A 72-year-old man with a history of pericardial patch closure of an atrial septal defect and dual-chamber pacemaker placement for sick sinus syndrome presented for ablation of symptomatic atrial flutter. His past arrhythmia history is complex and includes a history of ablation for atrial fibrillation (AF) 14 years prior, ablation of atypical flutter determined to involve the pericardial patch 6 years prior, and ablation of atrial flutter determined to be cavotricuspid isthmus (CTI) dependent-flutter 1 year prior. Due to symptomatic atrial arrhythmias documented clinically and via his pacemaker, he was referred for an EP study (Figure 1, top left and bottom left).
On arrival, he was in sinus rhythm with 1:1 AV conduction. We collected voltage and activation data with a high-density mapping catheter (Advisor HD Grid Mapping Catheter, Sensor Enabled, Abbott). In the right atrium (RA), the CTI line was intact and there was low voltage around the pericardial patch. In the left atrium (LA), we noted that the pulmonary veins had reconnected. Our initial strategy was repeat pulmonary vein isolation (PVI), and we were able to demonstrate entrance and exit block from all four veins after ablation.
Subsequent burst pacing induced multiple left atrial flutters, including clockwise mitral annular flutter (MAF, Figure 1, right). After placing a roof line, we turned our attention to the area between the left inferior pulmonary vein and mitral annulus, the posterior mitral isthmus (PMI). Despite extensive endocardial ablation, medial to lateral conduction persisted across this line when pacing from the left atrial appendage (LAA). Coronary sinus (CS) ablation, to ablate on the epicardial portion of the PMI, was performed as well, but medial to lateral conduction persisted across the PMI line.
Via the guiding sheath in the CS (Agilis NxT, Abbott) using venography, we demonstrated the presence of a prominent vein of Marshall (VOM). It was best appreciated in the RAO view (Figure 2). We advanced a luminal catheter (Inquiry Luma-Cath, Abbott) directly into the VOM and confirmed it with venography. We then injected contrast to show selective cannulation.
Next, during pacing from the LAA, we injected 1 cc of sterile ethanol at a time into the VOM over 2 minutes via the luminal catheter. After each injection, a saline flush was performed followed by contrast. We performed this 5 times for a total of 5 cc of 100% alcohol. During the third injection, the activation sequence changed in the coronary sinus to show that there was medial to lateral block across the PMI (Figure 3).
We then repeated a high-density map of the LA, and noted that there was a clear area of voltage reduction within the distribution of that vein and across the PMI (Figure 4). Pacing maneuvers, including differential pacing from the CS, showed bidirectional block across the PMI (Figure 5).
There were no procedural complications, the patient’s post-operative course was unremarkable, and there have been no atrial tachycardia (AT)/AF events longer than 30 seconds in 6 months of follow-up.
Mitral Isthmus and Mitral Flutter
The development of iatrogenic LA arrhythmias following PVI for atrial fibrillation is well described. Up to 30% of patients develop LA tachycardias and atypical atrial flutter following PVI procedures.1 MAF is one arrhythmia that is commonly seen following PVI, and is often associated with more symptoms and higher resistance to antiarrhythmic drugs than AF.2 As a result, ablation is commonly used to treat MAF.
The concept of a mitral isthmus was first described during the observation of intra-atrial conduction block during ablation of left lateral accessory pathways.3 In their study, Luria et al noted that ablation in the region between the left inferior pulmonary vein and mitral annulus caused conduction block in 6.9% of their 159 ablation procedures.3 The block was manifest as a change in the CS activation during ongoing orthodromic reciprocating tachycardia. Before block, the CS activation proceeded from distal to proximal. After block in the mitral isthmus, the activation in the CS changed from proximal to distal. The investigators described this mitral isthmus as analogous to the isthmus in the RA that is targeted during ablation of typical, CTI-dependent atrial flutter. The CTI isthmus lies between the tricuspid valve annulus and inferior vena cava. Luria et al hypothesized that there would be utility in ablating the mitral isthmus for AF and atypical atrial flutter.3
Ablation to obtain mitral isthmus block has subsequently and conventionally been performed by creating a line of block along the PMI between the mitral annulus and the left inferior pulmonary vein.4 To obtain bidirectional block, this procedure often requires additional epicardial ablation within the CS, which may increase the risk of complications such as left circumflex coronary artery injury.5 An alternative technique, named the “modified anterior line,” was described in 2010.6 Tzeis et al created lines of block from the anterolateral mitral annulus to the left superior pulmonary vein, medial to the LAA, which avoided the need for CS/epicardial ablation. In most of the cases in their series, bidirectional block was demonstrated with pacing medial and lateral to the line using the ablation catheter and following CS activation. This strategy was successful in achieving bidirectional block in 86% of patients in the study.6 Rare risks of ablation in this part of the LA are injury to the left circumflex artery and the artery to the sinus node.
