Cardiac Catheter Ablation

Number: 0165

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

Policy

Scope of Policy

This Clinical Policy Bulletin addresses cardiac catheter ablation and radio-ablation.

  1. Medical Necessity

    Aetna considers cardiac catheter ablation proceduresFootnote1* with electrophysiological studies medically necessary for any of the following arrhythmias:

    1. Atrial fibrillation (AF)

      In members with AF who meet any of the following:

      • Symptomatic AF when anti-arrhythmic drugs have been ineffective, contraindicated, not tolerated, or not preferred; or
      • AF with inadequately controlled ventricular rates; or
      • AF with an identified accessory pathway; or
      • Heart failure with reduced ejection fraction or suspected tachycardia-mediated cardiomyopathy; or
      • Symptomatic AF and heart failure with preserved ejection fraction; or
      • Hypertrophic cardiomyopathy with AF that is drug-resistant, drugs are not tolerated or are contraindicated, or the member does not wish to take them; or
      • SymptomaticFootnote2** AF amenable to catheter ablation where symptoms persist despite rate control; or
      • SymptomaticFootnote2** paroxysmal AF when rhythm control is desired; or
      • Recurrent implantable cardioverter-defibrillator (ICD) shocks delivered for atrial fibrillation with rapid ventricular response, when shocks are not manageable by reprogramming or adjustment of medications; or
      • Atrioventricular nodal ablation for members with AF, heart failure with reduced ejection fraction, and poor rate control; or
      • Atrioventricular nodal ablation for members with AF, heart failure with reduced ejection fraction, and biventricular pacing in whom an adequate pacing percentage cannot be achieved; or
      • Asymptomatic paroxysmal AF in a young member with few co-morbidities; or

    2. Atrioventricular nodal reentrant tachycardia (AVNRT)

      In members with atrioventricular node reentrant tachycardia; or

    3. Atrial tachycardia (AT) and atrial flutter (AFL)

      In members who meet any of the following:

      • Members with AFL; or
      • Members with focal or multifocal AT; or
      • Junctional tachycardia that is drug-resistant, drugs are not tolerated or are contraindicated, or the member does not wish to take them; or
      • Tachycardia-mediated cardiomyopathy; or
      • Tachy-brady syndrome/sinus node dysfunction; or

    4. Accessory pathways

      In members with accessory pathway tachycardia (including pre-excitation syndrome (e.g., Wolff-Parkinson-White syndrome)); or

      In member with Wolff-Parkinson-White syndrome without tachycardia who have a high-risk accessory pathway based on treadmill testing; or

    5. Ventricular arrhythmia

      In members who meet any of the following:

      • Arrhythmogenic right ventricular cardiomyopathy (ARVC) with recurrent sustainedFootnote3*** VT or frequent appropriate ICD shocks in whom a beta-blocker is ineffective or not tolerated.  Catheter ablation with availability of a combined endocardial/epicardial approach can be beneficial; or
      • Frequent (e.g., greater than 15% of beats) premature ventricular contractions (PVCs) who have declining ventricular function due to PVCs, when the PVCs are drug-resistant, or drugs are contraindicated or not tolerated, or the member does not desire long-term drug therapy; or 
      • Non-responders to cardiac resynchronization therapy with frequent unifocal premature ventricular contractions limiting optimal biventricular pacing despite drug therapy; or
      • Non-sustained VT that is symptomaticFootnote2** when the tachycardia is drug-resistant, drugs are contraindicated, or the member is drug-intolerant or does not desire long-term drug therapy; or
      • Recurrent episodes of idiopathic VF or polymorphic VT initiated by PVCs with consistent QRS morphology; or
      • Suspected epicardial substrate or circuit on ECG when the tachycardia is drug-resistant, or drugs are contraindicated or not tolerated, or the member does not desire long-term drug therapy; or
      • SymptomaticFootnote2** ventricular arrhythmias in a structurally normal heart (e.g., idiopathic, papillary muscle, outflow tract) where the arrhythmia is drug resistant, or drugs are contraindicated or not tolerated, or the member does not desire long-term drug therapy; or 
      • VT related to re-entry (e.g., bundle branch, His-Purkinje, or fascicular) when the tachycardia is drug-resistant, or drugs are contraindicated or not tolerated, or the member does not desire long-term drug therapy; or
      • Recurrent sustained monomorphic VT or recurrent appropriate ICD shocks not manageable by re-programming or concomitant drug therapy; or
      • Ischemic heart disease with recurrent monomorphic VT when anti-arrhythmic drug therapy failed, is contraindicated, is not tolerated, or is not desired.

      Footnote1* For purposes of this policy, pulsed pulsed field ablation is considered and equally acceptable alternative to standard radiofrequency ablation for medically necessary indications.

      Footnote2** Examples of symptoms include chest pain, dizziness, dyspnea or palpitations.

      Footnote3*** For purposes of this policy, sustained VT is that which lasts 30 seconds or more.

    6. Operative Ablation

      See CPB 0225 - Maze Procedure.

      Notes For members who undergo an electrophysiology study on the same day as an ablation, an electrophysiologic study is considered medically necessary if no prior electrophysiology study has been performed within the previous 3 months.  Two electrophysiologists are required to perform the ablation -- 1 to manipulate the catheters, and the other to guide the precise location for the ablation utilizing electrogram analysis and pacing.  The procedure includes temporary pacemaker placement if indicated.  When ablation of the His-bundle is indicated, a permanent pacemaker will always be placed because the ablation has caused a complete heart block. 

      Notes: The use of the CARTO system (an intra-cardiac electrophysiological 3-D mapping system) is considered medically necessary for guiding radiofrequency ablation in the treatment of arrhythmias.

  2. Experimental, Investigational, or Unproven

    1. Aetna considers cardiac catheter ablation procedures experimental, investigational, or unproven for all other indications as there is insufficient evidence in the peer-reviewed medical literature of the effectiveness of cardiac catheter ablation for these indications.
    2. Aetna considers the following procedures experimental, investigational, or unproven because their effectiveness has not been established:

      1. Alcohol ablation of vein of Marshall for the treatment of paroxysmal / persistent atrial fibrillation or peri-mitral flutter; 
      2. Cardio-neuro-ablation for the treatment of syncope; 
      3. Intra-myocardial infusion-needle catheter ablation for ventricular tachycardia;
      4. Non-invasive cardiac radio-ablation for the treatment of cardiac arrhythmias (e.g., atrial fibrillation (AF) and VT);
      5. Sinus node-sparing hybrid ablation for the treatment of sinus tachycardia/postural orthostatic sinus tachycardia.

  3. Related Policies

Table:

CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

CPT codes covered if selection criteria are met:
33250 - 33251 Operative ablation of supraventricular arrhythmogenic focus or pathway (e.g., Wolff-Parkinson-White, atrioventricular node re-entry), tract(s) and/or focus (foci); without cardiopulmonary bypass or with cardiopulmonary bypass
33254 Operative tissue ablation and reconstruction of atria, limited (e.g., modified maze procedure)
33256 Operative tissue ablation and reconstruction of atria, extensive (eg, maze procedure); with cardiopulmonary bypass
+ 33257 Operative tissue ablation and reconstruction of atria, performed at the time of other cardiac procedure(s), limited (e.g., modified maze procedure) (List separately in addition to code for primary procedure)
+ 33259 Operative tissue ablation and reconstruction of atria, performed at the time of other cardiac procedure(s), extensive (e.g., maze procedure), with cardiopulmonary bypass (List separately in addition to code for primary procedure)
33261 Operative ablation of ventricular arrhythmogenic focus with cardiopulmonary bypass
+ 93613 Intracardiac electrophysiologic 3-dimensional mapping [for guiding radiofrequency ablation in the treatment of arrhythmias]
93650 Intracardiac catheter ablation of atrioventricular node function, atrioventricular conduction for creation of complete heart block, with or without temporary pacemaker placement [not covered for intra-myocardial infusion-needle catheter ablation for ventricular tachycardia]
93653 Comprehensive electrophysiologic evaluation including insertion and repositioning of multiple electrode catheters with induction or attempted induction of an arrhythmia with right atrial pacing and recording, right ventricular pacing and recording, His recording with intracardiac catheter ablation of arrhythmogenic focus; with treatment of supraventricular tachycardia by ablation of fast or slow atrioventricular pathway, accessory atrioventricular connection, cavo-tricuspid isthmus or other single atrial focus or source of atrial re-entry
93654 Comprehensive electrophysiologic evaluation including insertion and repositioning of multiple electrode catheters with induction or attempted induction of an arrhythmia with right atrial pacing and recording, right ventricular pacing and recording, His recording with intracardiac catheter ablation of arrhythmogenic focus; with treatment of ventricular tachycardia or focus of ventricular ectopy including intracardiac electrophysiologic 3D mapping, when performed, and left ventricular pacing and recording, when performed
93655 Intracardiac catheter ablation of a discrete mechanism of arrhythmia which is distinct from the primary ablated mechanism, including repeat diagnostic maneuvers, to treat a spontaneous or induced arrhythmia (List separately in addition to code for primary procedure)[not covered for intra-myocardial infusion-needle catheter ablation for ventricular tachycardia]
93656 Comprehensive electrophysiologic evaluation including transseptal catheterizations, insertion and repositioning of multiple electrode catheters with induction or attempted induction of an arrhythmia with atrial recording and pacing, when possible, right ventricular pacing and recording, His bundle recording with intracardiac catheter ablation of arrhythmogenic focus, with treatment of atrial fibrillation by ablation by pulmonary vein isolation
93657 Additional linear or focal intracardiac catheter ablation of the left or right atrium for treatment of atrial fibrillation remaining after completion of pulmonary vein isolation (List separately in addition to code for primary procedure)

CPT codes not covered for indications listed in the CPB:
Cardio-neuroablation and sinus node sparing hybrid ablation –no specific code
0745T Cardiac focal ablation utilizing radiation therapy for arrhythmia; noninvasive arrhythmia localization and mapping of arrhythmia site (nidus), derived from anatomical image data (eg, CT, MRI, or myocardial perfusion scan) and electrical data (eg, 12-lead ECG data), and identification of areas of avoidance
0746T      conversion of arrhythmia localization and mapping of arrhythmia site (nidus) into a multidimensional radiation treatment plan
0747T      delivery of radiation therapy, arrhythmia

Other HCPCS codes related to the CPB: :
C1732 Catheter, Electrophysiology, diagnostic/ablation 3D or vector mapping
C1886 Catheter, extravascular tissue ablation, any modality (insertable)

ICD-10 codes covered if selection criteria are met:
I21.01 – I25.9 Ischemic heart disease
I42.8 Other cardiomyopathies [non-ischemic cardiomyopathy] [Arrhythmogenic right ventricular cardiomyopathy (ARVC)][suspected tachycardia-mediated cardiomyopathy]
I44.30 - I44.7
I45.0 - I45.4		 Bundle branch block
I45.6 Pre-excitation syndrome [Wolff-Parkinson-White syndrome]
I45.89 Other specified conduction disorders
I47.0, I47.20, I47.21, I47.29 Paroxysmal ventricular tachycardia, [unstable, rapid, multiple or polymorphic that cannot be localized by mapping - not covered] [benign non-sustained that does not cause symptoms - not covered][Other ventricular tachycardia [sustained monomorphic VT and polymorphic VT]]
I47.19 Other supraventricular tachycardia
I48.0 Paroxysmal atrial fibrillation
I48.11 - I48.19 Persistent atrial fibrillation
I48.20 – I48.21 Chronic atrial fibrillation
I48.3, I48.4, I48.92 Atrial flutter
I49.01 Ventricular fibrillation [recurrent episodes of idiopathic VF]
I49.3 Ventricular premature depolarization
I49.8 - I49.9 Other specified and unspecified cardiac arrhythmias [focal and multifocal atrial tachycardia]
I50.20 – I50.23 Systolic (congestive) heart failure
I50.30 – I50.33 Diastolic (congestive) heart failure
I97.710 - I97.711
I97.790 - I97.791
I97.88 - I97.89		 Intraoperative cardiac functional disturbances and postprocedural cardiac complications and disorders
Z86.74 Personal history of sudden cardiac arrest
Z95.810 Presence of automatic (implantable) cardiac defibrillator

ICD-10 codes not covered for indications listed in the CPB:
G90.A Postural orthostatic tachycardia syndrome [POTS]
I42.1 Obstructive hypertrophic cardiomyopathy
R00.0 Tachycardia, unspecified
R55 Syncope and collapse

Alcohol ablation of vein of Marshall:

CPT codes not covered for indications listed in the CPB:
93583 Percutaneous transcatheter septal reduction therapy (eg, alcohol septal ablation) including temporary pacemaker insertion when performed

ICD-10 codes not covered for indications listed in the CPB:
I48.0 Paroxysmal atrial fibrillation
I48.11 - I48.19 Persistent atrial fibrillation
I48.3 Typical atrial flutter [peri-mitral flutter]
I48.4 Atypical atrial flutter [peri-mitral flutter]

Background

Catheter ablation is a therapeutic technique using a tripolar electrode catheter to eliminate conduction defects, which cause tachycardia.  This technique involves a high level of current, which is channeled through a catheter to destroy the arrhythmic area of the heart.  It treats supraventricular tachycardia by ablating or modulating the atrioventricular (AV) node or ablating accessory conduction pathways; it treats ventricular tachycardia by ablating the arrhythmogenic focus (as an alternative to open heart surgical techniques).  Catheter ablation is an acceptable alternative to long-term drug therapy.  The role of catheter ablation as primary therapy for several arrhythmias has been described in position papers or technology assessments by the American Medical Association, the American College of Cardiology, and the North American Society of Pacing and Electrophysiology.

Bradley and Shen (2007) stated that non-randomized studies suggested that AV junction ablation and pacemaker implantation may improve quality of life, ejection fraction, and exercise tolerance in patients with symptomatic drug-refractory atrial fibrillation.  These researchers examined if recent randomized trials support the use of AV junction ablation in combination with conventional right ventricular pacemaker therapy or cardiac resynchronization therapy (CRT) in atrial fibrillation.  They performed a meta-analysis of randomized trials comparing AV junction ablation versus drugs or CRT versus right ventricular pacing for atrial fibrillation.  Six randomized trials with 323 patients compared AV junction ablation versus pharmacotherapy were included.  The majority of these trials did not individually report a statistically significant improvement in survival, stroke, hospitalization, functional class, atrial fibrillation-associated symptoms, left ventricular ejection fraction, exercise capacity, healthcare costs, or quality of life.  Overall, all-cause mortality was 3.5 % for AV junction ablation patients and 3.3 % for controls (relative risk [RR] 1.18, 99 % confidence interval [CI]: 0.26 to 5.22).  Three randomized trials with 347 patients compared CRT versus right ventricular pacing in atrial fibrillation.  These trials did not individually report a statistically significant improvement in survival, stroke, hospitalization, exercise capacity, or healthcare costs.  Cardiac resynchronization therapy was associated with a statistically significant improvement in ejection fraction in 2 of the 3 trials.  Overall, CRT was associated with a trend toward reduced all-cause mortality relative to controls (relative risk 0.51, 99 % CI: 0.22 to 1.16).  All-cause mortality was 7.1 % for CRT patients and 14 % for controls.  The authors concluded that limited randomized trial data have been published regarding AV junction ablation in combination with conventional pacemaker therapy or CRT for atrial fibrillation.  They stated that large-scale randomized trials are needed to assess the effectiveness of these therapies.

Khan and associates (2008) stated that pulmonary-vein (PV) isolation (ablation) is increasingly being used to treat atrial fibrillation in patients with heart failure.  In this prospective, multi-center clinical trial, these investigators randomly assigned patients with symptomatic, drug-resistant atrial fibrillation, an ejection fraction of 40 % or less, and New York Heart Association (NYHA) class II or III heart failure to undergo either PV isolation or AV-node ablation with biventricular pacing.  All patients completed the Minnesota Living with Heart Failure questionnaire (scores range of 0 to 105, with a higher score indicating a worse quality of life) and underwent echocardiography and a 6-min walk test (the composite primary end point).  Over a 6-month period, patients were monitored for both symptomatic and asymptomatic episodes of atrial fibrillation.  A total of 41 patients underwent PV isolation, and 40 underwent AV-node ablation with bi-ventricular pacing; none was lost to follow-up at 6 months.  The composite primary end point favored the group that underwent PV isolation, with an improved questionnaire score at 6 months (60 versus 82 in the group that underwent AV-node ablation with bi-ventricular pacing; p < 0.001), a longer 6-min walk test (340 m versus 297 m, p < 0.001), and a higher ejection fraction (35 % versus 28 %, p < 0.001).  In the group that underwent PV isolation, 88 % of patients receiving anti-arrhythmic drugs (AADs) and 71 % of those not receiving such drugs were free of atrial fibrillation at 6 months.  In the group that underwent PV isolation, PV stenosis developed in 2 patients, peri-cardial effusion in 1, and pulmonary edema in another; in the group that underwent AV-node ablation with biventricular pacing, lead dislodgment was found in 1 patient and pneumothorax in another.  The authors concluded that PV isolation was superior to AV-node ablation with bi-ventricular pacing in patients with heart failure who had drug-refractory atrial fibrillation.

Rottlaender et al (2009) stated that cryo-thermal ablation is a new method in cardiac electrophysiology for the percutaneous catheter ablation of cardiac arrhythmias.  Cryo-thermal mapping allows functional evaluation of a particular site prior to ablation.  Thus, the targeted tissue may be confirmed as safe for ablation.  This approach is useful in high-risk ablations (e.g., next to the AV node).  In cryo-thermal ablation, pressurized liquid nitrogen is delivered to the tip of the ablation catheter; cooling of the tip is temperature-controlled.  Cryo-thermal balloons are also available, in addition to standard cryo-thermal catheters, for the isolation of pulmonary veins.  The tissue freezing provides high catheter stability.  Cryo-thermal lesions have a similar depth to radiofrequency energy, but area and volume of the lesions are reduced.  Furthermore, they are well demarcated and the incidence of thrombus-formation is reduced.  Cryo-thermal ablation has been evaluated for the treatment of AVNRT, accessory pathways, atrial flutter, atrial fibrillation and ventricular tachycardia (VT) originating in the right ventricular outflow tract.  Current experience indicates that the method safe and painless.  However, its use seems to be limited by a longer ablation time and lower efficacy.  The authors stated that further studies evaluating long-term success of cryo-thermal ablation are needed.  For high-risk ablations, cryo-thermal energy is helpful and should be used for para-Hisian accessory pathways and difficult cases of AVNRT.  It has a widely demonstrated safety profile.  The clinical efficacy will have to be evaluated in further studies.

Furthermore, in a review on new technologies in atrial fibrillation ablation, Burkhardt and Natale (2009) stated that cryoablation therapy may not be as durable as radiofrequency, as observed in some studies of supraventricular tachycardia ablation.  At this point, balloon-based ablation systems (cryoablation, laser, and high-frequency ultrasound) have not been proven to be as effective as current techniques and do not appear to save procedure time.

