Occurrence of primarily noninducible atrioventricular nodal reentry tachycardia after radiofrequency delivery in the slow pathway region during empirical slow pathway modulation.

BACKGROUND: The first-line therapy for atrioventricular nodal reentry tachycardia (AVNRT) is catheter-based slow pathway modulation. If AVNRT is not inducible during an electrophysiological study, an empirical slow pathway modulation (ESPM) may be considered in patients with dual atrioventricular nodal physiology and/or a typical electrocardiogram (ECG). METHODS: We screened 149 symptomatic patients who underwent ESPM in our department between 1993 and 2013. All patients fulfilled the following criteria: (1) either dual atrioventricular nodal (AVN) physiology with up to 2 AVN echo beats or characteristic ECG documentation or both, (2) noninducibility of AVNRT by programmed stimulation, and (3) completion of a telephone questionnaire for long-term follow-up. Out of this population we retrospectively investigated 13 patients who were primarily noninducible but in whom an AVNRT occurred during or after radiofrequency (RF) delivery. RESULTS: When AVNRT occurred, the procedure lost its empirical character, and RF delivery was continued until the procedural endpoint of noninducibility of AVNRT. This endpoint was reached in all but one patient (92%). After a follow-up of 73 ± 15 months, this patient was the only one who reported no benefit from the procedure. CONCLUSIONS: Out of 149 initially noninducible patients, a considerable number (9%) exhibited AVNRT during or after RF delivery. These patients crossed over from empirical to controlled slow pathway modulation resulting in a good clinical outcome. Our observations should encourage electrophysiologists to repeat programmed stimulation even after initial empirical RF delivery to retest for inducibility.

Effective suppression of atrial fibrillation by the antihistaminic agent antazoline: First experimental insights into a novel antiarrhythmic agent.

INTRODUCTION: The antihistaminic antazoline (ANT) was reported to be highly effective and safe for rapid conversion of atrial fibrillation (AF). We therefore analyzed underlying mechanisms in an experimental whole-heart model. METHODS AND RESULTS: Isolated and retrogradely perfused rabbit hearts underwent a standardized protocol employing atrial burst pacing-induced AF in five of 20 hearts under baseline conditions (seven episodes). Thereafter, a combination of acetylcholine and isoproterenol was employed to enhance AF occurrence. Two monophasic action potential recordings on the left- and two on the right atrial epicardium showed a decrease in atrial action potential duration (aAPD, -25 msec, P<.05) and atrial effective refractory period (aERP; -52 msec, P<.01) after infusion of acetylcholine (1 µmol/L) and isoproterenol (1 µmol/L). This led to induction of AF in 14 of 20 hearts (145 episodes). Simultaneous infusion of ANT (20 µmol/L) led to a complete suppression of AF in all inducible hearts. Treatment with ANT also led to a significant increase in aAPD (+41 msec, P<.01) and aERP (+74 msec, P<.05), leading to a marked increase in atrial postrepolarization refractoriness (aPRR, +33 msec, P<.01). Results were compared to 13 rabbits treated with flecainide. Flecainide induced a significant increase in aPRR and resulted in induction of AF in seven of 13 hearts (51 episodes) while 11 of 13 hearts were inducible with acetylcholine and isoproterenol (93 episodes). CONCLUSION: Administration of ANT was highly effective in suppressing AF. The antiarrhythmic effect could be explained by a significant increase in postrepolarization refractoriness as a result of a more marked increase in aERP as compared with aAPD.

Severe proarrhythmic potential of risperidone compared to quetiapine in an experimental whole-heart model of proarrhythmia.

In several case reports, proarrhythmic effects of antipsychotic drugs have been reported. The aim of the present study was to investigate if application of risperidone or quetiapine has the potential to provoke polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In 24 isolated rabbit hearts, risperidone (5 and 10 µM, n = 12) or quetiapine (5 and 10 µM, n = 12) was infused after obtaining baseline data. Eight endocardial and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant QT prolongation after application of risperidone as compared with baseline (5 µM: +29 ms, 10 µM: +35 ms, p < 0.01) accompanied by an increase of action potential duration. Administration of risperidone also significantly increased spatial dispersion of repolarization (5 µM: +16 ms, 4 µM: +19 ms; p < 0.05) as well as temporal dispersion of repolarization. Lowering of potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EADs) in 8 of 12 hearts and polymorphic ventricular tachycardia resembling torsade de pointes in 6 of 12 hearts (10 µM, 49 episodes). The results were compared with hearts treated with quetiapine (5 and 10 µM). Quetiapine led to an increase in QT interval (5 µM: +10 ms; 10 µM: +28 ms; p < 0.05) and a similar increase of APD90. However, treatment with quetiapine did not result in significant alterations of spatial and temporal dispersion of repolarization. No ventricular arrhythmias were observed in this group. In the present study, quetiapine demonstrated a safe electrophysiologic profile despite significant QT prolongation. In contrast, risperidone led to a more marked prolongation of myocardial repolarization combined with a more marked increase of dispersion of repolarization.

