Impact of the extent of low-voltage zone on outcomes after voltage-based catheter ablation for persistent atrial fibrillation.

BACKGROUND: Low-voltage zones (LVZs), as measured by electroanatomic mapping, are thought to be associated with fibrosis. We reported the efficacy of atrial fibrillation (AF) ablation aiming to homogenize left atrial (LA) LVZ. The purpose of this study was to evaluate the impact of LVZ extension outcomes after LVZ homogenization in patients with nonparoxysmal AF. METHODS: This prospective observational cohort study included 172 patients with nonparoxysmal AF undergoing their initial ablation. LVZ was defined as an area with bipolar electrograms <0.5mV during sinus rhythm. LVZ extent was calculated as the percentage of LA surface area, and subsequently, LVZ was categorized into stages I (<5%), II (≥5% to <20%), III (≥20% to <30%), and IV (≥30%). Patients with LVZs underwent LVZ ablation aimed at homogenization of ≥80% of LVZs following pulmonary vein isolation. The primary endpoint was atrial tachyarrhythmia recurrence-free survival after a single procedure at 18 months off antiarrhythmic drugs. The association of %LVZ with recurrence-free survival was examined using Cox proportional hazard models. RESULTS: The survival rates were 76%, 74%, 57%, and 28% in patients with stages I, II, III, and IV LVZ, respectively. The difference was significant between stages I and IV (log-rank, p<0.001), while not significant between stages I vs. II and I vs. III (p=0.843, p=0.073, respectively). Cox proportional hazard model revealed that %LVZ was an independent predictor of recurrence-free survival (hazard ratio, 1.025 per 1% increase, p<0.001; unadjusted model). The results were similar after demographic and clinical covariate adjustments and after excluding 12 patients who did not achieve homogenization of ≥80% of LVZ. CONCLUSIONS: The extent of LVZ is an independent predictor for recurrence even after LVZ homogenization.

A case of Wolff-Parkinson-White syndrome presenting spontaneous mutual frequent transition between atrioventricular reciprocating tachycardia and atrioventricular nodal re-entrant tachycardia.

Atrioventricular reciprocating tachycardia (AVRT) and atrioventricular nodal re-entrant tachycardia (AVNRT) can coexist and present unidirectional transition (from AVRT to AVNRT, or from AVNRT to AVRT) in a single patient. Actually, such cases have already been reported previously. However, a case with spontaneous bidirectional transition of both tachycardias during supraventricular tachycardia has never been reported. This article describes a case with spontaneous, mutual, and frequent transition between AVRT and AVNRT.

Efficacy of Left Atrial Voltage-Based Catheter Ablation of Persistent Atrial Fibrillation.

BACKGROUND: Low-voltage zones (LVZs) represent fibrotic tissue and are substrates for atrial fibrillation (AF). We hypothesized that LVZ-based substrate modification along with pulmonary vein isolation (PVI) would improve outcomes in persistent AF (PeAF) patients with LVZs, whereas PVI alone would work in patients without LVZs. METHODS AND RESULTS: Voltage mapping of the left atrium (LA) was performed during sinus rhythm in 101 PeAF patients in whom LVZ was defined as an area with bipolar electrograms <0.5 mV. Thirty-nine patients had LVZs and underwent ablation of the entire LVZ area after PVI (LVZabl group). In the remaining 62 patients without LVZs, PVI alone was performed with no further substrate modifications (PVI group). An additional group of 16 consecutive PeAF patients with LVZ did not undergo any substrate modification after PVI and were used as a comparison group (LVZnon-abl group) despite having similar size of LVZs to that in the LVZabl group. After a single session, 28 (72%) patients in the LVZabl group had no recurrence, whereas 49 (79%) patients in the PVI group had no recurrence during 18 ± 7 months of follow-up (log-rank, P = 0.400). In the LVZnon-abl group, only 6 patients (38%) had no recurrence during 32 ± 7 months of follow-up, even after a mean number of sessions of 1.8 (log-rank, P < 0.001, compared with the LVZabl group). CONCLUSIONS: Additional LVZ-based substrate modification after PVI improved the outcome in PeAF patients with LVZs, whereas PVI alone worked in patients without LVZs, even in those with PeAF.