Computer-based electro-anatomical mapping systems are able to reconstruct cardiac anatomy and provide a straight-forward representation of chamber activation.  These systems capture and display details of intra-cardiac physiology and mark the site of interventions.  Currently, several mapping technologies are available in the electro-physiological laboratories (e.g., the CARTO system, and the EnSite 3000).  Electro-anatomic mapping systems combine 3 important functionalities:
  1. non-fluoroscopic localization of electro-physiological catheters in three-dimensional (3-D) space;
  2. analysis and 3-D display of activation sequences computed from local or calculated electrograms, and 3-D display of electrogram voltage ("scar tissue"); and
  3. integration of this "electro-anatomic" information with non-invasive images of the heart (mainly computed tomography or magnetic resonance images). 

Although better understanding and ablation of complex arrhythmias mostly relies on the 3-D integration of catheter localization and electrogram-based information to illustrate re-entrant circuits or areas of focal initiation of arrhythmias, the use of electro-anatomic mapping systems in atrial fibrillation is currently based on integration of anatomic images of the left atrium and non-fluoroscopic visualization of the ablation catheter.  Their use in the treatment of atrial fibrillation is mainly driven by safety considerations such as shorter fluoroscopy and procedure times, or visualization of cardiac (pulmonary veins) and extra-cardiac (esophagus) structures that need to be protected during the procedure (Knackstedt et al, 2008).

Liu and colleagues (2005) evaluated the characteristics of the CARTO system and the Ensite/NavX system and compared them on the aspects of procedural parameters and clinical effectiveness.  A total of 75 cases with paroxysmal or chronic symptomatic atrial fibrillation were randomly assigned to circumferential pulmonary vein ablation (CPVA) procedure guided by the Ensite/NavX system (group I, n = 40) and by the CARTO system (group II, n = 35).  After successful trans-septal procedure, the geometry of left atrium was created under the guidance of the 2 systems.  Radiofrequency energy was applied to circumferentially ablate tissues out of pulmonary veins' (PVs') ostia.  In cases with chronic atrial fibrillation, linear ablation was applied to modify the substrate of left atrium (LA).  The endpoint of the procedure was complete PVs isolation.  Seventy-five cases underwent the procedure successfully.  The total procedure and fluoroscopic durations in group II were significantly shorter than in group I [(150 +/- 23) mins and (18 +/- 17) mins versus (170 +/- 34) mins and (25 +/- 16) mins, p = 0.03 and 0.04, respectively].  There was no significant difference in the fluoroscopic and procedure durations for geometry creation between group I and group II [(8 +/- 4) mins and (16 +/- 11) mins versus (5 +/- 4) mins and (14 +/- 8) mins, respectively].  The fluoroscopic durations for CPVA were (15 +/- 5) mins in group I versus (10 +/- 6) mins in group II (p = 0.05), and the CPVA procedural durations were significantly shorter in group II than in group I [(18 +/- 11) mins versus (25 +/- 10) mins, p = 0.04].  Atrial fibrillation was terminated by radiofrequency delivery in 14 cases (35 %) in group I versus 5 cases (14 %) in group II (p = 0.035).  After CPVA, complete PV isolation was attained in 26 cases (65 %) in group I versus 11 cases (31 %) in group II (p = 0.004).  During a mean follow-up of 7 months, 32 (80 %) cases in group I and 24 (69 %) cases in group II were arrhythmia-free (p = 0.06).  One case developed pericardium effusion and another case was found to have intestinal artery thrombosis in group II.  One case had moderate hemothorax in group I.  All the complications were cured by proper treatment.  No PV stenosis was observed.  The authors concluded that the CPVA procedure for atrial fibrillation is safe and effective.  Although there is difference between the CARTO system and the Ensite/NavX system, the CPVA procedure guided by either of them yields similar clinical results.

Suleiman et al (2007) reported the early and late outcome in patients with different arrhythmias treated with radiofrequency ablation combined with the CARTO mapping and navigation system.  The study cohort comprised 125 consecutive patients with different cardiac arrhythmias referred for mapping and/or ablation procedures using the CARTO system.  Forty patients (32 %) had previous failed conventional ablation or mapping procedures and were referred by other centers.  The arrhythmia included atrial fibrillation (n = 13), atrial flutter (n = 38), atrial tachycardia (n = 25), ventricular tachycardia (n = 24), arrhythmogenic right ventricular dysplasia (n = 9), and supra-ventricular tachycardia (n = 16).  During the study period, a total of 125 patients (mean age of 49 +/- 19 years, 59 % males) underwent electro-physiological study and electro-anatomic mapping of the heart chambers.  Supra-ventricular arrhythmias were identified in 92 patients (73 %) and ventricular arrhythmias in 33 (27 %).  Acute and late success rates, defined as termination of the arrhythmia without anti-arrhythmic drugs, were 87 % and 76 % respectively.  One patient (0.8 %) developed a clinically significant complication.  The authors concluded that the CARTO system increased the safety, efficacy and efficiency of radiofrequency ablation.

Hindricks et al (2009) stated that radiofrequency catheter ablation of typical atrial flutter is one of the most frequent indications for catheter ablation in electrophysiology laboratories today.  Clinical utility of electro-anatomic mapping systems on treatment results and resource utilization compared with conventional ablation has not been systematically investigated in a prospective multi-center study.  In this prospective, randomized multi-center study, the findings of catheter ablation to cure typical atrial flutter using conventional ablation strategy were compared with electro-anatomically guided mapping and ablation (using the CARTO system).  Primary endpoints of the study were procedure duration and fluoroscopy exposure time, secondary endpoints were acute success rate, recurrence rate, and resource utilization.  A total of 210 patients (169 men, 41 women, mean age of 63 +/- 10 years) with documented typical atrial flutter were included in the study.  Acute ablation success, that is, demonstration of bi-directional isthmus block, was achieved in 99 of 105 patients (94 %) in the electro-anatomically guided ablation group and in 102 of 105 patients (97 %) in the conventional ablation group (p > 0.05).  Total procedure duration was comparable between both study groups (99 +/- 57 mins versus 88 +/- 54 mins, p > 0.05).  Fluoroscopy exposure time was significantly shorter in the electro-anatomically guided ablation group (7.7 +/- 7.3 mins versus 14.8 +/- 11.9 mins; p < 0.05).  Total recurrence rate of typical atrial flutter at 6 months of follow-up was comparable between the 2 groups (respectively for the CARTO and conventional group 6.6 % versus 5.7 %, p > 0.05).  The material costs per procedure in the electro-anatomically guided and conventional groups (NaviStar DS versus Celsius DS) was 3035 Euro (USD 3,870) and 2133 Euro (USD 2,720), respectively.  The authors concluded that this multi-center study documented that cavotricuspid isthmus ablation to cure typical atrial flutter was highly effective and safe, both in the conventional and the electro-anatomically guided ablation group.  The use of electro-anatomical mapping system significantly reduced the fluoroscopy exposure time by almost 50 %, however, at the expense of increased cost of the procedure.

Suleiman et al (2007) noted that catheter ablation is assuming a larger role in the management of patients with cardiac arrhythmias.  Conventional fluoroscopic catheter mapping has limited spatial resolution and involves prolonged fluoroscopy.  The non-fluoroscopic electro-anatomic mapping technique (CARTO) has been developed to overcome these drawbacks.  These researchers reported the early and late outcome in patients with different arrhythmias treated with radiofrequency ablation combined with the CARTO mapping and navigation system.  The study cohort comprised 125 consecutive patients with different cardiac arrhythmias referred to our center from January 1999 to July 2005 for mapping and/or ablation procedures using the CARTO system.  Forty patients (32 %) had previous failed conventional ablation or mapping procedures and were referred by other centers.  The arrhythmia included atrial fibrillation (n = 13), atrial flutter (n = 38), atrial tachycardia (n = 25), ventricular tachycardia (n = 24), arrhythmogenic right ventricular dysplasia (n = 9), and supraventricular tachycardia (n = 16).  During the study period, a total of 125 patients (mean age of 49 +/- 19 years, 59 % males) underwent electrophysiological study and electro-anatomic mapping of the heart chambers.  Supraventricular arrhythmias were identified in 92 patients (73 %) and ventricular arrhythmias in 33 (27%).  Acute and late success rates, defined as termination of the arrhythmia without anti-arrhythmic drugs, were 87 % and 76 % respectively.  One patient (0.8 %) developed a clinically significant complication.  The authors concluded that the CARTO system advances the understanding of arrhythmias, and increases the safety, efficacy and efficiency of radiofrequency ablation.

Colín Lizalde Lde (2007) stated that in 1992 the radiofrequency ablation program was started, with very good results in patients with supraventricular tachycardias and normal hearts or minimal structural defects.  Nevertheless, the results are not as good for the patients with structural defects, which are actually seen more frequently, those are cases with more complex arrhythmias, are patients with cardiac surgery that show a complex arrhythmogenic substrate or patients previously treated with conventional ablation which tachycardia recurs.  In these cases, the electro-anatomic CARTO system has been very useful.  In the last 2 years, 74 procedures with the CARTO system were performed, of which 56 have been supraventricular arrhythmias, improving substantially the success rates.  The authors concluded that the electro-anatomical mapping allowed the more accurate identification of the arrhythmogenic substrate, achieving better success rates in recurrent tachycardia after conventional ablation, or in cases with more complex arrhythmogenic substrates.

Wu et al (2013) examined acute and long-term outcome after catheter ablation of supraventricular tachycardia in patients after the Mustard or Senning operation for D-transposition of the great arteries.  This single-center retrospective analysis included 26 patients (mean age of 28.7 ± 6.7 years, 8 females) after Mustard (n = 15) or Senning (n = 11) operation who underwent catheter ablation for intra-atrial re-entrant tachycardia (IART) or AV nodal re-entrant tachycardia (AVNRT) from January 2004 to May 2011.  The electrophysiological studies were performed using a 3-D mapping system (CARTO).  Remote magnetic navigation (RMN) was available since 2008.  Follow-up on an out-patient basis was conducted 3, 6, and 12 months after ablation and yearly thereafter.  In the 26 patients, 34 procedures were performed (1 procedure n = 19; 2 procedures, n = 6; and 3 procedures, n = 1).  Overall, 34 tachycardia forms (IART n = 30; AVNRT n = 4) were ablated manually (n = 25) or by RMN (n = 9).  Acute success reached in 29/34 forms (85.3 %).  Mean fluoroscopy time (FT) was 28.2 ± 20.7 mins and mean procedure duration (PD) was 290.9 ± 107.6 mins.  After a mean follow-up of 34.1 ± 24.5 months, 25/26 (96.2 %) patients were free from IART or AVNRT.  In the 9 RMN ablations (mean follow-up of 14.2 ± 5.8 months) acute and long-term success was 100 %.  Fluoroscopy time and PD were significantly reduced using RMN compared with manual ablation (11.9 ± 6.2 versus 34.6 ± 20.6 mins, 225.7 ± 24.1 versus 312 ± 118.2 mins, p = 0.02).  The authors concluded that catheter ablation of IART or AVNRT in patients post-Mustard/Senning operation for D-transposition of the great arteries (d-TGA) has a high acute success rate.  The recurrence rate for IART is about 30 %; however, after a second ablation, long-term results are excellent.  They stated that remote magnetic navigation seems to improve single-procedure acute and long-term success and significantly reduces FT and PD.

Svintsova et al (2013) stated that the use of radiofrequency ablation (RFA) for the management of supraventricular tachycardia (SVT) in infants and small children remains controversial.  The aim of this study was to evaluate the safety and efficacy of RFA in critically ill small children (less than 1 year of age) with drug-resistant tachycardia accompanied by arrhythmogenic cardiomyopathy and heart failure.  The study included 15 patients age 5.3 ± 3.7 months.  Wolff-Parkinson-White syndrome and atrial tachycardia were detected in 8 (53.3 %) and 7 (46.7 %) of patients, respectively.  Patients with structural heart pathology, including congenital heart diseases and laboratory-confirmed myocarditis, were excluded from the study.  Indications for RFA included drug-refractory SVT accompanied by arrhythmogenic cardiomyopathy and heart failure.  Unsuccessful ablation was observed in 2 1-month-old patients who underwent successful ablation 3 months later.  The follow-up period ranged from 0.5 to 8 years (average of 3.9 years). Only 1 patient (6.7 %) had tachycardia recurrence 1 month after RFA.  The short- and long-term RFA success rates were 86.7 and 93.3 %, respectively.  The study did not show any procedure-related complications.  Heart failure disappeared within 5 to 7 days.  Complete normalization of heart chamber sizes was documented within 1 month after effective RFA.  A 3-D CARTO system (Biosense Webster, Inc.,) was used in 3 patients with body weight greater than 7 kg.  The use of the CARTO system resulted in a remarkable decrease of the fluoroscopy time without vascular injury or other procedure-related complications in all cases.  The authors concluded these findings suggested that RFA may be considered the method of choice for SVT treatment in small children when drug therapy is ineffective and arrhythmogenic cardiomyopathy progresses.

Spar et al (2013) noted that traditional imaging for ablation of supraventricular tachycardia has been fluoroscopy, although 3-D electro-anatomic mapping (3D) has been demonstrated to reduce radiation exposure.  This study compared a technique for the reduction of radiation, low-dose fluoroscopy (LD), with standard-dose fluoroscopy (SD) and 3D with SD (3D-SD).  This was a single institutional retrospective cohort study.  All patients undergoing initial ablation for AV reentrant tachycardia (AVRT) or AV nodal reentrant tachycardia (AVNRT) from 2009 to 2012 were reviewed and divided into 3 groups:
  1. SD,
  2. 3D (CARTO or NavX) with SD, or
  3. LD. 

LD uses the same equipment as SD but included customized changes to the manufacturer's lowest settings by decreasing the requested dose to the detector.  Primary outcomes were fluoroscopy time and dose area product exposure.  A total of 181 patients were included.  The median age was 15.0 years (3.3 to 20.8); 59 % had AVRT, 35 % had AVNRT, and 6 % had both AVRT and AVNRT.  LD decreased the dose area product (DAP) compared with SD (637.0 versus 960.1 cGy*cm², p = 0.01) with no difference in fluoroscopy time.  3D-SD decreased fluoroscopy time compared with SD (9.9 versus 18.3 minutes, p < 0.001) with DAP of 570.1.0 versus 960.1 cGy*cm² (p = 0.16).  LD and 3D-SD had comparable DAP (637.0 versus 570.1 cGy*cm², p = 0.67), even though LD had significantly longer fluoroscopy time (19.9 versus 9.9 minutes, p < 0.001).  The authors concluded that LD during catheter ablation of AVRT and AVNRT significantly reduced the DAP compared with SD and had similar radiation exposure compared with 3D with SD.

Pass et al (2015) noted that “ALARA - As Low As Reasonably Achievable" protocols reduce patient radiation dose.  Addition of electro-anatomical mapping may further reduce dose.  From 6/11 to 4/12, a novel ALARA protocol was utilized for all patients undergoing supraventricular tachycardia ablation, including low frame rates (2 to 3 frames/second), low fluoro dose/frame (6 to 18 nGy/frame), and other techniques to reduce fluoroscopy (ALARA).  From 6/12 to 3/13, use of CARTO® 3 (C3) with "fast anatomical mapping" (ALARA+C3) was added to the ALARA protocol.  Intra-vascular echo was not utilized.  Demographics, procedural, and radiation data were analyzed and compared between the 2 protocols.  A total of 75 patients were included: 42 ALARA patients, and 33 ALARA+C3 patients.  Patient demographics were similar between the 2 groups.  The acute success rate in ALARA was 95 %, and 100 % in ALARA + C3; no catheterization-related complications were observed.  Procedural time was 125.7 minutes in the ALARA group versus 131.4 in ALARA+C3 (p = 0.36).  Radiation doses were significantly lower in the ALARA + C3 group with a mean air Kerma in ALARA + C3 of 13.1 ± 28.3 mGy (SD) compared with 93.8 ± 112 mGy in ALARA (p < 0.001).  Mean dose area product was 92.2 ± 179 uGym2 in ALARA + C3 compared with 584 ± 687 uGym2 in ALARA (p < 0.001).  Of the 33 subjects (42 %) in the ALARA + C3 group, 14 received less than or equal to 1 mGy exposure.  The ALARA + C3 dosages are the lowest reported for a combined electro-anatomical-fluoroscopy technique.  The authors concluded that addition of CARTO® 3 to ALARA protocols markedly reduced radiation exposure to young people undergoing supraventricular tachycardia ablation while allowing for equivalent procedural efficacy and safety.

American College of Cardiology guidelines on ventricular arrhythmias and sudden cardiac death (Zipes, et al., 2006) state that 3-dimensional mapping systems permit anatomical reconstructions and correlation of EP characteristics with anatomy. These systems have led to an approach whereby circuits can be mapped during sinus rhythm and can facilitate ablation in the ischemic patient who often does not tolerate VT well. Use of these techniques may result in better long-term success rates. American College of Cardiology guidelines on supraventricular arrhythmias (Blomstrom-Lundqvist et al, 2003) state that, in patients with prior surgical repair, both CTI-dependent and non–CTI-dependent (so-called “incisional” or scar) atrial flutter occur and can coexist in a single patient. If catheter ablation is warranted… ablation may be best performed in an experienced center with advanced, three-dimensional mapping equipment for defining non-CTI- dependent arrhythmias. Heart Rhythm Society guidelines on atrial fibrillation (Calkins et al, 2012) state that it is well known that mapping and ablation of atrial fibrillation (AF) require accurate navigation in the LA. This can be obtained using standard fluoroscopy or more commonly with electroanatomic mapping systems that combine anatomic and electrical information by a catheter point-by-point mapping, allowing an accurate anatomic reconstruction of a 3D shell of the targeted cardiac chamber. The use of these 3D mapping systems has been demonstrated to reduce fluoroscopy duration.

Lawrenz and colleagues (2011) examined the safety and effectiveness of endocardial radiofrequency ablation of septal hypertrophy (ERASH) for left ventricular outflow tract (LVOT) gradient reduction in hypertrophic obstructive cardiomyopathy (HOCM).  A total of 19 patients with HOCM were enrolled; in 9 patients, the left ventricular septum was ablated, and in 10 patients, the right ventricular septum was ablated.  Follow-up examinations (echocardiography, 6-min walk test, bicycle ergometry) were performed 3 days and 6 months after ERASH.  After 31.2 +/- 10 radiofrequency pulses, a significant and sustained LVOT gradient reduction could be achieved (62 % reduction of resting gradients and 60 % reduction of provoked gradients, p = 0.0001).  The 6-min walking distance increased significantly from 412.9 +/- 129 m to 471.2 +/- 139 m after 6 months, p = 0.019); and New York Heart Association functional class was improved from 3.0 +/- 0.0 to 1.6 +/- 0.7 (p = 0.0001).  Complete AV block requiring permanent pacemaker implantation occurred in 4 patients (21 %); 1 patient had cardiac tamponade.  The authors concluded that ERASH is a new therapeutic option in the treatment of HOCM, allowing significant and sustained reduction of the LVOT gradient as well as symptomatic improvement with acceptable safety by inducing a discrete septal contraction disorder.  They stated that ERASH may be suitable for patients not amenable to trans-coronary ablation of septal hypertrophy or myectomy.  The drawbacks of this study included the lack of a control group, small sample size and short-term follow-up.  These findings need to be validated by more research.

