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

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

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*

Here, we report a case of electrical injury-induced reversible advanced second-degree atrioventricular (AV) block. A 28-year-old male visited the emergency department for palpitations 3 days after receiving an electrical injury from 220 volt alternating current. The initial electrocardiogram (ECG) showed sinus rhythm and first-degree AV block with a prolonged PR interval of 400 ms. There was no structural heart disease or electrolyte imbalance. Follow up ECGs acquired 4-6 days after the electrical injury showed intermittent AV block with a prolonged PR interval of 400-460 ms. Exercise treadmill and atropine provocation tests performed 6 days after electrical injury induced advanced second-degree AV block. His bundle electrogram showed intermittent AH block in a Wenckebach pattern with a prolonged AH interval of 220-360 ms and a normal HV interval. Episodes of AV block decreased remarkably 4 weeks after the electrical injury, and the prolonged PR interval returned to 220 ms after 5 months.
Adult ; Atrioventricular Block* ; Atropine ; Electricity ; Electrocardiography ; Electrophysiologic Techniques, Cardiac ; Emergency Service, Hospital ; Follow-Up Studies ; Heart Diseases ; Humans ; Male

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

Abnormal enhanced transmural dispersion of repolarization (TDR) plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes (TDP) which can be induced in long-QT (LQT) syndrome. Taking advantage of an in vitro rabbit model of LQT2, we detected the effects of KN-93, a CaM-dependent kinase (CaMK) II inhibitor on repolarization heterogeneity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypokalemic, hypomagnesaemic Tyrode's solution. At a basic length (BCL) of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave (Tp-e) were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 (0.5 μmol/L) could inhibit EAD, R-on-T extrasystole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demonstrated KN-93, a CaMKII inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.
Action Potentials ; drug effects ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; etiology ; physiopathology ; prevention & control ; Benzylamines ; pharmacology ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; antagonists & inhibitors ; metabolism ; Electrocardiography ; Electrophysiologic Techniques, Cardiac ; Endocardium ; drug effects ; physiopathology ; Heart ; drug effects ; physiopathology ; In Vitro Techniques ; Long QT Syndrome ; complications ; Pericardium ; drug effects ; physiopathology ; Piperidines ; pharmacology ; Protein Kinase Inhibitors ; pharmacology ; Pyridines ; pharmacology ; Rabbits ; Sulfonamides ; pharmacology ; Torsades de Pointes ; etiology ; physiopathology ; prevention & control