Methods and Results—Patients who underwent cardiac evaluation with nuclear stress imaging or cardiac catheterization and had wQRS (BBB, PVC or pQRS) were studied. f-wQRS was defined by the presence of >2 notches on the R wave or the S wave, and had to be present in >2 contiguous inferior (II, III, aVF), lateral (I, aVL, V₆) or anterior (V₁-V₅) leads. ECG analyses of 879 patients (age 66.7±11.4 years, male: 97%, mean follow-up 29±18 months) with BBB (n=310), PVC (n=301) and pQRS (n=268) revealed f-wQRS in 415 (47.2%) patients. Myocardial scar was present in 440 (50%) patients. The sensitivity, specificity, positive predictive value and negative predictive value of f-wQRS for myocardial scar were 86.8%, 92.5%, 92.0% and 87.5%, respectively. The sensitivity and specificity for diagnosing myocardial scar were 88.6% and 94.4%, 81.4% and 88.4% and, 89.8% and 95.7%, for f-BBB, f-PVC and f-pQRS, respectively. f-wQRS was associated with mortality after adjusting for age, ejection fraction and diabetes (p=0.017).

Conclusions—f-wQRS on a standard 12-lead ECG is a moderately sensitive and highly specific sign for myocardial scar in patients with known or suspected CAD. f-wQRS is also an independent predictor of mortality.

Methods and Results—Among 269 consecutive transseptal punctures, 13 (5%) were unsuccessful in 12 different patients (11 men aged 52±12 years) using the conventional Brockenbrough technique. All 12 patients had previously undergone at least one transseptal catheterization. The needle position in relation to the fossa ovalis was assessed by fluoroscopy in orthogonal views and was confirmed with contrast injection and by visualizing the characteristic "tenting" of the fossa ovalis. Prior to using RF energy, there were a median of 6 unsuccessful attempts to perforate the septum conventionally, with one pericardial puncture (with a non significant effusion). RF transseptal puncture was then performed by delivering unipolar RF with manual contact between the ablation catheter and the proximal extremity of the needle at the patient's groin. RF transseptal puncture was achieved at the first attempt in all patients within a median of 1 second (IQ range 1 - 4) and without any complication. The only parameter predictive of a septum resistant to conventional puncture was the total number of transseptal catheterizations (3.2±1 vs. 1.8±1, p<0.001).

Conclusion—Transmission of radiofrequency energy from the ablation catheter up to the tip of the transseptal needle provides an easy and safe method for piercing the fossa ovalis when the conventional approach fails due to a resistant septum.

Methods and Results—Continuous rapid pacing (1200 bpm, 2x threshold, TH) was performed at the left atrial appendage. Group 1 (N=7): 6-hour pacing immediately followed by ganglionated plexi (GP) ablation; Group 2 (N=7): GP ablation immediately followed by 6-hour pacing; Group 3 (N=4): administration of autonomic blockers, atropine (1 mg/kg) and propranolol (0.6 mg/kg) immediately followed by 6-hour pacing. The effective refractory period (ERP) and window of vulnerability (WOV, in milliseconds), i.e., the difference between the longest and the shortest coupling interval of the premature stimulus which induced AF, were measured at 2x TH and 10x TH at the left atrium, right atrium and pulmonary veins every hour before and after GP ablation or autonomic blockade. In Group 1, ERP was markedly shortened in the first two hours and then stabilized both at 2x TH and 10x TH; however, WOV was progressively widened throughout the 6-hour period. After GP ablation, ERP was significantly longer than before ablation and AF could not be induced (WOV=0) at either 2x TH or 10x TH. In Group 2 and 3, rapid atrial pacing failed to shorten the ERP. AF could not be induced in 6/7 dogs in Group 2 and 4/4 dogs in Group 3 during the 6-hour pacing period.

Conclusion—The ICANS plays a crucial role in the acute stages of atrial electrical remodeling induced by rapid atrial pacing.

Methods and Results—Eighty-one consecutive patients undergoing AF ablation followed by esophageal endoscopy (EGD) were included in this observational study. All patients underwent extra-ostial electrical PV isolation using an electro-anatomical mapping system and irrigated RF ablation. All RF applications on the posterior LA were limited to 35 Watts. A commercially available, single-thermocouple esophageal probe was used to monitor LET in a subset of patients (n=67). In these cases, applications were promptly interrupted when LET was ≥38.5°C; further applications were performed at reduced power to obtain a LET <38.5°C. EGD was performed 1-3 days post-procedure. Ablation-related esophageal ulcerations were identified in 9/81 (11%) patients. All patients were asymptomatic. Of these 81 patients, LET monitoring during ablation occurred in 67 (83%) of patients. Esophageal injury was observed more frequently (36% vs. 6%, p< 0.006) in the group without LET monitoring.

Conclusions—These data suggest that LET monitoring may be associated with a reduction in esophageal injury compared to power limitation alone.

Methods and Results—From 1999 to 2006, 493 consecutive patients (358 male, 57±16yo) underwent 623 VT ablations: 131 had no structural heart disease (SHD), 213 ischemic cardiomyopathies (ICMP) and 149 non-ischemic cardiomyopathies (NICMP). Whereas the main substrate is ICMP, the proportion of NICMP has increased from 27% to 35% (p=0.06) from the 1999-2002 to the 2003-2006 period. The procedure abolished or modified inducible VTs in ≥75% of patients in all groups, but abolition of all monomorphic VTs was achieved in 125 (83%) patients without SHD, 180 (65%) with ICMP and 99 (51%) with NICMP (p<0.0001). During a mean follow-up of 3.3±2.4 years, no deaths occurred in patients without SHD but 75 patients (35%) with ICMP and 26 patients (17%) with NICMP died after a median of 13 months. Multivariate Cox regression analysis found age, ejection fraction and need for preprocedural mechanical hemodynamic support, predicted mortality.

