Nonthrombogenic Roles of the Left Atrial Appendage

Abstract and Introduction

Abstract

The atrial appendage (LAA) is a well-established source of cardioembolism in patients with atrial fibrillation. Therefore, research involving the LAA has largely focused on its thrombogenic attribute and the utility of its exclusion in stroke prevention. However, recent studies have highlighted several novel functions of the LAA that may have important therapeutic implications. In this paper, we provide a concise overview of the LAA anatomy and summarize the emerging data on its nonthrombogenic roles.

Introduction

The left atrial appendage (LAA) is widely regarded as a major source of thromboembolism in patients with atrial fibrillation (AF).^[1] This hypothesis gave rise to the concept of eliminating the LAA from the systemic circulation to lower the risk of stroke in AF patients.^[2] In the last 2 decades, several studies documented the efficacy of transcatheter and surgical left atrial appendage closure (LAAC) in reducing thromboembolic risk, establishing LAAC as an effective stroke prophylaxis strategy in selected AF patients.^[3] The rapidly evolving LAAC field refueled the interest in understanding probable roles of the LAA in neurohormonal regulation, arrhythmogenesis, and left atrial (LA) function. However, LAA remains largely discussed in the context of its thrombogenic role both in the literature and in clinical practice. In this paper, we review the proposed nonthrombogenic roles of the LAA and discuss their potential therapeutic implications (Central Illustration).

(Enlarge Image)

Central Illustration.

Nonthrombogenic Roles of the Left Atrial Appendage
This figure illustrates the key 4 nonthrombogenic functions of the left atrial appendage.

Table 1. Summary of Studies Investigating the Hemodynamic Effect of Transcatheter Left Atrial Appendage Closure
First Author	Cohort	Main Endpoint	Findings
Phan et al³⁹	188 patients (47 LAAC, 141 control)	Change in LA remodeling (LAAC vs control)	• LA dimension increased (+3.9 mm) • LA volume index increased (+5.9 mL/m²) • E and E/e' ratio increased (+14.6 cm/s and +2.3)
Mertens et al⁴¹	85 LAAC patients	Change in LAP after LAAC^a	• LAP increased from 12.6 ± 3.9 to 15.5 ± 5.2 mm Hg • Proportion of patients with LAP >15 increased (20% to 45%)
Asmarats et al³⁶	31 LAAC patients	Change in stroke volume at 24 h	• No significant change in LV stroke volume (72.4 ± 16.0 mL vs 73.3 ± 15.7 mL) or LA stroke volume (15.6 ± 4.2 mL vs 14.6 ± 4.2 mL)
Coisne et al³⁷	33 LAAC patients	Change in LA mechanical function at 45 d	• LA reservoir function improved (LA reservoir volume increased from 19.5 ± 6.5 mL/m² to 25 ± 6.4 mL/m², and peak atrial longitudinal strain increased from 15.5% ± 5.4% to 17.8% ± 7.1%) • LA booster function improved (peak atrial contraction strain increased from 14.4% ± 6.4% to 18.1% ± 5.4%,^b and 3D-LA ejection fraction increased from 37.7% ± 11.5% to 50.2% ± 13%)
Ijuin et al³⁸	95 LAAC patients	Change in LA mechanical function at 45 d	• LA reservoir function improved (peak atrial longitudinal strain increased from 12.4% ± 8.4% to 16.0% ± 10.6%) • LA booster function improved (peak atrial contraction strain increased from 5.8% ± 3.9% to 10.6% ± 7.6%^b)
Murtaza et al³⁵	25 LAAC patients	Change in LA mechanical function at 30 d	• Volumetric analysis showed significant improvement in LA reservoir function (LA expansion index 58.1 [37.8–85.2] vs 75.3 [52.3–98.0]), conduit function (passive emptying fraction 21.0 [13.8–34.7] vs 28.6 [21.9–35.9]), and booster fraction (12.6 [8.8–25.5] vs 13.3 [9.7–29.9]). However, strain analysis showed no change in LA conduit or reservoir functions
Sharma et al⁴⁰	67 LAAC patients	Change in LA, LV, and RV function 24 h	• LA reservoir function improved (peak atrial longitudinal strain increased from 20.6 ± 12.2 to 22.9 ± 12.9) LVEF increased (52.4% ± 12.6% to 56.7% ± 12.7%) • Mitral E/e' increased (14.1 ± 6.5 to 18.3 ± 10.8) • RV global longitudinal strain increased (−17.5 ± 4.6 to −19.6 ± 5.7)

