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

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.

FIGURE 1

Comparison between left atrial pressure (LAP), left atrial electrical and left atrial mechanical parameters in patients with and without atrial cardiomyopathy (ACM). In patients with ACM (red boxes and whiskers), LAP (A) and left atrial electrical parameters [invasive atrial activation time (IAAT), amplified p-wave duration (aPWD), (B)] were significantly increased. In contrast, left atrial mechanical parameters [left atrial emptying fraction (LA-EF), left atrial strain during reservoir phase (LASr), conduit phase (LAScd), and contraction phase (LASct), (C) were significantly reduced in ACM compared to patients without ACM (green boxes and whiskers). Boxes include data between lower and upper quartiles and whiskers mark 10th and 90th percentiles.

FIGURE 2

Correlations between atrial cardiomyopathy (ACM) extent and left atrial pressure (LAP), electrical parameters and mechanical parameters. LAP (A), left atrial electrical parameters [invasive atrial activation time (IAAT), amplified p-wave duration (aPWD), (B)] and left atrial mechanical parameters [left atrial emptying fraction (LA-EF), left atrial strain during reservoir phase (LASr), conduit phase (LAScd), and contraction phase (LASct), (C)] correlated significantly with ACM extent [assessed as left atrial area displaying low-voltage substrate (LA-LVS) <0.5 mV]. The dashed line marks the border between absence (<2 cm² LA-LVS extent at 0.5 mV threshold) and presence of relevant ACM.

FIGURE 3

Diagnosis of relevant atrial cardiomyopathy (ACM) based on left atrial pressure (LAP), left atrial electrical and mechanical parameters. Receiver-operating curve analysis determined a LAP ≥12.4 mmHg as predictor for relevant ACM with a sensitivity of 72% and a specificity of 60% (A). The corresponding values for the left atrial electrical parameters (B) were ≥143 ms (sensitivity 84% and specificity 80%) for the invasive atrial activation time (IAAT) and ≥153 ms (sensitivity 80% and specificity 79%) for the amplified p-wave duration (aPWD). The values for the left atrial mechanical parameters (C) were ≤33% for LA-EF (sensitivity 84% and specificity 72%), ≤23% for LASr (sensitivity 84% and specificity 84%), ≤13.4% for LAScd (sensitivity 88% and specificity 80%), and ≤6.8% for LASct (sensitivity 80% and specificity 64%).

FIGURE 4

Association of pathological cut-off values for left atrial function and atrial cardiomyopathy (ACM) extent. ACM extent for patients with calculated cut-off values for presence of ACM (red boxes and whiskers) compared to cut-off values for absence of ACM (green boxes and whiskers) are depicted. With the exception of left atrial pressure [LAP, (A)], all left atrial electrical [invasive atrial activation time (IAAT), amplified p-wave duration (aPWD), (B)] and left atrial mechanical parameters [left atrial emptying fraction (LA-EF), left atrial strain during reservoir phase (LASr), conduit phase (LAScd), and contraction phase (LASct), (C)] allowed significant differentiation between high and low ACM extent: 4.3 (0.7–20.6) cm² versus 1.1 (0.2–12.2) cm² for LAP, 13.1 (3.2–27.6) cm² versus 0.5 (0–1.2) cm² for IAAT, 14.7 (4.0–26.9) cm² versus 0.8 (0.2–1.8) cm² for aPWD, 9.6 (3.8–26.6) cm² versus 0.7 (0–2.8) cm² for LA-EF, 17.7 (4.1–29.1) cm² versus 0.5 (0.1–1.5) cm² for LASr, 14.6 (3.5–29.4) cm² versus 0.6 (0.1–1.9) cm² for LAScd, and 11.5 (3.0–25.0) cm² versus 0.7 (0.2–3.7) cm² for LASct. Boxes include data between lower and upper quartiles and whiskers mark 10th and 90th percentiles.

FIGURE 5

Arrhythmia recurrence after pulmonary vein isolation (PVI). Kaplan–Meier curves illustrate arrhythmia recurrence after PVI in patients with relevant atrial cardiomyopathy [ACM defined as ≥2 cm² left atrial low-voltage substrate (LA-LVS) extent at 0.5 mV threshold, red curve in A], prolonged left atrial electrical conduction parameters [invasive atrial activation time (IAAT), red curve in B] and impaired left atrial mechanical parameters [left atrial emptying fraction (LA-EF) and left atrial strain during contraction phase (LASct), red curves in C] compared to patients with normal cut-offs (green curves).

FIGURE 6

Pathophysiology of atrial cardiomyopathy (ACM). This illustration summarizes the pathophysiology of ACM and the diagnostic possibilities to detect the different pathophysiological mechanisms. The representative patient illustrated has a relevant ACM with a left atrial low-voltage substrate (LA-LVS) at 0.5 mV threshold of 25 cm², a hypertensive left atrial pressure (LAP) of 23 mmHg, an impaired left atrial emptying fraction (LA-EF) of 9%, an impaired left atrial strain during reservoir phase (LASr) of 7.8%, during conduit phase (LAScd) of 5.7%, and during contraction phase (LASct) of 2.1% as well as a prolonged amplified p-wave duration (aPWD) of 181 ms.