Comparison of Radiofrequency Catheter Ablation Between Asymptomatic and Symptomatic Persistent Atrial Fibrillation: A Propensity Score Matched Analysis.

BACKGROUND: Whether patients with asymptomatic atrial fibrillation (AF) could benefit from radiofrequency catheter ablation (RFCA) remains unclear. This study aimed to compare the outcomes of RFCA between asymptomatic and symptomatic AF. METHODS: Sixty-six patients with asymptomatic persistent AF who underwent the primary ablation for AF were enrolled; 132 patients with symptomatic persistent AF were matched using propensity score matching. All patients underwent circumferential pulmonary vein isolation in combination with linear ablation using AF termination as the primary procedural endpoint. RESULTS: Sinus rhythm (SR) was restored by ablation in 18 (27.3%) patients in the asymptomatic group and 93 (70.5%) in the symptomatic group (P < 0.001). Combined with intravenous infusion of ibutilide (1 mg), the numbers were 45 (68.2%) and 116 (87.8%), respectively (P = 0.001). At 1-year follow-up, SR was present in 23 (34.8%) patients in the asymptomatic group and 78 (59.1%) in the symptomatic group without any antiarrhythmic medication after a single procedure (P = 0.001). Of the 43 patients experiencing recurrence in the asymptomatic group, 16 (37.2%) had recurrent atrial tachycardia (AT)-related symptoms. Multivariate analysis showed that asymptomatic AF was independently associated with AF failed to be terminated by ablation (OR: 7.1; 95% CI: 3.4 to 14.9; P < 0.001) and recurrence (OR: 2.2; 95% CI: 1.1 to 4.4; P = 0.018). Patients with asymptomatic AF showed less improvement in quality of life postablation than those with symptoms. CONCLUSION: Current catheter ablation techniques showed worse outcomes in asymptomatic AF patients than in those with symptoms. Recurrent AT could cause significant symptoms in previously asymptomatic patients.

Catheter ablation for ventricular tachycardia following surgical treatment of pulmonary stenosis with intact ventricular septum.

AIMS: This study was aimed to report the characteristics and treatment of ventricular tachycardia (VT) following surgical treatment of pulmonary stenosis with intact ventricular septum. METHODS AND RESULTS: Five patients underwent radiofrequency catheter ablation for sustained monomorphic left bundle branch block (LBBB) type VT who previously underwent surgical treatment of pulmonary stenosis. Except stimulation, voltage and activation mapping was performed using three-dimensional (3D) electro-anatomic mapping and ablation was applied accordingly. Four VTs were induced during EP study. Two VTs were focal and the earliest activity was targeted in the right ventricular apex (RVA). The other two VTs were reentrant and the critical isthmus located in the mid-lateral wall and anterior wall of right ventricle, respectively. Ablation abolished all inducible VTs in four patients. In the patient whose VT was non-inducible, radiofrequency (RF) energy was delivered to the RVA where pacing mapping matched the clinical VT. One focal VT recurred 60 months after the initial RF ablation. Repeat mapping and ablation was performed and no VT recurred over a 24-month period. CONCLUSIONS: The mechanism of VT following surgical treatment of pulmonary stenosis can be either focal or reentrant. Ablation of this subgroup of VT is feasible.

Cavotricuspid-Dependent Atrial Flutter in Patients With Prior Atriotomy: 12-Lead ECG Interpretation and Electroanatomical Characteristics.

BACKGROUND: The aim of this study was to describe the electrocardiogram (ECG) morphology and electroanatomical characteristics of counterclockwise tricuspid annular atrial flutter (CCWTA-AFL) in the patients with prior atriotomy. METHODS AND RESULTS: This retrospective study included 34 patients with CCWTA-AFL after cardiac surgery and 20 patients with typical CCWTA-AFL without prior surgery. For patients in the postsurgical group, 19 had single-loop CCWTA-AFL and 15 had a double loop CCWTA-AFL. For single loop CCWTA-AFL the F-wave in lead I was very flat in l7 of 19 patients. The F-wave morphology in the inferior leads and V1 were found to be similar to typical AFL in 14 of 19 patients. For double loop CCWTA-AFL, F-waves were positive in lead I in 13 out of 15 patients. A long isoelectric activation was measured between F-waves in most of the patients. The presence of isoelectric segments between F-waves suggested a double loop AFL, which had a sensitivity of 86.7% and a specificity of 100%. Moreover, flat F-waves in lead I suggested a single loop AFL, which had a sensitivity of 89.5% and specificity of 86.7%. All patients in the group without prior cardiac surgery had typical ECGs features of CCWTA-AFL. None of the patients showed isoelectric segments between F-waves in the inferior leads. The amplitudes of most of the leads were higher than those for single loop CCWTA-AFL in patients with prior surgery.

