Efficacy of cryo-ablation during atrioventricular nodal reentrant tachycardia.

Because of the low atrioventricular (AV) block risk during cryo-ablation, it has become possible to treat AV nodal reentrant tachycardia (AVNRT) during arrhythmia. This study aimed to investigate the clinical outcomes of performing cryo-ablation for AVNRT during arrhythmia. Twenty-three patients with AVNRT treated by cryo-ablation during arrhythmia were enrolled. Cryo-ablation was performed gradually from the bottom to above the paraseptal tricuspid annulus until AVNRT was terminated. If the slow pathway was not eliminated despite cryo-ablation terminating the AVNRT, additional cryo-ablation was performed at a higher site until the slow pathway elimination was achieved. AVNRT was terminated by cryo-ablation in all 23 patients. However, the slow pathway was only eliminated in 6 patients. Among the remaining 17 patients, the slow pathway could not be ablated because transient AV block occurred during cryo-ablation at a higher site in 8 patients; however, cryo-ablation at a higher site successfully eliminated the slow pathway in the other 9 patients. In these 9 patients, the distance from the bottom of tricuspid annulus to the site of slow pathway elimination was significantly longer than that from bottom of tricuspid annulus to the AVNRT termination site (20.1 ± 5.3 vs 14.7 ± 4.5 mm: p = 0.027). During follow-up, AVNRT recurrence was confirmed in 3 patients. In 1 of these 3 patients, even a slow pathway elimination was achieved by cryo-ablation at the AVNRT termination site. The AVNRT termination site may not be the ideal site for performing cryo-ablation.

Unique mechanism of mitral valve prolapse in atrial septal defect: Three-dimensional insights into mitral complex geometry using real-time transesophageal echocardiography.

BACKGROUND: Mitral valve prolapse (MVP) is often identified in patients with atrial septal defect (ASD), which occasionally require surgical intervention at the time of ASD closure or even long after the surgery. Ventricular and valvular geometric characteristics in preoperative ASD patients were evaluated by three-dimensional (3D) transesophageal echocardiography. METHODS AND RESULTS: Mitral valve (MV) complex geometry was quantitatively measured by 3D transesophageal echocardiography in 11 ASD patients (Qp/Qs > 1.5) and 11 controls. The ASD group had a significantly larger indexed prolapse volume and height, with a larger anterior mitral leaflet than controls (0.53 [0.33-0.75] vs 0.057 [0.027-0.11] mL/m2 , P = .0001; 2.89 [2.13-3.50] vs 0.92 [0.48-1.32] mm/m2 , P < .0001; 391.3 [346.4-445.1] vs 295.3 (281.9-330.0) mm2 /m2 , P = .011, respectively). The right ventricular (RV)-to-left ventricular (LV) end-systolic diameter ratio was larger in the ASD group than in the control group (1.34 [0.96-1.45] vs 0.85 [0.75-0.88], P = .004). The indexed inter-papillary muscle distance (IPMD) was significantly shorter in the ASD group than in the control group (7.77 [6.55-8.24] vs 9.71 [8.64-10.8] mm/m2 , P = .011). IPMD was significantly correlated with the RV-LV end-systolic diameter ratio (r = -.70, P = .017). CONCLUSIONS: Inward shift of the LV papillary muscle tips due to RV dilation may be a major mechanism of MV prolapse in ASD. At the same time, positive remodeling of the anterior leaflet was observed in the ASD group, which may compensate for the billowing leaflet geometry to maintain effective coaptation. Three-dimensional assessment of the MV apparatus geometry will help to further understand perioperative mitral regurgitation in patients with ASD.

Implant Characteristics of Quadripolar and Bipolar Left Ventricular Leads for Cardiac Resynchronization Therapy.

Several studies have reported that the left ventricular (LV) lead implant success rate ranges between 88.0% and 92.4%. Coronary venous anatomy differs among patients thus, necessitating multiple types of leads. To date, the implant success rate among Japanese patients utilizing a pre-specified family LV leads (including bipolar and quadripolar) is not well known. The Attain Success Japan Study enrolled patients indicated for a de novo or an upgrade cardiac resynchronization therapy implant. Patients were followed for 3 months, and the implant success rates with Medtronic Attain family LV leads as well as the incidence of complications related to the LV lead were evaluated.Three hundred 53 patients were enrolled from 29 sites in Japan; 346 patients had LV lead implant attempts. The LV lead was successfully implanted in 336 patients (97.1%). Bipolar and quadripolar LV lead implants were successful in 97.2% and 99.2% of patients, respectively (P = 0.43). Four complications (1.2%) related to the LV leads were reported; all of which occurred in patients receiving bipolar LV leads. The quadripolar LV leads were more frequently implanted in the apical segment compared with bipolar leads (21.6% versus 3.8%, P < 0.01). This study demonstrated a high implant success rate and a low LV lead-related complication rate, regardless of bipolar, or quadripolar in a Japanese cohort of patients.