Sreeram et al (2011) evaluated the effectiveness of radiofrequency catheter ablation (RFCA) in the treatment of HOCM in children.  In 32 children, at a median age of 11.1 (range of 2.9 to 17.5) years and weight of 31 (15 to 68) kg, ablation of the hypertrophied septum was performed using a cool-tip ablation catheter via a femoral arterial approach.  The median number of lesions was 27 (10 to 63) and fluoroscopic time was 24 (12 to 60) mins.  The majority of patients showed an immediate decrease in the catheter pullback gradient (mean 78.5 +/- 26.2 mm Hg pre-RFCA versus mean 36.1 +/- 16.5 mm Hg post-RFCA, p < 0.01) and a further reduction in the Doppler echocardiographic gradient (mean 96.9 +/- 27.0 mm Hg pre-RFCA versus 32.7 +/- 27.1 mm Hg post-RFCA, p < 0.01) at follow-up.  One patient died due to a paradoxical increase in left ventricular outflow tract obstruction, and another had persistent AV block that required permanent pacing.  Six patients required further procedures (surgery, pacing, or further RFCA) during a median follow-up of 48 (3 to 144) months.  The authors concluded that these preliminary findings of RFCA for septal reduction in children with hypertrophic cardiomyopathy are promising and merit further evaluation.

McLellan et al (2013) noted that pulmonary vein reconnection is a major limitation of pulmonary vein isolation (PVI) for symptomatic AF.  Adenosine (ADO) may unmask dormant PV conduction and facilitate consolidation of PV isolation.  These investigators performed a systematic review of the literature to determine the impact of routine ADO administration on clinical outcomes in patients undergoing PVI.  References and electronic databases reporting AF ablation and ADO following PVI were searched through to July 31, 2012.  A total of 6 studies included 544 patients to assess the impact of catheter ablation to target ADO-induced PV reconnection on AF ablation outcome and 3 studies included 612 patients to assess the impact of ADO testing on AF ablation outcome.  Relative risks were calculated and combined in a meta-analysis using random effects modeling.  Routine ADO testing for PV reconnection with additional targeted ablation resulted in a significant increase in freedom from AF post-PVI (risk ration [RR] 1.25; 95 % CI: 1.12 to 1.40; p < 0.001).  However, within the group of patients undergoing ADO testing, those with reconnection identified a population with a trend to reduction in freedom from AF despite the use of further targeted ablation in the reconnection group (RR 0.91 with 95 % CI: 0.81 to 1.03; p = 0.15).  The authors concluded that routine ADO testing is associated with an improvement in freedom from AF post-PVI.  Paradoxically acute ADO-induced PV reconnection may portend a greater likelihood of AF recurrence despite additional ablation.  The authors stated that randomized controlled trials (RCTs) are needed to determine the role of ADO testing post-PVI.

Macle et al (2012) stated that PVI has emerged as an effective therapy for paroxysmal AF.  However, AF recurs in up to 50 % of patients, generally because of recovery of PV conduction.  Adenosine given during the initial procedure may reveal dormant PV conduction, thereby identifying the need for additional ablation, leading to improved outcomes.  The Adenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination (ADVICE) study is a prospective multi-center RCT assessing the impact of ADO-guided PVI in preventing AF recurrences.  Patients undergoing a first PVI procedure for paroxysmal AF will be recruited.  After standard PVI is completed, all patients will receive intravenous ADO in an attempt to unmask dormant conduction.  If dormant conduction is elicited, patients will be randomized to no further ablation (control group) or additional ADO-guided ablation until dormant conduction is abolished.  If no dormant conduction is revealed, randomly selected patients will be followed in a registry.  The primary outcome is time to first documented symptomatic AF recurrence.  Assuming that dormant conduction is present in 50 % of patients post-PVI and symptomatic AF recurs in 45 % of controls, 244 patients with dormant conduction will be needed to obtain greater than 90 % power to detect a difference of 20 %.  Thus, a total of 488 patients will be enrolled and followed for 12 months.  The authors concluded that the ADVICE trial will examine if a PVI strategy incorporating elimination of dormant conduction unmasked by intravenous ADO will decrease the rate of recurrent symptomatic AF compared with standard PVI.

Cheung et al (2013) noted that ADO can unmask dormant pulmonary vein conduction following PVI.  Adenosine can also induce ectopy in electrically silent PVs following isolation, possibly via activation of autonomic triggers.  These researchers sought to identify the implications of ADO-induced PV ectopy for AF recurrence following PVI.  A total of 152 patients (age of 60 ± 11 years; 63 % paroxysmal AF) undergoing PVI for AF were studied.  After each PV was isolated, ADO was administered and the presence of ADO-induced PV reconnection and PV ectopy were recorded.  Dormant conduction was targeted with additional ablation.  Adenosine-induced PV ectopy was seen in 45 (30 %) patients and dormant conduction was seen in 44 (29 %) patients.  After a median follow-up of 374 days, 48 (32 %) patients had recurrent AF after a single ablation procedure.  Rates of freedom from AF among patients with ADO-induced PV ectopy were significantly lower than patients without ADO-induced PV ectopy (63 % versus 76 % at 1 year; log rank = 0.014).  Rates of freedom from AF among patients with dormant conduction were also lower than patients without dormant conduction (64 % versus 76 % at 1 year; log rank = 0.062).  With multi-variate analysis, ADO-induced PV ectopy was found to be the only independent predictor of AF after PVI (HR 1.90; 95 % CI: 1.06 to 3.40; p = 0.032).  The authors concluded that ADO-induced PV ectopy is a predictor of recurrent AF following PVI and may be a marker of increased susceptibility to autonomic triggers of AF.

Morales et al (2013) examined if dormant conduction across the cavo-tricuspid isthmus (CTI) may be revealed by ADO after ablation-induced bi-directional block, and its association with recurrent flutter.  Patients undergoing catheter ablation for CTI-dependent flutter were prospectively studied.  After confirming bi-directional block across the CTI by standard pacing maneuvers, ADO (greater than or equal to 12 mg IV) was administered to assess resumption of conduction, followed by isoproterenol (ISP) bolus.  Further CTI ablation was performed for persistent (but not transient) resumption of conduction.  Bi-directional block across the CTI was achieved in all 81 patients (63 males), age of 61.2 ± 11.0 years.  The trans-CTI time increased from 71.9 ± 18.1 milliseconds pre-ablation to 166.2 ± 26.4 milliseconds post=ablation.  Adenosine elicited resumption of conduction across the CTI in 7 patients (8.6 %), 2 of whom had transient recovery.  No additional patient with dormant conduction was identified by ISP.  Over a follow-up of 11.8 ± 8.0 months, atrial flutter recurred in 4 (4.9 %) patients, 3/7 (42.9 %) with a positive ADO challenge versus 1/74 (1.3 %) with a negative response, p = 0.0016 (relative risk: 31.7).  The authors concluded that ADO challenge following atrial flutter ablation provoked transient or persistent resumption of conduction across the CTI in almost 9 % of patients and identified a subgroup at higher risk of flutter recurrence.  Moreover, they state that it remains to be determined whether additional ablation guided by ADO testing during the index procedure may further improve procedural outcomes.

Sapp and colleagues (2013) stated that ablation of VT is sometimes unsuccessful when ablation lesions are of insufficient depth to reach arrhythmogenic substrate.  These researchers reported the initial experience with the use of a catheter with an extendable/retractable irrigated needle at the tip capable of intra-myocardial mapping and ablation.  Sequential consenting patients with recurrent VT underwent ablation with the use of a needle-tipped catheter.  At target sites, the needle was advanced 7 to 9 mm into the myocardium, permitting pacing and recording.  Infusion of saline/iodinated contrast mixture excluded perforation and ensured intra-myocardial deployment.  Further infusion was delivered before and during temperature-controlled RF energy delivery through the needle.  All 8 patients included (6 males; mean age of 54 years) with a mean left ventricular ejection fraction of 29 % were refractory to multiple anti-arrhythmic drugs, and 1 to 4 previous catheter ablation attempts (epicardial in 4) had failed.  Patients had 1 to 7 (median of 2) VTs present or inducible; 2 were incessant.  Some intra-myocardial VT mapping was possible in 7 patients.  A mean of 22 (limits of 3 to 48) needle ablation lesions were applied in 8 patients.  All patients had at least 1 VT terminated or rendered non-inducible.  During a median of 12 months follow-up, 4 patients were free of recurrent VT, and 3 patients were improved, but had new VTs occur at some point during follow-up.  Two died of the progression of pre-existing heart failure without recurrent VT.  Complications included tamponade in 1 patient and heart block in 2 patients.  The authors concluded that intra-myocardial infusion-needle catheter ablation is feasible and permits control of some VTs that have been refractory to conventional catheter ablation therapy, warranting further study.

Asakai et al (2015) noted that since the introduction of transcatheter ablation in the late 1980s, there has been significant technical development.  With a very high success rate and low complication rate, ablation has now become the standard of care in children and adults.  However, long-term data remain insufficient and the application of ablation therapy in small children is debatable.  These investigators reviewed current treatment strategies and results in toddlers and infants.  There has been improvement in success rate and complication rate for ablation in small children.  The authors concluded that technological advancements in non-fluoroscopic electro-anatomical mapping systems (3D systems) have led to the reduction of radiation and have facilitated ablations in complex cases; however, long-term effects of ablation lesions in small children remain a potential concern.

Hakalahti et al (2015) performed a systematic review and meta-analysis of the available data to r evaluate the safety and effectiveness of RFA versus AADs.  Five databases were searched for RCTs comparing RFA and AAD therapy as first-line treatment of AF in August 2014.  A total of 3 studies with 491 patients with recurrent symptomatic AF were included.  The patients were relatively young and the majority of them had paroxysmal AF (98.7 %) and no major co-morbidity.  Radiofrequency catheter ablation was associated with significantly higher freedom from AF recurrence compared with AAD therapy [RR 0.63, 95 % CI: 0.44 to 0.92, p = 0.02].  The difference in the rate of symptomatic AF recurrences was not statistically significant (RR 0.57, 95 % CI: 0.30 to 1.08, p = 0.09).  There was 1 procedure-related death and 7 tamponades with RFA, whereas symptomatic bradycardia was more frequent with AAD therapy.  The authors concluded that RFA appeared to be more effective than medical therapy as first-line treatment of paroxysmal AF in relatively young and otherwise healthy patients, but may also cause more severe adverse effects.  They stated that these findings support the use of RFA as first-line therapy in selected patients, who understand the benefits and risks of the procedure.

Verma et al (2015) noted that catheter ablation is less successful for persistent atrial fibrillation than for paroxysmal atrial fibrillation.  Guidelines suggested that adjuvant substrate modification in addition to PVI is needed in persistent atrial fibrillation.  These researchers randomly assigned 589 patients with persistent AF in a 1:4:4 ratio to ablation with PVI alone (67 patients), PVI plus ablation of electrograms showing complex fractionated activity (263 patients), or PVI plus additional linear ablation across the left atrial roof and mitral valve isthmus (259 patients).  The duration of follow-up was 18 months.  The primary end-point was freedom from any documented recurrence of AF lasting longer than 30 seconds after a single ablation procedure.  Procedure time was significantly shorter for PVI alone than for the other 2 procedures (p < 0.001).  After 18 months, 59 % of patients assigned to PVI alone were free from recurrent AF, as compared with 49 % of patients assigned to PVI plus complex electrogram ablation and 46 % of patients assigned to PVI plus linear ablation (p = 0.15).  There were also no significant differences among the 3 groups for the secondary end-points, including freedom from AF after 2 ablation procedures and freedom from any atrial arrhythmia.  Complications included tamponade (3 patients), stroke or transient ischemic attack (3 patients), and atrio-esophageal fistula (1 patient).  The authors concluded that among patients with persistent AF, they found no reduction in the rate of recurrent AF when either linear ablation or ablation of complex fractionated electrograms was performed in addition to PVI.

Non-Invasive Cardiac Radio-Ablation for Cardiac Arrhythmias

Cuculich and colleagues (2017) stated that recent advances have enabled non-invasive mapping of cardiac arrhythmias with electrocardiographic imaging and non-invasive delivery of precise ablative radiation with stereotactic body radiation therapy (SBRT).  These investigators combined these techniques to perform catheter-free, electrophysiology-guided, non-invasive cardiac radio-ablation for VT.  They targeted arrhythmogenic scar regions by combining anatomical imaging with non-invasive electrocardiographic imaging during VT that was induced by means of an implantable cardioverter-defibrillator (ICD).  SBRT simulation, planning, and treatments were performed with the use of standard techniques.  Patients were treated with a single fraction of 25 Gy while awake.  Efficacy was assessed by counting episodes of VT, as recorded by ICDs.  Safety was assessed by means of serial cardiac and thoracic imaging.  From April through November 2015, a total of 5 patients with high-risk, refractory VT underwent treatment.  The mean non-invasive ablation time was 14 minutes (range of 11 to 18).  During the 3 months before treatment, the patients had a combined history of 6,577 episodes of VT. During a 6-week post-ablation "blanking period" (when arrhythmias may occur owing to post-ablation inflammation), there were 680 episodes of VT.  After the 6-week blanking period, there were 4 episodes of VT over the next 46 patient-months, for a reduction from baseline of 99.9 %.  A reduction in episodes of VT occurred in all 5 patients.  The mean left ventricular ejection fraction (LVEF) did not decrease with treatment.  At 3 months, adjacent lung showed opacities consistent with mild inflammatory changes, which had resolved by 1 year.  The authors concluded that in 5 patients with refractory VT, non-invasive treatment with electrophysiology-guided cardiac radio-ablation markedly reduced the burden of VT.  Moreover, they stated that because of the novelty of non-invasive radio-ablation, its potential for harm, as well as small number of patients in this study (n = 5), this approach should not be considered to be suitable for clinical use, pending the results of further investigation.  Furthermore, there are well-described late toxic effects of radiotherapy to the heart for large-field fractionated dose treatments, as has been reported in the treatment of lymphoma and breast cancer.  The potential late effects of high-dose SBRT exclusively to focal areas of previously injured heart are unknown.  The volumes of myocardium that were subjected to radiotherapy in these patients (from 17 to 81 ml) were large enough that effects on specialized cardiac structures (papillary muscles, coronary arteries, conduction system, and valves) are of potential concern, as is the risk of overall effects on ventricular function, although no such effects were observed during the 12-month follow-up period in the 4 surviving subjects in this study.  The risk of thromboembolism, as observed in patient 5, warrants cautious consideration.  These researchers have initiated a prospective, phase I/II clinical trial (ENCORE-VT) to evaluate the safety and efficacy of SBRT.

Zei and Soltys (2017) noted that stereotactic radio-ablation is a commonly utilized technology to non-invasively treat solid tumors with precision and efficacy.  Using a robotic arm mounted delivery system, multiple low-dose ionizing radiation beams are delivered from multiple angles, concentrating ablative energy at the target tissue.  Recently, this technology has been evaluated for treatment of cardiac arrhythmias.  These investigators presented the basic underlying principles, proof-of-principle studies, and clinical experience with stereotactic arrhythmia radio-ablation.  Most recently, stereotactic radio-ablation has been used to treat a limited number of patients with malignant arrhythmias, including VT and AF.  The authors concluded that given the early stage of evaluation of this technology, more investigation and clinical experience are needed.  They stated that current pre-clinical and clinical experiences have suggested early efficacy and safety; however, additional clinical data under properly designed clinical trials are needed.

Zei and colleagues (2018) noted that stereotactic radio-ablation (SR), a commonly used therapy to treat malignant tumors, has been used to treat refractory VT, but the feasibility of treating AF with SR is unknown.  These researchers evaluated the safety and efficacy of SR targeting PV antral tissues as a potential therapy for AF.  A total of 17 adult canines and 2 adult swine underwent surgical fiducial marker placement, 3-dimensional anatomic rendering computed tomography angiogram (CTA) of the left atrium, and creation of a treatment plan targeting the right superior PVs; 4 treatment doses (15, 20, 25, and 35 Gy) were administered to 4 cohorts.  Subjects were monitored for 3 to 6 months, followed by electrophysiological testing, gross pathological examination, and histopathology in 2 subjects.  All subjects received SR treatment without complication.  Electrophysiology study and gross pathological analysis demonstrated treatment effect in all treated PVs at 35 Gy and 25 Gy (n = 11 of 11 [100 %]), with a partial effect at 20 Gy (n = 4 of 5 [80 %]; 1 did not undergo repeat electrophysiology study) and 15 Gy (n = 1 of 2 [50 %]).  No evidence of collateral injury was found in tissues directly adjacent to the treated PVs.  In 2 subjects, detailed histopathology showed evidence of circumferential, transmural scar at the PV ablation sites, with sparing of the surrounding structures.  The authors concluded that SR is safe and effective for creating precise circumferential scar and electrical isolation of the right superior PV in an experimental model, with dose dependence between delivered radio-ablative energy and observed electrical effects.

Lydiard and associates (2018) noted that stereotactic arrhythmia radio-ablation (STAR) is an emerging treatment option for AF.  However, it faces possibly the most challenging motion compensation scenario: both respiratory and cardiac motion.  Multi-leaf collimator (MLC) tracking is clinically used for lung cancer treatments but its capabilities with intra-cardiac targets is unknown.  These investigators reported the 1st results of MLC tracking for intra-cardiac targets.  Five AF STAR plans of varying complexity were created.  All delivered 5  ×  10 Gy to both PV antra; 3 healthy human target motion trajectories were acquired with ultrasound (US) and programmed into a motion platform.  Plans were delivered with a linac to a dosimeter placed on the motion platform.  For each motion trace, each plan was delivered with no MLC tracking and with MLC tracking with and without motion prediction.  Dosimetric accuracy was assessed with γ-tests and dose metrics; MLC tracking improved the dosimetric accuracy in all measurements compared to non-tracking experiments.  The average 2 %/2 mm γ-failure rate was improved from 13.1 % with no MLC tracking to 5.9 % with MLC tracking (p  <  0.001) and 7.2 % with MLC tracking and no motion prediction (p  <  0.001).  MLC tracking significantly improved the consistency between planned and delivered target dose coverage.  The 95 % target coverage with the prescription dose (V100) was improved from 60 % of deliveries with no MLC tracking to 80 % of deliveries with MLC tracking (p  =  0.03).  MLC tracking was successfully implemented for the first time for intra-cardiac motion compensation.  MLC tracking provided significant dosimetric accuracy improvements in AF STAR experiments, even with challenging cardiac and respiratory-induced target motion and complex treatment plans.  The authors concluded that these results warrant further investigation and optimization of MLC tracking for intra-cardiac target motion compensation.

Robinson and colleagues (2019) noted that case studies have suggested the efficacy of catheter-free, electrophysiology-guided non-invasive cardiac radio-ablation for VT using stereotactic body radiation therapy, although prospective data are lacking.  These researchers carried out a prospective phase I/II clinical trial of non-invasive cardiac radio-ablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs).  Arrhythmogenic scar regions were targeted by combining non-invasive anatomic and electric cardiac imaging with a standard stereotactic body radiation therapy workflow followed by delivery of a single fraction of 25 Gy to the target.  The primary safety end-point was treatment-related serious adverse events (AEs) in the first 90 days.  The primary efficacy end-point was any reduction in VT episodes (tracked by indwelling implantable cardioverter defibrillators) or any reduction in PVC burden (as measured by a 24-hour Holter monitor) comparing the 6 months before and after treatment (with a 6-week blanking window after treatment).  Health-related quality of life (QOL) was assessed using the Short Form-36 (SF-36) questionnaire.  A total of 19 patients were enrolled (17 for VT, 2 for PVC cardiomyopathy).  Median non-invasive ablation time was 15.3 mins (range of 5.4 to 32.3). In the first 90 days, 2/19 patients (10.5 %) developed a treatment-related serious AE.  The median number of VT episodes was reduced from 119 (range of 4 to 292) to 3 (range of 0 to 31; p < 0.001).  Reduction was observed for both implantable cardioverter defibrillator shocks and anti-tachycardia pacing.  VT episodes or PVC burden were reduced in 17/18 evaluable patients (94 %). The frequency of VT episodes or PVC burden was reduced by 75 % in 89 % of patients.  Overall survival (OS) was 89 % at 6 months and 72 % at 12 months.  Use of dual anti-arrhythmic medications decreased from 59 % to 12 % (p = 0.008)’ QOL improved in 5 of 9 SF-36 domains at 6 months.  The authors concluded that non-invasive electrophysiology-guided cardiac radio-ablation was associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in anti-arrhythmic drug use, and improvement in QOL.