Spatial Relation Between Left Atrial Anatomical Contact Areas and Circular Activation in Persistent Atrial Fibrillation.

INTRODUCTION: Atrial low-voltage zones (LVZs) may be related to maintenance of atrial fibrillation (AF). The influence of left atrial (LA) contact areas (CoAs) on reentrant or rotor-like sources maintaining AF has not been investigated. METHODS AND RESULTS: Forty patients with persistent AF (PsAF) were analyzed. Three representative CoA regions in the LA (ascending aorta: anterior wall; descending aorta: left inferior pulmonary vein; and vertebrae: posterior wall) were visualized by enhanced CT. Using circular catheters, the LVZs (<0.5 mV) were assessed after restoration of SR, and local activation mapping and frequency domain analyses were performed after induction of AF. Circular activation during AF was visually defined as sites with ≥2 rotations by serial electrograms encompassing >80% of the mean AF cycle length. A pivot was defined as the core of the localized circular activation. Anterior (39/40 patients, 98%), left pulmonary vein antrum (27/40, 68%), and posterior (19/40, 48%) CoAs were identified, and 80% (68/85) of those sites were overlapped by or close (<3 mm) to LVZs. Thirty-six (90%) patients demonstrated circular activation (3.1±1.7 sites/patients) along with significantly higher organized dominant frequencies (6.3 ± 0.5 Hz, regularity-index: 0.26 [0.23-0.41]) within the LA, and the average electrogram amplitude of those pivots was 0.30 mV (0.18-0.52). Of those sites, 55% (66/120) were located at or close to CoA regions. Catheter ablation including of LVZs neighboring CoAs terminated AF in 9 (23%) patients. CONCLUSIONS: External anatomical structures contacting the LA may be related to unique conduction properties in diseased myocardium necessary for PsAF maintenance.

Long-term results of pulmonary vein antrum isolation in patients with atrial fibrillation: an analysis in regards to substrates and pulmonary vein reconnections.

AIMS: To examine the impact of left atrial (LA) low-voltage zones (LVZs) on atrial fibrillation (AF) recurrence after pulmonary vein antrum isolation (PVAI) without LA substrate modification. METHODS AND RESULTS: Seventy-six patients with AF (paroxysmal/persistent 65/11) were prospectively enroled. Left atrial voltage maps were constructed during sinus rhythm using NavX to identify LVZs (<0.5 mV), and PVAI without any LA substrate modification was performed using an open-irrigation catheter. After PVAI, 20 mg of adenosine triphosphate (ATP) was injected. Adenosine triphosphate-induced PV reconnections were eliminated by touch-up ablation when unmasked. Voltage maps revealed LVZs in 24 patients (32%) and no LVZs in 52 (68%). During 24 ± 7 months of follow-up, 15 patients (63%) with LVZs and 10 (19%) without had AF recurrences off antiarrhythmic drugs (log-rank P < 0.001). A multivariate logistic regression analysis revealed that LVZ areas [odds ratio (OR): 1.12 per 1 cm(2), 95% confidence interval (CI): 1.04-1.23, P = 0.001] and ATP-induced reconnection (OR: 2.08, 95% CI: 1.01-4.91, P = 0.046) were significant predictors of recurrence. In those with LVZs, the LVZ area was strongly correlated with the LA body volume (r = 0.81, P < 0.001) and a unique predictor of recurrence (OR: 1.17 per 1 cm(2), 95% CI: 1.01-1.55, P = 0.031), while in those without an LVZ, ATP-induced PV reconnection was a unique predictor (OR: 3.24, 95% CI: 1.15-15.39, P = 0.025). CONCLUSION: The LVZ area was an independent predictor of recurrence after PVAI without any LA substrate modification. Adenosine triphosphate-induced PV reconnection was also an independent predictor, especially in those without LVZs.

A new method of a pulmonary vein map to identify a conduction gap on the pulmonary vein antrum ablation line.