Left atrial appendage orifice dimensions in Japanese atrial fibrillation population measured by multiplane transesophageal echocardiography.

BACKGROUND: Successful implantation of the WATCHMAN device requires an accurate understanding of left atrial appendage (LAA) anatomy and orifice dimensions. Racial differences are observed in LAA size when comparing Asians with non-Asians. METHODS: A total of 170 patients (123 male, 67.4 ± 9.2 years) with paroxysmal or persistent atrial fibrillation (AF) underwent transesophageal echocardiography before catheter ablation or cardioversion (September 2018 to September 2019). As per the recommendations of the WATCHMAN device, the maximal LAA ostial diameters were measured at multiplane angles of 0°, 45°, 90°, and 135°. RESULTS: The majority of patients (121/170, 71%) had an LAA orifice size within 17-25 mm. Fifteen (8.8%) patients had undersized (< 17 mm) and eight (0.5%) had oversized (> 31 mm) LAA. One patient in this population had no LAA. LAA size was significantly larger in patients with persistent AF than in those with paroxysmal AF (23.3 ± 4.2 mm vs. 20.0 ± 3.0 mm, p < 0.001) and in male patients than in female patients (22.4 ± 4.2 vs. 20.9 ± 3.7 mm, p = 0.03). LAA orifice dimension was significantly correlated with CHADS2 score, the left atrial volume (LAV), E/e', and the left ventricular ejection fraction. Persistent AF, body mass index, and LAV were independently associated with LAA orifice dimension in multivariate analysis. CONCLUSION: This study demonstrated the distribution of LAA orifice dimension in the Japanese AF patients. This finding should be used as a reference to understand the racial characteristics of LAA size for the WATCHMAN procedure.

Impact of osteogenic activity on degenerative aortic valve disease in patients with osteoporotic hip fracture.

BACKGROUND: Previous studies have proposed that osteogenic and apoptotic processes of valve interstitial cells contribute to the mineralization and then calcification of the aortic valve. Osteoblast-like cells subsequently mediate calcification of the aortic valve as part of a highly regulated process analogous to skeletal bone formation. The objective of this study was to evaluate the pathogenesis of the sclerotic/calcific changes in the aortic valve from histological and biological findings, and investigate the role of osteoblasts in the calcified pathway of aortic stenosis. METHODS: Preoperative echocardiography in 550 consecutive patients with osteoporotic hip fracture were retrospectively examined (475 females, mean 25th-75th, 89 [85-93] years). One hundred sixteen patients were under medical treatment with anti-osteoporosis drugs. We evaluated the prevalence and degree of degenerative changes in the aortic valve and examined the associations of bone turnover biomarkers N-terminal pro-peptide of type 1 collagen (P1NP) and serum tartrate-resistant acid phosphatase (TRACP-5b) with degenerative calcific changes in the aortic valve. RESULTS: Of 550 patients, 112 patients (20.9%) showed no leaflet calcification; 296 (53.8%), 1 leaflet calcification; and 142 (25.8%), 2 ≥ leaflets calcification. Significant (peak velocity ≥ 3.0m/s) Aortic stenosis was found in 43 patients (7.8%). In patients who were not taking anti-osteoporotic drugs, P1NP was higher in the 2 ≥ leaflets calcification group than in the other groups (p < 0.01). TRACP-5b was not significantly different among the three groups (p = 0.15). CONCLUSIONS: Degenerative changes in the aortic valve were related to bone biomarker activation in osteoporotic hip fracture patients.

Repeated sirolimus-eluting stent implantation to treat sirolimus-eluting stent and bare-metal stent restenosis.