Vein of Marshall and Vein of Marshall Ablation
The VOM and ligament of Marshall (LOM) are embryologic remnants of the left superior vena cava, and have been observed to be a source of initiating triggers for AF as well as a conduit for parasympathetic and sympathetic innervation of the LA and CS.7 The extracardiac LOM contains the intracardiac (but epicardial) VOM along with autonomic nerves and a muscle sleeve (called the “Marshall bundle”). The VOM is located in the epicardial aspect of the left lateral ridge between the left pulmonary veins and the LAA. The VOM is in close anatomic proximity to the PMI.
Ablation of the LOM from an endocardial approach, alcohol infusion into the VOM via the CS, and surgical excision have been described as methods to treat AF, accessory pathways, and MAF. Ethanol infusion into the VOM has been found to be useful in terminating MAF and in achieving bidirectional block in AF ablation patients with de novo MAF as well as in those with recurrent MAF despite prior ablation.8
The Vein of Marshall Ethanol Infusion for Persistent Atrial Fibrillation (VENUS) trial was presented at the American College of Cardiology Virtual Annual Scientific Session Together With World Congress of Cardiology (ACC 2020/WCC).9 The trial enrolled patients with persistent AF undergoing their first ablation for the arrhythmia. The primary outcome was freedom from AT/AF ≥30 seconds after 3 months. Investigators showed that a strategy of VOM alcohol ablation in addition to standard catheter ablation was superior to standard catheter ablation alone in reducing AT/AF burden and recurrence. In the group treated with VOM ablation and catheter ablation compared with standard catheter ablation, the primary outcome occurred in 49.2% vs 38% (P=.037).9 This trial holds promise for the future study of VOM alcohol infusion. Beyond the VOM, other left atrial veins may be targets for delivering therapies as well.10
In this patient’s case, the substrate present at the time of the procedure was complicated by multiple prior ablations and prior cardiac surgery. It is not surprising that MAF was inducible in this scenario. The challenge was creating bidirectional block across the PMI. To achieve this endpoint, ablation was required in the endocardial LA, epicardial CS, and epicardial VOM. The VOM ablation had the added benefit of being an adjunctive therapy for the management of AF. In complex cases, having a variety of techniques to accomplish the ablation goal has significant value.
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Disclosures: Dr. Frisch has no conflicts of interest to report regarding the content herein. Outside the submitted work, he reports receiving honoraria for lectures hosted by Abbott.
- Deisenhofer I, Estner H, Zrenner B, et al. Left atrial tachycardia after circumferential pulmonary vein ablation for atrial fibrillation: incidence, electrophysiological characteristics, and results of radiofrequency ablation. Europace. 2006;8:573-582.
- Bai R, Di Biase L, Mohanty P, et al. Ablation of perimitral flutter following catheter ablation of atrial fibrillation: impact on outcomes from a randomized study (PROPOSE). J Cardiovasc Eiectrophysioi. 2012;23:137-144.
- Luria DM, Nemec J, Etheridge SP, et al. Intra-atrial conduction block along the mitral valve annulus during accessory pathway ablation: evidence for a left atrial “isthmus”. J Cardiovasc Electrophysiol. 2001;12(7):744-749.
- Jaïs P, Hocini M, Hsu LF, et al. Technique and results of linear ablation at the mitral isthmus. Circulation. 2004;110:2996-3002.
- Chugh A, Makkar A, Yen Ho S, et al. Manifestations of coronary arterial injury during catheter ablation of atrial fibrillation and related arrhythmias. Heart Rhythm. 2013;10(11):1638-1645.
- Tzeis S, Luik A, Jilek C, et al. The modified anterior line: an alternative linear lesion in perimitral flutter. J Cardiovasc Electrophysiol. 2010;21:665-670.
- Rodríguez-Mañero M, Schurmann P, Valderrábano M. Ligament and vein of Marshall: a therapeutic opportunity in atrial fibrillation. Heart Rhythm. 2016;13:593-601.
- Báez-Escudero JL, Morales PF, Dave AS, et al. Ethanol infusion in the vein of Marshall facilitates mitral isthmus ablation. Heart Rhythm. 2012;9:1207-1215.
- Vein of Marshall ethanol infusion for persistent atrial fibrillation – VENUS. American College of Cardiology. Published March 29, 2020. Available at https://www.acc.org/latest-in-cardiology/clinical-trials/2020/03/26/22/46/venus. Accessed May 11, 2020.
- Valderrábano M, Morales P, Rodríguez-Mañero M, Lloves C, Schurmann P, Dave A. The human left atrial venous circulation as a vascular route for atrial pharmacological therapies: effects of ethanol infusion. JACC Clin Electrophysiol. 2017;3:1020-1032.