Objective: To determine the electrophysiological effects and related mechanisms of late sodium current inhibitors on hearts with short QT intervals. Methods: The electrophysiological study was performed on isolated Langendorff perfused rabbit hearts. A total of 80 New Zealand White rabbits were used and 34 hearts without drug treatment were defined as control group A, these hearts were then treated with I_KATP opener pinacidil, defined as pinacidil group A. Then, 27 hearts from pinacidil group A were selected to receive combined perfusion with sodium channel inhibitors or quinidine, a traditional drug used to treat short QT syndrome, including ranolazine combined group (n=9), mexiletine combined group (n=9), and quinidine combined group (n=9). Nineteen out of the remaining 46 New Zealand rabbits were selected as control group B (no drug treatments, n=19), and then treated with pinacidil, defined as pinacidil group B (n=19). The remaining 27 rabbits were treated with sodium inhibitors or quinidine alone, including ranolazine alone group (n=9), mexiletine alone group (n=9), and quinidine alone group (n=9). Electrocardiogram (ECG) physiological parameters of control group A and pinacidil group A were collected. In control group B and pinacidil group B, programmed electrical stimulation was used to induce ventricular arrhythmias and ECG was collected. ECG physiological parameters and ventricular arrhythmia status of various groups were analyzed. The concentrations of pinacidil, ranolazine, mexiletine and quinidine used in this study were 30, 10, 30 and 1 μmol/L, respectively. Results: Compared with control group A, the QT interval, 90% of the repolarization in epicardial and endocardial monophasic action potential duration (MAPD₉₀-Epi, MAPD₉₀-Endo) was shortened, the transmural dispersion of repolarization (TDR) was increased, and the effective refractor period (ERP) and post-repolarization refractoriness (PRR) were reduced in pinacidil group A (all P<0.05). Compared with the pinacidil group A, MAPD₉₀-Epi, MAPD₉₀-Endo, QT interval changes were reversed in quinidine combined group and mexiletine combined group (all P<0.05), but not in ranolazine combined group. All these three drugs reversed the pinacidil-induced increases of TDR and the decreases of ERP and PRR. The induced ventricular arrhythmia rate was 0 in control group B, and increased to 10/19 (χ²=13.6, P<0.05) in pinacidil group B during programmed electrical stimulation. Compared with the pinacidil group B, incidences of ventricular arrhythmia decreased to 11% (1/9), 11% (1/9) and 0 (0/9) (χ²=4.5, 4.5, 7.4, P<0.05) respectively in ranolazine group, mexiletine group and quinidine group. Conclusions: Inhibition of late sodium current does not increase but even decreases the risk of malignant arrhythmia in hearts with a shortened QT interval. The antiarrhythmic mechanism might be associated with the reversal of the increase of TDR and the decrease of refractoriness (including both ERP and PRR) of hearts with shortened QT interval.
Rabbits ; Animals ; Quinidine/therapeutic use* ; Mexiletine/therapeutic use* ; Pinacidil/therapeutic use* ; Sodium ; Ranolazine/therapeutic use* ; Electrophysiologic Techniques, Cardiac ; Arrhythmias, Cardiac/drug therapy*

Atrial Fibrillation/surgery* ; Catheter Ablation ; Electrophysiologic Techniques, Cardiac ; Humans ; Pulmonary Veins/surgery* ; Recurrence ; Treatment Outcome