Electrophysiology of human cardiac atrial and ventricular telocytes.

Telocytes (TCs) with exceptionally long cellular processes of telopodes have been described in human epicardium to act as structural supporting cells in the heart. We examined myocardial chamber-specific TCs identified in atrial and ventricular fibroblast culture using immunocytochemistry and studied their electrophysiological property by whole-cell patch clamp. Atrial and ventricular TCs with extended telopodes and alternating podoms and podomers that expressed CD34, c-Kit and PDGFR-ß were identified. These cells expressed large conductance Ca²âº-activated K⁺ current (BK(Ca)) and inwardly rectifying K⁺ current (IK(ir)), but not transient outward K⁺ current (I(to)) and ATP-sensitive potassium current (K(ATP)). The active channels were functionally competent with demonstrated modulatory response to H2 S and transforming growth factor (TGF)-ß1 whereby H2S significantly inhibited the stimulatory effect of TGF-ß1 on current density of both BKCa and IK(ir). Furthermore, H2S attenuated TGF-ß1-stimulated KCa1.1/Kv1.1 (encode BK(Ca)) and Kir2.1 (encode IK(ir)) expression in TCs. Our results show that functionally competent K⁺ channels are present in human atrial and ventricular TCs and their modulation may have significant implications in myocardial physiopathology.

Prospective randomized study to assess the efficacy of site and rate of atrial pacing on long-term progression of atrial fibrillation in sick sinus syndrome: Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) Study.

BACKGROUND: Atrial-based pacing is associated with lower risk of atrial fibrillation (AF) in sick sinus syndrome compared with ventricular pacing; nevertheless, the impact of site and rate of atrial pacing on progression of AF remains unclear. We evaluated whether long-term atrial pacing at the right atrial (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF. METHODS AND RESULTS: We randomized 385 patients with paroxysmal AF and sick sinus syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98), RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The primary outcome was the occurrence of persistent AF (AF documented at least 7 days apart or need for cardioversion). Demographic data were homogeneous across both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF). After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence interval, 0.79-1.75; P=0.65) or continuous atrial overdrive pacing ON versus OFF (hazard ratio=1.17; 95% confidence interval, 0.79-1.74; P=0.69) did not prevent the development of persistent AF. CONCLUSIONS: In patients with paroxysmal AF and sick sinus syndrome requiring pacemaker implantation, an alternative atrial pacing site at the RA septum or continuous atrial overdrive pacing did not prevent the development of persistent AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00419640.

Pectus excavatum: uncommon electrical abnormalities caused by extrinsic right ventricular compression.

We report a case of pectus excavatum associated with ventricular tachycardia provoked by exercise in a 19-year-old man. Although this chest deformity has been associated with supraventricular dysrhythmias, documented ventricular tachycardia has only been reported once. Our patient's ventricular dysrhythmia was treated by surgical correction of his pectus excavatum only, and at 3 years follow-up he has had no recurrence of his ventricular tachycardia.

Assessment of left ventricular preload by cardiac magnetic resonance imaging predicts exercise capacity in adult operated tetralogy of Fallot: a retrospective study.