BACKGROUND: In-stent restenosis (ISR) remains a persistent, unresolved issue even in the era of percutaneous coronary intervention (PCI) using drug-eluting stents. The present study compares the clinical and angiographic outcomes of using sirolimus-eluting stents (SES) for re-intervention against ISR that was originally treated with sirolimus-eluting or bare-metal (BMS) stents. METHODS AND RESULTS: This prospective single-center registry investigated 179 ISR lesions in 158 consecutive patients (53 lesions in 49, and 126 in 109 patients originally treated with SES and BMS, respectively), who had undergone re-intervention with SES. The patients were clinically and angiographically followed up at 8 months after re-PCI. The incidence of re-restenosis (29 vs 12%, P<0.01), ischemia-driven target lesion revascularization (TLR; 21 vs 8%, P<0.05) and major adverse cardiac events (MACE; 21 vs 9%, P<0.05) were significantly greater in ISR lesions originally treated with SES than in those originally treated with BMS at 8 months after re-PCI. Moreover, late luminal loss was significantly greater in the group with post-SES restenosis (P<0.05). Even after adjustment, post-SES restenosis was the only independent predictor of re-restenosis and MACE (P<0.05, each). CONCLUSIONS: Although the re-restenosis rate is acceptable, the incidence rates of late restenosis, ischemia-driven TLR and MACE are higher after repeated SES implantation to treat SES, than BMS restenosis. These results might affect the mid-term clinical outcomes of re-intervention with SES.

A Novel Predictive Model for In-Hospital Mortality Based on a Combination of Multiple Blood Variables in Patients with ST-Segment-Elevation Myocardial Infarction.

In emergency clinical settings, it may be beneficial to use rapidly measured objective variables for the risk assessment for patient outcome. This study sought to develop an easy-to-measure and objective risk-score prediction model for in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI). A total of 1027 consecutive STEMI patients were recruited and divided into derivation (n = 669) and validation (n = 358) cohorts. A risk-score model was created based on the combination of blood test parameters obtained immediately after admission. In the derivation cohort, multivariate analysis showed that the following 5 variables were significantly associated with in-hospital death: estimated glomerular filtration rate <45 mL/min/1.73 m2, platelet count <15 × 104/µL, albumin ≤3.5 g/dL, high-sensitivity troponin I >1.6 ng/mL, and blood sugar ≥200 mg/dL. The risk score was weighted for those variables according to their odds ratios. An incremental change in the scores was significantly associated with elevated in-hospital mortality (p < 0.001). Receiver operating characteristic curve analysis showed adequate discrimination between patients with and without in-hospital death (derivation cohort: area under the curve (AUC) 0.853; validation cohort: AUC 0.879), and there was no significant difference in the AUC values between the laboratory-based and Global Registry of Acute Coronary Events (GRACE) score (p = 0.721). Thus, our laboratory-based model might be helpful in objectively and accurately predicting in-hospital mortality in STEMI patients.

A multicenter study comparing the outcome of catheter ablation of atrial fibrillation between cryoballoon and radiofrequency ablation in patients with heart failure (CRABL-HF): Study design.

BACKGROUND: Catheter ablation of atrial fibrillation (AF) is increasingly performed worldwide in patients with heart failure (HF). However, it has been recently emphasized that AF ablation in patients with HF is associated with increased risks of procedure-related complications and mortality. There are little data about the differences in the efficacy and safety between cryoballoon (CB) and radiofrequency (RF) ablation of AF in patients with HF. METHODS: The CRABL-HF study is designed as a prospective, multicenter, open-label, controlled, and randomized clinical trial comparing the efficacy and safety of AF ablation between CB and RF ablation in patients with HF (LVEF ≤40%) (UMIN Clinical Trials Registry UMIN000032433). The CRABL-HF study will consist of 110 patients at multicenter in Japan. The patients will be registered and randomly assigned to either the CB ablation or RF ablation group with a 1:1 allocation. The primary endpoint of this study is the occurrence of atrial tachyarrhythmias (ATs) at 1 year with a blanking period of 90 days after ablation. Key secondary endpoints are the success rate of the pulmonary vein isolation, total procedural time, left atrial dwelling time, total fluoroscopy time, radiation exposure, complication rate, composite of all-cause mortality or HF hospitalizations, cardiovascular events, change in left ventricular ejection fraction, and change in quality of life. RESULTS: The results of this study are currently under investigation. CONCLUSION: The CRABL-HF study is being conducted to compare the efficacy and safety of catheter ablation of AF between CB and RF ablation in patients with HF.

Japan ablation registry: cryoablation in atrioventricular nodal reentrant tachycardia ("JARCANRET study"): results from large multicenter retrospective investigation.