These researchers stated the findings of this phase I/II clinical trial support continued research into non-invasive cardiac radio-ablation, with a multi-institutional trial planned.  They noted that with limited numbers of patients (18 evaluable patients) and a lack of long-term safety and efficacy data, this treatment remains investigational.

Krug and associates (2020) noted that single-session cardiac stereotactic body radiotherapy, called cardiac radiosurgery (CRS) or radio-ablation (RA), may offer a potential therapeutic option for patients with refractory VT and electrical storm who are otherwise ineligible for catheter ablation.  However, there is only limited clinical experience.  These researchers presented the first-in-patient treatment using (CRS/RA) for VT in Germany.  A 78-year old man with dilated cardiomyopathy and significantly reduced EF (15 %) presented with monomorphic VT refractory to poly-anti-arrhythmic medication and causing multiple implantable cardioverter-defibrillator (ICD) interventions over the course of several weeks, necessitating prolonged treatment on an intensive care unit (ICU).  Ultra-high-resolution electro-anatomical voltage mapping (EVM) revealed a re-entry circuit in the cardiac septum inaccessible for catheter ablation.  Based on the EVM, CRS/RA with a single-session dose of 25 Gy (83 % isodose) was delivered to the VT substrate (8.1 cc) using a c-arm-based high-precision linear accelerator on November 30, 2018.  CRS/RA was performed without incident and dysfunction of the ICD was not observed.  Following the procedure, a significant reduction in monomorphic VT from 5.0 to 1.6 episodes per week and of ICD shock interventions by 81.2 % was observed.  Besides peri-procedural nausea with a single episode of vomiting, no treatment-associated AEs were noted.  Unfortunately, the patient died 57 days after CRS/RA due to sepsis-associated cardiac circulatory failure after Clostridium difficile-associated colitis developed during rehabilitation.  Histopathologic examination of the heart as part of a clinical autopsy revealed diffuse fibrosis on most sections of the heart without apparent differences between the target area and the posterior cardiac wall serving as a control.  The authors concluded that CRS/RA appeared to be a possible therapeutic option for otherwise untreatable patients suffering from refractory VT and electrical storm.  A relevant reduction in VT incidence and ICD interventions was observed, although long-term outcome and consequences of CRS/RA remain unclear.  These researchers stated that clinical trials are strongly needed and have been initiated.

Neuwirth and co-workers (2019) noted that SBRT for VTs could be an option after failed catheter ablation.  These investigators analyzed the long-term efficacy and toxicity of SBRT applied as a bail-out procedure.  Patients with structural heart disease and unsuccessful catheter ablations for VTs underwent SBRT.  The planning target volume (PTV) was accurately delineated using exported 3D electro-anatomic maps (EAMs) with the delineated critical part of re-entry circuits.  This was defined by detailed EAM and by pacing maneuvers during the procedure.  Using the ICD lead as a surrogate contrast marker for respiratory movement compensation, 25 Gy was delivered to the PTV using CyberKnife.  These researchers evaluated occurrences of sustained VT, electrical storm, anti-tachycardia pacing, and shock; time to death; and radiation-induced events.  From 2014 until March 2017, a total of 10 patients underwent radio-surgical ablation (mean PTV, 22.15 ml; treatment duration, 68 mins).  After radiosurgery, 4 patients experienced nausea and 1 patient presented gradual progression of mitral regurgitation.  During the follow-up (median of 28 months), VT burden was reduced by 87.5 % compared with baseline (p = 0.012), and 3 patients suffered non-arrhythmic deaths.  After the blanking period, VT recurred in 8 of 10 patients.  The mean time to first anti-tachycardia pacing and shock were 6.5 and 21 months, respectively.  The authors concluded that SBRT appeared to show long-term safety and effectiveness for VT ablation in structural heart disease inaccessible to catheter ablation.  They reported 1 possible radiation-related toxicity and promising OS, warranting evaluation in a prospective, multi-center clinical trial.

The authors stated that this study had several drawbacks.  First, the findings were based on retrospective evaluation with no pre-specified specific primary or secondary outcome.  Second, positron emission tomography (PET) was not available for scar identification.  Third, target delineation was based on an indirect comparison of intra-cardiac maps with CT images, and no direct image registration with CARTO was possible in this first series.  Encouraged by the present pilot data, these investigators have initiated a prospective, multi-center clinical trial in patients with structural heart disease and refractory monomorphic VT who underwent at least 2 failed catheter ablations (with at least 1 performed at a high-volume expert center).  In this trial, the target volume for stereotactic ablation will be defined by a combination of EAM, imaging, and functional techniques (pacing).  Merged data will be incorporated directly into CT images for more precise therapeutic planning.

Kovacs and associates (2021) noted that several studies have suggested STAR as a therapeutic option for patients suffering from therapy-refractory VT or ventricular fibrillation (VF).  These researchers carried out a systematic review of human reports of STAR for structural VT/VF to examine its safety and effectiveness.  All identified publications were assessed for inclusion.  This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.  A total of 13 studies were included resulting in a population of 57 patients.  Median age was 64 years (range of 34 to 83), 31 patients (54 %) had ischemic cardiomyopathy and 50 patients (88 %) had prior catheter ablation (CA) for VT/VF.  A mean planned target volume of 64.4 cc (range of 3.5 to 238) with a mean safety margin of 3.3 mm (0 to 5) was treated with 25 Gy.  Immediately following STAR, 4 patients (7 %) experienced an electrical storm.  During a mean follow-up duration of 410 days, all patients suffering from sustained VT/VF prior to STAR (n = 55) had a reduction of their sustained VT/VF-burden after STAR, but recurrence occurred in 41 patients (75 %) during follow-up.  A total of 46 patients (81 %) had an adverse effect from therapy, but no treatment-related death occurred.  Evidence of scar-formation after STAR either by imaging, invasive mapping or histopathology was found in 6 of 9 examined patients (67 %).  The authors concluded that from the still very limited experience, STAR appeared safe and effective in patients with structural heart disease and therapy-refractory sustained VT/VF.  It was associated with a significant short-term reduction of sustained VT/VF-burden, but recurrences were common.

Carbucicchio and colleagues (2021) presented the preliminary results of the STRA-MI-VT Study, a spontaneous, phase-Ib/II clinical trial, designed to prospectively examine the safety and effectiveness of SBRT in patients with advanced cardiac disease and intractable VT.  Cardiac computed tomography (CT) integrated by electro-anatomical mapping was used for substrate identification and merged with dedicated CT scans for treatment plan preparation.  A single 25-Gy radio-ablation dose was delivered by a LINAC-based volumetric modulated arc therapy technique in a non-invasive matter.  The primary safety endpoint was treatment-related adverse effects during acute and long-term follow-up (FU), obtained by regular in-hospital controls and ICD remote monitoring.  The primary effectiveness endpoint was the reduction at 3 and 6 months of VT episodes and ICD shocks.  A total of 7 out of 8 patients (men; age of 70 ± 7 years; ejection fraction (EF), 27 ± 11 %; 3 ischemic, 4 non-ischemic cardiomyopathies) underwent SBRT.  At a median 8-month FU, no treatment-related serious AE occurred; 3 patients died from non-SBRT-related causes.  A total of 4 patients completed the 6-month FU: the number of VT decreased from 29 ± 33 to 11 ± 9 (p = 0.05) and 2 ± 2 (p = 0.08), at 3 and 6 months, respectively; shocks decreased from 11 to 0 and 2, respectively.  At 6 months, all patients showed a significant reduction of VT episodes and no electrical storm recurrence, with the complete regression of iterative VTs in 2/2 patients.  The authors concluded that the findings of the STRA-MI-VT Study suggested that SBRT can be considered an alternative option for the treatment of VT in patients with structural heart disease and highlighted the need for further clinical investigation addressing its safety and effectiveness, especially over the long-term.  These researchers stated that this study had several drawbacks.  This was a non-randomized study carried out at a single center.  Furthermore, findings were preliminary and referred to a small number of patients (n = 8) and a relatively short FU (median of 8 months).

Munshi (2021) noted that SBRT is a high precision technique that is commonly used for malignant lesions in lung, liver, pancreas and spine.  Recent reports suggested promise in use of SBRT as a tool in atrial and ventricular cardiac arrhythmias.  In a systematic review , the author examined the use of SBRT technology for this novel indication.  A PubMed search was carried out for studies published between 1990 and 2020.  All original articles, case reports, case-series studies of treated patients were included in the analyses.  Out of the 55 articles in PubMed search, this investigator found 1 phase I/II clinical case series, 3 clinical case reports, 3 animal studies and 4 dosimetric studies related to cardiac SBRT for arrhythmias; all studies used a uniform cardiac dose of 25 Gy.  The author concluded that available pre-clinical, dosimetric and clinical studies have suggested that SBRT for cardiac arrhythmias could become a potential alternative in suitable patients; cardiac as well as radiation oncologic communities await further data and experience in this modality, including safety and outcomes.

Whitaker and co-workers (2022) stated that stereotactic ablative radiotherapy (SABR), or SBRT, has recently been used in the field of arrhythmia management.  It has been most widely examined in the treatment of VT but may also have potential in the treatment of other arrhythmias as well, often termed STAR.  The non-invasive delivery of treatment for VT has the potential to spare an often physiologically vulnerable group of patients the burden of long catheter ablation procedures with the potential for prolonged periods of hemodynamic instability.  Cardiac SABR also has the capacity to direct ablative therapy at substrate that is inaccessible using current trans-catheter techniques.  For these reasons cardiac SABR has generated significant enthusiasm as an emerging therapeutic modality for VT.  The authors reviewed the pre-clinical data pertaining to the use of SABR in cardiac tissue and recent clinical evidence regarding the application of SABR in the field of arrhythmia management.

Alcohol Ablation of Vein of Marshall for the Treatment of Paroxysmal / Persistent Atrial Fibrillation

Valderrabano et al (2009a) noted that vein of Marshall (VOM) is an attractive target during ablation of atrial fibrillation (AF) due to its autonomic innervation, its location anterior to the left pulmonary veins and drainage in the coronary sinus.  These researchers studied 17 dogs.  A coronary sinus venogram showed a VOM in 13, which was successfully cannulated with an angioplasty wire and balloon.  In 5 dogs, electro-anatomical maps of the left atrium were performed at baseline and after ethanol infusion in the VOM, which demonstrated a new crescent-shaped scar, extending from the annular left atrium towards the posterior wall and left pulmonary veins.  In 4 other dogs, effective refractory periods (ERP) were measured at 3 sites in the left atrium, before and after high-frequency bilateral vagal stimulation.  The ERP decreased from 113.6 +/- 35.0 ms to 82.2 +/- 25.4 ms (p < 0.05) after vagal stimulation.  After VOM ethanol infusion, vagally-mediated ERP decrease was eliminated (from 108.6 +/- 24.1 ms to 96.4 +/- 16.9 ms, p = NS).  The abolition of vagal effects was limited to sites near the VOM (ERP: 104 +/- 14 ms, versus 98.6 +/- 12.2 ms post-vagal stimulation, p = ns), as opposed to sites remote to VOM (ERP: 107.2 +/- 14.9 ms, versus 78.6 +/- 14.7ms post-vagal stimulation, p < 0.05).  To test feasibility in humans, 5 patients undergoing pulmonary vein antral isolation had successful VOM cannulation and ethanol infusion: left atrial voltage maps demonstrated new scar involving the infero-posterior left atrial wall extending towards the left pulmonary veins.  The authors concluded that ethanol infusion in then VOM achieved significant left atrial tissue ablation, abolished local vagal responses and was feasible in humans.

Valderrabano et al (2009b) delineated the safety and ablative effects of ethanol infusion in the VOM during catheter ablation of AF.  Patients undergoing pulmonary vein antral isolation (PVAI; n = 14) gave consent for adjunctive VOM ethanol infusion.  In 10 of 14 patients, the VOM was cannulated with an angioplasty wire and balloon.  Echocardiographic contrast was injected in the VOM under echocardiographic monitoring.  Two infusions of 100 % ethanol (1 ml each) were delivered via the angioplasty balloon in the VOM.  LA bipolar voltage maps were created before and after ethanol infusion.  Radiofrequency ablation (RFA) times needed to isolate each PV and other procedural data were compared with those of 10 age-, sex-, AF type- and LA size-matched control subjects undergoing conventional PVAI.  The VOM communicated with underlying myocardium, as shown by echocardiographic contrast passage into the LA.  There were no acute complications related to VOM ethanol infusion, which led to the creation of a low-voltage area in the LA measuring 10.6 +/- 7.6 cm(2) and isolation of the left inferior PV in 4 of 10 patients; RFA time needed to achieve isolation of the left inferior PV was reduced (2.2 +/- 4 mins versus 11.4 +/- 10.3 mins in control subjects, p < 0.05).  The authors concluded that VOM ethanol infusion was safe in humans, decreased RFA time in the left inferior PV, and may have a role as an adjunct to PVAI.

Dave et al (2012) stated that AF or atrial flutter can recur after PVAI.  The VOM has been linked to the genesis of AF.  These researchers hypothesized that the VOM may play a role in AF recurrences and that VOM ethanol infusion may have therapeutic value in this setting.  A total of 61 patients with recurrent AF or atrial flutter after PVAI were studied.  The VOM was successfully cannulated in 54; VOM and PV electrograms were recorded, and differential PV-VOM pacing was performed.  VOM signals were present in all patients; however, VOM triggers of AF could not be demonstrated.  VOM tachycardia was present in 1 patient.  Left inferior (LIPV) and left superior (LSPV) reconnection was present in 32 and 30 patients, respectively.  Differential pacing in VOM and LIPV showed VOM-mediated LIPV reconnection in 5/32 patients.  In others, VOM and PV connected indirectly via left atrial tissues.  Up to 4 1-cc infusions of 98 % ethanol were delivered in the VOM.  Regardless of the reconnection pattern, ethanol infusion eliminated LIPV and LSPV reconnection in 23/32 and 13/30 patients, respectively.  Ethanol terminated VOM and LIPV tachycardias in 2 patients.  There were no acute procedural complications.  The authors concluded that VOM signals were consistently present in recurrent AF; and VOM may rarely play a role in PV reconnection.  However, VOM ethanol infusion could be useful in patients with recurrent AF after PVAI, assisting in achieving re-disconnection of reconnected left PVs.

Pambrun et al (2019) noted that beyond pulmonary veins (PV) isolation, the ablation strategy for persistent AF remains controversial.  Substrate ablation may provide a high termination rate but at the cost of impaired atrial physiology and recurrent complex re-entries.  To overcome these pitfalls, these investigators examined a new lesion set based on important anatomical considerations.  The case series included 10 consecutive patients with persistent AF; and 3 atrial structures were successively targeted: (i) coronary sinus and VOM (CS-VOM) musculature elimination; (ii) PVs isolation; and (iii) anatomical isthmuses block.  The lesion set completion was the procedural end-point.  Step 1: VOM ethanol infusion was feasible in all cases (mean time of 33.4 ± 9.4 mins), mean RF time for CS-VOM bundles was 14.4 ± 6.9 mins.  Step 2: mean RF time for PV isolation was 27.7 ± 9.3 mins.  Step 3: mean RF time for mitral, roof, and cavo-tricuspid lines was 5.7 ± 2.3, 8.1 ± 4.3, and 5.9 ± 1.9 mins, respectively.  The lesion set was achieved in all patients.  Mean procedure time was 270 ± 29.9 mins.  AF termination and non-inducibility were, respectively, obtained in 50 % and 90 % of the patients.  After a 6-month follow-up, all patients were free from arrhythmia recurrence.  The authors concluded that the present case series reported a new ablation strategy systematically targeting anatomical structures previously identified as possibly involved in the fibrillatory process and the recurrent tachycardias.  The resulting lesion set provided good short-term outcomes.  These researchers stated that although promising, these preliminary results need to be confirmed in the larger prospective study.

Liu et al (2019) clarified the effect of VOM ethanol infusion for treating VOM triggers and/or mitral flutter after first-attempt endocardial ablation in patients with non-paroxysmal AF.  Of the 254 consecutive patients (age of 56 ± 10 years; 221 men) undergoing catheter ablation for drug-refractory non-paroxysmal AF, 32 (12.6 %) received VOM ethanol infusion.  The patients were stratified into group 1 (pulmonary vein isolation [PVI], substrate modification, VOM ethanol infusion), group 2 (PVI, substrate modification), and group 3 (PVI alone).  Propensity-matched analysis (n = 128) of long-term outcomes (3.9 ± 0.5 years) revealed a higher AF recurrence risk in group 2 (hazard ratio [HR], 4.17; 95 % confidence interval [95 % CI]: 1.63 to 10.69; p = 0.003) and group 3 (HR, 1.82; 95 % CI: 1.09 to 3.04; p = 0.021) than in group 1, as well as a higher atrial arrhythmia recurrence risk in group 2 than in group 1 (HR, 2.42; 95 % CI: 1.16 to 5.03; p = 0.018).  A higher procedural termination rate was observed in group 1 than groups 2 and 3 (41.7 % versus 17.2 % versus 18.8 %; p = 0.042).  On multi-variate analysis, VOM ethanol injection was an independent predictor of freedom from recurrence of AF (HR, 0.20; 95 % CI: 0.08 to 0.52; p = 0.001) and atrial arrhythmia (HR, 0.35; 95 % CI: 0.17 to 0.74; p = 0.005), whereas a left atrial diameter of greater than 45 mm and hypertension were independent risk factors for recurrence.  Peri-procedural complications rates were comparable among the groups.  The authors concluded that adjunctive VOM ethanol infusion was safe and effective for treating non-paroxysmal AF in patients with VOM triggers and/or refractory mitral flutter, providing good long-term freedom from AF and atrial arrhythmia.