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is predominantly an inherited cardiomyopathy with typical histopathological characteristics of fibro-fatty infiltration mainly involving the right ventricular (RV) inflow tract, RV outflow tract, and RV apex in the majority of patients. The above pathologic evolution frequently brings patients with ARVD/C to medical attention owing to the manifestation of syncope, sudden cardiac death (SCD), ventricular arrhythmogenesis, or heart failure. To prevent future or recurrent SCD, an implantable cardiac defibrillator (ICD) is highly desirable in patients with ARVD/C who had experienced unexplained syncope, hemodynamically intolerable ventricular tachycardia (VT), ventricular fibrillation, and/or aborted SCD. Notably, the management of frequent ventricular tachyarrhythmias in ARVD/C is challenging, and the use of antiarrhythmic drugs could be unsatisfactory or limited by the unfavorable side effects. Therefore, radiofrequency catheter ablation (RFCA) has been implemented to treat the drug-refractory VT in ARVD/C for decades. However, the initial understanding of the link between fibro-fatty pathogenesis and ventricular arrhythmogenesis in ARVD/C is scarce, the efficacy and prognosis of endocardial RFCA alone were limited and disappointing. The electrophysiologists had broken through this frontier after better illustration of epicardial substrates and broadly application of epicardial approaches in ARVD/C. In recent works of literature, the application of epicardial ablation also successfully results in higher procedural success and decreases VT recurrences in patients with ARVD/C who are refractory to the endocardial approach during long-term follow-up. In this article, we review the important evolution on the delineation of arrhythmogenic substrates, ablation strategies, and ablation outcome of VT in patients with ARVD/C.
Anti-Arrhythmia Agents ; Arrhythmogenic Right Ventricular Dysplasia ; Cardiomyopathies ; Catheter Ablation ; Catheters ; Death, Sudden, Cardiac ; Defibrillators ; Epicardial Mapping ; Follow-Up Studies ; Heart Failure ; Humans ; Prognosis ; Recurrence ; Syncope ; Tachycardia ; Tachycardia, Ventricular ; Ventricular Fibrillation

For over 3 decades, it has been known that reentry circuits for ventricular tachycardia (VT) are not limited to the subendocardial myocardium. Rather, intramural or subepicardial substrates may also give rise to VT, particularly in those with non-ischemic cardiomyopathy. Percutaneous epicardial mapping and ablation has been successfully introduced for the treatment of such subepicardial VT. Herein, we review the indications for epicardial ablation and the identification of epicardial VT by electrocardiographic and imaging modalities. We also discuss the optimal technique for epicardial access and the implications of epicardial fat which has the potential to mimic scar, decreasing the specificity of electrogram morphology and impeding energy delivery to the tissue. Finally, we also report on possible complications of the procedure and strategies to mitigate adverse events.
Cardiomyopathies ; Catheter Ablation ; Cicatrix ; Electrocardiography ; Epicardial Mapping ; Myocardium ; Sensitivity and Specificity ; Tachycardia, Ventricular

BACKGROUND AND OBJECTIVES: Although ablation of complex fractionated atrial electrograms (CFAE) in atrial fibrillation (AF) is one of the strategies for atrial substrate modification, the mechanism behind CFAE as an electrophysiological substrate remains unclear. We investigated structural differences between CFAE sites and their matched non-CFAE sites by comparing their histopathologic characteristics in canine AF models. METHODS: Atrial electrograms of four dogs were obtained from the epicardial site. AF was induced through burst atrial pacing at 600 bpm for 30 min. CFAE sites were identified during AF according to patterns visualized on the electrograms, and their matched non-CFAE sites were selected in the adjacent region, within 5 mm of each CFAE site. Tissues were harvested from CFAE sites and their matched non-CFAE sites at various locations in both atria. Histopathologic differences were identified between CFAE and non-CFAE sites. RESULTS: A total of 24 atrial tissues (12 with CFAE, 12 with non-CFAE) were evaluated. The atrial myocardium was significantly thicker at CFAE sites (1757.5±560.5 µm) than at non-CFAE sites (1279.5±337.2 µm) (p=0.036). At CFAE sites, it was filled with a significantly larger amount of fibrotic tissue than at non-CFAE sites (22.8±6.9% versus 7.2±4.7%, p < 0.001). Results were consistent across various tissue locations. The distribution of autonomic nerve innervation was similar between CFAE and non-CFAE sites. CONCLUSION: This study provides a better understanding of histological characteristics of CFAE sites, namely a thicker wall and greater amount of fibrosis. These findings may be associated with the development of CFAE and its pathophysiological contribution to AF.
Animals ; Atrial Fibrillation ; Autonomic Pathways ; Catheter Ablation ; Dogs ; Electrophysiologic Techniques, Cardiac ; Fibrosis ; Myocardium

