M Khairy P Rodriguez-Santiago A Talajic M Tardif JC Thibault B et al. Catheter cryoablation of the atrioventricular node in patients with atrial fibrillation: a novel technology for ablation of cardiac arrhythmias . J Cardiovasc Electrophysiol 2001 ; 12 : 439 – 44 . Google Scholar Crossref Search ADS PubMed WorldCat 62 Sarabanda AV Bunch TJ Johnson SB Mahapatra S Milton MA Leite LR et al. Efficacy and safety of circumferential pulmonary vein isolation using a novel cryothermal balloon ablation system . J Am Coll Cardiol 2005 ; 46 : 1902 – 12 . Google Scholar Crossref Search ADS PubMed WorldCat 63 Kuck KH Brugada J Furnkranz A Metzner A Ouyang F Chun KR et al. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation . N Engl J Med 2016 ; 374 : 2235 – 45 . Google Scholar Crossref Search ADS PubMed WorldCat 64 Su WW Reddy VY Bhasin K Champagne J Sangrigoli RM Braegelmann KM et al. Cryoballoon ablation of pulmonary veins for persistent atrial fibrillation: results from the multicenter STOP Persistent AF trial . Heart Rhythm 2020 ;24;S1547–5271 (Online ahead of print). Google Scholar OpenURL Placeholder Text WorldCat 65 Brace CL. Microwave tissue ablation: biophysics, technology, and applications . Crit Rev Biomed Eng 2010 ; 38 : 65 – 78 . Google Scholar Crossref Search ADS PubMed WorldCat 66 Tse HF Liao S Siu CW Yuan L Nicholls J Leung G et al. Determinants of lesion dimensions during transcatheter microwave ablation . Pacing Clin Electrophysiol 2009 ; 32 : 201 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 67 Laughner JI Sulkin MS Wu Z Deng CX Efimov IR. Three potential mechanisms for failure of high intensity focused ultrasound ablation in cardiac tissue . Circ Arrhythm Electrophysiol 2012 ; 5 : 409 – 16 . Google Scholar Crossref Search ADS PubMed WorldCat 68 Neven K Metzner A Schmidt B Ouyang F Kuck KH. Two-year clinical follow-up after pulmonary vein isolation using high-intensity focused ultrasound (HIFU) and an esophageal temperature-guided safety algorithm . Heart Rhythm 2012 ; 9 : 407 – 13 . Google Scholar Crossref Search ADS PubMed WorldCat 69 Neven K Schmidt B Metzner A Otomo K Nuyens D De Potter T et al. Fatal end of a safety algorithm for pulmonary vein isolation with use of high-intensity focused ultrasound . Circ Arrhythm Electrophysiol 2010 ; 3 : 260 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 70 Dukkipati SR Cuoco F Kutinsky I Aryana A Bahnson TD Lakkireddy D et al. Pulmonary vein isolation using the visually guided laser balloon: a prospective, multicenter, and randomized comparison to standard radiofrequency ablation . J Am Coll Cardiol 2015 ; 66 : 1350 – 60 . Google Scholar Crossref Search ADS PubMed WorldCat 71 Cuculich PS Schill MR Kashani R Mutic S Lang A Cooper D et al. Noninvasive cardiac radiation for ablation of ventricular tachycardia . N Engl J Med 2017 ; 377 : 2325 – 36 . Google Scholar Crossref Search ADS PubMed WorldCat 72 Robinson CG Samson PP Moore KMS Hugo GD Knutson N Mutic S et al. Phase I/II trial of electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia . Circulation 2019 ; 139 : 313 – 21 . Google Scholar Crossref Search ADS PubMed WorldCat 73 DeSimone CV Kapa S Asirvatham SJ. Electroporation: past and future of catheter ablation . Circ Arrhythm Electrophysiol 2014 ; 7 : 573 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 74 Jiang C Davalos RV Bischof JC. A review of basic to clinical studies of irreversible electroporation therapy . IEEE Trans Biomed Eng 2015 ; 62 : 4 – 20 . Google Scholar Crossref Search ADS PubMed WorldCat 75 Reddy VY Neuzil P Koruth JS Petru J Funosako M Cochet H et al. Pulsed field ablation for pulmonary vein isolation in atrial fibrillation . J Am Coll Cardiol 2019 ; 74 : 315 – 26 . Google Scholar Crossref Search ADS PubMed WorldCat 76 Reddy VY Koruth J Jais P Petru J Timko F Skalsky I et al. Ablation of atrial fibrillation with pulsed electric fields: an ultra-rapid, tissue-selective modality for cardiac ablation . JACC Clin Electrophysiol 2018 ; 4 : 987 – 95 . Google Scholar Crossref Search ADS PubMed WorldCat Authors Open in new tabDownload slide Open in new tabDownload slide Biography: Dr. Habibi is a cardiac Electrophysiologist at Valley Health System in New Jersey. He received his medical degree from Tehran University of Medical Sciences. He did his Cardiology fellowship at Albert Einstein College of Medicine and post-doctoral research fellowship and Electrophysiology fellowship at Johns Hopkins University. His research interests are atrial remodeling in general population and in patients with atrial fibrillation undergoing catheter ablation. Dr. Habibi is the author of many articles in using CMR in risk stratification of general population and atrial fibrillation patients for stroke and cardiovascular outcomes. He is a recipient of ACC young investigator award for his research. Open in new tabDownload slide Open in new tabDownload slide Biography: Ronald D. Berger received his B.S., M.S., and Ph.D degrees in Electrical Engineering from M.I.T. and his MD from Harvard Medical School. He is currently Professor of Medicine, Professor of Biomedical Engineering, and the Nicholas J. Fortuin Professor in Cardiology at Johns Hopkins University. He is Director of Inpatient Cardiology and Director of the Cardiac Electrophysiology Fellowship Program at Johns Hopkins Hospital. As Fellowship Director, he has trained over 60 fellows in Cardiac Electrophysiology. Dr. Berger has made important contributions in several areas of investigation, applying signal processing and electrical engineering concepts to solve problems in arrhythmia diagnosis and management. He has published over 280 papers in the medical literature and holds over 30 U.S. patents. Dr. Berger has received multiple awards for his research, including a FIRST Award from the NIH, an Established Investigator Award from the AHA, and an Abell Foundation Award for Research Translation. Open in new tabDownload slide Open in new tabDownload slide Biography: Dr. Hugh Calkins is the Catherine Ellen Poindexter Professor of Cardiology and Professor of Medicine at the Johns Hopkins University School of Medicine. Dr. Calkins graduated from Williams College and Harvard Medical School. He trained in Internal Medicine at the Massachusetts General Hospital. He received his cardiology fellowship training at Johns Hopkins. His first faculty position was at the University of Michigan. He has directed the EP Program at Johns Hopkins since 1992. Dr Calkins has published more than 650 manuscripts and book chapters. He is recognized nationally and internationally for the pioneering role he has played in the development of radiofrequency catheter ablation for treatment of cardiac arrhythmias. Dr Calkins served as President of the Heart Rhythm Society from 2014-2015. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Radiofrequency ablation: technological trends, challenges, and opportunities
JF - Europace
DO - 10.1093/europace/euaa328
DA - 2020-11-30
UR - https://www.deepdyve.com/lp/oxford-university-press/radiofrequency-ablation-technological-trends-challenges-and-SoNGxw6vUd
SP - 1
EP - 1
VL - Advance Article
IS - 
DP - DeepDyve
ER -