Kitamura et al (2019) stated that ethanol infusion of the VOM may be effective to treat Marshall bundle-related atrial tachycardia (MB-AT).  However, methods and clinical results of ethanol infusion for MB-AT have been not established.  In an observational, single-center study, these researchers evaluated the accessibility of the VOM and the success rate of ethanol infusion using a femoral approach for MB-AT.  This trial included consecutive patients who had MB-AT and in whom these investigators attempted to treat MB-AT during AT by ethanol infusion.  When the VOM was able to be cannulated following VOM venogram using a femoral approach, the authors systematically performed ethanol infusion with selective balloon occlusion of the VOM.  They analyzed in detail the efficacy of ethanol infusion of VOM in patients who were in MB-AT during ethanol infusion.  These researchers enrolled 54 consecutive patients in whom they attempted to treat MB-AT by ethanol infusion.  Of those, the VOM was accessible in 92.5 % of patients (50 of 54).  Of the 50 patients treated by ethanol infusion during MB-AT, AT was successfully terminated in 56 % percent of the patients (28 of 50) by solo treatment of ethanol infusion without RF ablation.  The remainder required additional RF application to terminate the MB-AT.  A mean of 6.2 ± 2.8 ml of ethanol was infused resulting in the low-voltage area significantly larger than that before ethanol infusion (12.7 ± 8.3 versus 6.6 ± 5.3 cm2, p < 0.001).  The authors concluded that the present study demonstrated that the VOM was highly accessible and MB-AT was amenable to treatment by ethanol infusion by using a femoral approach.

Valderrabano et al (2019) noted that PVI is effective in the treatment of paroxysmal AF, its success rates in persistent AF are suboptimal.  Ablation strategies to improve outcomes including additional lesions beyond PVI have not consistently shown benefit.  Recurrence as PMF is a common form of ablation failure.  The VOM contains myocardial connections and abundant sympathetic and para-sympathetic innervation implicated in the genesis and maintenance of AF, and is anatomically co-localized with the mitral isthmus, the ablation target of PMF.  These researchers examined the safety and efficacy of VOM ethanol infusion when added to PVI in patients undergoing either de-novo ablation of persistent AF or after a previous ablation failure.  VENUS-AF and MARS-AF are prospective, multi-center, randomized, controlled trials.  VENUS-AF will enroll patients undergoing their 1st catheter ablation of persistent AF.  MARS-AF will enroll patients undergoing ablation after previous ablation failure(s).  Patients (n = 405) will be randomized to PVI alone or in combination with VOM ethanol infusion.  The primary end-points include procedural safety and freedom from AF or AT of more than 30 seconds on 30-day continuous event monitors at 6 and 12 months after randomization procedure (single-procedure success), off anti-arrhythmic drugs.  Key secondary end-points include AF burden, freedom from AF/AT after repeat procedures and quality of life (QOL).  The authors concluded that the VENUS-AF and MARS-AF will determine the safety and potential rhythm control benefit of VOM ethanol infusion when added to PVI in patients with persistent AF undergoing de-novo or repeat ablation, respectively.

Kato et al (2019) stated that ethanol injections into the VOM (EIM) are considered to be a good therapeutic option for atrial tachyarrhythmias, however, the safety remains to be determined.  To elucidate what would affect the safety and potential complications of an EIM, these investigators examined the anatomical features of the VOM and patient background.  They performed the EIM before the conventional PVI for drug-resistant AF in 88 patients and evaluated the anatomical features of the VOM and their background.  All procedures were completed, however, other than myocardial staining, trivial contrast medium leaked out of the VOM into the pericardial space, that is, extravasation of contrast medium with capillary rupture, during the EIM in 20 patients (22.7 %) regardless of the features of the VOM.  No pericardial effusions requiring further intervention developed after the extravasation, which resolved by the next day on echocardiography in 18 of those patients.  However, 2 patients who had extravasation other than during the initial contrast injection required additional therapeutic intervention for non-negligible pericardial effusions.  Their body weights were significantly lower and the latter 2 patients were also small lean women with heart failure and a preserved ejection fraction.  The authors concluded that the physical constitution, regardless of the characteristics of the VOM, could be strongly associated with adverse events (AEs) during the EIM.  These investigators must take extreme care in smaller patients with poor compliant hearts during the EIM.

The authors stated that this study had several drawbacks.  First, this was a retrospective cohort study that included very few complications.  Thus, they could not perform multivariate analyses to determine the predictors of the Intervention(+) group, which required additional intervention, and there might not have been an adequate statistical power even in the univariate analyses.  However, all the cases in the Intervention(+) group were physically small women and the multi-variate analyses showed that the body weight was the only significant predictor of the ML(+) group, which included the Intervention(+) group, suggesting that leanness might be one of the important risk factors of the extravasation of the contrast medium with capillary rupture leading to AEs.  Furthermore, out of all the patients, only 2 cases suffering from HFpEF required intervention.  They might have had a decreased heart compliance with an increased central venous pressure, which could have been responsible for the serious complications.  It was not possible to statistically analyze the correlation between the existence of HFpEF and the complications, however, it might still remain necessary to clarify whether the heart compliance could affect the results.  Second, these researchers experienced 2 cases with complications during the early phase even when injecting the ethanol very slowly (1 ml over more than 1 min).  After that, these researchers fortunately did not experience any further serious complications since they began performing the ethanol injection using the same size syringe but by delivering the ethanol more slowly and gently than before.  However, these investigators encountered several patients with trivial extravasation associated with a capillary rupture that resolved without any further intervention.  The authors did not measure the accurate pressure using a manometer during the injections, and thus, they could not objectively determine the threshold related to the serious complications.  Finally, the extravasation of the contrast medium with capillary rupture was determined visually with fluoroscopy, so the authors might have missed an imperceptible extravasation.  Further, the above hypotheses were based upon the pathophysiological findings observed in only 1 case.  These researchers stated that further investigation is needed to clarify the mechanisms of the complications of the EIM to perform a safer EIM.

Furthermore, an UpToDate review on “Paroxysmal atrial fibrillation” (Spragg and Kumar, 2019) does not mention alcohol ablation of vein of Marshall as a therapeutic option.

Okishige and co-workers (2020) ethanol infusion (EI) in the vein of Marshall (VOM) has multi-factorial effects that could be synergistic to PVI in ablation of AF.  The effectiveness of RFA versus cryoablation when combined with a EI-VOM has never been examined.  These researchers examined outcome differences of AF ablation using RF versus cryoablation when combined with EI-VOM.  Consecutive patients (n = 132) underwent catheter ablation of paroxysmal AF with either RF or cryo-balloon (CB) for PVI combined with EI-VOM.  Bi-directional conduction block at the mitral isthmus was attempted.  The end-point was the freedom from any atrial arrhythmias documented after a blanking period of 90 days after the procedure.  Kaplan-Meier estimates of the arrhythmia-free survival after 1 year were 63.8 % (RF + EI-VOM), and 82.7 % (CB + EI-VOM), respectively.  Comparison between CB + EI-VOM versus RF + EI-VOM reached a significance (p = 0.0292).  The peri-procedural complication rate was comparable in both groups (5.0 % RF, 5.8 % CB; p = 0.14) with a significant difference in the incidence of phrenic nerve palsy (0 % RF, 2.0 % CB; p < 0.05).  The authors concluded that the EI-VOM failed to demonstrate any significant improvement in the ablation long-term results of paroxysmal AF; however, CB ablation combined with EI-VOM had a significantly improved outcome compared to a PVI with an RFA combined with EI-VOM.

The authors stated that this study had several drawbacks.  First, this trial constituted a non-randomized analysis of consecutive patients, including the initial patients treated with the 2nd-generation CB device.  However, all operators were well-trained in CB ablation and beyond the learning curve, minimizing any time-dependent confounders.  Second, the group sizes were small; however, a number of the efficacy parameters differed significantly between the groups.  Third, the assignment of the study patients into the 4 groups might not be appropriate, because grouping of patients depended on whether the VOM was present or not.  Fourth, a comparison of PVI versus PVI plus EI-VOM might be unfair due to the additive effects of creating a lesion in the mitral isthmus region.  Fifth, the evaluation of the success and complication rates was complex.  Sixth, a procedure trying to construct the mitral isthmus block (MIB) was not carried out in Group RF+ EI-VOM, and this might have affected the rate of freedom from AF / atrial tachycardia (AT).  However, all recurrent arrhythmias were AF instead of left-sided ATs rotating along the mitral annulus; thus, it was unlikely that the absence of the MIB could affect the clinical results in Group RF + EI-VOM.  Seventh, by definition, successful maintenance of sinus rhythm strongly relies on the length of the follow-up, which varies from center to center.  Because these investigators reported on the 12-month follow-up data from out-patient clinic visits or telephone interviews, they could not exclude that AF recurrent episodes could have been missed in some patients.  Eighth, the examinations to evaluate the efficacy of ablation procedure such as periodic 12-lead ECG and Holter monitoring recording might not be sufficient to strictly investigate the clinical efficacy of each ablation modality.  Finally, there was no comparison between a control group in the present study.

In a randomized clinical trial, Valderrbano and colleagues (2020) examined if vein of Marshall ethanol infusion could improve ablation results in persistent AF when added to catheter ablation.  The Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) Trial was an investigator-initiated, National Institutes of Health (NIH)-funded, randomized, single-blinded trial carried out in 12 centers in the U.S.  Patients (n = 350) with persistent AF referred for 1st ablation were enrolled from October 2013 through June 2018; follow-up concluded in June 2019.  Patients were randomly assigned to catheter ablation alone (n = 158) or catheter ablation combined with vein of Marshall ethanol infusion (n = 185) in a 1:1.15 ratio to accommodate for 15 % technical vein of Marshall ethanol infusion failures.  The primary outcome was freedom from AF or atrial tachycardia for longer than 30 seconds after a single procedure, without anti-arrhythmic drugs, at both 6 and 12 months.  Outcome assessment was blinded to randomization treatment.  There were 12 secondary outcomes, including AF burden, freedom from AF after multiple procedures, peri-mitral block, and others.  Of the 343 randomized patients (mean [SD] age of 66.5 [9.7] years; 261 men), 316 (92.1 %) completed the trial.  Vein of Marshall ethanol was successfully delivered in 155 of 185 patients.  At 6 and 12 months, the proportion of patients with freedom from AF/atrial tachycardia after a single procedure was 49.2 % (91/185) in the catheter ablation combined with vein of Marshall ethanol infusion group compared with 38 % (60/158) in the catheter ablation alone group (difference, 11.2 % [95 % CI: 0.8 % to 21.7 %]; p = 0.04).  Of the 12 secondary outcomes, 9 were not significantly different, but AF burden (zero burden in 78.3 % versus 67.9 %; difference, 10.4 % [95 % CI: 2.9 % to 17.9 %]; p = 0.01), freedom from AF after multiple procedures (65.2 % versus 53.8 %; difference, 11.4 % [95 % CI: 0.6 % to 22.2 %]; p = 0.04), and success achieving peri-mitral block (80.6 % versus 51.3 %; difference, 29.3 % [95 % CI: 19.3 % to 39.3 %]; p < 0.001) were significantly improved in vein of Marshall-treated patients; AEs were similar between groups.  The authors concluded that among patients with persistent AF, addition of vein of Marshall ethanol infusion to catheter ablation, compared with catheter ablation alone, increased the likelihood of remaining free of AF or atrial tachycardia at 6 and 12 months.  Moreover, these researchers stated that further research is needed to evaluate longer-term efficacy.

Liu and associates (2020) noted that in randomized studies, the strategy of PVI plus linear ablation has failed to increase success rates for persistent AF (PeAF) ablation when compared with PVI alone.  Peri-mitral re-entry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a 1st ablation procedure; and EI-VOM has been shown to facilitate a durable mitral isthmus linear lesion.  This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded “2C3L” for ablation of PeAF.  The PROMPT-AF study is a prospective, multi-center, randomized trial involving blinded assessment of outcomes.  Patients (n = 276) undergoing their 1st catheter ablation of PeAF will be randomized to either the upgraded “2C3L” arm or PVI arm in a 1:1 fashion.  The upgraded “2C3L” technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavo-tricuspid isthmus.  The follow-up duration is 12 months.  The primary end-point is the rate of documented atrial tachycardia arrhythmias of greater than 30 seconds, without any anti-arrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months).  The authors stated that the PROMPT-AF study will examine the efficacy of the fixed “2C3L” approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de-novo ablation.

Alcohol Ablation of Vein of Marshall for the Treatment of Peri-Mitral Flutter

Takigawa and colleagues (2020) hypothesized that an epicardial approach using EI-VOM may improve the result of ablation for peri-mitral flutter (PMF).  These researchers studied 103 consecutive patients with PMF undergoing high-resolution mapping.  The first 71 were treated with RFA alone (RF-group), and the next 32 underwent EI-VOM followed by RFA on the endocardial and epicardial mitral isthmus (EI-VOM/RF-group).  Contact force was not measured during ablation; acute and 1-year outcomes were compared.  Flutter termination rates were similar between the RF-group (63/71, 88.7 %) and EI-VOM/RF-group (31/32, 96.8 %, p = 0.27).  Atrial tachycardia (AT) terminated with EI-VOM alone in 22/32 (68.6 %) in the EI-VOM/RF-group.  Bi-directional block of mitral isthmus was always achieved in the EI-VOM/RF-group, but significantly less frequently achieved in the RF-group (62/71, 87.3 %; p = 0.05).  Median RF duration for AT termination/conversion was shorter [0 s (0 to 6) in the EI-VOM/RF-group than 312 s (55 to 610) in the RF-group, p < 0.0001], as well as for mitral isthmus block in the EI-VOM/RF-group [246 s (0 to 663)] than in the RF-group [900 s (525 to 1,310), p < 0.0001].  Pericardial effusion was observed in 1/32 (3.2 %) in EI-VOM/RF-group and 5/71 (7.0 %) in RF-group (p = 0.66); 2 in RF-group required drainage and 1 of them developed subsequent ischemic stroke.  One-year follow-up showed fewer recurrences in the EI-VOM/RF-group [6/32 (18.8 %)] than in the RF-group [29/71 (40.8 %), p = 0.04].  By multi-variate analysis, only EI-VOM was significantly associated with less AT recurrence (HR = 0.35, p = 0.018).  The authors concluded that EI-VOM may reduce RF duration needed for PMF termination as well as for mitral isthmus block without severe complications, and the mid-term outcome may be improved by this approach.  This was a relatively small study (n = 32 in the EI-VOM/RF-group) with mid-term results.  These preliminary findings need to be validated by well-designed studies with larger sample size and long-term follow-up.

Derval et al (2021) noted that beyond PVI, the optimal ablation strategy for persistent AF, remains poorly defined.  In a prospective, single-center study, these researchers examined a novel comprehensive ablation strategy (Marshall bundle elimination, PVI, and line completion for anatomical ablation of persistent AF [Marshall-PLAN]) strictly based on anatomical considerations.  Left atrial (LA) sites were sequentially targeted as follows: coronary sinus and vein of Marshall (CS-VOM) musculature; PVI; and anatomical isthmuses (mitral, roof, and CTI).  The primary endpoint was 12-month freedom from AF/ AT.  A total of 75 consecutive patients were included (age of 61 ± 9 years; 10 women; AF duration 9 ± 11 months; mean LA volume 197 ± 43 ml).  VOM ethanol infusion was completed in 69 patients (92 %).  The full Marshall-PLAN lesion set (VOM, PVI, mitral, roof, and CTI with block) was successfully completed in 68 patients (91 %).  At 12 months, 54 of 75 patients (72 %) were free from AF/AT after a single procedure (no anti-arrhythmic drugs) in the overall cohort.  In the subset of patients with a complete Marshall-PLAN lesion set (n = 68), the single procedure success rate was 79 %.  After 1 or 2 procedures, 67 of 75 patients (89 %) remained free from AF/AT (no anti-arrhythmic drugs).  After 1 or 2 procedures, VOM ethanol infusion was complete in 72 of 75 patients (96 %).  The authors concluded that a novel ablation strategy that systematically targeted anatomical atrial structures (VOM ethanol infusion, PVI, and pre-specified linear lesions) was feasible, safe, and associated with a high rate of freedom from arrhythmia recurrence at 12 months in patients with persistent AF.

Kamakura et al (2021) stated that the growing interest in the vein of Marshall ethanol infusion calls for a better understanding of the events that could occur during this procedure.  By including the largest number of patients (n = 700) to-date, these researchers clarified the associated feasibility, pitfalls, and complications of this approach; these findings could aid in optimizing vein of Marshall ethanol infusion.  The authors concluded that although highly feasible with a low complication rate, further research is needed to identify patients who would benefit most from vein of Marshall ethanol infusion.

Rodriguez-Manero et al (2021) described evolving alternative strategies for the management of AF, focusing on non-invasive and percutaneous autonomic modulation.  This modulation could be achieved, among other approaches, via tragus stimulation, renal denervation, cardiac afferent denervation, alcohol injection in the vein of Marshall, baroreceptor activation therapy and endocardial ganglionated plexi (GP) ablation.  The authors concluded that although promising, these therapies are currently under investigation but could play a role in the treatment of AF in combination with conventional PVI in the near future.  These researchers stated that larger RCTs are needed to better define the subset of AF patients who would benefit most from catheter-based autonomic modification, along with the best approach to achieve it and the effect on the success rate.

Li et al (2022) stated that the long-term outcomes of ablation with vein of Marshall ethanol infusion (VOM-ABL) compared with ablation alone in patients with AF remains elusive.  In a meta-analysis, these investigators examined if VOM-ABL showed better long-term benefits and screened the potential determinants of outcome impact of VOM-ABL procedure.  PubMed, Cochrane Library, Web of Science, and Embase were searched up to September 1, 2021.  Studies comparing the long-term (1-year or longer) outcomes between VOM-ABL and ablation alone were included.  Subgroup analysis identified potential determinants for VOM-ABL procedure.  Compared with ablation alone, VOM-ABL was associated with a significantly higher rate of long-term freedom from AF/AT (RR, 1.28; 95 % CI: 1.12 to 1.47; p = 0.00) and successful mitral isthmus (MI) block (RR, 1.52; 95 % CI: 1.16 to 1.99; p = 0.00); while there was no significant difference in pericardial effusion, stroke/transient ischemic attack (TIA), and all-cause death.  Subgroup analysis identified 2 significant treatment-covariate interactions: one was ablation strategy subgroup (PVI plus linear and/or substrate ablation [PVI+]; RR, 1.41; 95 % CI: 1.27 to 1.56 versus PVI; RR, 1.05; 95 % CI: 0.92 to 1.19, p = 0.00 for interaction) for freedom from AF/AT, while the other was VOM-ABL group sample size subgroup (greater than or equal to 100; RR, 1.98; 95 % CI: 1.24 to 3.17 versus less than 100; RR, 1.20; 95 % CI: 1.10 to 1.30, p = 0.04 for interaction) for MI block.  The authors concluded that the findings of this meta-analysis demonstrated that VOM-ABL exhibited superior effectiveness and comparable safety over ablation alone in AF patients with long-term follow-up.  Moreover, PVI+ and VOM-ABL group sample size of greater than or equal to 100 may be associated with a great impact on freedom from AF/AT and MI block, respectively.  Moreover, these researchers stated that more RCTs with large cohorts and longer follow-up are needed for further demonstrating the clinical outcomes.