BACKGROUND AND OBJECTIVES: The earliest atrial (A)/ventricular (V) activation potential, or accessory pathway (AP) potential are commonly used as ablation targets for atrioventricular (AV) APs. However, these targets are sometimes ambiguous. SUBJECTS AND METHODS: We reviewed 119 catheter ablation cases in 112 patients diagnosed with orthodromic atrioventricular reentrant tachycardia (AVRT) or Wolff-Parkinson-White (WPW) syndrome. Local A/V amplitude potentials with the earliest activation or AP potential were measured shortly before achieving antegrade AP conduction block, ventriculoatrial block during right ventricle (RV) pacing, or AVRT termination with no AP conduction. RESULTS: APs were located in the left lateral (55.5%), left posterior (17.6%), left posteroseptal (10.1%), midseptal (1.7%), right posteroseptal (7.6%), right posterior (1.7%), and right lateral (5.9%) regions. The mean earliest activation time was 16.7±15.5 ms, mean A/V potential was 1.1±0.9/1.0±0.9 mV, and mean A/V ratio was 1.7±2.0. There was no statistically significant difference between the activation methods (antegrade vs. RV pacing vs. orthodromic AVRT) or AP locations (left vs. right atrium). However, when the local A/V ratio was divided into 3 groups (≤0.6, 1.0±0.3, and ≥1.4), the antegrade approach resulted in an A/V ratio greater than 1.0±0.3 (86.7%, p=0.007), and the orthodromic AVRT state resulted in a ratio of less than 1.0±0.3 (87.5%, p<0.001). CONCLUSION: The mean local A/V potential and ratio did not differ by activation method or AP location. However, a different A/V ratio based on activation method (≥1.0±0.3, antegrade approach; and ≤1.0±0.3, orthodromic AVRT state) could be a good adjuvant marker for targeting AV APs.
Catheter Ablation* ; Catheters* ; Electrophysiologic Techniques, Cardiac ; Heart Ventricles ; Humans ; Methods ; Tachycardia ; Tachycardia, Supraventricular

A 56-year-old man with an implantable cardioverter-defibrillator (ICD) presented with unexplained heart palpitations, which were usually aggravated after ingesting alcohol. He had a history of coronary artery bypass graft surgery 8 years ago, and an ICD was placed (i.e. a single ventricular shock coil with integrated atrial-sensing rings [VDD ICD lead]) 1.5 years ago for primary prevention of sudden cardiac death associated with ischemic cardiomyopathy. Repeated electrocardiograms and echocardiograms showed no evidence of atrial flutter-fibrillation; this was clearly demonstrated using several atrial electrogram strips during the ICD analysis.
Atrial Fibrillation ; Cardiomyopathies ; Coronary Artery Bypass ; Death, Sudden, Cardiac ; Defibrillators* ; Defibrillators, Implantable ; Electrocardiography ; Electrophysiologic Techniques, Cardiac ; Heart ; Humans ; Middle Aged ; Primary Prevention ; Shock ; Stroke ; Transplants

Although 3D-complex fractionated atrial electrogram (CFAE) mapping is useful in radiofrequency catheter ablation for persistent atrial fibrillation (AF), the directions and configuration of the bipolar electrodes may affect the electrogram. This study aimed to compare the spatial reproducibility of CFAE by changing the catheter orientations and electrode distance in an in-silico left atrium (LA). We conducted this study by importing the heart CT image of a patient with AF into a 3D-homogeneous human LA model. Electrogram morphology, CFAE-cycle lengths (CLs) were compared for 16 different orientations of a virtual bipolar conventional catheter (conv-cath: size 3.5 mm, inter-electrode distance 4.75 mm). Additionally, the spatial correlations of CFAE-CLs and the percentage of consistent sites with CFAE-CL<120 ms were analyzed. The results from the conv-cath were compared with that obtained using a mini catheter (mini-cath: size 1 mm, inter-electrode distance 2.5 mm). Depending on the catheter orientation, the electrogram morphology and CFAE-CLs varied (conv-cath: 11.5±0.7% variation, mini-cath: 7.1±1.2% variation), however the mini-cath produced less variation of CFAE-CL than conv-cath (p<0.001). There were moderate spatial correlations among CFAE-CL measured at 16 orientations (conv-cath: r=0.3055±0.2194 vs. mini-cath: 0.6074±0.0733, p<0.001). Additionally, the ratio of consistent CFAE sites was higher for mini catheter than conventional one (38.3±4.6% vs. 22.3±1.4%, p<0.05). Electrograms and CFAE distribution are affected by catheter orientation and electrode configuration in the in-silico LA model. However, there was moderate spatial consistency of CFAE areas, and narrowly spaced bipolar catheters were less influenced by catheter direction than conventional catheters.
Atrial Fibrillation ; Catheter Ablation ; Catheters ; Electrodes* ; Electrophysiologic Techniques, Cardiac* ; Heart ; Heart Atria ; Humans