BACKGROUND: Electrical isolation of the pulmonary veins (PV) is crucial for atrial fibrillation (AF) ablation. Conduction gaps on the circumferential PV antrum ablation (CPVA) line sometimes remain, which are sometimes difficult to identify. METHODS AND RESULTS: CPVA of the ipsilateral superior and inferior PVs was performed during sinus rhythm or coronary sinus pacing using the NavX system in 22 AF patients, in whom 1 round of CPVA failed to disconnect 26 individual PVs (30%) in 18 patients. In these patients, a local activation map within the CPVA line (PV map) was created by a 20-pole circular mapping catheter with the use of the NavX, with 71 ± 37 sampling points per PV antrum. The conduction gap was defined as a site on the CPVA line, from which the activation proceeded toward the entire PV. The mapped PV antra were comprised of the left superior PV in 11, right superior PV in 10, left inferior PV in 3, right inferior PV in 1 and a left common PV in 1 PV(s). The conduction gaps were identified at 1.4 ± 0.7 sites per PV antrum, with an electrogram amplitude of 0.8 ± 0.7 mV. A point ablation at the gap completely isolated 24 out of 26 PV antra (92%) with 1.9 ± 1.3 applications. CONCLUSIONS: The PV map was useful for quickly and accurately identifying the conduction gap(s) after 1 round of CPVA.

Characterization of non-pulmonary vein foci with an EnSite array in patients with paroxysmal atrial fibrillation.

AIMS: Non-pulmonary vein (PV) foci are sometimes difficult to identify and eliminate. The EnSite array (EA) reveals the detailed beat-to-beat virtual activation. This study aimed to characterize non-PV foci using the EA. METHODS AND RESULTS: Sixty-five patients with paroxysmal atrial fibrillation (AF) were included. All had ectopy initiating AF and/or focal atrial tachycardia analysed using the EA. All patients underwent PV isolation (PVI) and additional ablation of non-PV foci if present. The EA revealed 59 PV foci in 48 patients (Group P) and 19 non-PV foci in 17 patients (Group N). In Group N, 12 patients (71%) also had 17 PV foci. The non-PV foci were frequently distributed in the left atrial (LA) roof (n = 5) and superior vena cava (n = 5). Pulmonary vein isolation during on-going AF terminated AF in 34 of 37 in Group P (92%) and 4 of 14 in Group N (29%) patients (P < 0.0001). All non-PV foci were eliminated by an EA-guided ablation. During a 23 ± 10 month follow-up, 11 patients (17%) had AF recurrences, mainly due to LA-PV reconnection. CONCLUSION: Non-PV foci are prevalent in the LA roof and SVC sites, but can originate from other sites as well. When non-PV foci are observed, PVI may be insufficient and should be supplemented with non-PV foci ablation.

Radiofrequency catheter ablation of ventricular tachyarrhythmia under navigation using EnSite array.

BACKGROUND: EnSite array (EA) provides virtual activation of ventricular tachycardia (VT) and premature ventricular contraction (PVC) on a beat-to-beat basis. METHODS AND RESULTS: Fifty-five consecutive patients (age 52+/-16 years) with 79 VTs/PVCs undergoing EA-guided radiofrequency catheter ablation (RFA) were studied, of whom 7 patients had organic heart diseases. A virtual activation map showed that 66 VTs/PVCs originated from the right ventricle (RV), including the RV outflow tract in 57, lateral wall of RV in 4, His bundle region in 3 and tricuspid annulus in 2. Ten VTs/PVCs originated from the left ventricle (LV), including the LV endocardium in 7 and aortic sinus cusp in 3. The origins of 3 PVCs, one each in 3 patients, were not identified. Six of 38 VTs were sustained and the remaining 32 VTs were non-sustained. RFA eliminated all but 3 focal PVCs, and all macroreentrant VTs at a critical conducting pathway, which was identified by the combined use of contact voltage and virtual activation maps. There were 11+/-9 applications, and the radiofrequency energy and fluoroscopy time were 11,354+/-13,360 J and 30+/-21 min, respectively. All patients with acute success were free of any symptoms during a follow up of 21+/-11 months. CONCLUSIONS: EA-guided RFA is safe and effective for VT/PVC, irrespective of its origin, mechanism, sustainability, hemodynamic condition, and underlying heart disease.

Characterization of bipolar electrograms during sinus rhythm for complex fractionated atrial electrograms recorded in patients with paroxysmal and persistent atrial fibrillation.