PURPOSE: Cryoenergy has been demonstrated to be a safe alternative to radiofrequency ablation for catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT). This study aimed to evaluate the safety and efficacy of cryoablation in patients with AVNRT. METHODS: A multicenter retrospective study was performed. Two hundred eighty-three consecutive patients with AVNRT underwent cryoablation. Cryomapping at - 30 °C and - 80 °C was performed to predict cryoablation outcome and ascertain antegrade conduction. Cryoenergy was delivered subsequently at the same spot (cryoablation at - 80 °C) for 240 s. RESULTS: Ablation procedure was acutely successful in 281 out of 283 patients (99.3%). Of note, 22 patients (10.1%) had transient AV block during the cryoablation, but no injurious effects on AV conduction were provoked during cryomapping. During a follow-up period of 367 ± 35 days, the recurrence rate was 3.9% (11 out of 281). There were no significant differences among the patients with a complete elimination of slow pathway conduction, AH jump without an echo beat, and AH jump with a single echo beat, in terms of the long-term recurrence of AVNRT. CONCLUSIONS: Cryoablation of AVNRT appears to be effective both acutely and during the long-term with a minimal risk of unwanted injuries to the conduction system. It seems to be important to monitor the antegrade conduction during cryoenergy applications, even when cryomapping demonstrates a safe location for cryoablation. The recurrence rate of AVNRT did not differ according to the properties of the residual slow pathway conduction.

Reverse Remodeling of the Mitral Valve Complex After Radiofrequency Catheter Ablation for Atrial Fibrillation: A Serial 3-Dimensional Echocardiographic Study.

BACKGROUND: Mitral regurgitation is frequently complicated with atrial fibrillation without apparent organic changes in the leaflet, which occasionally improves after successful radiofrequency catheter ablation. We aimed to evaluate a possible geometric effect of radiofrequency catheter ablation on the mitral valve apparatus. METHODS: Forty-three consecutive patients who underwent successful catheter ablation for persistent atrial fibrillation (maintaining sinus rhythm for 6 months after their procedure) were examined by serial real-time 3-dimensional transesophageal echocardiography before and 6 months after catheter ablation. Mitral valve complex geometry was measured using dedicated software for 3-dimensional transesophageal echocardiography. RESULTS: Mitral valve apparatus showed significant reverse remodeling along with left atrial reverse remodeling 6 months after successful catheter ablation (50.5 [39.2-61.0] versus 36.4 [28.9-43.1] mL/m2; P<0.001). The degree of mitral regurgitation decreased in a majority of patients (mitral regurgitation jet area; 1.83 [0.78-3.09] versus 0.77 [0.36-1.47] cm2; P<0.001). Annular area significantly decreased (5.32±0.91 versus 4.73±0.76 cm2/m2; P<0.001) in both anterior-posterior and medial-lateral directions. Mitral annular contraction significantly recovered after maintaining sinus rhythm for 6 months (7.51 [4.82-9.62]% versus 9.71 [6.27-13.85]%; P=0.008). There were no significant changes in tenting volume or tenting height (0.46 [0.27-0.89] versus 0.51 [0.32-0.72] mL/m2, P=0.744; 2.34 [1.75-3.48] versus 2.76 [1.99-3.08] mm/m2, P=0.717). The leaflet surface area also significantly decreased after catheter ablation (5.74 [5.01-6.33] versus 5.19 [4.63-5.64] cm2/m2; P<0.001). CONCLUSIONS: Maintaining sinus rhythm after successful catheter ablation promotes reverse remodeling in the mitral valve apparatus and improves so-called atrial functional mitral regurgitation. The positive geometric effect of catheter ablation would be expected to be a possible contributor to better outcomes in patients with atrial fibrillation, in addition to the postprocedural freedom from rhythm disturbance.

Full-metal jacket technique using second-generation drug-eluting stent: clinical and angiographic follow-up in 2 years.

