Clinical Outcomes of low-voltage area-guided left atrial linear ablation for non-paroxysmal atrial fibrillation patients.

BACKGROUND: The therapeutic effect of low-voltage area (LVA)-guided left atrial (LA) linear ablation for non-paroxysmal atrial fibrillation (non-PAF) is uncertain. We aimed to investigate the efficacy of LA linear ablation based on the preexisting LVA and its effects on LA reverse remodeling in non-PAF patients. METHODS: We retrospectively evaluated 145 consecutive patients who underwent radiofrequency catheter ablation for drug-refractory non-PAF. CARTO-guided bipolar voltage mapping was performed in atrial fibrillation (AF). LVA was defined as sites with voltage ≤ 0.5 mV. If circumferential pulmonary vein isolation couldn't convert AF into sinus rhythm, additional LA linear ablation was performed preferentially at sites within LVA. RESULTS: After a mean follow-up duration of 48 ± 33 months, 29 of 145 patients had drugs-refractory AF/LA tachycardia recurrence. Low LA emptying fraction, large LA size and high extent of LVA were associated with AF recurrence. There were 136 patients undergoing LA linear ablation. The rate of linear block at the mitral isthmus was significantly higher via LVA-guided than non-LVA-guided linear ablation. Patients undergoing LVA-guided linear ablation had larger LA size and higher extent of LVA, but the long-term AF/LA tachycardia-free survival rate was higher than the non-LVA-guided group. The LA reverse remodeling effects by resuming sinus rhythm were noted even in patients with a diseased left atrium undergoing extensive LA linear ablation. CONCLUSIONS: LVA-guided linear ablation through targeting the arrhythmogenic LVA and reducing LA mass provides a better clinical outcome than non-LVA guided linear ablation, and outweighs the harmful effects of iatrogenic scaring in non-PAF patients.

Optical Mapping Approaches on Muscleblind-Like Compound Knockout Mice for Understanding Mechanistic Insights Into Ventricular Arrhythmias in Myotonic Dystrophy.

BACKGROUND: Cardiac arrhythmias are common causes of death in patients with myotonic dystrophy (dystrophia myotonica [DM]). Evidence shows that atrial tachyarrhythmia is an independent risk factor for sudden death; however, the relationship is unclear. METHODS AND RESULTS: Control wild-type (Mbnl1+/+; Mbnl2+/+ ) and DM mutant (Mbnl1-/-; Mbnl2+/- ) mice were generated by crossing double heterozygous knockout (Mbnl1+/-; Mbnl2+/- ) mice. In vivo electrophysiological study and optical mapping technique were performed to investigate mechanisms of ventricular tachyarrhythmias. Transmission electron microscopy scanning was performed for myocardium ultrastructural analysis. DM mutant mice were more vulnerable to anesthesia medications and program electrical pacing: 2 of 12 mice had sudden apnea and cardiac arrest during premedication of general anesthesia; 9 of the remaining 10 had atrial tachycardia and/or atrioventricular block, but none of the wild-type mice had spontaneous arrhythmias; and 9 of 10 mice had pacing-induced ventricular tachyarrhythmias, but only 1 of 14 of the wild-type mice. Optical mapping studies revealed prolonged action potential duration, slower conduction velocity, and steeper conduction velocity restitution curves in the DM mutant mice than in the wild-type group. Spatially discordant alternans was more easily inducible in DM mutant than wild-type mice. Transmission electron microscopy showed disarranged myofibrils with enlarged vacuole-occupying mitochondria in the DM mutant group. CONCLUSIONS: This DM mutant mouse model presented with clinical myofibril ultrastructural abnormality and cardiac arrhythmias, including atrial tachyarrhythmias, atrioventricular block, and ventricular tachyarrhythmias. Optical mapping studies revealed prolonged action potential duration and slow conduction velocity in the DM mice, leading to vulnerability of spatially discordant alternans and ventricular arrhythmia induction to pacing.

Piceatannol facilitates conduction block and ventricular fibrillation induction in ischemia-reperfused rabbit hearts with pacing-induced heart failure.

BACKGROUND: Piceatannol, a hydroxystilbene natural product, has been reported to exert antiarrhythmic action via INa inhibition and slow INa inactivation in ischemia-reperfused (IR) rat hearts. The present study aimed to clarify the proarrhythmic property of piceatannol during regional IR injury in failing rabbit hearts. METHODS: Heart failure (HF) was induced by rapid right ventricular pacing for 4 weeks. The IR model was created by coronary artery ligation for 30 min, followed by reperfusion for 15 min in vivo. Simultaneous voltage and intracellular Ca(2+) (Cai) optical mapping was then performed in isolated Langendorff-perfused hearts (n=11 in each HF and control group). Action potential duration (APD) restitution, arrhythmogenic alternans and VF inducibility were evaluated by a dynamic pacing protocol. Conduction velocity was measured along lines across the IR and non-IR zones during pacing. Piceatannol (10 µM) was administered after baseline studies. RESULTS: In the HF group, piceatannol decreased conduction velocity, induced rate-dependent regional inhomogeneity of conduction delay and wavelength shortening, slowed Cai decay, and facilitated arrhythmogenic alternans instead of APD prolongation to increase VF inducibility. In the control group, the proarrhythmic effects of piceatannol on APD restitution, arrhythmogenic alternans and conduction delay were offset by its antiarrhythmic effects (APD and wavelength prolongation), resulting in a neutral effect on VF inducibility. CONCLUSIONS: Piceatannol (10 µM) is proarrhythmic in failing rabbit hearts with regional IR injury. The increased VF inducibility by piceatannol in HF suggests that its undesirable effects are more pronounced than its benefits in failing hearts.

The mechanisms of atrial fibrillation.

In this article we have reviewed the mechanisms of atrial fibrillation (AF) with special emphasis on the thoracic veins. Based on a number of features, the thoracic veins are highly arrhythmogenic. The pulmonary vein (PV)-left atrial (LA) junction has discontinuous myocardial fibers separated by fibrotic tissues. The PV muscle sleeve is highly anisotropic. The vein of Marshall (VOM) in humans has multiple small muscle bundles separated by fibrosis and fat. Insulated muscle fibers can promote reentrant excitation, automaticity, and triggered activity. The PV muscle sleeves contain periodic acid-Schiff (PAS)-positive large pale cells that are morphologically reminiscent of Purkinje cells. These special cells could be the sources of focal discharge. Antiarrhythmic drugs have significant effects on PV muscle sleeves both at baseline and during AF. Both class I and III drugs have effects on wavefront traveling from PV to LA and from LA to PV. Separating the thoracic veins and the LA with ablation techniques also prevents PV-LA interaction. By reducing PV-LA interaction, pharmacological therapy and PV isolation reduce the activation rate in PV, intracellular calcium accumulation, and triggered activity. Therefore, thoracic vein isolation is an important technique in AF control. We conclude that thoracic veins are important in the generation and maintenance of AF.