Atrial Fibrillation-Associated Remodeling Does Not Promote Atrial Thrombus Formation in Canine Models

Abstract

The most important complication of atrial fibrillation (AF) is thromboembolic stroke. Although AF-related remodeling is considered important in atrial thrombogenesis, its role never has been directly tested. This study assessed effects of AF-related remodeling on the atrial thrombogenic milieu by using radiofrequency ablation (RFA) to create a quantifiable prothrombotic nidus. We studied normal control dogs (control, n=16) and 3 canine AF-models: (1) atrial tachycardia remodeling (ATR; n=16) induced by atrial tachypacing (400 bpm for 1 week, with atrioventricular block and ventricular pacing at 80 bpm); (2) congestive heart failure (CHF; n=14) attributable to ventricular tachypacing (240 bpm for 2 weeks); and (3) chronic AF (CAF; n=8) induced by atrial tachypacing (35±3 days) without atrioventricular block. CAF dogs had AF for 13±1 days until euthanization. After remodeling was established, RFA lesions were created in both atria. Half the ATR and CHF dogs were subjected to atrial tachypacing during 7-day post-RFA follow-up. Electrophysiological and echocardiographic studies were performed before RFA and 7 days after RFA, and then hearts were removed and atrial thrombi were quantified by histomorphometry. Burst-pacing-induced AF duration was significantly greater in ATR, CHF, and CAF groups versus control group. The atrial effective refractory period shortened in ATR and CAF groups. Left atrial diameter was significantly larger with CHF, but not with ATR. Neither total thrombus volume nor thrombus volume per lesion differed significantly among groups. Table.Properties of Ablation Lesions and Atrial Thrombi Experimental GroupControl (n=16)ATR (n=16)CHF (n=14)CAF (n=8)N of ablation lesions per dog6.9±0.36.6±0.27.2±0.26.9±0.4Ablation lesion area, mm(2)53.1±3.558.3±4.857.7±4.944.3±3.7Ablation lesion depth, mm5.2±0.25.1±0.35.3±0.25.2±0.2Ablation lesion volume, mm(3)205.2±17.8211.6±17.6231.5±29.0176.8±22.2N of thrombi per dog5.4±0.44.7±0.35.6±0.46.5±0.4Presence of thrombus, %80±572±577±695±3Mean thrombus volume in both atria, mm(3)20.8±3.414.9±2.212.2±2.622.5±5.6Mean thrombus volume in left atria, mm(3)8.2±1.54.0±0.95.5±1.68.1±3.3Mean thrombus volume in right atria, mm(3)30.1±5.422.7±4.317.9±4.132.8±8.3Total thrombus volume in both atria, mm(3)140.5±21.399.7±16.886.1±17.5131.1±22.7Total thrombus volume in left atria, mm(3)22.8±5.311.8±3.317.0±3.723.3±6.4Total thrombus volume in right atria, mm(3)117.7±21.587.8±17.269.1±16.1107.8±23.3Thrombus volume normalized to ablation lesion area in both atria, mm(3)/mm(2)0.5±0.10.4±0.11.5±1.10.8±0.3Thrombus volume normalized to ablation lesion volume in both atria0.2±0.10.1±0.00.5±0.40.3±0.1 ATR indicates atrial tachycardia remodeling; CAF, chronic atrial fibrillation; and CHF, congestive heart failure. There were no statistically significant differences for any groups vs control group for any of these variables studied. None of the AF substrates tested, including sustained atrial tachycardia/AF itself, enhanced post-RFA atrial thrombus formation. Indices of electrical and structural remodeling did not predict post-RFA thrombogenic potential. Contrary to widely held but previously untested notions, we were unable to demonstrate prothrombotic effects of AF-related remodeling.