Dual atrioventricular nodal non-re-entrant tachycardia.

Dual atrioventricular nodal non-re-entrant tachycardia (DAVNNT), also known as 'double fire', has recently received more attention since it was demonstrated to mimic more common arrhythmias such as atrial premature beats, atrial fibrillation, and ventricular tachycardia. This is important, since mistaken differential diagnoses and the resulting therapeutic decisions have severe consequences for affected patients. DAVNNT is characterized by conduction characteristics of the atrioventricular (AV) node that leads to a double antegrade conduction of one sinoatrial nodal activity via the slow and fast AV nodal pathways. As a result, the most significant hint from an electrocardiogram (ECG) is a P wave followed by two narrow QRS complexes. Although DAVNNT is rather a rare arrhythmia, it now appears to be more common than previously thought. To date, 68 cases including 3 small single-centre observational studies accumulated over the last 5 years have demonstrated the feasibility and safety of radiofrequency catheter ablation for DAVNNT. Catheter ablation treats this arrhythmia effectively by modifying or eliminating slow pathway function. Here, we review the current state of DAVNNT knowledge systematically and address current challenges presented by this 'ECG chameleon from the AV node'.

Electrophysiological profile of vernakalant in an experimental whole-heart model: the absence of proarrhythmia despite significant effect on myocardial repolarization.

AIM: The most recent European Society of Cardiology (ESC) update on atrial fibrillation has introduced vernakalant (VER) for pharmacological cardioversion of atrial fibrillation. The aim of the present study was to investigate the safety profile of VER in a sensitive model of proarrhythmia. METHODS AND RESULTS: In 36 Langendorff-perfused rabbit hearts, VER (10, 30 µM, n = 12); ranolazine (RAN, 10, 30 µM, n = 12), or sotalol (SOT, 50; 100 µM, n = 12) were infused after obtaining baseline data. Monophasic action potentials and a 12-lead electrocardiogram showed a significant QT prolongation after application of VER as compared with baseline (10 µM: +25 ms, 30 µM: +50 ms, P < 0.05) accompanied by an increase of action potential duration (APD). The increase in APD90 was accompanied by a more marked increase in effective refractory period (ERP) leading to a significant increase in post-repolarization refractoriness (PRR, 10 µM: +30 ms, 30 µM: +36 ms, P < 0.05). Vernakalant did not affect the dispersion of repolarization. Lowered potassium concentration in bradycardic hearts did not provoke early afterdepolarizations (EADs) or polymorphic ventricular tachycardia (pVT). Comparable results were obtained with RAN. Hundred micromolars of SOT led to an increase in QT interval (+49 ms) and APD90 combined with an increased ERP and PRR (+23 ms). In contrast to VER, 100 µM SOT led to a significant increase in dispersion of repolarization and to the occurrence of EAD in 10 of 12 and pVT in 8 of 12 hearts. CONCLUSION: In the present study, application of VER and SOT led to a comparable prolongation of myocardial repolarization. Both drugs increased the PRR. However, VER neither affect the dispersion of repolarization nor induce EAD and therefore did not cause proarrhythmia.

Ventricular arrhythmias from the mitral annulus: patient characteristics, electrophysiological findings, ablation, and prognosis.

