Left Atrial Hypertension, Electrical Conduction Slowing, and Mechanical Dysfunction - The Pathophysiological Triad in Atrial Fibrillation-Associated Atrial Cardiomyopathy

Front Physiol. 2021 Aug 5:12:670527. doi: 10.3389/fphys.2021.670527. eCollection 2021.

Abstract

Background: Atrial fibrillation (AF) is the most common arrhythmia and a significant burden for healthcare systems worldwide. Presence of relevant atrial cardiomyopathy (ACM) is related to persistent AF and increased arrhythmia recurrence rates after pulmonary vein isolation (PVI).

Objective: To investigate the association of left atrial pressure (LAP), left atrial electrical [invasive atrial activation time (IAAT) and amplified p-wave duration (aPWD)] and mechanical [left atrial emptying fraction (LA-EF) and left atrial strain (LAS)] functional parameters with the extent of ACM and their impact on arrhythmia recurrence following PVI.

Materials and methods: Fifty patients [age 67 (IQR: 61-75) years, 78% male] undergoing their first PVI for persistent AF were prospectively included. LAP (maximum amplitude of the v-wave), digital 12-lead electrocardiogram, echocardiography and high-density endocardial contact mapping were acquired in sinus rhythm prior to PVI. Arrhythmia recurrence was assessed using 72-hour Holter electrocardiogram at 6 and 12 months post PVI.

Results: Relevant ACM (defined as left atrial low-voltage extent ≥2 cm2 at <0.5 mV threshold) was diagnosed in 25/50 (50%) patients. Compared to patients without ACM, patients with ACM had higher LAP [17.6 (10.6-19.5) mmHg with ACM versus 11.3 (7.9-14.0) mmHg without ACM (p = 0.009)]. The corresponding values for the electrical parameters were 166 (149-181) ms versus 139 (131-143) ms for IAAT (p < 0.0001), 163 (154-176) ms versus 148 (136-152) ms for aPWD on surface-ECG (p < 0.0001) and for the mechanical parameters 27.0 (17.5-37.0) % versus 41.0 (35.0-45.0) % for LA-EF in standard 2D-echocardiography (p < 0.0001) and 15.2 (11.0-21.2) % versus 29.4 (24.9-36.6) % for LAS during reservoir phase (p < 0.0001). Furthermore, all parameters showed a linear correlation with ACM extent (p < 0.05 for all). Receiver-operator-curve-analysis demonstrated a LAP ≥12.4 mmHg [area under the curve (AUC): 0.717, sensitivity: 72%, and specificity: 60%], a prolonged IAAT ≥143 ms (AUC: 0.899, sensitivity: 84%, and specificity: 80%), a prolonged aPWD ≥153 ms (AUC: 0.860, sensitivity: 80%, and specificity: 79%), an impaired LA-EF ≤33% (AUC: 0.869, sensitivity: 84%, and specificity: 72%), and an impaired LAS during reservoir phase ≤23% (AUC: 0.884, sensitivity: 84%, and specificity: 84%) as predictors for relevant ACM. Arrhythmia recurrence within 12 months post PVI was significantly increased in patients with relevant ACM ≥2 cm2, electrical dysfunction with prolonged IAAT ≥143 ms and mechanical dysfunction with impaired LA-EF ≤33% (66 versus 20, 50 versus 23 and 55 versus 25%, all p < 0.05).

Conclusion: Left atrial hypertension, electrical conduction slowing and mechanical dysfunction are associated with ACM. These findings improve the understanding of ACM pathophysiology and may be suitable for risk stratification for new-onset AF, arrhythmia recurrence following PVI, and development of novel therapeutic strategies to prevent AF and its associated complications.

Keywords: atrial cardiomyopathy; atrial conduction abnormalities; atrial fibrillation; left atrial pressure; left atrial strain; pathophysiology; pulmonary vein isolation.