The Left Atrial Appendage in Sinus Rhythm and Atrial Fibrillation - From Functional Structure to Potential Thromboembolic Reservoir - Rationale for Medical or Radical Exclusion

Sep 30, 2026

The left atrial appendage (LAA) is a highly dynamic structure that governs left atrial reservoir function, pressure and volume modulation, and endocrine hormone secretion during sinus rhythm. In atrial fibrillation (AF), electrical and structural remodeling, impaired contractility, and LAA blood stasis shift it toward the dominant site of thrombus formation and embolic events. This review links physiological LAA function to its pathological AF transformation, then evaluates evolving rationale and unresolved controversies. It synthesizes mechanistic, anatomical, and clinical evidence on anticoagulation, device-based exclusion, surgical closure, residual leaks, device-related thrombosis, and post-procedural antithrombotic management. Emerging directions focus on minimizing residual foreign material, reducing thrombogenicity, and achieving durable, more complete (“radical”) exclusion to personalize stroke prevention strategies.

LanguageEnglish

CategoryHealthcare

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Pages18

Reading Time45 min

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Introduction

Embryology and Physiology of the Adult Left Atrial Appendage

Review The Left Atrial Appendage in Sinus Rhythm and Atrial Fibrillation: From Functional Structure to Potential Thromboembolic Reservoir, Rationale for Medical or Radical Exclusion Jacob Zeitani 1, *, Ermal Likaj 2, Marco Stefano Nazzaro 3, Alban Dibra 4, Kolja Sievert 5 and Horst Sievert 5 Academic Editor: Michael Spartalis Received: 28 November 2025 Revised: 24 December 2025 Accepted: 27 December 2025 Published: 30 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Neurosciences and Rehabilitation Department, University of Ferrara, 44121 Ferrara, Italy 2 Cardiac Surgery Department, Mother Teresa University, 020983 Tirana, Albania 3 Cardiology Department, S. Camillo Hospital, 00100 Rome, Italy 4 Cardiology Department, Mother Teresa University, 020983 Tirana, Albania 5 Cardiovascular Center Frankfurt, 60389 Frankfurt, Germany * Correspondence: jacob.zeitani@unife.it Abstract The left atrial appendage (LAA) is a highly dynamic anatomical structure that plays a key role in left atrial reservoir function, pressure and volume modulation, and endocrine hormone secretion during sinus rhythm. However, its physiological contribution is profoundly altered in atrial fibrillation (AF). Electrical and structural remodeling, impaired contractility, and blood stasis within the LAA collectively transform this functional component into the principal cardiac source of thrombus formation and embolic events in patients with AF. This review focuses on the conceptual continuum from physiological LAA function in sinus rhythm to its pathological transformation in AF and the evolving rationale for progressively more complete (“radical”) anatomical exclusion A variety of strategies, including systemic anticoagulation therapy, percutaneous device-based exclusion, and surgical closure, are currently employed, each with specific indications, limitations, and procedure-related risks. Beyond summarizing available techniques, this review critically synthesizes mechanistic, anatomical, and clinical data to address unresolved controversies regarding patientselection, residual leaks, device-related thrombosis, and post-procedural antithrombotic management. Finally, emerging directions toward minimizing residual foreign material, reducing thrombogenicity, and achieving durable exclusion are discussed, supporting amore personalized and radical approach to stroke prevention in AF. Keywords: atrial fibrillation (AF); device occlusion; direct oral anticoagulation (DOAC); left atrial appendage (LAAO); surgical excision; thrombus; transcatheter 1. Introduction The left atrial appendage (LAA) plays an essential role in maintaining normal cardiac physiology during sinus rhythm, contributing to left atrial reservoir function, volume regulation, and endocrine signaling [1–3] . However, clinical attention toward this structure intensifies markedly with the development of atrial fibrillation (AF) . In AF, profound alterations in electrical activation, mechanical contractility, and intracavitary blood flow transform the LAA from a functional, highly dynamic atrial component into the predominant cardiac source of thromboembolism [4,5] . AF is associated with an approximately five-fold increase in ischemic stroke risk, and more than 90% of left atrial thrombi in nonvalvular AF originate from the LAA. Although this association was firmly established in clinical trials during the 1970s and 1980s, effective stroke-prevention strategies were initially limited, leaving patients exposed to substantial thromboembolic risk [6,7] . Clot formation reflects a complex interplay between LAA anatomy, atrial mechanical dysfunction, and the patient’s clinical risk profile, as captured by contemporary risk stratification schemes such as the CHA2DS2-VA score, in which female sex is no lo

FAQs

What role does the left atrial appendage (LAA) play during sinus rhythm?

During sinus rhythm, the LAA supports left atrial reservoir function, regulates pressure and volume, and contributes to endocrine hormone secretion.

How does atrial fibrillation (AF) change the LAA’s function and thromboembolic risk?

In AF, electrical and structural remodeling, impaired contractility, and blood stasis transform the LAA from a functional component into the principal source of thrombus formation and embolic events.

What strategies are discussed for stroke prevention related to the LAA?

The review discusses systemic anticoagulation, percutaneous device-based exclusion, and surgical closure, including considerations of indications, limitations, procedure-related risks, and management of residual leaks and thrombosis.

Sep 30, 2026

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