Comparison of various late gadolinium enhancement magnetic resonance imaging methods with high-definition voltage and activation mapping for detection of atrial cardiomyopathy.

AIMS: Atrial cardiomyopathy (ACM) is associated with increased arrhythmia recurrence rates after pulmonary vein isolation (PVI). We compare the most common left atrial (LA) late gadolinium enhancement magnetic resonance imaging (LGE-MRI)-methods [Utah-method and image intensity ratio (IIR)-methods] and endocardial voltage mapping for ACM-detection and outcome prediction after PVI for atrial fibrillation (AF). METHODS AND RESULTS: In this prospective observational study, 37 ablation-naive patients (66 ± 9 years, 84% male) with persistent AF underwent LA-LGE-MRI and high-definition voltage and activation mapping (2129 ± 484 sites) in sinus rhythm prior to PVI. The MRI-post-processing-analyses were performed by two independent expert laboratories. Arrhythmia recurrence was recorded within 12 months following PVI. The global ACM-extent was highly variable: median LA low-voltage substrate (LA-LVS) was 12.9% at <1.0 mV and 2.7% at <0.5 mV; median LA-LGE-extent using the Utah-method was 18.3% and 0.03-93.1% using the IIR-methods. The LA activation time was significantly correlated with LA-LVS (r = 0.76 at <0.5 mV and r = 0.82 at <1.0 mV, both P < 0.0001), but not with LA-LGE-extent. The highest regional matching between LA-LVS <0.5 mV and LA-LGE was found for the anterior wall in 57% of patients using the Utah-method and in 59% using IIR 1.20. The corresponding values for the posterior wall were 19% and 38%, respectively. Arrhythmia recurrence occurred in 15(41%) patients. Freedom from arrhythmia was significantly lower in those with LA-LVS ≥2 cm2 at 0.5 mV but not in those with LGE ≥20% (Utah-stages III and IV): 43% vs. 81%, P = 0.009 and 50% vs. 67%, P = 0.338, respectively. CONCLUSION: Comparison of the most common LA-LGE-MRI methods and endocardial voltage mapping revealed large discrepancies in global and regional ACM-extent.

Non-invasive body surface electrocardiographic imaging for diagnosis of atrial cardiomyopathy.

AIMS: Atrial cardiomyopathy (ACM) is associated with new-onset atrial fibrillation, arrhythmia recurrence after pulmonary vein isolation (PVI) and increased risk for stroke. At present, diagnosis of ACM is feasible by endocardial contact mapping of left atrial (LA) low-voltage substrate (LVS) or late gadolinium-enhanced magnetic resonance imaging, but their complexity limits a widespread use. The aim of this study was to assess non-invasive body surface electrocardiographic imaging (ECGI) as a novel clinical tool for diagnosis of ACM compared with endocardial mapping. METHODS AND RESULTS: Thirty-nine consecutive patients (66 ± 9 years, 85% male) presenting for their first PVI for persistent atrial fibrillation underwent ECGI in sinus rhythm using a 252-electrode-array mapping system. Subsequently, high-density LA voltage and biatrial activation maps (mean 2090 ± 488 sites) were acquired in sinus rhythm prior to PVI. Freedom from arrhythmia recurrence was assessed within 12 months follow-up. Increased duration of total atrial conduction time (TACT) in ECGI was associated with both increased atrial activation time and extent of LA-LVS in endocardial contact mapping (r = 0.77 and r = 0.66, P < 0.0001 respectively). Atrial cardiomyopathy was found in 23 (59%) patients. A TACT value of 148 ms identified ACM with 91.3% sensitivity and 93.7% specificity. Arrhythmia recurrence occurred in 15 (38%) patients during a follow-up of 389 ± 55 days. Freedom from arrhythmia was significantly higher in patients with a TACT <148 ms compared with patients with a TACT ≥148 ms (82.4% vs. 45.5%, P = 0.019). CONCLUSION: Analysis of TACT in non-invasive ECGI allows diagnosis of patients with ACM, which is associated with a significantly increased risk for arrhythmia recurrence following PVI.

Predictive value of late gadolinium enhancement cardiovascular magnetic resonance in patients with persistent atrial fibrillation: dual-centre validation of a standardized method.

Aims: With recurrence rates up to 50% after pulmonary vein isolation (PVI) in persistent atrial fibrillation (AF), predictive tools to improve patient selection are needed. Patient selection based on left atrial late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been proposed previously (UTAH-classification). However, this approach has not been widely established, in part owed to the lack of standardization of the LGE quantification method. We have recently established a standardized LGE-CMR method enabling reproducible LGE-quantification. Here, the ability of this method to predict outcome after PVI was evaluated. Methods and results: This dual-centre study (n = 219) consists of a prospective derivation cohort (n = 37, all persistent AF) and an external validation cohort (n = 182; 66 persistent, 116 paroxysmal AF). All patients received an LGE-CMR prior to first-time PVI-only ablation. LGE was quantified based on the signal-intensity-ratio relative to the blood pool, applying a uniform LGE-defining threshold of >1.2.  In patients with persistent AF in the derivation cohort, left atrial LGE-extent above a cut-off value of 12% was found to best predict relevant low-voltage substrate (≥2 cm two with <0.5 mV during sinus rhythm) and arrhythmia-free survival 12 months post-PVI. When applied to the external validation cohort, this cut-off value was also predictive of arrhythmia-free survival for both, the total cohort and the subgroup with persistent AF (LGE < 12%: 80% and 76%; LGE > 12%: 55% and 44%; P = 0.007 and P = 0.029, respectively). Conclusion: This dual-centre study established and validated a standardized, reproducible LGE-CMR method discriminating PVI responders from non-responders, which may improve choice of therapeutic approach or ablation strategy for patients with persistent AF.