The aims of this study are to evaluate the efficacy of percutaneous coronary intervention (PCI) using full-metal jacket (FMJ) with second-generation drug-eluting stents (DES). A single-center, non-randomized, retrospective study was performed from May 2005 to February 2014 at Miyazaki Medical Association Hospital, Japan. PCI using FMJ with DES was performed to treat 240 very long lesions (> 60 mm) in 240 patients. Subjects were divided into a first-generation or second-generation DES group. The primary endpoint was the incidence of major adverse cardiac events (MACE) at 2 years. MACE included all-cause death, myocardial infarction (MI), cerebrovascular event, and target vessel revascularization. The secondary endpoint was binary restenosis (> 50% stenosis) assessed by angiography at 1 year of follow-up. Second-generation DES were implanted to treat 121 lesions, and the first-generation DES were implanted to treat 119 lesions. Since 35 patients were lost to follow-up, the final analysis included 102 patients with second-generation DES and 103 with first-generation DES. At the 2-year follow-up, the incidence of MACE was significantly less in the second-generation DES group (9.8% vs. 20.4%, p = 0.03). The incidence of binary restenosis at 1 year was also significantly lower in the second-generation DES group (6.7% vs 29.1%, p < 0.01). When PCI was performed using FMJ with DES to treat very long lesion, the angiographic and clinical outcomes were better with second-generation than first-generation DES.

Atrial fibrillation ablation with esophageal cooling with a cooled water-irrigated intraesophageal balloon: a pilot study.

INTRODUCTION: A left atrioesophageal fistula is an uncommon but devastating complication that may occur during atrial fibrillation (AF) ablation, and may be due to thermal injury occurring during the radiofrequency (RF) ablation. We examined the feasibility of an esophageal cooling (ECO) method using a cooled water-irrigated intraesophageal balloon (IB). METHODS AND RESULTS: Eight patients with drug-refractory AF underwent RF catheter ablation to encircle the ipsilateral pulmonary veins. During the RF ablation at the posterior left atrium, the esophageal lumen was cooled using a 9-Fr. IB catheter with a balloon length of 40 mm and diameter of 10 mm, in which cooled water, with a water temperature of 4.5 +/- 3.1 degrees C, was irrigated while the luminal esophageal temperature (LET) was measured with an intraesophageal probe placed at a site close to the tip of the ablation catheter. In the control, the LET increased from 36.4 +/- 0.8 degrees C to 40.5 +/- 1.7 degrees C within 26.1 +/- 8.2 seconds during 3.9 +/- 1.2 RF energy applications, whereas with the ECO the LET decreased to 30.2 +/- 2.9 degrees C at baseline (P<0.01 vs control), and increased only to 33.5 +/- 2.9 degrees C (P<0.01 vs control) at most, within 30 seconds during 3.9 +/- 1.2 RF energy applications. All pulmonary veins were successfully isolated in all patients without any complications. During a follow-up period of 3.1 +/- 1.2 months, no esophageal injuries were observed and all but one patient have been free from any symptoms. CONCLUSIONS: Use of an IB successfully lowers LET. This might have the potential of preventing esophageal injury, although further study is required.

Colchicine reduced pericardial effusion due to postcardiac injury syndrome following cardiac resynchronization therapy implantation.

We present a case of postcardiac injury syndrome with pericardial effusion following cardiac resynchronization therapy implantation which was treated by only colchicine. Although treatment using colchicine is not as common as NSAIDs or steroids, colchicine seems to be an effective and safe treatment option for the syndrome.

Effects of amiodarone on electrical and structural remodeling induced in a canine rapid pacing-induced persistent atrial fibrillation model.

Structural in addition to electrical remodeling may be induced by persistent atrial fibrillation per se and make atrial fibrillation refractory to antiarrhythmic drug therapy. Matrix metalloproteinases (MMPs) contribute to structural remodeling in the interstitial space. Amiodarone is effective in treating persistent atrial fibrillation compared with other antiarrhythmic drugs. In mongrel dogs, right atrial pacing at 540 beats/min (bpm) was performed along with ventricular pacing at 100 bpm for 6 weeks after atrioventricular node ablation. Right atrial pacing at 400 bpm was continued for 4 weeks with (n=5) or without (n=5) oral amiodarone (30 mg/kg/day). In sham dogs, only ventricular pacing was done with (n=4) or without (n=6) amiodarone. In atrial pacing without amiodarone group, electrical remodeling characterized by monophasic action potential duration shortening, loss of action potential duration-rate adaptation and depressed conduction velocity and structural remodeling characterized by slightly but significantly increased interstitial fibrosis and enhanced MMP-2 activity compared with sham group were observed, and sustained atrial fibrillation was easily induced. In atrial pacing with amiodarone group, both electrical and structural remodeling were reversed and sustained atrial fibrillation was not induced. In sham group with amiodarone, action potential duration prolongation and depressed conduction velocity compared with sham without amiodarone were observed, but either increased fibrosis or enhanced MMP-2 activity was not observed. Not only electrical but structural remodeling were induced in a canine persistent atrial fibrillation model. Amiodarone reversed both of them, which may be related to its high efficacy in preventing recurrence of persistent atrial fibrillation.