BACKGROUND: The optimal timing of pulmonary homograft valve replacement (PVR) is uncertain. Cardiopulmonary exercise testing (CPET) and cardiac magnetic resonance (CMR) are often used to guide the clinical decision for PVR in operated tetralogy of Fallot (TOF) patients with significant pulmonary regurgitation (PR). We aim to study the relationship between exercise capacity and CMR in these patients. METHODS: The study is a single-centre retrospective analysis of 36 operated TOF patients [median 21.4 (interquartile range 16.4, 26.4) years post-repair; 30 NYHA I, 6 NYHA II; median age 25.2 (interquartile range 19.5-31.7) years, 29 males] with significant PR on CMR who underwent CPET within 15 [median 2.0 (interquartile range 0.8-7.2)] months from CMR. CPET parameters were compared with 30 age- and sex-matched healthy controls [median age 27.8 (interquartile range 21.0-32.8) years; 24 males]. RESULTS: Peak systolic blood pressure (177 versus 192 mmHg, p = 0.007), Mets (7.3 versus 9.9, p < 0.001), peak oxygen consumption (VO2max) (29.2 versus 34.5 ml/kg/min, p < 0.001) and peak oxygen pulse (11.0 versus 13.7 ml/beat, p = 0.003) were significantly lower in TOF group versus control. Univariate analyses showed negative correlation between PR fraction and anaerobic threshold. There was a positive correlation between indexed left (LV) and right (RV) ventricular end-diastolic volumes, as well as indexed LV and effective RV stroke volumes, on CMR and VO2max and Mets achieved on CPET. These remained significant after adjustment for age and sex. CONCLUSIONS: TOF subjects have near normal exercise capacity but significantly lower Mets, VO2max and peak oygen pulse achieved compared to controls. Increased PR fraction in TOF subjects was associated with lower anaerobic threshold. Higher indexed effective RV stroke volume, a measure of LV preload, was associated with higher VO2max and Mets achieved, and may potentially be used as a predictor of exercise capacity.

Generation of patient-specific induced pluripotent stem cell-derived cardiomyocytes as a cellular model of arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disorder associated with sudden cardiac death. Its pathophysiology is still poorly understood. We aimed to produce an in vitro cellular model of ARVC using patient-specific induced pluripotent stem cell (iPSC)-derived cardiomyocytes and determine whether the model could recapitulate key features of the disease phenotype. METHODS AND RESULTS: Dermal fibroblasts were obtained from a 30-year-old man with a clinical diagnosis of ARVC, harbouring a plakophilin 2 (PKP2) gene mutation. Four stable iPSC lines were generated using retroviral reprogramming, and functional cardiomyocytes were derived. Gene expression levels of desmosomal proteins (PKP2 and plakoglobin) in cardiomyocytes from ARVC-iPSCs were significantly lower compared with cardiomyocytes from control iPSCs (P< 0.01); there were no significant differences in the expression of desmoplakin, N-cadherin, and connexin 43 between the two groups. Cardiomyocytes derived from ARVC-iPSCs exhibited markedly reduced immunofluorescence signals when stained for PKP2 and plakoglobin, but similar levels of staining for desmoplakin, N-cadherin, and connexin 43 compared with control cardiomyocytes. Transmission electron microscopy showed that ARVC-iPSC cardiomyocytes were larger and contained darker lipid droplets compared with control cardiomyocytes. After 2 weeks of cell exposure to adiopgenic differentiation medium, ARVC-iPSC cardiomyocytes were found to contain a significantly greater amount of lipid, calculated using Oil Red O staining, compared with controls (734 ± 35.6 vs. 8.1 ± 0.49 a.u., respectively; n = 7, P = 0.001). CONCLUSION: Patient-specific iPSC-derived cardiomyocytes display key features of ARVC, including reduced cell surface localization of desmosomal proteins and a more adipogenic phenotype.

Almanac 2013: cardiac arrhythmias and pacing--an editorial overview of selected research that has driven recent advances in clinical cardiology.

Important advances have been made in the past few years in the fields of clinical cardiac electrophysiology and pacing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial fibrillation (AF), which has transpired into improved methods of detection, risk stratification, and treatments. The introduction of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symptomatic AF. Another area of intense research in the field of cardiac arrhythmias and pacing is in the use of cardiac resynchronisation therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark randomised controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves symptoms, many subsequent studies have been performed to further refine the selection of patients for CRT and determine the clinical characteristics associated with a favourable response. The field of sudden cardiac death and implantable cardioverter defibrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on improved methods for patient selection, risk stratification, and management.This review covers the major recent advances in these areas related to cardiac arrhythmias and pacing.

Hydrogen sulphide suppresses human atrial fibroblast proliferation and transformation to myofibroblasts.