AIMS: Complex fractionated atrial electrogram (CFAE) has been reported to relate to maintain atrial fibrillation (AF). The aims of this study were to investigate the relationship between CFAE and background conditions during sinus rhythm (SR). METHODS AND RESULTS: Electroanatomical mapping using an EnSite Array was performed in 20 patients (paroxysmal AF:persistent AF = 16:4) who underwent pulmonary vein antrum isolation (PVAI). Contact bipolar electrograms were recorded before PVAI, during SR, and subsequently during induced AF. Peak-to-peak voltages and morphologies of the electrograms during SR were compared between sites with and without CFAE during AF. Among 1947 points obtained during SR, 974 (50%) were included in CFAE sites and 973 (50%) in non-CFAE sites. Electrogram amplitude during SR was higher at the CFAE sites than at the non-CFAE sites (2.4 +/- 1.7 vs. 1.9 +/- 1.9 mV; P < 0.0001), whereas fractionated or double electrograms were found in a similar range between the two areas (2 vs. 3%; P = 0.21). When analysed further in terms of AF termination by PVAI followed by confirmation of non-inducibility, the voltage of electrograms at the CFAE sites was lower (2.1 +/- 1.7 vs. 2.6 +/- 1.8 mV; P = 0.0001) and the morphology was more complex in patients without AF termination compared with those with AF termination. CONCLUSION: Our results suggest that in paroxysmal and persistent AF with minimally damaged LA, the CFAE sites in patients with AF termination by PVAI alone represent healthy atrial tissue with rapid electrical activity in response to an AF driver located in the pulmonary vein. However, in patients without AF termination, they represent more damaged tissue responsible for maintaining AF.

Radiofrequency catheter ablation of atrial tachycardia under navigation using the EnSite array.

BACKGROUND: Atrial tachycardia (AT) is sometimes difficult to eliminate by radiofrequency ablation (RFA), but the EnSite array (EA) visualizes the beat-to-beat virtual activation of any tachycardia. METHODS AND RESULTS: The 51 patients with 74 ATs (mean age 57+/-18 years, 28 males) undergoing EA-guided RFA were included; 14 patients had had previous open heart surgery and 5 had organic heart disease. RFA was performed at the AT focus for focal AT (n=48) with an endpoint of AT termination and subsequent non-inducibility. RFA was performed at a critical conducting pathway for reentrant AT (n=26) with creation of a block line in the critical reentry circuit. EA revealed that 57 ATs originated in the right atrium (77%) and 17 originated in the left atrium (23%); all but 1 were successfully eliminated. Fluoroscopic time was 19+/-11 min, the number of RFA applications was 8+/-7, and the radiofrequency energy was 10,711+/-12,655 J. No complications were noted. All but 2 patients were free of any symptoms during a follow-up of 16+/-9 months. CONCLUSIONS: EA-guided RFA is safe and effective for AT, irrespective of its mechanism, sustainability or origin, and regardless of underlying heart disease. (Circ J 2010; 74: 59 - 65).

Real-time 3-dimensional imaging of the esophagus and left atrium with a noncontact mapping system.

BACKGROUND: Recognizing the relative location of the esophagus to the left atrial posterior wall (LAPW) is required to avoid esophageal injury during atrial fibrillation ablation. METHODS AND RESULTS: The 24 patients undergoing circumferential pulmonary vein isolation (CPVI) each had the geometry of their left atrium (LA) and esophagus constructed by a noncontact mapping system with EnSite version 6.0J. The esophageal course relative to the LAPW was found to be to the left in 12, middle in 8, right in 2, and obliquely left-to-right in 2 patients, and in 13 patients (54%) it was located on or near either the left or right CPVI line. The mean distance between the esophagus and LAPW was shorter at the bottom line of the LAPW connecting both inferior pulmonary veins (3 +/- 3 mm) than at the LA roof line connecting both superior pulmonary veins (6 +/- 6 mm, P<0.01). CONCLUSIONS: The location of the esophagus relative to the LAPW varies with the patient, but a close location to either CPVI line was found in approximately 50% and a close location between the esophagus and LAPW was found in the inferior and middle locations in most patients.

Plaunotol and geranylgeraniol induce caspase-mediated apoptosis in colon cancer.