The authors stated that this meta-analysis had several drawbacks.  First, compared with as-grouped analysis, a higher or lower outcome result was shown by as-treated analysis.  In addition, as-treated analysis was expected to make a more accurate evaluation of safety and effectiveness with VOM-ABL procedure.  In this study, the same statistical analysis style was used to examine MI block and all-cause death.  However, as-treated analysis was carried out on some eligible studies and as-grouped analysis on the other eligible studies in terms of the effectiveness outcome (freedom from AF/AT) and safety outcome (including pericardial effusion and stroke/TIA).  These researchers found that the subgroup analysis results were consistent with the pooled results and no significant difference was observed between the 2 analyses styles; thus, indicating that both analyses could produce similar results.  Second, no significant trend for treatment-covariate interaction was identified in the VOM-ABL group sample size subgroup for the rate of freedom from AF/AT with p = 0.38 for interaction, which may be attributed to more than 20 patients in VOM-ABL groups of all eligible studies.  Third, similar to other meta-analysis, some potential biases may have influenced these findings.  Therefore, these investigators conducted a sensitivity analysis, as well as Egger's and Begg's tests, and these results indicated that no single study dominated the combined heterogeneity and no publication bias was presented, suggesting that these findings were considered to be robust.  Furthermore, the successful MI block represented the total rate of MI block at the end of the procedure, rather than the long-term rate of MI block, which could be assessed in a redo procedure for checking the MI block after long-term follow-up.  Additionally, only 1 randomized comparative study was enrolled, and the remaining were observational studies.  Moreover, only 1 study was included with more than 3-year follow-up while no study with 5- or 10-year follow-up, which made it a challenge to objectively evaluate the long-term safety and effectiveness between VOM-ABL and ablation alone.  Meanwhile, subgroup analysis results may be subjected to a limited number of available studies (e.g., only 1 study included PVI only and cryo-balloon ablation), which led subgroup results to be interpreted with caution. 

In a state-of-the-art review on the ablative strategy for AF, Palama et al (2022) stated that “Beyond PVI and attempts to understand and to treat the persistent AF mechanisms, other atrial anatomical structures can be considered targets, either by catheter ablations, by surgical techniques, or better yet, with hybrid approaches.  If, from a purely conceptual point of view, the reduction of the atrial critical mass operated by extensive ablations should improve the outcome in terms of AF free survival, the results of the STAR-AF-2 reaffirmed the concept “less may be more”.  However, to date, transcatheter ablative approaches with mitral, roof, and CTI block have been proposed with the addition of coronary sinus and vein of Marshall (CS-VOM) musculature treatment (even with ethanol infusion) (Derval et al, 2021)”.

Moreover, the current version of UpToDate review on “Paroxysmal atrial fibrillation” (Spragg and Kumar, 2019) still does not mention alcohol ablation of vein of Marshall as a therapeutic option.

ThermoCool SmartTouch SurroundFlow Catheter for Atrial Fibrillation Ablation

Gonna and associates (2017) stated that the Biosense Webster ThermoCool SmartTouch Surround Flow (STSF) catheter (STSFc) is a recently developed ablation catheter incorporating Surround Flow (SF) technology to ensure efficient cooling and force sensing to quantify tissue contact.  In the authors’ unit, it superseded the ThermoCool SF catheter (STc) from the time of its introduction in May 2015.  Procedure-related data were collected prospectively for the first 100 ablation procedures carried out in the authors’ department using the STSFc.  From a data-base of 654 procedures performed in the authors’ unit using the SF catheter, these investigators selected one to match each STSF procedure, matching for procedure type, operator experience, patient age, and gender.  The groups were well-matched for patient age, gender, and procedure type.  Procedure duration was similar in both groups (mean of 225.5 versus 221.4 mins, inter-quartile range [IQR] 106.5 versus 91.5, p = 0.55), but fluoroscopy duration was shorter in the STSF group (mean of 25.8 versus 30.0, IQR 19.6 versus 18.5, p = 0.03).  No complication occurred in the STSF group.  Complications occurred in 2 cases in the SF group (1 peri-cardial effusion requiring drainage and 1 need for permanent pacing).  Complete procedural success was achieved in 98 cases in the STSF group and 94 cases in the SF group (p = 0.15).  The composite end-point of procedure failure or acute complication was less common in the STSF group (2 versus 8, p = 0.05).  The authors concluded that the STSFc was safe and effective in treating a range of arrhythmias.  Compared with the SF catheter, it showed a trend towards improved safety-efficacy balance.

Chen and colleagues (2020) noted that the STSFc is an advanced catheter integrating contact force sensing and Surround Flow technology; however, comparative data between STSFc and contact force sensing catheter (STc) are limited.  In a meta-analysis, these researchers compared the safety and effectiveness between the STSFc and the STc for the treatment of atrial fibrillation (AF).  The Medline, PubMed, Embase, and Cochrane Library databases were searched for studies comparing STSFc and STc.  A total of 4 trials involving 727 patients were included in the study.  Pool-analyses demonstrated that, compared with STc ablation, STSFc ablation was more beneficial in terms of procedural times (standard mean difference [SMD]: -0.22; 95 % confidence interval [CI]: -0.37 to -0.07, p = 0.005) and irrigation fluid volume (SMD: -1.94; 95 % CI: -2.65 to -1.22, p < 0.0001).  There was no significant difference between STSFc and STc (risk ratio [RR]: 1.02; 95 % CI: 0.86 to 1.21, p = 0.79) for free-from AF.  Evidence of complications were low and similar for both groups (RR: 0.83; 95 % CI: 0.19 to 3.55, p = 0.80).  Furthermore, patients administered STSFc ablation tended to have shorter fluoroscopic times (SMD: -0.20; 95 % CI: -0.63 to 0.23, p = 0.21).  The authors concluded that STSFc ablation was associated with reducing procedural times and irrigation fluid volume.  Furthermore, STSFc ablation tended to shorten fluoroscopic times; thus, STSFc ablation would be a better choice for AF patients especially in patients with heart failure.  Moreover, these researchers stated that more well‐designed and large‐scale RCTs are needed to confirm these findings.

The authors stated that this meta‐analysis had several drawbacks:  First, publication bias could not be completely excluded, as with any literature search of data-bases, and inclusion of only published data contributed to bias.  Second, the numbers of included studies was limited to only 4 trials.  Third, most of the studies were designed as prospective, non‐randomized trials.  Fourth, in the context of important clinical outcomes from complications and long‐term follow‐up, the included studies, these researchers acknowledged that fewer studies had reported the related end‐points, which made the pooled analysis relatively weak.

Cardio-Neuro-Ablation for the Treatment of Syncope

Pachon et al (2005) noted that cardiac neuro-ablation is a new technique for management of patients with dominantly adverse para-sympathetic autonomic influence.  The technique is based on RFA of autonomic connections in the 3 main ganglia around the heart.  Their connections are identified by Fast-Fourier Transforms (FFTs) of endocardial signals: sites of autonomic nervous connections show fractionated signals with FFTs shifted to the right.  In contrast, normal myocardium without these connections does not show these features.  RFA is thought to inflict permanent damage on the para-sympathetic autonomic influence because its cells are adjacent to the heart whereas sympathetic cells are remote.  A total of 21 patients (mean age of 48 years), neurally-mediated reflex syncope in 6, functional high-grade AV block (AVB) in 7 and sinus node dysfunction in 13 (there was overlap between the 2nd and 3rd groups) were treated.  Follow-up for a mean of 9.2 months demonstrated success in all cases with relief of symptoms; no complications occurred.

Pachon et al (2011) stated that neural-meditated reflex or neuro-cardiogenic or vasovagal syncope (NMS) is usually mediated by a massive vagal reflex.  These investigators reported the long-term outcome of NMS therapy based on endocardial RF catheter ablation of the cardiac vagal nervous system aiming permanent attenuation or elimination of the cardioinhibitory reflex (cardio-neuro-ablation).  A total of 43 patients (18 F / 25 M, 32.9 ± 15 years of age) without apparent cardiopathy (LVEF = 68.6 ± 5 %) were included . All had recurrent NMS (4.7 ± 2 syncope/patient) with important cardio-inhibition (pauses = 13.5 ± 13 s) at head-up tilt test (HUT), normal electrocardiogram (ECG), and normal atropine test (AT).  Subjects underwent atrial endocardial RFA using spectral mapping to track the neurocardiac interface (AF Nest Mapping).  The follow-up (FU) consisted of clinical evaluation, ECG (1 month/every 6 months/or symptoms), Holter (every 6 months/or symptoms), HUT (greater than or equal to 4 months/or symptoms), and AT (end of ablation and greater than or equal to 6 months).  A total of 44 ablations (48 ± 9 points/patient) were performed.  Only 3 cases of spontaneous syncope occurred in 45.1 ± 22 months (2 vasodepressor, 1 undefined).  Only 4 partial cardio-inhibitory responses occurred in post-ablation HUT without pauses or asystole (sinus bradycardia).  Long-term AT (21.7 ± 11 months post) was negative in 33 (76.7 %, p < 0.01), partially positive in 7 (16.3 %), and normal in 3 patients only (6.9 %) reflecting long-term vagal denervation (AT-Δ%HR pre 79.4 % × 23.2 % post).  The post-ablation stress test and Holter showed no abnormalities; and no major complications occurred.  The authors concluded that endocardial RF catheter ablation of severe neural-meditated reflex syncope prevented pacemaker implantation and showed excellent long-term results in well selected patients.  Despite no action in vaso-depression it appeared to cause enough long-term vagal reflex attenuation, eliminating the cardio-inhibition, and keeping most patients asymptomatic.  Indication was based on clinical symptoms, reproduction of severe cardioinhibitory syncope, and normal atropine response.

Aksu et al (2016) noted that cardio-neuro-ablation (CNA) is a lesser-known technique for management of patients with excessive vagal activation on the basis of RF catheter ablation (RFCA) of the areas related to the 3 main autonomic ganglia around the heart.  These investigators examined the effectiveness of selective and/or stepwise RFCA of these areas via right atrium (RA) and/or left atrium (LA) in the patients with recurrent syncope due to excessive vagal activity.  A total of 22 patients presenting symptomatic functional brady-arrhythmias, NMS, symptomatic AVB, and symptomatic sinus node dysfunction (SND; number = 8, 7, 7, respectively) were enrolled.  The 3 main para-cardiac ganglia were targeted via RA and LA in the patients with NMS and SND.  The procedure was performed via RA in the patients with AVB, followed by RFCA of all ganglia via LA, if AV conduction disorder persists.  The sites showing fragmented potentials were identified by electrical mapping and verified by high-frequency stimulation and ablated until atrial electrical potential was completely eliminated (less than 0.1 mV).  Subjects with NMS and SND were free from new syncopal episode at a mean 12.3 ± 3.4 months and 9.5 ± 3.1 months follow-up, respectively.  Ablation from RA was successful in 6 of 7 patients with AB.  Despite the increased heart rate, the resolution of AVB following the RFCA could not be achieved in 1 patient who had partial resolution with atropine infusion on admission.  The authors concluded that CNA may be an alternative and safe strategy to reduce NMS episodes, and to treat functional AVB and symptomatic SND, especially in young patients.

Debruyne et al (2018) stated that bi-atrial, extensive, and complex ablation strategies have been published for the treatment of NMS, SND, and functional AVB.  These researchers developed a less extensive and more specific approach compared with previously published CNA strategies, called cardio-neuromodulation.  It is based on tailored vagolysis of the sino-atrial (SA) node via partial ablation of the anterior right-ganglionated plexus, preferentially through a right-sided approach.  Patients with syncope were enrolled between December 2016 and December 2017.  They were assigned to group A if they had a positive HUT test and to group B if they presented with a pause of greater than or equal to 3 seconds.  The area to target during cardio-neuromodulation was designed off-line on a CT scan.  Slow heart rates and pauses were compared during 24-hour rhythm registration at baseline, at 1-month follow-up, and 6-month follow-up.  Syncope burden was assessed before the procedure and at 3- and 6-month follow-up.  A total of 20 patients underwent cardio-neuromodulation via a right-sided approach (12 in group A, 8 in group B).  The 1st application of RF energy led to a P-P interval shortening of greater than 120 ms in all 20 patients.  After a mean ± SD ablation time of 7 ± 4 mins and mean ablated surface area of 11 ± 6 mm2, the P-P interval shortened by 219 ± 160 ms (p < 0.001).  The number of beats of less than 50/min during 24-hour rhythm registration was reduced by a median of 100 % at 6-month follow-up (p < 0.001).  Syncope burden was reduced by 95 % at 6-month follow-up (p < 0.001).  The authors concluded that these findings indicated that cardio-neuromodulation, via a right-sided and CT-guided procedure, was safe, fast, and highly reproducible in preventing inappropriate functional sinus bradycardia and syncope recurrence.

Hu and Yao (2020) stated that CNA is an emerging therapy to treat vasovagal syncope, functional AVB and sinus dysfunction.  Currently, there are several effective approaches due to the complex modulation of autonomic nervous system (ANS).  These investigators described techniques of this innovative therapy based on published literature and their experiences.  Th authors concluded that a few clinical trials have revealed the effectiveness of this innovative strategy for vasovagal syncope and autonomic related bradycardias.  However, there are still many underlying questions that need to be answered by more controlled clinical trials, which may also change the guidelines for the treatment of syncope and arrhythmia in the future.

Aksu et al (2021) noted that although para-sympathetic effects of CNA in vagally-mediated brady-arrhythmias (VMB) were studied, sympathetic effects have not been elucidated, yet.  These investigators examined the acute and medium-term outcomes of CNA as well as the impact of CNA on ventricular re-polarization by using corrected QT interval (QTc) measurements.  A total of 65 patients (58.5 % men; age of 39.4 ± 14 years) undergoing CNA were included in the study.  Patients who underwent CNA due to VMB were divided into 2 groups: bi-atrial CAN; and right-sided CNA.  QTc was calculated at 3 time-points: before the procedure (time-point 1); 24 hours post-ablation (time-point 2); and at the last follow-up visit (time-point 3).  The mean follow-up time was 20.0 ± 20 months.  Acute success was achieved in 64 (98.4 %) of cases.  In the whole cohort, from time-point 1 to 2, a significant shortening in QTcFredericia, QTcFramingham, and QTcHodges was observed that remained lower than baseline in time-point 3.  Although the difference between measurements in time-point 1 and 2 was not statistically significant for QTcBazett, a significant shortening was detected between time-point 1 and 3.  There was significant difference between groups for shortening in QTcFredericia and QTcFramingham (p = 0.01).  Event-free survival (EFS) was detected in 90.7 % (59/65) of cases.  The authors concluded that these findings demonstrated a significant shortening of QTc in addition to high acute and medium-term success rates following CNA.  The most likely mechanism was the effect of CNA on the sympathetic system as well as on the para-sympathetic system.  Bi-atrial ablation was found related to higher QTc shortening effect.  Moreover, these researchers stated that further randomized, controlled, and multi-center studies are needed to confirm the promising results presented in this study.

The authors stated that the retrospective nature of the study was a major drawback.  However, strict inclusion and exclusion criteria were used to select study patients and CNA was performed only in a very small subset of patients who were resistant to all the currently available therapeutic options.  A combination of different conditions was detected in some patients.  Although accompanying diseases were noted for all cases and the most possible diagnoses for occurrence of syncope were indicated in the text, the pathophysiology of syncope may not be clear in all patients with accompanying SND or AB.  Although these researchers tried to demonstrate cause-effect relationship, the diagnosis of SND and AVB as the cause of syncope could be challenging.  Further studies are needed to better understand the role of CNA in this mixed population.  The number of patients undergoing right-sided ablation was small.  In addition, the main reason for syncope was AVB in 4 (57.1 %) of 7 cases in right-sided ablation group.  On the contrary, the cause of syncope was vasovagal syncope in 43 (74.1 %) of 58 cases.  In this study, the mean follow-up was 20.0 ± 20 months.  Even though patients treated improved after the ablation, the results should be confirmed in a larger number of patients with a longer follow-up.  Although the minimal level of heart rate increase that predicted a good clinical outcome is still unknown, RR interval at 12- and 24-month post-ablation remained lower than baseline.  Although bi-atrial ablation was found related to higher QTc shortening effect, time-based changes on RR interval were similar between groups.

Gorev et al (2021) reported on a case of successful treatment for syncopal episodes caused by intermittent AVB in a patient with paroxysmal AF/atrial flutter using CNA.  The authors concluded that patients with intermittent or permanent bradycardia should be additionally investigated, with attention paid to the highest possible heart rate and the response to atropine infusion.  Patients without structural conduction system disease may benefit from non-standard treatment approaches like CNA rather than from PM implantation.  Moreover, these researchers stated that prospective studies evaluating the efficacy risks and benefits of CNA for vagally-mediated bradycardia should be carried out.

Piotrowski, et al. (2022) sought to assess the effects of cardio-neuro-ablation (CNA) on syncope recurrences in patients with vasovagal syncope (VVS). This study was a prospective, open, randomized, controlled, investigator-initiated trial comparing CNA versus optimal nonpharmacologic therapy in patients with cardioinhibitory VVS. Patients were included if they had documented symptomatic cardioinhibitory or mixed VVS and positive atropine test. CNA was performed using radiofrequency ablation of the ganglionated plexi from the left and right atria. Follow-up lasted 2 years. Primary endpoint was time to first syncope recurrence. Secondary endpoints included changes in sinus rhythm and heart rate variability measured in Holter electrocardiography at baseline and 3, 12, and 24 months after CNA, as well as changes in quality of life at baseline and after completion of follow-up.  A total of 48 patients (17 male, mean age 38 ± 10 years, 24 in CNA group, 24 in control group) entered the study. The primary endpoint occurred in 2 patients (8 %) from the CNA group versus 13 control patients (54 %) (p = 0.0004).  After CNA the mean sinus rhythm at 24-hour Holter electrocardiography was significantly faster and heart rate variability parameters significantly changed toward parasympathetic withdrawal compared with baseline values. Quality of life significantly improved in the CNA group (30 ± 10 points versus 10 ± 7 points; p = 0.0001), whereas it remained stable in control patients (31 ± 10 points versus 30 ± 10 points; p = 0.5501).  The investigators concluded that this was the first randomized study documenting efficacy of CNA in patients with cardioinhibitory VVS.  Larger studies are needed to confirm these findings.  A commentary by Link (2022) stated that "a trial incorporating sham ablations would be useful and is certainly needed before wide acceptance of this technique".

Furthermore, an UpToDate review on “Syncope in adults: Management and prognosis” (Benditt, 2022) does not mention cardio-neuro-ablation / CNA as a management / therapeutic option.   

Catheter Ablation for the Treatment of Bradycardia-Tachycardia Syndrome

Magnano et al (2022) noted that atrial fibrillation catheter ablation (AFCA) should be considered as a strategy to avoid pace-maker (PM) implantation for patients with bradycardia-tachycardia syndrome (BTS), but lack of evidence is remarkable.  These investigators carried out a random-effects model meta-analysis on safety and effectiveness data from controlled trials and observational studies.  They compared AF recurrence, AF progression, procedural complication, additional procedure, cardiovascular death, cardiovascular hospitalization, heart failure (HF) and stroke in patients undergoing AFCA versus PM implantation.  PubMed/Medline, Cochrane Database and Google Scholar were screened, and 4 retrospective studies were selected.  A total of 776 patients (371 in the AFCA group, and 405 in the PM group) were included.  After a median follow-up of 67.5 months, lower AF recurrence [odds ratio (OR) 0.06, CI: 0.02 to 0.18, I2 = 82.42 %, p < 0.001], AF progression (OR 0.12, CI: 0.06 to 0.26, I2 = 0 %, p < 0.001), HF (OR 0.12, CI: 0.04 to 0.34, I2 = 0 %, p < 0.001), and stroke (OR 0.30, CI: 0.15 to 0.61, I2 = 0 %, p = 0.001) were observed in the AFCA group.  No differences were observed in cardiovascular death and hospitalization (OR 0.48, CI: 0.10 to 2.28, I2 = 0 %, p = 0.358 and OR 0.43, CI: 0.14 to 1.29, I2 = 87.52 %, p = 0.134, respectively).  Higher need for additional procedures in the AFCA group was highlighted (OR 3.65, CI: 1.51 to 8.84, I2 = 53.75 %, p < 0.001).  PM implantation was avoided in 91 % of BTS patients undergoing AFCA.  The authors concluded that AFCA in BTS patients appeared to be more effective than PM implantation in reducing AF recurrence and PM implantation may be waived in most BTS patients treated by AFCA.  Moreover, the need for additional procedures in AFCA patients was balanced by long-term benefit in clinical endpoints.