BACKGROUND: Symptomatic, premature ventricular contractions (PVCs) frequently originate in the right ventricular outflow tract, less frequently in the left ventricular outflow tract, aortic root, or mitral annulus (MA). Little is known about the patient population presenting with MA PVC and/or ventricular tachycardia (VT). OBJECTIVE: To characterize the subgroup of ventricular arrhythmias arising from the MA. METHODS: Among 404 consecutive patients who presented for catheter ablation of idiopathic PVC/VT over a period of 9 years, patients who were found to have an ablation site at the MA were analyzed for clinical and electrophysiological parameters. RESULTS: Twenty-two (5%) patients (mean age 45 ± 18 years; range 16-76 years; 14 [64%] men) had PVC/VT arising from the MA. History of PVC ranged from 2 days in a case with suspected focal myocarditis to 19 years. No patient had severely depressed left ventricular function or significant heart disease, which was determined by echocardiogram, magnetic resonance imaging, and/or coronary angiogram. Sites of origin were distributed around the MA with no preferential area. Ablation was successful in 13 of 16 (81%) patients. One 28-year-old female patient with normal magnetic resonance imaging and no structural heart disease died suddenly 3 months after ablation. CONCLUSIONS: Ventricular arrhythmias from the MA represent a rare subgroup of idiopathic PVC/VT. They appear to occur at any age and do not indicate underlying structural heart disease. Catheter ablation has a success rate comparable to that of outflow tract tachycardia. Prognosis remains unclear.

Electrophysiological characteristics of ventricular tachyarrhythmias in cardiac sarcoidosis versus arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Recent evidence suggests that cardiac sarcoidosis (CS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) can manifest very similarly. OBJECTIVE: To investigate whether there are significant demographic and electrophysiological differences between patients with CS and ARVC. METHODS: We prospectively compared patients with proven CS or ARVC who underwent radiofrequency catheter ablation of ventricular tachycardias by using 3-dimensional electroanatomical mapping. Furthermore, we evaluated whether the diagnostic criteria for ARVC would have excluded ARVC in patients with CS. RESULTS: Eighteen patients (13 men; mean age 44.9 years) were included. All 18 patients had mild to moderately reduced right ventricular ejection fraction. Patients with cardiac sarcoidosis (n = 8) had a significantly lower mean left ventricular ejection fraction (35.6±19.3 vs 60.6±9.4; P = .002). Patients with CS had a significantly wider QRS (0.146 vs 0.110s; P = .004). Five of 8 (63%) patients with CS fulfilled the diagnostic ARVC criteria. Ventricular tachycardias (VTs) with a left bundle branch block pattern were documented in all but one patient (with CS). Programmed ventricular stimulation induced an average of 3.7 different monomorphic VTs in patients with CS vs 1.8 in patients with ARVC (P = .01). VT significantly more often originated in the apical region of the right ventricle in CS vs ARVC (P = .001), with no other predilection sites. Ablation success and other electrophysiological parameters were not different. CONCLUSIONS: The current diagnostic ARVC guidelines do not reliably exclude patients with CS. Clinical and electrophysiological parameters that were characteristic of CS in our patients include reduced left ventricular ejection fraction, a significantly wider QRS, right-sided apical VT, and more inducible forms of monomorphic VT.

Randomized study comparing duty-cycled bipolar and unipolar radiofrequency with point-by-point ablation in pulmonary vein isolation.

BACKGROUND: Pulmonary vein (PV) electrical isolation is a therapeutic option in atrial fibrillation (AF). New technologies may reduce the complexity of the procedure. OBJECTIVE: The aim of the present study was to compare immediate results and short-term efficacy of a new circular ablation catheter (PVAC) with a conventional point-by-point ablation. METHODS: The prospective study enrolled 80 consecutive patients with paroxysmal AF or persistent AF, refractory to antiarrhythmic drugs, who were randomized to radiofrequency ablation using duty-cycled bipolar and unipolar radiofrequency by a decapolar circular catheter (PVAC group) or to point-by-point ablation supported by a 3-dimensional mapping system (3D group). RESULTS: Forty patients per group were included. Mean age was 58 ± 10 years, 64% were male; 55% had paroxysmal AF, 45% had persistent AF. There were no significant differences between groups. Complete electrical isolation was reached in all but 1 PV, which was not isolated in the PVAC group because of phrenic nerve capture. Procedure and fluoroscopy times were lower in the PVAC group: 171 ± 40 minutes vs. 224 ± 27 minutes, P < .001; 26 ± 8 minutes vs. 35 ± 9 minutes, P < .001; respectively. There were no major complications. During a mean follow-up of 254 ± 99 days, 72% in the PVAC group and 68% in the 3D group were free of AF recurrences irrespective of the initial AF type (P = NS). CONCLUSION: PVAC represents a safe alternative for PV isolation. It reduces both procedure and fluoroscopy time. The short- and middle-term efficacy is comparable to a conventional point-by-point antral ablation technique.