Structural and electrophysiological determinants of atrial cardiomyopathy identify remodeling discrepancies between paroxysmal and persistent atrial fibrillation.

Background: Progressive atrial fibrotic remodeling has been reported to be associated with atrial cardiomyopathy (ACM) and the transition from paroxysmal to persistent atrial fibrillation (AF). We sought to identify the anatomical/structural and electrophysiological factors involved in atrial remodeling that promote AF persistency. Methods: Consecutive patients with paroxysmal (n = 134) or persistent (n = 136) AF who presented for their first AF ablation procedure were included. Patients underwent left atrial (LA) high-definition mapping (1,835 ± 421 sites/map) during sinus rhythm (SR) and were randomized to training and validation sets for model development and evaluation. A total of 62 parameters from both electro-anatomical mapping and non-invasive baseline data were extracted encompassing four main categories: (1) LA size, (2) extent of low-voltage-substrate (LVS), (3) LA voltages and (4) bi-atrial conduction time as identified by the duration of amplified P-wave (APWD) in a digital 12-lead-ECG. Least absolute shrinkage and selection operator (LASSO) and logistic regression were performed to identify the factors that are most relevant to AF persistency in each category alone and all categories combined. The performance of the developed models for diagnosis of AF persistency was validated regarding discrimination, calibration and clinical usefulness. In addition, HATCH score and C2HEST score were also evaluated for their performance in identification of AF persistency. Results: In training and validation sets, APWD (threshold 151 ms), LA volume (LAV, threshold 94 mL), bipolar LVS area < 1.0 mV (threshold 4.55 cm2) and LA global mean voltage (GMV, threshold 1.66 mV) were identified as best determinants for AF persistency in the respective category. Moreover, APWD (AUC 0.851 and 0.801) and LA volume (AUC 0.788 and 0.741) achieved better discrimination between AF types than LVS extent (AUC 0.783 and 0.682) and GMV (AUC 0.751 and 0.707). The integrated model (combining APWD and LAV) yielded the best discrimination performance between AF types (AUC 0.876 in training set and 0.830 in validation set). In contrast, HATCH score and C2HEST score only achieved AUC < 0.60 in identifying individuals with persistent AF in current study. Conclusion: Among 62 electro-anatomical parameters, we identified APWD, LA volume, LVS extent, and mean LA voltage as the four determinant electrophysiological and structural factors that are most relevant for AF persistency. Notably, the combination of APWD with LA volume enabled discrimination between paroxysmal and persistent AF with high accuracy, emphasizing their importance as underlying substrate of persistent AF.

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

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.

Echocardiographic diagnosis of atrial cardiomyopathy allows outcome prediction following pulmonary vein isolation.

BACKGROUND: Relevant atrial cardiomyopathy (ACM), defined as a left atrial (LA) low-voltage area ≥ 2 cm2 at 0.5 mV threshold on endocardial contact mapping, is associated with new-onset atrial fibrillation (AF), higher arrhythmia recurrence rates after pulmonary vein isolation (PVI), and an increased risk of stroke. The current study aimed to assess two non-invasive echocardiographic parameters, LA emptying fraction (EF) and LA longitudinal strain (LAS, during reservoir (LASr), conduit (LAScd) and contraction phase (LASct)) for the diagnosis of ACM and prediction of arrhythmia outcome after PVI. METHODS: We prospectively enrolled 60 consecutive, ablation-naive patients (age 66 ± 9 years, 80% males) with persistent AF. In 30 patients (derivation cohort), LA-EF and LAS cut-off values for the presence of relevant ACM (high-density endocardial contact mapping in sinus rhythm prior to PVI at 3000 ± 1249 sites) were established in sinus rhythm and tested in a validation cohort (n = 30). Arrhythmia recurrence within 12 months was documented using 72-h Holter electrocardiograms. RESULTS: An LA-EF of < 34% predicted ACM with an area under the curve (AUC) of 0.846 (sensitivity 69.2%, specificity 76.5%) similar to a LASr < 23.5% (AUC 0.878, sensitivity 92.3%, specificity 82.4%). In the validation cohort, these cut-offs established the correct diagnosis of ACM in 76% of patients (positive predictive values 87%/93% and negative predictive values 73%/75%, respectively). Arrhythmia recurrence in the entire cohort was significantly more frequent in patients with LA-EF < 34% and LASr < 23.5% (56% vs. 29% and 55% vs. 26%, both p < 0.05). CONCLUSION: The echocardiographic parameters LA-EF and LAS allow accurate, non-invasive diagnosis of ACM and prediction of arrhythmia recurrence after PVI.