Posterior Wall Isolation in Catheter Ablation for the Treatment of Atrial Fibrillation

In an observational, single-center study, Bisignani et al (2021) examined the impact of left atrial posterior wall isolation (LA-PWI) in addition to PVI versus PVI alone, performed using cryo-balloon ablation (CB-A), in patients with persistent AF (PerAF) on a mid-term follow-up of 12 months.  A total of 80 consecutive patients indicated to index CB-A for the treatment of drug-resistant PAF were included.  The first 50 patients (62.5 %) underwent PVI only, and the following 30 patients (37.5 %) underwent LAPWI + PVI.  Acute isolation was achieved in all PVs in both groups.  The LA-PW was successfully isolated in 29 out of 30 (97 %) patients; in the remaining patient, adjunct RFA was needed.  The total procedure time and the mean fluoroscopy time were significantly shorter in patients who underwent PVI only (p < 0.001).  The freedom from AF at 12 months was not significantly different between the 2 groups (LA-PWI + PVI = 90 % versus PVI = 88 %) (log-rank p = 0.816).  The authors concluded that LA-PWI in addition to PVI by the means of CB-A did not appear to reduce the risk of AF recurrence if compared with the standard PVI on a mid-term follow-up of 12 months.  Moreover, these researchers stated that larger randomized trials are needed to confirm these findings.

The authors stated that this trial reported a single-center experience.  In addition, it was observational in nature; thus, results should not be generalized.  Furthermore, no pharmacological testing was used to elicit non-PVI foci neither before nor after ablation.  No long-term monitoring has been carried out (loop recorder or 7-day Holter); accordingly, the arrhythmia recurrence rate and asymptomatic episodes might have been under-estimated.  Esophageal damage might have been under-estimated as no esophagogastroduodenoscopy (EGDS) was conducted following ablation.

Liu et al (2022) noted that the clinical outcomes of PVI alone for PerAF remain unclear.  Adjuvant posterior wall isolation (PWI) has become a potential supplementary strategy for improving the outcome of PerAF ablation.  In a meta-analysis, these investigators examined the effect of PWI added to catheter ablation for PerAF.  PubMed, Embase, and Cochrane Library databases were searched for studies comparing the outcomes of PerAF ablation with and without PWI.  The effectiveness outcomes were recurrence of atrial arrhythmia (AA), AF, and AT, and the safety outcome was AEs.  A total of 8 studies with 1,428 patients were included in the pooled analyses.  The results showed that PWI significantly reduced the recurrence of AA (RR = 0.69, 95 % CI: 0.55 to 0.87, p = 0.002, I2 = 63 %) and AF (RR = 0.57, 95 % CI: 0.40 to 0.80, p = 0.001, I2 = 70 %).  AT recurrence (RR = 0.92, 95 % CI: 0.67 to 1.27, p = 0.63, I2 = 42 %) and AEs (RR = 1.11, 95 % CI: 0.67 to 1.84, p = 0.70, I2 = 0 %) were comparable between the 2 groups.  In the sub-analyses, the effectiveness of PWI in reducing AA recurrence was consistent in patients who underwent cryo-ablation or debulking ablation.  The authors concluded that PWI effectively decreased AA recurrence following PerAF ablation without increasing the risk of AT or procedure-related complications; however, more randomized studies are needed to confirm these findings.

Uetake et al (2022) stated that modification of the low-voltage zone in the LA (LA-LVZ) in addition to PVI has not shown sufficient improvement in arrhythmia-free survival in patients with PerAF.  In addition, the effect of electrical PWI is controversial.  In a retrospective study, these investigators examined the impact of existence of LA-LVZ on the outcome of patients undergoing additional PWI for PerAF.  A total of 347 patients with PerAF who underwent primary catheter ablation with LA-LVZ based strategy were analyzed.  Voltage mapping in the LA was carried out during sinus rhythm.  Additional LVZ ablation was carried out in patients with LA-LVZ.  The operators decided whether additional PWIs were to be conducted.  Of 347 patients, 108 had LA-LVZ.  In the LVZ group, patients with additional PWI (n = 70) had higher rates of freedom from tachyarrhythmia recurrence than those without (77.1 % versus 42.1 %, p < 0.001).  Additionally, even when patients were limited to those with LA-LVZ in areas other than the posterior wall (n = 85), PWI had higher success rates (80.9 % versus 42.1 %, p < 0.001).  In contrast, in patients without LVZ (n = 239), there was no significant difference in the rate of successful outcome between those with and without PWI (81.3 % versus 88.1 %, p = 0.112).  On the other hand, patients with PWI had greater AT recurrence rate than those without PWI (10.0 % versus 2.5 %, p = 0.003).  The authors concluded that PWI, in addition to PVI and LVZ modification, may improve single procedural outcomes in patients with PerAF who have LVZ, regardless of the distribution in the LA.  A combination of voltage-guided ablation and PWI may be a simple, tailored, and effective ablation strategy.

In a prospective, non-randomized, single-center study, Bisignani et al (2022) examined the feasibility and safety of a new cryo-balloon ablation system in achieving PVI + LA-PWI isolation.  A total of 40 consecutive patients, undergoing PVI + LA-PWI with the novel POLARx, were compared to 40 consecutive patients who underwent the same procedure with the established Arctic Front Advance PRO.  Acute isolation was achieved in all PVs in both groups and LA-PWI was achieved in 38 patients (95 %) in the POLARx group and in 36 patients (90 %) in Arctic Front group.  Procedural outcomes were similar between both groups, except for lower temperatures during cryo-energy in the POLARx group, for both PVI and LA-PWI.  The authors concluded that LA-PWI + PVI with the novel POLARx Cryo-balloon was feasible and safe; the results were comparable with the Arctic Front Advance PRO system.  Moreover, these researchers stated that long-term follow‐up studies are needed to examine the clinical outcome.

The authors stated that this study had several drawbacks.  This trial was a non‐randomized analysis of consecutive patients carried out in a relatively limited number of patients (n = 40 in the treatment group).  In addition, it reported a single-center experience.  Furthermore, no esophagogastroduodenoscopy was carried out after ablation, esophageal damage might have been under-estimated.  Finally, the lack of a clinical follow‐up or re-map prevented from defining any algorithms, such as a temperature‐guided approach, for the new ablation system.

Sinus Node-Sparing Hybrid Ablation for the Treatment of Sinus Tachycardia / Postural Orthostatic Sinus Tachycardia

de Asmundis et al (2019) stated that the ideal treatment of inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) still needs to be defined.  Medical treatment yielded sub-optimal results, endocardial ablation of the sinus node (SN) may risk phrenic nerve damage and open-heart surgery may be accompanied by unjustified invasive risks.  These researchers described their first experience of 50 consecutive patients (41 females, 22.83 ± 3.91 years) having undergone a novel hybrid thoracoscopic ablation for drug-resistant IST (n = 39, 78 %) or POTS (n = 11, 22 %).  The SN was identified with the help of 3D mapping.  Surgery was carried out via 3 (5-mm) ports from the right side.  A minimally invasive approach with a RF bipolar clamp was used to a new target sparing the SN region, to isolate the superior and the inferior caval veins, and a crista terminalis line was made.  All lines were inter-connected.  Normal sinus rhythm was restored in all patients at the end of the procedure.  All patients discontinued medication during the follow-up.  After a blanking period of 6 months all patients presented stable sinus rhythm.  At a mean of 28.4 ± 1.2 months, normal SN ruction and chronotropic response to exercise was present.  In the 11 patients initially diagnosed with POTS, no syncope occurred.  During the follow-up, pericarditis was the most common complication (39 patients, 78 %) with complete resolution in all cases.  The authors concluded that these preliminary results of their first experience with a SN-sparing novel hybrid ablation of IST/POTS, using surgical thoracoscopic video-assisted epicardial ablation combined with concomitant endocardial 3D mapping may prove to be a safe and efficient therapeutic option in patients with symptomatic, drug-resistant IST and POTS.

The European Society of Cardiology guidelines on “The management of patients with supraventricular tachycardia” (Brugada et al, 2020) stated that “The limited and disappointing evidence, reported from small observational studies, suggests that catheter ablation should not be considered as part of the routine management of most patients with IST [inappropriate sinus tachycardia]”.

In a retrospective study, de Asmundis et al (2022) described their first multi-center experience of 255 consecutive patients (235 females, 25.94 ± 3.84 years) having undergone a novel SN-sparing hybrid thoracoscopic ablation for drug-resistant IST (n = 204, 80 %) or POTS (n = 51, 20 %).  As previously described, the SN was identified with 3D mapping.  Surgery was performed through 3 (5-mm) ports from the right side.  A minimally invasive approach with a bipolar RF clamp was used to ablate targeted areas while sparing the SN region.  The targeted areas included isolation of the superior and the inferior caval veins, and a crista terminalis line was made.  All lines were inter-connected.  Normal sinus rhythm was restored in all patients at the end of the procedure.  All patients discontinued medication during the follow-up.  After a blanking period of 6 months, all patients presented stable sinus rhythm.  At a mean of 4.07 ± 1.8 years, normal SN reduction and chronotropic response to exercise were present.  In the 51 patients initially diagnosed with POTS, no syncope occurred.  During follow-up, pericarditis was the most common complication (121 patients: 47 %), with complete resolution in all cases.  Pneumothorax was observed in 5 patients (1.9 %), only 3 (1.1 %) required surgical drainage; and 5 patients (1.9 %) required a dual-chamber pacemaker due to sinus arrest of greater than 5 s.  The authors concluded that these preliminary findings of a novel SN-sparing hybrid ablation for the treatment of IST/POTS, using surgical thoracoscopic video-assisted epicardial ablation combined with endocardial 3D mapping, appeared to be a successful approach.  This promising treatment for patients with symptomatic IST and POTS offers a complete restoration of the normal heart rate (HR) and HR variability (HRV), with a total reduction of all symptoms.  Moreover, these researchers stated that larger, prospective, multi-center studies are needed to confirm these findings.

The authors stated that this study had several drawbacks.  The trial was a retrospective study.  Most of the electrocardiographic markers analyzed in the study were dynamic and the real prevalence of these parameters was difficult to evaluate.  Furthermore, these investigators did not carry out any official “QOL” testing, which should be considered moving forward.

Lakkireddy et al (2022) stated that medical treatment of IST remains sub-optimal; and RFA of the sinus node has poor success and higher complication rates.  In a prospective, multi-center registry, these researchers compared clinical outcomes of the novel SN-sparing hybrid ablation technique with those of RF-SN modification for IST management.  They compared the SN-sparing hybrid ablation strategy with RF-SN modification.  The hybrid procedure was performed using an RF bipolar clamp, isolating superior vena cava/inferior vena cava with the creation of a lateral line across the crista terminalis while sparing the SN region (identified by endocardial 3D mapping).  RF-SN modification was performed by endocardial and/or epicardial mapping and ablation at the site of earliest atrial activation.  Of the 100 patients (hybrid ablation group, n = 50; RF-SN group, n = 50), 82 % were women, and the mean age was 22.8 years.  Normal sinus rhythm and HR were restored in all patients in the hybrid group (versus 84 % in the RF-SN group; p = 0.006).  Hybrid ablation was associated with significantly better improvement in mean daily HR and peak 6-minute walk HR compared with RF-SN ablation.  The RF-SN group had a significantly higher rate of redo procedures (100 % versus 8 %; p < 0.001), phrenic nerve injury (14 % versus 0 %; p = 0.012), lower acute pericarditis (48 % versus 92 %; p < 0.0001), permanent pace-maker implantation (50 % versus 4 %; p < 0.0001) than did the hybrid ablation group.  The authors concluded that the novel SN-sparing hybrid ablation procedure appeared to be a safer and more effective treatment for patients with symptomatic drug-resistant IST with long-term durability than RF-SN ablation.

These researchers stated that several potential limitations deserve special mention.  Since all procedures were performed by high-volume experienced operators, findings should not be generalized to low-volume operators.  Furthermore, extensive experience with the hybrid ablation approach (i.e., AF or ventricular arrhythmia ablation) explains minimal to no procedure-related complications.  The increase in the mean number of ICU stays after hybrid ablation could account for increased healthcare utilization; however, this could be partially equipoised by higher procedure success; thus, avoiding redo ablation compared with RF-SN ablation, and low procedure-related complications.  Although 1 previous study (with no comparator arm) demonstrated procedural safety and efficacy, this trial was the 1st study demonstrating the safety and effectiveness of the hybrid ablation approach compared with the RF-SN ablation approach.  The pathophysiology of IST is poorly understood, and the superiority of the hybrid approach could not be clearly explained.  The strategic isolation of the SVC/IVC/CT could probably result in regional sympathetic denervation while sparing the SN; thus, explaining the positive outcomes of the hybrid ablation procedure.  Gaps in the lateral CT line could create iatrogenic re-entrant atrial arrhythmias that might have to be dealt with, by a repeat procedure, even though such risk was lower (with only 2 patients having re-entrant tachycardia because of the gap in the crista lesion that was promptly mapped and ablated), and longer follow-up data (beyond 12 months) are needed to ascertain.  These investigators did not have systematic Holter data from these patients to comment on the HRV changes pre- and post-procedure.  These researchers stated that in the future, they should consider extensive autonomic investigation with vagal stimulation, acute stellate ganglion stimulation, and long-term HRV study to confirm the proposed sympathetic denervation theory.  They stated that an appropriately sized multi-center RCT is needed to determine the reproducibility of these findings.

In an editorial that accompanied the study of Lakkireddy et al (2022), Pachon and Pachon (2022) stated that they consider that currently IST ablation should be included as class IIa or IIb at least, and the study by Lakkireddy et al reinforced their position.

Furthermore, an UpToDate review on “Sinus tachycardia: Evaluation and management” (Homoud, 2022) does not mention sinus node-sparing hybrid approach as a management / therapeutic option.

Catheter Ablation Using Pulmonary Vein Isolation With Posterior Left Atrial Wall Isolation for the Treatment of Persistent Atrial Fibrillation

Kistler et al (2023) stated that PVI alone is less effective in patients with persistent AF compared with paroxysmal AF.  The left atrial posterior wall may contribute to maintenance of persistent AF, and posterior wall isolation (PWI) is a common PVI adjunct.  However, PWI has not been subjected to randomized comparison.  In an investigator-initiated, randomized, multi-center study, these researchers compared PVI with PWI versus PVI alone in patients with persistent AF undergoing 1st-time catheter ablation.  This trial entailed 11 centers in 3 countries (Australia, Canada, and the U.K.).  Symptomatic patients with persistent AF were randomized 1:1 to either PVI with PWI or PVI alone.  Subjects were enrolled between July 2018 and March 2021, with 1-year follow-up completed March 2022.  The PVI with PWI group (n = 170) underwent wide antral PVI followed by PWI involving linear ablation at the roof and floor to achieve electrical isolation.  The PVI-alone group (n = 168) underwent wide antral PVI alone.  Primary endpoint was freedom from any documented atrial arrhythmia of more than 30 seconds without anti-arrhythmic medication at 12 months, after a single ablation procedure.  The 23 secondary outcomes included freedom from atrial arrhythmia with/without anti-arrhythmic medication after multiple procedures, freedom from symptomatic AF with/without anti-arrhythmic medication after multiple procedures, AF burden between study groups at 12 months, procedural outcomes, and complications.  Among 338 patients randomized (median age of 65.6 years; 76.9 % men), 330 (97.6 %) completed the study.  After 12 months, 89 patients (52.4 %) assigned to PVI with PWI were free from recurrent atrial arrhythmia without anti-arrhythmic medication after a single procedure, compared with 90 (53.6 %) assigned to PVI alone (between-group difference, -1.2 %; HR of 0.99; 95 % CI: 0.73 to 1.36; p = 0.98).  Of the secondary endpoints, 9 showed no significant difference, including freedom from atrial arrhythmia with/without anti-arrhythmic medication after multiple procedures (58.2 % for PVI with PWI versus 60.1 % for PVI alone; HR of 1.10; 95 % CI: 0.79 to 1.55; p = 0.57), freedom from symptomatic AF with/without anti-arrhythmic medication after multiple procedures (68.2 % versus 72 %; HR of 1.20; 95 % CI: 0.80 to 1.78; p = 0.36) or AF burden (0 %; IQR of  0 % to 2.3 %) versus 0 % (IQR of 0 % to 2.8 %; p = 0.47).  Mean procedural times (142 mins [SD, 69] versus 121 mins [SD, 57]; p < 0.001) and ablation times (34 mins [SD, 21] versus 28 mins [SD, 12]; p < 0.001) were significantly shorter for PVI alone.  There were 6 complications for PVI with PWI and 4 for PVI alone.  The authors concluded that in patients undergoing 1st-time catheter ablation for persistent AF, the addition of PWI to PVI alone did not significantly improve freedom from atrial arrhythmia at 12 months compared with PVI alone.  These investigators stated that these findings did not support the empirical inclusion of PWI for ablation of persistent AF.

Gunawardene et al (2023) noted that left atrial PWI (LAPWI) may improve rhythm control in addition to PVI in persistent AF (persAF) patients undergoing catheter ablation (CA); however, LAPWI may be challenging when using thermal energy sources.  These investigators examined the safety and effectiveness of LAPWI carried out by non-thermal pulsed field ablation (PFA), which delivers micro-second high-voltage electrical fields, in CA for patients with persAF.  Consecutive persAF patients from 2 German centers were prospectively enrolled.  There were 2study cohorts: First -- the LAPWI cohort, which included PFA-guided (re-)PVI with LAPWI for first-time and/or repeat ablation procedures; and second -- a comparative persAF cohort with a PFA PVI-only approach without LAPWI for first-time ablation within the same timeframe.  Patients were followed-up by routine Holter ECGs.  A total of 79 persistent AF patients were included in the study: 59/79 patients were enrolled in the LAPWI cohort, including 16/59 index (27 %) and 43/59 repeat ablation procedures (73 %).  A total of 16 patients (16/79; 21 %) were in the PVI-only cohort without LAPWI.  Of the patients treated with LAPWI, procedure time and fluoroscopy time was 91 ± 30 mins and 15 ± 7 mins, respectively.  The acute PVI rate was 100 % in all first-time ablation patients (32 patients (16 PVI only, 16 PVI plus LAPWI), 196/196 PVs).  Of the 43 re-do patients in the LAPWI cohort, re-PVI was necessary in 33 % (14/43) of patients (27 PVs; 1.9 PV per-patient); in 67 % (29/43), all PVs were isolated, and antral ablation of the PV ostia was carried out in 48 % (14/29).  LAPWI was performed successfully in all 59 (100 %) patients of the LAPWI cohort.  Two minor complications occurred.  No esophageal lesion was detected in the LAPWI cohort (n = 33/59 (56 %) patients underwent endoscopy).  After 354 ± 197 days of follow-up, freedom from atrial arrhythmias was 79.3 % (95 % CI: 62 % to 95 %) in the complete LAPWI cohort (n = 14/59 (24 %) on anti-arrhythmic drug (AAD): class Ic n = 9, class III n = 5).  There was no difference regarding acute procedural and clinical outcome compared to the PVI-only cohort.  The authors concluded that LAPWI guided by PFA was feasible and safe in patients undergoing CA for persAF and showed favorable outcomes.  These researchers stated that in the context of durable PVI, PFA-guided LAPWI may be an effective adjunctive therapeutic option.

