Regional Cardiac Remodeling Signatures Across Atria and Ventricles Revealed by Vein of Marshall and Anterior Interventricular Vein Sampling

Summary

Collecting the blood in the vein of Marshall (VOM) is a feasible and highly reproducible method for real-time detection of human atrial biochemical profiles. VOM-derived blood provides a unique window for studying atrial remodeling, which may help provide a platform for future mechanism research and the discovery of biomarkers.

Abstract

The incidence rate of atrial fibrillation is increasing year by year, which is characterized by time progression, but its mechanism is unknown. Vein of Marshall (VOM), also known as the left atrial oblique vein, plays a crucial role in collecting venous return from atrial tissue. VOM originates from the posterior wall of the left atrium and is closely related to structures such as the left atrial appendage and pulmonary vein. VOM plays an important role in the occurrence and maintenance of atrial fibrillation, but there have been no other reports on its role in atrial fibrillation-related diseases. In this research, the authors innovatively used over-the-wire (OTW) balloons to collect blood samples from the VOM patients before atrial fibrillation ablation surgery for biochemical analysis. This study measured a recognized biomarker associated with the onset of atrial fibrillation: atrial natriuretic peptide (ANP), a biomarker of atrial stretching and structural remodeling, a biologically active natriuretic peptide that plays an important role in atrial fibrillation. Compared with samples from the anterior interventricular vein (AIV) and coronary sinus (CS), ANP concentration was significantly upregulated in VOM blood, indicating that VOM blood better captures atrial-specific biochemical signals. This research found that VOM blood provides a good representation of the microenvironment associated with atrial fibrillation, providing scientific evidence for the search for biomarkers and therapeutic targets for the future.

Introduction

Vein of Marshall (VOM), also known as the left atrial oblique vein, plays a crucial role in collecting venous return from atrial tissue. VOM originates from the posterior wall of the left atrium and is closely related to structures such as the left atrial appendage and pulmonary vein¹. Its unique anatomical location and venous network structure enable direct or indirect electrical connections and fluid interactions with the left atrium and pulmonary veins^2,3. VOM plays an important role in the occurrence and maintenance of atrial fibrillation, but its role in atrial fibrillation-related diseases has not been reported in other studies. This research aims to establish and validate a new catheter-based selective Marshall vein (VOM) blood-collection technique and to evaluate its application value for obtaining atrial-specific molecular signals related to the pathophysiology of atrial fibrillation. Its development is based on the fact that the structure/autonomic nervous system remodeling of atrial fibrillation occurs in local atrial tissue, but it is difficult to directly obtain atrial tissue for dynamic biochemical evaluation in clinical practice In the study, in 22 patients who underwent catheter ablation of atrial fibrillation, the authors used a fluoroscopy guided "over the wire balloon catheter" to selectively insert VOM and collect blood. Simultaneously collect the anterior interventricular vein (AIV), coronary sinus (CS), and left atrial cavity (LA) Blood sample control, using ELISA (Enzyme-Linked Immunosorbent Assay) to detect atrial natriuretic peptide (ANP). This research detected the ANP content in VOM blood through an ELISA experiment and compared it with the ANP content in AIV and CS blood^4,5.

Previous studies have shown that VOM ethanol infusion can be used as an auxiliary means of atrial fibrillation ablation and produce local ablation effects^6,7,8. This method allows us to better explore the physiological and biochemical conditions under which atrial fibrillation occurs. It is feasible in patients who can successfully insert VOM anatomically during atrial fibrillation catheter ablation; it requires some experience with interventions and fluoroscopy equipment, and is not suitable for patients with VOM developmental disorders during intubation or for those who are not suitable for increased operating time.

Protocol

The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Xinhua Hospital (XHEC-C-2023-128-2). All items required in this protocol are listed in the Table of Materials.

CAUTION: Avoid forceful guidewire advancement, deep catheter engagement, and high-pressure balloon inflation during the procedure. The balloon should be inflated gently and only to the minimum pressure necessary for catheter stabilization and partial venous occlusion. Continuous fluoroscopic monitoring of the guidewire, catheter tip, balloon position, and contrast flow is essential throughout the procedure. VOM manipulation should be stopped immediately if resistance, contrast extravasation, vessel staining, suspected dissection, or unstable catheter positioning is encountered. VOM blood sampling should be abandoned in any patient in whom safe catheter positioning cannot be consistently maintained.

1. Preoperative preparation

NOTE: The pre-ablation evaluation and anticoagulation strategy follow the central standard for routine ablation procedures; activated clotting time (ACT) should be monitored during the procedure and maintained within the institutional therapeutic range (typically 300–350 s) during left atrial instrumentation. Anticoagulation with heparin during surgery to make the ACT greater than 300.

1. After establishing venous access, place a ten-pole electrode to the CS and get access to the LA through the atrial septum, ensuring that fluoroscopy and contrast conditions are available, and ensure that fluoroscopy and contrast conditions are available.

2. VOM recognition and intubation

1. Entering CS: Place the Judkins catheter and Runthrough guidewire into the CS along the ten-pole electrode.
2. CS imaging localization VOM: Identify and localize the vein of Marshall (VOM) under fluoroscopic guidance after successful engagement of the coronary sinus (CS).
3. Advance the CS sheath or guiding catheter into the proximal CS and perform CS venography using a small amount of contrast medium.
4. Acquire venographic images in multiple fluoroscopic projections, including right anterior oblique and left anterior oblique views, to clearly define the CS anatomy and identify venous branches.
5. Locate the VOM ostium near the region of the valve of Vieussens, typically close to the junction between the CS and the great cardiac vein.
6. Recognize the VOM as a small oblique venous branch that usually courses superiorly and posteriorly toward the left atrium and left pulmonary vein region. Carefully distinguish the VOM from adjacent CS branches by evaluating its origin, direction, caliber, and venographic course.
7. If the VOM ostium is not clearly visualized on initial CS venography, rotate or reposition the guiding catheter and repeat contrast injection under a different fluoroscopic projection.
8. Use a subselective catheter to explore the proximal CS region when branch anatomy remains unclear.
9. Confirm the VOM by selective contrast injection before advancing the guidewire or OTW balloon catheter. Avoid forceful catheter or guidewire manipulation during this step to reduce the risk of venous dissection, perforation, or contrast extravasation.