Unroofed coronary sinus detected by 2D/3D echocardiography in a patient referred to catheter ablation for atrial fibrillation.

A 67-year-old female visited our echo lab for a preoperative screening exam before radiofrequency catheter ablation for atrial fibrillation. Transthoracic echocardiography revealed abnormal color flow signal in the right atrium, and following 2D/3D transesophageal echocardiography proved partial type of unroofed coronary sinus. Absence of associated congenital abnormalities was ruled out by Doppler and contrast echo examinations. Surgical findings confirmed exactly the same anatomical abnormalities as preoperative 2D/3D echocardiography. Echocardiography plays an important role in finding unexpected underlying cardiac diseases in patients who are referred to arrhythmia clinics. In the present case with atrial fibrillation, we could accurately diagnose an unroofed coronary sinus syndrome during preoperative transthoracic and transesophageal echocardiography prior to planned radiofrequency catheter ablation. .

The Course of Ischemic Mitral Regurgitation in Acute Myocardial Infarction After Primary Percutaneous Coronary Intervention: From Emergency Room to Long-Term Follow-Up.

BACKGROUND: Previously published evidence on ischemic mitral regurgitation (IMR) and its adverse prognosis after myocardial infarction has been based on the severity of IMR in the subacute or chronic period of myocardial infarction. However, the state of IMR can vary from the early stage to the chronic stage as a result of various responses of myocardium after primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: Standard echocardiography was serially performed in 546 consecutive patients with first-onset acute myocardial infarction (1) immediately after their arrival (pre-PCI), (2) before discharge (early post-PCI), and (3) 6 to 8 months after PCI (late post-PCI). The course of IMR after primary PCI and the prognostic impact of the IMR in each phase were investigated. IMR was found in 193/546 (35%) patients at the emergency room. In the acute phase after PCI, IMR improved in 63 patients. IMR worsened in 78 patients despite successful PCI. Shorter onset-to-reperfusion time and nontotal occlusion before PCI were the independent predictors of early improvement of IMR. In the chronic phase, IMR improved in 79 patients and worsened in 36 patients. Lower peak creatine kinase-myocardial band was an independent predictor of late improvement of IMR. IMR before PCI worsened 30-day prognosis (P=0.02), and persistent IMR in the chronic phase worsened long-term prognosis (P=0.04) after primary PCI. CONCLUSIONS: Degrees of IMR changed in the early and chronic phase after primary PCI for acute myocardial infarction. IMR on arrival and persistent IMR in the chronic phase worsened short-term and long-term prognosis after acute myocardial infarction, respectively.

Mechanism of ST elevation and ventricular arrhythmias in an experimental Brugada syndrome model.

BACKGROUND: Although phase 2 reentry is said to be responsible for initiation of ventricular tachycardia (VT) in Brugada syndrome, information about the activation sequence during VT is limited. METHODS AND RESULTS: We developed an experimental Brugada syndrome model using a canine isolated right ventricular preparation cross-circulated with arterial blood of a supporter dog and examined the VT mechanism. Two plaque electrodes (35x30 mm) containing 96 bipolar electrodes were attached to the endocardium and epicardium. Saddleback and coved types of ST elevation in transmural ECG were induced by pilsicainide, a pure sodium channel blocker, and pinacidil, a KATP channel opener. Eighteen polymorphic VT episodes were recorded in 9 of the 12 preparations associated with ST elevation. Fourteen episodes spontaneously developed in 5 preparations after an extrasystole during basic drive pacing. Analysis of local recovery times revealed increased dispersion especially in epicardium, and the extrasystole originated from a site with a short recovery time, suggesting that phase 2 reentry was its mechanism. The other 4 VTs in 4 preparations were induced by premature stimulation. Analysis of the activation sequences during VT revealed reentry between epicardium and endocardium or reentry around an arc of a functional block confined to epicardium or endocardium with bystander activation of the other. CONCLUSIONS: Electrical heterogeneity in the recovery phase was induced in this experimental Brugada syndrome model, which can be a substrate for the development of phase 2 reentry and the subsequent reentry around an arc of the functional block, resulting in sustained VT.