Cardiac fibroblasts are crucial in pathophysiology of the myocardium whereby their aberrant proliferation has significant impact on cardiac function. Hydrogen sulphide (H2S) is a gaseous modulator of potassium channels on cardiomyocytes and has been reported to attenuate cardiac fibrosis. Yet, the mechanism of H2S in modulating proliferation of cardiac fibroblasts remains poorly understood. We hypothesized that H2S inhibits proliferative response of atrial fibroblasts through modulation of potassium channels. Biophysical property of potassium channels in human atrial fibroblasts was examined by whole-cell patch clamp technique and their cellular proliferation in response to H2S was assessed by BrdU assay. Large conductance Ca(2+)-activated K(+) current (BK(Ca)), transient outward K(+) current (I(to)) and inwardly rectifying K(+) current (IK(ir)) were found in human atrial fibroblasts. Current density of BK(Ca) (IC50 = 69.4 µM; n = 6), I(to) (IC50 = 55.1 µM; n = 6) and IK(ir) (IC50 = 78.9 µM; n = 6) was significantly decreased (P < 0.05) by acute exposure to NaHS (a H2S donor) in atrial fibroblasts. Furthermore, NaHS (100-500 µM) inhibited fibroblast proliferation induced by transforming growth factor-ß1 (TGF-ß1; 1 ng/ml), Ang II (100 nM) or 20% FBS. Pre-conditioning of fibroblasts with NaHS decreased basal expression of Kv4.3 (encode I(to)), but not KCa1.1 (encode BK(Ca)) and Kir2.1 (encode IK(ir)). Furthermore, H2S significantly attenuated TGF-ß1-stimulated Kv4.3 and α-smooth muscle actin expression, which coincided with its inhibition of TGF-ß-induced myofibroblast transformation. Our results show that H2S attenuates atrial fibroblast proliferation via suppression of K(+) channel activity and moderates their differentiation towards myofibroblasts.

Clinical markers of organ dysfunction associated with increased 1-year mortality post-implantable cardioverter defibrillator implantation.

AIMS: Guidelines from the ESC and ACC/AHA recommend implantable cardioverter defibrillators (ICDs) be implanted in clinically indicated patients with a reasonable expectation of >1 year survival. Our study aimed to assess if selected clinical markers of organ dysfunction were associated with increased 1-year mortality despite ICD therapy. METHODS AND RESULTS: We retrospectively studied 283 patients with de novo ICDs implanted for primary or secondary prevention in ischaemic heart disease and dilated cardiomyopathy. We investigated the association of the following clinical markers of organ dysfunction with 1 year mortality: liver dysfunction (aspartate transaminase/alanine transaminase ≥ 3× upper limit of normal or prothrombin time/international normalized ratio ≥ 1.5 in the absence of anticoagulation), respiratory dysfunction (recent mechanical ventilation within 3 months prior to ICD implant), renal dysfunction (creatinine ≥150 µmol/L or glomerular filtration rate ≤ 30 mL/min/1.73 m(2)), anaemia (Hb ≤ 100 g/L), and prior cerebral vascular injury. With no organ dysfunction, 1 year mortality was 1.9%. In the presence of a single organ dysfunction, mortality was increased to 14.3%. With two or more markers of organ dysfunction mortality was 38.1% at 1 year (log-rank test P < 0.001). CONCLUSIONS: Clinical markers of liver dysfunction, recent mechanical ventilation, and renal impairment were independently associated with increased 1 year mortality. Presence of more than one clinical marker of organ dysfunction was associated with significantly increased risk of mortality in our study.

Role of tumor necrosis factor-α in the pathogenesis of atrial fibrosis and development of an arrhythmogenic substrate.

BACKGROUND: Although tumor necrosis factor-α (TNF-α) levels are increased in patients with atrial fibrillation (AF), its role in the pathogenesis of AF is unclear. We investigated whether direct delivery of TNF-α could induce atrial fibrosis. METHODS AND RESULTS: TNF-α (4 µg/kg) was injected into the tail vein of 20 male Swiss albino mice (TNF group) and saline into 20 control mice (CON group). The dose was carefully chosen to avoid any significant decrease in left ventricular (LV) function. Animals were killed after 16 weeks and their atria examined for fibrosis. We found increased atrial fibrosis in the TNF group compared with the CON group [372.8±21.5 arbitrary units (a.u.) vs. 56.9±6.5 a.u., respectively, mean±SEM; P<0.0001] and decreased connexin-40 immunofluorescence [7.5±0.4 a.u vs. 40.4±1.9 a.u, respectively; P<0.0001]. Transforming growth factor-ß [TGF-ß: 95.6±1.8 a.u vs. 29.4±5.8 a.u; P<0.001], α-smooth muscle actin (α-SMA: 97.9±13.0 a.u vs. 50.1±18.5 a.u; P<0.05] and matrix metalloproteinase 2 (MMP-2)/GAPDH levels [157.3±26.4 a.u vs. 105.8±13.3 a.u; P<0.05] were also increased in the TNF group. CONCLUSIONS: TNF-α is involved in the pathogenesis of atrial fibrosis and altered connexin-40 expression in mice through the TGF-ß signaling pathway, activation of myofibroblasts and increased secretion of MMPs. Collectively, these changes may contribute to the arrhythmogenic substrate and development of AF.