BACKGROUND: Plaunotol, a kind of isoprenoid extracted from a Thai medical plant, plau-noi, is structurally similar to geranylgeraniol (GGOH), another isoprenoid reported to exert strong anticancer effects. Recently, we have reported on its inhibitory effects on tumor angiogenesis and direct effects on gastric cancer cells. Here, we aimed to test whether plaunotol could have some therapeutic effect on colon cancer. MATERIALS AND METHODS: Human colon cancer cell line DLD1 was used. Tumor cells were cultured in the presence of plaunotol or GGOH, and their proliferation was measured by MTS assay. Apoptosis was evaluated by Annexin V and propidium iodide double-staining or terminal-deoxynucleotidyl assay. The activation of caspase-3, -8, and -9 was analyzed by flow cytometry and Western blot analysis for PRRP cleavage. RESULTS: Plaunotol and GGOH strongly inhibited the proliferative activity of DLD1, dependent on induction of apoptosis. The induction of apoptosis by either plaunotol or GGOH was dependent on the activation of both caspase-8 and caspase-9 pathways. CONCLUSIONS: Plaunotol would be a potential anticancer agent against colon cancer, and since it is already available in Japan and Thailand for clinical use as an anti-ulcer/antigastritis agent, clinical trials will be designed to confirm the present findings.

Pilot study of anti-angiogenic vaccine using fixed whole endothelium in patients with progressive malignancy after failure of conventional therapy.

Vaccines targeting tumour angiogenesis were recently shown to inhibit tumour growth in animal models. However, there is still a lack of information about the clinical utility of anti-angiogenic vaccination. Therefore, here, we aimed to test the clinical effects of a vaccine using glutaraldehyde-fixed human umbilical vein endothelial cells (HUVECs). Six patients with recurrent malignant brain tumours and three patients with metastatic colorectal cancer received intradermal injections of 5x10(7) HUVECs/dose (in total 230 vaccinations). ELISA and flow cytometry revealed immunoglobulin response against HUVECs' membrane antigens. ELISPOT and chromium-release cytotoxicity assay revealed a specific cellular immune response against HUVECs, which were lysed in an effectors:targets ratio-dependent manner. Gadolinium-contrasted MRI showed partial or complete tumour responses in three malignant brain tumour patients. Except for a DTH-like skin reaction at the injection site, no adverse effect of vaccination could be observed. Our results suggest that the endothelial vaccine can overcome peripheral tolerance of self-angiogenic antigens in clinical settings, and therefore should be useful for adjuvant immunotherapy of cancer.

Plaunotol induces apoptosis of gastric cancer cells.

Although some isoprenoids, such as taxans and geranylgeraniol (GGOH), have been reported to have strong anticancer activities, the effect of plaunotol, the isoprenoid extracted from the leaves of Plau-noi, on cancer has not yet been evaluated. Here, we aimed to investigate the effect of plaunotol on gastric cancer cell lines. Three gastric cancer cell lines, namely MKN-45, MKN-74 and AZ-521 were used. Plaunotol was tested at 10, 20, 30 and 40 micromol/L. Plaunotol dose-dependently inhibited the growth of all gastric cancer cells, dependent on the induction of apoptosis. Caspases-8, -9 and -3, were found to be activated in the apoptotic cells. The expression of Bax protein was increased, but Bcl-2 and Bcl-xL protein expressions were not significantly affected. Plaunotol should be a promising new antitumor agent, and since it is already available for clinical use in Japan, its anticancer properties should be confirmed in clinical trials.

Catheter ablation of premature ventricular contractions originating from the His bundle region.

We describe a 35-year-old man with idiopathic frequent premature ventricular contractions (PVCs) originating from the His-bundle region, where a low frequency ventricular potential was recorded in the bipolar recording and QR pattern in the unipolar recording. Electro-anatomical mapping revealed a confined low voltage zone (<1.2 mV) in the His-bundle region, and the activation spread out radially to the entire right ventricle. The PVCs were successfully abolished without any atrioventricular block by a step-wise incremental radiofrequency energy application to the His-bundle region. The patient has remained free from PVCs or any symptoms without medication during a 23 month follow-up period.