Conclusion—The substrate causing VT in patients requiring ablation is evolving and determines the long term outcome. In the setting of a normal heart, VT ablation is associated with low risk of subsequent mortality with no deaths occurring over a mean follow-up >3years. In contrast, in patients with SHD and recurrent VT, VT ablation can be helpful to suppress drug refractory VT, but long term mortality remains significant.

Methods and Results—In 7 Langendorff-perfused sheep hearts AF was initiated by a burst of 6 pulses (CL 80-150ms) delivered to the left inferior or right superior PV ostium 100-150 ms after the sinus impulse in the presence of 0.5 µM acetylcholine. The exposed septal-PLA endocardial area was mapped with high spatio-temporal resolution (DI-4-ANEPPS, 1000-fr/s) during AF initiation. Isochronal maps for each paced beat preceding AF onset were constructed to localize areas of conduction delay and block. Phase movies allowed the determination of the wavebreak sites at the onset of AF. Thereafter, the PLA myocardial wall thickness was quantified by echocardiography, and the fiber direction in the optical field of view was determined after peeling off the endocardium. Finally, isochrone, phase and conduction velocity maps were superimposed on the corresponding anatomical pictures for each of the 28 episodes of AF initiation. The longest delays of the paced PV impulses, as well as the first wavebreak, occurred at those boundaries along the SPB that showed sharp changes in fiber direction and the largest and most abrupt increase in myocardial thickness.

Conclusions—Waves propagating from the PVs into the PLA originating from a simulated pulmonary vein tachycardia triggered reentry and vagally mediated AF by breaking at boundaries along the SPB where abrupt changes in thickness and fiber direction resulted in sink-to-source mismatch and low safety for propagation.

Methods and Results—One hundred and five probands with BrS were screened for ion channel gene mutations using single strand conformation polymorphism (SSCP) electrophoresis and direct sequencing. A missense mutation (R99H) in KCNE3 (MiRP2) was detected in one proband. The R99H mutation was found 4/4 phenotype positive and 0/3 phenotype-negative family members. Chinese hamster ovary (CHO)-K1 cells were co-transfected using wild-type (WT) or mutant KCNE3 and either WT KCND3 or KCNQ1. Whole-cell patch clamp studies were performed after 48 hours. Interactions between Kv4.3 and KCNE3 were analyzed in co-immunoprecipitation experiments in human atrial samples. Co-transfection of R99H-KCNE3 with KCNQ1 produced no alteration in current magnitude or kinetics. However, co-transfection of R99H KCNE3 with KCND3 resulted in a significant increase in the I_to intensity compared to WT KCNE3+KCND3. Using tissues isolated from left atrial appendages of human hearts, we also demonstrate that K_v4.3 and KCNE3 can be co-immunoprecipitated.

Conclusions—These results provide definitive evidence for a functional role of KCNE3 in the modulation of Ito in the human heart and suggest that mutations in KCNE3 can underlie the development of BrS.

Methods and Results—Standard and floating glass microelectrodes were used to record action potentials from epicardial, M-cell, and endocardial regions of the arterially-perfused LV wedge, from tissue slices isolated from these regions, as well as from isolated Purkinje fibers. A transmural ECG was simultaneously recorded across the wedge. Under baseline conditions and in the presence of I_Ks block (chromanol 293B), hyperthermia (39-40°C) abbreviated APD in tissue slices from all three regions. In the presence of I_Kr block (E-4031), hyperthermia prolonged APD and induced or augmented EADs in M cell and Purkinje preparations at pacing cycle lengths ≥ 800 ms, but abbreviated APD in epicardium and endocardium, resulting in a marked accentuation of TD-APD. Ryanodine prevented the hyperthermia-induced EAD. In perfused wedge preparations, hyperthermia abbreviated APD throughout both in the absence or presence of I_Kr or I_Ks block and did not induce EADs or TdP. Combined I_Kr and I_Ks block increased TD-APD, and induced EADs (4/12) and spontaneous TdP (3/12) at 36-37°C; hyperthermia (39-40°C) further accentuated TD-APD and facilitated the development of EAD activity (9/12) and TdP (6/12).

Conclusions—Our findings suggest that hyperthermia can be associated with an increased arrhythmic risk when the repolarization reserve of the myocardium is compromised.

Methods and Results—Mutational analysis of SNTA1 was performed on 39 LQTS patients (QTc ≥ 480ms) with previously negative genetic-screening for the known LQTS-causing genes. We identified a novel A257G-SNTA1 missense mutation, which affects a highly conserved residue, in 3 unrelated LQTS probands but not in 400 ethnic-matched control alleles. Only one of these probands had a preexisting family history of LQTS and sudden death with an additional intronic variant in KCNQ1. Electrophysiological analysis was performed using HEK-293 cells stably expressing hNa_v1.5 and transiently transfected with either wild type (WT) or mutant SNTA1, and in neonatal rat cardiomyocytes transiently expressing with either WT or mutant SNTA1. In both HEK293 cells and neonatal rat cardiomyocytes increased peak sodium currents were noted along with a 10 mV negative shift of the onset and peak of currents of the I-V relationships. In addition, A257G-SNTA1 shifted the steady-state activation (V_h) leftward by 9.4 mV, while the voltage-dependent inactivation kinetics and the late sodium currents were similar to WT-SNTA1.

Conclusion—SNTA1 is a new susceptibility gene for LQTS. A257G-SNTA1 can cause gain-of-function of Na_v1.5 similar to the LQT3.