Table 1. Summary of Studies Investigating the Hemodynamic Effect of Transcatheter Left Atrial Appendage Closure

First Author

Cohort

Main Endpoint

Findings

Phan et al³⁹

188 patients (47 LAAC, 141 control)

Change in LA remodeling (LAAC vs control)

• LA dimension increased (+3.9 mm)
• LA volume index increased (+5.9 mL/m²)
• E and E/e' ratio increased (+14.6 cm/s and +2.3)

Mertens et al⁴¹

85 LAAC patients

Change in LAP after LAAC^a

• LAP increased from 12.6 ± 3.9 to 15.5 ± 5.2 mm Hg
• Proportion of patients with LAP >15 increased (20% to 45%)

Asmarats et al³⁶

31 LAAC patients

Change in stroke volume at 24 h

• No significant change in LV stroke volume (72.4 ± 16.0 mL vs 73.3 ± 15.7 mL) or LA stroke volume (15.6 ± 4.2 mL vs 14.6 ± 4.2 mL)

Coisne et al³⁷

33 LAAC patients

Change in LA mechanical function at 45 d

• LA reservoir function improved (LA reservoir volume increased from 19.5 ± 6.5 mL/m² to 25 ± 6.4 mL/m², and peak atrial longitudinal strain increased from 15.5% ± 5.4% to 17.8% ± 7.1%)
• LA booster function improved (peak atrial contraction strain increased from 14.4% ± 6.4% to 18.1% ± 5.4%,^b and 3D-LA ejection fraction increased from 37.7% ± 11.5% to 50.2% ± 13%)

Ijuin et al³⁸

95 LAAC patients

Change in LA mechanical function at 45 d

• LA reservoir function improved (peak atrial longitudinal strain increased from 12.4% ± 8.4% to 16.0% ± 10.6%)
• LA booster function improved (peak atrial contraction strain increased from 5.8% ± 3.9% to 10.6% ± 7.6%^b)

Murtaza et al³⁵

25 LAAC patients

Change in LA mechanical function at 30 d

• Volumetric analysis showed significant improvement in LA reservoir function (LA expansion index 58.1 [37.8–85.2] vs 75.3 [52.3–98.0]), conduit function (passive emptying fraction 21.0 [13.8–34.7] vs 28.6 [21.9–35.9]), and booster fraction (12.6 [8.8–25.5] vs 13.3 [9.7–29.9]). However, strain analysis showed no change in LA conduit or reservoir functions

Sharma et al⁴⁰

67 LAAC patients

Change in LA, LV, and RV function 24 h

• LA reservoir function improved (peak atrial longitudinal strain increased from 20.6 ± 12.2 to 22.9 ± 12.9) LVEF increased (52.4% ± 12.6% to 56.7% ± 12.7%)
• Mitral E/e' increased (14.1 ± 6.5 to 18.3 ± 10.8)
• RV global longitudinal strain increased (−17.5 ± 4.6 to −19.6 ± 5.7)

Nonthrombogenic Roles of the Left Atrial Appendage

JACC Review Topic of the Week

Abstract and Introduction

Abstract

Introduction

Tables

References

Authors and Disclosures

Authors and Disclosures

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Appendix

Central Illustration.

Central Illustration.

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