BACKGROUND/AIMS: There have been reports that interatrial septal (IAS) thickness is increased in patients with atrial fibrillation (AF). This study was performed to investigate whether IAS thickness determined by transthoracic echocardiography (TTE) represents the amount of left atrium (LA) structural and functional remodeling. METHODS: The study population consisted of 104 consecutive patients who underwent catheter ablation (CA) for AF (paroxysmal atrial fibrillation [PAF], 82; persistent atrial fibrillation [PeAF], 22). IAS thickness and left atrium volume (LAV) using TTE, and LA voltage (LAVOL) using 3-dimensional electroanatomical mapping system were assessed during sinus rhythm. RESULTS: IAS thickness was significantly correlated with maximal LAV (LAVmax) (r = 0.288, p = 0.003), mean LAVOL (r = -0.537, p < 0.001), total left atrium emptying fraction (LAEFtotal; r = -0.213, p = 0.030), and active LAEF (LAEFactive; r = -0.249, p = 0.014). IAS thickness was greater in the high-risk group (> or = 2) compared to other groups according to CHA2DS2-VASc score (p = 0.019). During a follow-up of 19.6 months, 23 subjects (22.1%; PAF, 17; PeAF, 6) had recurrence of arrhythmia. Univariate analysis showed that LAVmax, minimal LAV, mean LAVOL, LVEFtotal, LVEFactive, and IAS thickness were associated with recurrence of arrhythmia. However, on multivariate analysis, only mean LAVOL and LAEFactive were independent risk factors for recurrence. CONCLUSIONS: Although IAS thickness showed significant correlations with parameters for LA structural and functional remodeling, this parameter alone could not independently predict recurrence of arrhythmia after CA for AF.
Action Potentials ; Adult ; Aged ; Area Under Curve ; Atrial Fibrillation/physiopathology/*radiography/surgery/*ultrasonography ; *Atrial Function, Left ; *Atrial Remodeling ; Atrial Septum/physiopathology/*radiography/*ultrasonography ; Catheter Ablation ; Chi-Square Distribution ; *Echocardiography, Doppler ; Electrophysiologic Techniques, Cardiac ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; *Multidetector Computed Tomography ; Multivariate Analysis ; Predictive Value of Tests ; Prospective Studies ; ROC Curve ; Recurrence ; Risk Factors ; Time Factors ; Treatment Outcome

We report the case of a 64-year-old male with persistent atrial fibrillation (AF) terminated by ethanol infusion into vein of Marshall as add-on therapy. Three-dimensional automated complex fractionated atrial electrogram (CFAE) during AF revealed clustering of CFAE at perimitral isthmus (PMI) and its unipolar mapping showed rotor-like activation, which was suggested to be critical in the perpetuation of AF. AF was organized to atrial tachycardia (AT) by 100% ethanol infusion in the vein of Marshall. Adjunctive radiofrequency ablation at PMI successfully terminated AT and led to bidirectional block of PMI.
Atrial Fibrillation* ; Catheter Ablation ; Electrophysiologic Techniques, Cardiac ; Ethanol* ; Humans ; Male ; Middle Aged ; Tachycardia ; Veins*