The authors stated that this study had several drawbacks.  First, the design of this 2-center study was explorative; thus, the sample size was small, limiting the impact of these findings.  Second, the follow-up did not include continuous or daily ECG monitoring, which might result in the missing of short paroxysmal AF episodes.  Third, no QOL questionnaires were provided during follow-up and patients were only asked about symptom improvement following ablation in a dichotomous assessment.  Fourth, only re-hospitalization data were available, while no data regarding healthcare costs were available.  Fifth, these investigators presented only acute re-mapping data on acute LAPWI.  There was no chronic re-mapping information compared to previously published studies about LAPWI; thus, there was no information regarding chronic PFA lesion patterns in this trial.  Sixth, this trial was not randomized and there was no control group, including thermal energy sources.  Seventh, this study included the learning curve of the novel penta-spline PFA system and, owing to the parameter-specific nature of PFA, the results described in this study cannot be conflated with other PFA systems.

Furthermore, an UpToDate review on “Catheter ablation for the treatment of atrial fibrillation: Technical considerations for non-electrophysiologists” (Passman, 2023) states that “Ablation targets in persistent atrial fibrillation -- In contrast to patients with paroxysmal AF, patients with persistent AF (and in particular longstanding persistent AF) often have multiple triggers distributed throughout the atria in addition to triggers within the PV.  It is thought that mechanisms that maintain rather than trigger the arrhythmia are more important in these individuals.  These observations may explain the reduced efficacy of CA procedures that are limited to PVI in patients with longstanding persistent AF seen in most studies.  In these patients, additional lesions are often needed to prevent recurrence of AF.  These lesions are often placed anatomically in the left atrial posterior wall and roof, in the left atrial appendage, coronary sinus, or in the right atrium.  Additional targets include sites of complex fractionated electrograms and rotors.  Though the goal of additional lesion sets are to modify the AF substrate, these approaches may also result in pro-arrhythmia through the creation of new reentrant circuits.  Data supporting the benefits and optimal approach for the treatment of persistent AF are inconclusive and are often individualized by patient and operator.  Additional ablation targets/techniques outside the PVs include … Posterior wall isolation”.

Pulsed Field Ablation for the Treatment of Chronic / Paroxysmal Atrial Fibrillation

Reddy et al (2023) noted that catheter-based PVI is an effective treatment for paroxysmal AF; PFA may limit damage to tissues outside the myocardium.  In a randomized, single-blind, non-inferiority study, these researchers compared the safety and effectiveness of PFA with conventional thermal ablation.  They assigned patients with drug-refractory paroxysmal AF in a 1:1 ratio to undergo PFA or conventional RFA or cryo-balloon ablation (CBA).  The primary effectiveness endpoint was freedom from a composite of initial procedural failure, documented atrial tachy-arrhythmia after a 3-month blanking period, anti-arrhythmic drug use, cardioversion, or repeat ablation.  The primary safety endpoint included acute and chronic device- and procedure-related serious AEs.  A total of 305 patients were assigned to undergo PFA, and 302 were assigned to undergo thermal ablation.  At 1 year, the primary effectiveness endpoint was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3 %) who underwent PFA, and 194 patients (estimated probability, 71.3 %) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95 % Bayesian credible interval, -5.2 to 9.2; posterior probability of non-inferiority, > 0.999).  Primary safety endpoint events occurred in 6 patients (estimated incidence, 2.1 %) who underwent PFA and 4 patients (estimated incidence, 1.5 %) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95 % Bayesian credible interval, -1.5 to 2.8; posterior probability of non-inferiority, > 0.999).  The authors concluded that among patients with paroxysmal AF receiving a catheter-based therapy, PFA was non-inferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachy-arrhythmia after a 3-month blanking period, anti-arrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious AEs at 1 year.

The authors stated that this study had several drawbacks.  First, some episodes of asymptomatic recurrence of AF may have been missed because continuous invasive monitoring was not used.  However, in contrast to the results of other recent studies, the findings of this trial represented single-procedure outcomes in which treatment success did not allow the use of class I or III anti-arrhythmic drugs, and patients underwent follow-up ECG monitoring and 72-hour Holter monitoring.  Second, follow-up was limited to 1 year; thus, comparative longer-term outcomes are unknown.  However, recurrence of symptomatic AF appeared infrequent between years 2 to 5 in a recent single-center study involving patients with paroxysmal AF who were followed for 5 years.  Third, this study examined a single PFA catheter technology in patients with paroxysmal AF only; therefore, the outcomes were not generalizable to other PFA systems or to patients with non-paroxysmal AF.

In an editorial that accompanied the study by Reddy et al (2023), Bunch (2023) stated that in the search for improved safety and effectiveness with catheter ablation, PFA has emerged as a potential candidate.  As a nonthermal tool, PFA employs high-voltage electrical fields on a micro-second scale that result in cellular membrane instability and electrophoresis resulting in cell death.  Early experience with PFA reported it to be highly effective in eliminating electrical potentials or arrhythmogenic substrate with selectivity to the targeted myocardium without evidence of collateral injury to surrounding tissues.  The editorialist stated that despite both hope and hype with PFA, an adequately powered comparison against standard ablation tools for AF was lacking.  Bunch noted that there were several interesting findings from the study by Reddy et al.  Procedure times were much shorter with PFA than with thermal ablation, a clear advantage in resource-constrained electrophysiology laboratories.  After 1 year of follow-up, 73.3 % of the patients who underwent PFA and 71.3 % of those who underwent thermal ablation were free of recurrent atrial arrhythmias.  These results were disappointing for PFA, given the lack of incremental improvement over currently available methods.  This outcome was not attributable to lack of procedural effectiveness.  Peri-procedural success with PFA was extraordinary for a new technology, with 99.6 % of the patients having complete PVI.  The results were also disappointing given that delivery of PFA was not altered during the procedure owing to the location of the esophagus (an alteration that is commonly performed with RFA).  These findings were similar to those of a prospective non-inferiority trial of PFA for AF that showed the technology to be non-inferior with respect to freedom from AF at 1 year (66 % for paroxysmal AF and 55 % for persistent AF) as compared with performance objectives guided by a consensus statement (greater than 50 % for paroxysmal AF and greater than 40 % for persistent AF).  The stagnant effectiveness results with this technology, despite near 100 % procedural success, brought up fundamental questions regarding ablation for AF in general that are founded in the incomplete understanding of the mechanisms underlying the genesis of AF and its recurrence, a divergence of the field away from strategies based on physiology to those based on anatomy only, and the persistent need to embrace treatment of the broad systemic causes of AF that also drive its progression.  The author concluded that PFA reduced the time to durable PVI as compared with thermal ablation but did not improve arrhythmia-free outcomes.  Strong conclusions regarding the safety of PFA for esophageal injury were premature and would require patience as the collective experience increases.  If the risk of esophageal injury is mitigated or solved with PFA, this would be a big step forward, and a sign that the technology may live up to the hype.

Badertscher et al (2023) stated that that PFA has emerged as a novel treatment technology for patients with AF.  Cryo-balloon is the most often used single-shot technology.  A direct comparison to a novel CB system is lacking.  In a non-randomized, single-center study, these investigators compared PVI using PFA versus a novel CB system regarding safety, effectiveness, myocardial injury, and outcomes.  A total of 181 consecutive patients underwent PVI and were included (age of 64 ± 9.7 years, EF of 0.58 ± 0.09, left atrial size of 40 ± 6.4 mm, paroxysmal AF 64 %).  A total of 106 patients (59 %) underwent PFA and 75 patients (41 %) underwent CBA.  The median procedure time, left atrial dwell time, and fluoroscopic time were similar between the PFA and the CBA group with 55 mins (IQR of 43 to 64) versus 58 mins (IQR of 48 to 69); p < 0.087; 38 mins (30 to 49) versus 37 mins (31 to 48); p = 0.871); and 11 mins (IQR of 9.3 to 14) versus 11 mins (IQR of 8.7 to 16); p < 0.81, respectively.  A total of 3 procedural complications were observed in the PFA group (2 tamponades, 1 temporary ST elevation), and 3 complications in the CBA group (3× reversible phrenic nerve palsies).  During the median follow-up of 404 days (IQR of 208 to 560), AF recurrence was similar in the PFA group and the CBA group with 24 % versus 30 % (p = 0.406).  The authors concluded that procedural characteristics were very similar between PFA and CBA in regard to procedure duration fluoroscopy time and complications; and AF-free survival did not differ between the PFA and CBA groups.

The authors stated that this study had several drawbacks . First, this was a single-center, non-randomized comparison of patients participating in a prospective registry.  However, although a selection bias may exist, patient characteristics were similar between groups.  Second, these researchers did not uniformly use implantable loop recorders in all patients, which is currently considered the gold standard for rhythm monitoring in clinical trials following AF ablation.  Third, since PFA is relatively new, and currently has only 1 commercially available catheter, the optimal number of applications and type of lesion set is unknown.  Further refinement might potentially improve the effectiveness of PFA for PVI.  Fourth, information on PV re-connection patterns was limited to patients with recurrence of AF undergoing a repeat procedure.  Fifth, very recently, a new CB (PolarX Fit, Boston Scientific) was introduced and received CE marking in April 2023.  This novel CB offers a dual diameter balloon size in one catheter to deliver an individualized fit.  These researchers stated that further studies comparing PFA with the novel PolarX Fit are needed.

Hu et al (2023) noted that AF is associated with a range of symptoms, including palpitations, cognitive impairment, systemic embolism, and increased mortality.  Despite years of research, the precise mechanisms underlying AF remain elusive.  Current understanding suggests that factors like stretch-induced fibrosis, epicardial adipose tissue (EAT), chronic inflammation, autonomic nervous system (ANS) imbalances, as well as genetic mutations all play significant roles in its development.  In recent years, the advent of wearable devices has revolutionized AF diagnosis, enabling timely detection and monitoring; however, balancing early diagnosis with efficient resource utilization presents new challenges for healthcare providers.  The management of patients with AF centers on stroke prevention and symptom alleviation.  Patients at high risk of thrombo-embolism require anti-coagulation therapy, and emerging pipeline drugs, especially factor XI inhibitors, hold promise in achieving effective anti-coagulation with reduced bleeding risks.  The authors stated that the scope of indications for CA in AF has expanded significantly; PFA, as a novel energy source, shows potential for improving success rates while ensuring safety.

Verma et al (2023) stated that pulsed field ablation uses electrical pulses to cause non-thermal irreversible electroporation and induce cardiac cell death.  Pulsed field ablation may have effectiveness comparable to traditional catheter ablation while preventing thermally-mediated complications.  PULSED AF pivotal study (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF) was a prospective, global, multi-center, non-randomized, paired single-arm study in which patients with paroxysmal (n = 150) or persistent (n = 150) symptomatic AF refractory to class I or III anti-arrhythmic drugs were treated with pulsed field ablation.  All subjects were monitored for 1 year using weekly and symptomatic trans-telephonic monitoring; 3-, 6-, and 12-month ECGs; and 6- and 12-month 24-hour Holter monitoring.  The primary effectiveness end-point was freedom from a composite of acute procedural failure, arrhythmia recurrence, or anti-arrhythmic escalation through 12 months, excluding a 3-month blanking period to allow recovery from the procedure.  The primary safety end-point was freedom from a composite of serious procedure- and device-related AEs.  Kaplan-Meier methods were used to assess the primary end-points.  Pulsed field ablation was shown to be effective at 1 year in 66.2 % (95 % CI: 57.9 to 73.2) of patients with paroxysmal AF and 55.1 % (95 % CI: 46.7 to 62.7) of patients with persistent AF.  The primary safety end-point occurred in 1 patient (0.7 %; 95 % CI: 0.1 to 4.6) in both the paroxysmal and persistent AF cohorts.  The authors concluded that PULSED AF showed a low-rate of primary safety AEs (0.7 %) and provided effectiveness consistent with established ablation technologies using a novel irreversible electroporation energy to treat patients with AF.

The authors stated that this study had several drawbacks.  First, it had a single-arm design, although pre-defined performance objectives were guided by a 2017 international consensus statement on catheter ablation.  In addition, historical trials with similar monitoring methods allowed for some indirect comparison.  Second, establishing safety end-points in new trials could be challenging because some complications, such as atrio-esophageal fistula, happened very rarely (0.02 % to 0.11 %).  Endoscopic visualization could have confirmed the absence of esophageal erosions or ulcerations that may progress to fistula formation.  However, these researchers did not observe any clinical signs of esophageal injury, such as spasm or dysphagia, nor did they observe any esophageal temperature rise.  Third, the majority of the study participants were White, which did not represent the global diversity of the AF population, but was closer to insurance database rates observed in the U.S.  These researchers stated that catheter design and waveform modifications in the future could improve effectiveness beyond what is available currently.  It should also be noted that this study was fully funded by Medtronic Inc.

Furthermore, an UpToDate review on “Overview of catheter ablation of cardiac arrhythmias” (Levy, 2023) states that “Pulsed field ablation -- A new ablation modality, pulsed field ablation (PFA) holds promise for the treatment of AF and perhaps other arrhythmias, such as VT.  PFA uses a series of very brief, high-amplitude electrical pulses to desiccate tissue by electroporation of the sarcolemmal membrane without significantly heating the tissue.  Moreover, this energy form seems to be specific to myocardial tissue, as other tissues seem to be resistant to this modality.  PFA systems are approved for use in Europe (CE Mark), and are undergoing clinical trials in the United States”.  This UTD review does not mention the use of pulsed field ablation for the treatment of chronic/persistent AF.

Metzner et al (2024) noted that PVI is a well-established strategy for the treatment of paroxysmal AF (PAF).  Despite RCTs and real-world data showing the promise of PFA for this treatment, long-term safety and effectiveness data demonstrating single-procedure outcomes off anti-arrhythmic drugs remain limited.  In a prospective, non-randomized, multi-center study, these investigators examined the long-term safety and effectiveness of PFA using the pentaspline catheter for the treatment of PAF.  This trial enrolled patients with PAF undergoing de-novo PVI with PFA, who were followed for 12 months with weekly trans-telephonic monitoring and a 72-hour Holter ECG at 6 and 12 months.  The primary safety endpoint was a composite of device- or procedure-related serious AEs out to 7 days post-ablation, and PV stenosis or atrio-esophageal fistula out to 12 months.  Treatment success was a composite of acute PVI and chronic success, which included freedom from any documented atrial tachyarrhythmia longer than 30 s, use of anti-arrhythmic drugs, or cardioversion after a 3-month blanking period, or use of amiodarone or repeat ablation at any time.  The study enrolled 179 PAF patients (age of 62 ± 10 years, 39 % women) at 13 centers.  At the index procedure, all PVs were successfully isolated with the pentaspline PFA catheter.  Procedure and left atrial dwell times, with a 20-min waiting period, were 71.9 ± 17.6 and 41.0 ± 13.3 mins, respectively.  Fluoroscopy time was 11.5 ± 7.4 mins.  Notably, monitoring compliance was high, with 88.4 % and 90.3 % with weekly events and 72-hour Holter monitors, respectively.  Freedom from the composite primary effectiveness endpoint was 66.6 %, and 41 patients had atrial tachyarrhythmia recurrence, mostly recurrent AF (31 patients).  The composite safety endpoint occurred in 2 patients (1.1 %), 1 tamponade, and 1 TIA.  There was no coronary spasm, PV stenosis, or atrio-esophageal fistula.  There were 4 cases of transient phrenic nerve palsy, but all resolved during the index procedure.  The authors concluded that PVI using a pentaspline PFA catheter was effective in treating PAF patients despite rigorous endpoint definitions and high monitoring compliance, and showed favorable safety.

These researchers stated that this study (the FARA-Freedom Trial) was designed as a post-market clinical follow-up study examining single-procedure success based on standard of care (SOC) in 6 countries and at 13 centers.  This was a single-arm study with 12-month follow-up.  The patient rhythm monitoring compliance was notably high in this trial, this combined with 72-hour Holter monitor, and strict treatment success definitions made direct comparisons to other study outcomes challenging.

Chaumont et al (2024) stated that cryo-balloon ablation is currently the gold standard technique for single-shot PVI; and PFA has recently emerged as an interesting non-thermal alternative energy for PVI.  In a prospective, comparative study, these researchers examined the safety and long-term effectiveness of PVI using the pentaspline PFA catheter in comparison to cryo-balloon ablation.  Between January 2021 and December 2022, these investigators included all consecutive patients of their center in whom a 1st PVI-only procedure was carried out using PFA or cryo-balloon.  The choice of the energy was based on patients' preference between general anesthesia (PFA) and local anesthesia (cryo-balloon).  The primary endpoint was freedom from documented atrial arrhythmia recurrence after a 3-month blanking period.  A total of 301 patients (PAF in 220 patients) underwent a 1st PVI procedure performed using PFA (n = 151) or cryo-balloon (n = 150).  Complete short-term PVI was obtained in 144 of 150 patients (96 %) in the cryo-balloon group, and in all patients of the PFA group (p = 0.01).  Procedure duration was significantly longer in the cryo-balloon group.  Transient and persistent phrenic nerve injuries were observed in the cryo-balloon group only (13/150 and 2/150, respectively).  One-year freedom from atrial arrhythmia was significantly higher in the PFA group compared with the cryo-balloon group (87.9 % versus 77.7 %; adjusted HR, 0.53 [95 % CI: 0.30 to 0.96]; p = 0.037).  The authors concluded that the findings of this trial suggested that PFA could overcome safety limitations of cryo-balloon with optimal effectiveness.  Moreover, these researchers stated that RCTs are needed to further examine the potential superiority of PFA over cryo-balloon.

The authors stated that this study had several drawbacks.  First, although patient populations were similar and prospectively included, this study was not randomized.  As the choice of the energy was solely based on patients' preference between general and local anesthesia, these investigators could not exclude an impact of the anesthesia modality on 1‐year outcomes.  Although PFA is too painful to be performed under local anesthesia only, the procedures could also have been carried out under deep sedation rather than general anesthesia.  On the other hand, the use of general anesthesia in the cryo-balloon group could have resulted in less patient movement, allowing easier catheter positioning and providing more favorable procedural conditions.  However, the physical properties of cryo-energy allow strong tissue adhesion, and thus perfect stability of the cryo-balloon during ablation.  Second, the use of longer rhythm monitoring may have resulted in a lower treatment success rate; however, it could also have possibly detected short and rare asymptomatic AF recurrences with little clinical impact.  This drawback applied to both groups and did not impact the value of the relative comparison.  Third, these researchers could not exclude a bias on the post-intervention treatment, which could have differed between groups and influenced the recurrence rates.

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