Almanac 2013: cardiac arrhythmias and pacing-an editorial overview of selected research that has driven recent advances in clinical cardiology.

Important advances have been made in the past few years in the fields of clinical cardiac electrophysiology and pacing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial fibrillation (AF), which has transpired into improved methods of detection,risk stratification, and treatments. The introduction of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symptomatic AF.Another area of intense research in the field of cardiac arrhythmias and pacing is in the use of cardiac resynchronisation therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark randomised controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves symptoms,many subsequent studies have been performed to further refine the selection of patients for CRT and determine the clinical characteristics associated with a favourable response. The field of sudden cardiac death and implantable cardioverter defibrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on improved methods for patient selection, risk stratification, and management. This review covers the major recent advances in these areas related to cardiac arrhythmias and pacing.

Catheter ablation of ventricular fibrillation triggers and electrical storm.

Ventricular fibrillation (VF) and electrical storm remain challenging conditions to manage despite the availability of various treatment modalities. Insertion of an implantable cardioverter defibrillator (ICD) remains the gold standard method for lowering the risk of sudden cardiac death in patients deemed to be at greatest risk of ventricular arrhythmias. However, ICDs do not alter the underlying substrate responsible for the arrhythmic events and a significant proportion of patients with ICDs may experience VF storm which may be life threatening and difficult to control with medication. Catheter ablation (CA) of the triggers or abnormal electrical substrate responsible for VF storm is an important treatment option in rare cases. In this article, we present an overview of the current theories underlying the mechanisms of VF and discuss how the technique of CA may be used to treat the triggers of VF and electrical storm. We review the literature on outcomes in patients who have undergone CA for VF in a variety of different settings, including those with structural heart disease and structurally normal hearts (e.g. patients with inherited arrhythmogenic diseases and idiopathic VF) and discuss the future directions in this field.

Successful ablation of sinus node reentrant tachycardia using remote magnetic navigation system.

Ablation of sinus node reentrant tachycardia (SNRT) may be difficult with risk of sinus node injury by using conventional catheters. We report successful ablation of SNRT by using remote magnetic navigation system (Stereotaxis).

A randomized-controlled trial comparing conventional with minimal catheter approaches for the mapping and ablation of regular supraventricular tachycardias.

AIMS: To compare the use of a minimal (MIN) with a conventional (CON) catheter approach for the mapping and ablation of regular supraventricular tachycardias (SVT) and typical atrial flutter (AFL) in the setting of a randomized-controlled trial. METHODS AND RESULTS: Two hundred patients (age 51.2 +/- 15.9 years, 99 male) were randomized to a MIN or CON group. The MIN approach involved using two catheters for AFL, one to three for other SVT (ablation catheter included), whereas the CON approach involved three and five catheters, respectively. Acute procedural success was similar between the two groups. There was no significant difference in overall procedure times, fluoroscopy times, or radiation doses. Procedure times were shorter for AFL ablation in MIN compared with CON [60 (30-150) vs. 85 (40-200) min, median (range), P = 0.03] from subgroup analysis. A median of three (one to six) catheters was used in MIN and five (three to seven) in CON (P < 0.0001). Catheter costs were significantly lower in MIN compared with CON [6.1 (2-61) vs. 8.5 (4.4-21.3) units, P < 0.0001, where one unit is equivalent to the cost of a diagnostic quadripolar catheter]. At 6-week follow-up, two patients in MIN (2.1%) and three patients in CON (3.2%) had documented recurrence of the index arrhythmia. CONCLUSION: The use of a MIN approach in the treatment of SVT and AFL is as effective, quick, and safe as using a CON approach and is therefore more cost-effective.

The Singapore Heart Failure Risk Score: Prediction of Survival in Southeast Asian Patients.