3. VOM and control site blood collection

1. VOM blood collection: Inflate the OTW balloon slowly and stepwise under fluoroscopy in the target segment to stabilize the position (while minimizing mixing with the CS backbone), and slowly collect the VOM blood sample through the OTW system. After blood collection, gently rinse the lumen with heparinized saline to prevent clotting.
2. AIV blood collection (ventricular vein control): Withdraw the catheter system to the CS/large cardiac vein direction and enter the AIV under contrast imaging. Use the OTW balloon positioning method to withdraw blood as a non-atrial source control.
3. CS main stem and LA cavity blood collection: Obtain CS main stem blood by withdrawing at the CS sheath/catheter position. Collect LA blood after successful transseptal puncture and placement of the transseptal sheath in the left atrium, preferably before ablation energy delivery.

4. Sample processing

1. ANP: Collect the blood in pre-cooled EDTA tubes, and protease inhibitors such as aprotinin are added as soon as possible and placed on ice; Centrifuge the blood at 4 °C within 1 h (e.g. 1600 g x 15 min), separate the plasma and store it at -20 °C or lower (long-term recommendation -80 °C).

5. Criteria for minimizing CS-VOM blood mixing

1. Advance the OTW balloon catheter into the VOM, inflate the balloon gently with diluted contrast or saline until the catheter position is stable, and minimize reflux from the VOM into the CS trunk.
2. Use only the effective and safe balloon inflation volume and pressure required for partial venous occlusion, and confirm adequate balloon positioning by fluoroscopy and contrast injection.
3. Verify stable balloon placement, reduced contrast backflow into the CS trunk, and absence of vessel staining or extravasation.
4. Aspirate VOM blood slowly through the OTW catheter using gentle negative pressure; avoid rapid or forceful aspiration to prevent venous collapse, hemolysis, and CS contamination.
5. Stop aspiration if the sample volume is insufficient or aspiration resistance increases, adjust the catheter or balloon position gently rather than increasing suction force, discard samples with obvious hemolysis, visible clotting, or suspected CS contamination.

Results

The method of this study adopts a perspective-guided OTW balloon microcatheter strategy, which can achieve partitioned collection of atrial- and ventricular-specific reflux venous blood during catheter ablation of atrial fibrillation: identification and selective entry into the Marshall vein (VOM) and the anterior interventricular vein (AIV) through coronary sinus angiography. Simultaneously, control samples were obtained from the main coronary sinus (CS) and left atrial cavity (LA, intracavitary reference) (

Discussion

This study proposes and validates a new blood sampling approach and method: collecting blood samples from the Marshall vein (VOM) and the anterior interventricular vein (AIV) under catheterization. Due to the lack of routine methods for obtaining atrial tissue samples in clinical practice, the understanding of the mechanisms of atrial fibrillation (AF) and atrial remodeling is limited. Marshall vein is located within the mitral isthmus, critical for perimitral atrial tachycardia¹⁰. The vein of Mar...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
8F venous sheath	TERUMO	RS A80K10SQ	8F venous introducer sheath; used to establish venous access and introduce the CS sheath or guiding catheter during VOM and AIV sampling.
BMW guidewire	Abbott	1001780-HC	0.014-inch hydrophilic coronary guidewire; 190 cm length; 3 cm radiopaque tip
contrast agent	Visipaque	86978446001021	Nonionic iso-osmolar iodinated contrast medium; used for CS venography and selective visualization of the VOM and AIV during catheter positioning.
CS sheath	Synaptic	D6010282092DNRT	Coronary sinus guiding sheath; used to access the coronary sinus and provide support for selective catheterization of the VOM and AIV.
EDTA collection tubes	Lianke Bio	PL18-703C-7	Pre-cooled EDTA blood collection tube; used for plasma collection and prevention of coagulation during VOM, AIV, CS, and LA blood sampling
guidewire	TERUMO	TW-AS418FA	Hydrophilic angiographic guidewire; used to assist selective catheter positioning and vessel navigation during CS venography and VOM/AIV cannulation.
Judkins catheter	Medtronic	LA6JR40	Judkins right catheter; used to assist retrograde exploration of the proximal coronary sinus and selective visualization of the VOM ostium.
Microcatheter	TERUMO	NC-F863A	used to provide guidewire and assist selective advancement into the VOM or AIV during regional venous blood sampling
OTW balloon catheter	DK MEDTECH	OIB-2015	1.5–2.5 mm over-the-wire coronary balloon catheter; used for superselective VOM/AIV cannulation, temporary low-pressure occlusion, and regional venous blood collection under fluoroscopic guidance.
protease inhibitors	beyotime	P1005	The protease inhibitor cocktail for general use (100X) from Biyun Tian is a universal mixture of protease inhibitors used for cell or tissue protein extraction, including 200 mM AEBSF, 30 μM Aprotinin, 13 mM Bestatin, 1.4 mM E64, and 1 mM Leupeptin in DMSO
Refrigerated centrifuge	Eppendorf	5811000015	used to centrifuge EDTA blood samples at 4 °C for plasma separation