INTRODUCTION: Numerous heart failure risk scores have been developed but there is none for Asians. We aimed to develop a risk calculator, the Singapore Heart Failure Risk Score, to predict 1- and 2-year survival in Southeast Asian patients hospitalised for heart failure. MATERIALS AND METHODS: Consecutive patients admitted for heart failure were identified from the Singapore Cardiac Databank Heart Failure registry. The follow-up was 2 to 4 years and mortality was obtained from national registries. RESULTS: The derivation (2008-2009) and 2 validation cohorts (2008-2009, 2013) included 1392, 729 and 804 patients, respectively. Ten variables were ultimately included in the risk model: age, prior myocardial infarction, prior stroke, atrial fibrillation, peripheral vascular disease, systolic blood pressure, QRS duration, ejection fraction and creatinine and sodium levels. In the derivation cohort, predicted 1- and 2-year survival was 79.1% and 68.1% compared to actual 1- and 2-year survival of 78.2% and 67.9%. There was good agreement between the predicted and observed mortality rates (Hosmer-Lemeshow statistic = 14.36, P = 0.073). C-statistics for 2-year mortality in the derivation and validation cohorts were 0.73 (95% CI, 0.70-0.75) and 0.68 (95% CI, 0.64-0.72), respectively. CONCLUSION: We provided a risk score based on readily available clinical characteristics to predict 1- and 2-year survival in Southeast Asian patients hospitalised for heart failure via a simple online risk calculator, the Singapore Heart Failure Risk Score.

Use of non-contact mapping in the treatment of right atrial tachycardias in patients with and without congenital heart disease.

AIMS: Right atrial (RA) tachycardias may involve several mechanisms other than typical isthmus-dependent flutters, particularly in patients with congenital heart disease (CHD) or structural heart disease. We aimed at investigating the clinical utility of non-contact mapping in the diagnosis and ablation of these complex arrhythmias. METHODS AND RESULTS: Non-contact mapping was used to treat RA tachycardias in 22 patients (12 with CHD and 10 without CHD). Ablation strategy consisted of creating linear lesions between scars (in macro-re-entrant circuits) or targeting areas of earliest activation and breakout points (in focal tachycardias). Eleven of the 12 tachycardias in the CHD group were atypical macro-re-entrant flutters. The majority (9 of 12) involved the RA free wall, whereas the remainder involved upper loop re-entry. In contrast, 9 of the 12 tachycardias in the non-CHD group were focal and 3 were macro-re-entrant. Acute procedural success was 88%. During a follow-up of 26 +/- 21 months, 90% of the patients reported either no symptoms (60%) or symptoms reduced to <50% pre-ablation levels (30%). CONCLUSIONS: Non-contact mapping can provide important information on the mechanism of complex RA tachycardias in patients both with and without CHD. This can be useful in formulating ablation strategies.

Identification of an INa-dependent and Ito-mediated proarrhythmic mechanism in cardiomyocytes derived from pluripotent stem cells of a Brugada syndrome patient.

Brugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS patient (BrS1) to evaluate the roles of Na+ currents (INa) and transient outward K+ currents (Ito) in BrS induced action potential (AP) changes. To understand the role of these current changes in repolarization we employed dynamic clamp to "electronically express" IK1 and restore normal resting membrane potentials and allow normal recovery of the inactivating currents, INa, ICa and Ito. HiPSC-CMs were generated from BrS1 with a compound SCN5A mutation (p. A226V & p. R1629X) and a healthy sibling control (CON1). Genome edited hiPSC-CMs (BrS2) with a milder p. T1620M mutation and a commercial control (CON2) were also studied. CON1, CON2 and BrS2, had unaltered peak INa amplitudes, and normal APs whereas BrS1, with over 75% loss of INa, displayed a loss-of-INa basal AP morphology (at 1.0 Hz) manifested by a reduced maximum upstroke velocity (by ~80%, p < 0.001) and AP amplitude (p < 0.001), and an increased phase-1 repolarization pro-arrhythmic AP morphology (at 0.1 Hz) in ~25% of cells characterized by marked APD shortening (~65% shortening, p < 0.001). Moreover, Ito densities of BrS1 and CON1 were comparable and increased from 1.0 Hz to 0.1 Hz by ~ 100%. These data indicate that a repolarization deficit could be a mechanism underlying BrS.