Resetting of atrial tachycardia by a scanned extrastimulus at a downstream site on a multielectrode catheter: a simple diagnostic maneuver for locating the macroreentrant atrial tachycardia circuit.

PURPOSE: Entrainment is a useful method for locating reentrant atrial tachycardia (AT) circuits, but alterations or termination of the AT can derail this process. We assessed whether resetting an upstream site of a neighboring electrode by a scanned extrastimulus at a downstream site (when the upstream tissue was refractory) could diagnose that site within the AT circuit. METHODS: The procedure was applied to 48 ATs with a cycle length (CL) of 238 ± 42 ms (26 common flutters, 8 perimitral flutters, 7 left atrial [LA] roof-dependent AT, 3 LA scar-related macroreentrant ATs, 2 pulmonary vein-gap reentry tachycardias, 1 right atrial scar-related macroreentrant AT, and 1 with an unidentified circuit). Entrainment and scanned extrastimulation were attempted at the cavotricuspid isthmus, LA roof, and mitral isthmus and/or critical AT isthmus. RESULTS: Within the circuit, the post-pacing interval minus the ATCL after entrainment was < 30 ms for all ATs and resetting of the AT cycle by ≥ 5 ms occurred in 94% of the ATs. No ATs were reset by extrastimulation outside the circuit. The positive predictive value of both maneuvers for locating the circuit was 100%, and the negative predictive value of the extrastimulation was similar to that of entrainment (96% vs. 100%, P = 0.25). The incidence of an AT alteration was lower with extrastimulation than with entrainment (1% vs. 9%, P = 0.01). For ATs with a CL < 210 ms, extrastimulation yielded a good diagnostic performance without any AT alterations. CONCLUSION: AT resetting by a scanned extrastimulus is diagnostic and avoids AT alterations.

Modified ablation index: a novel determinant of a successful first-pass left atrial posterior wall isolation.

Although a left atrial posterior wall isolation (LAPWI) in addition to a pulmonary vein isolation is a well-accepted option for persistent atrial fibrillation (AF), a complete isolation can be challenging. This study aimed to evaluate the performance of a modified ablation index (AI) (AI/bipolar voltage along the ablation line) for predicting a durable LAPWI. The study included 55 consecutive patients, aged 65 ± 11 years, who underwent an electroanatomic mapping-guided LAPWI of AF. The association between the gaps (first-pass LAPWI failure and/or acute LAPW reconnections), voltage amplitude along the roof and floor lines, and thickness of the LAPW was investigated. Gaps occurred in 22 patients (40%) and in 26 (8%) of the 330 line segments. Gaps were associated with a relatively high bipolar voltage (3.38 ± 1.83 vs. 1.70 ± 1.12 mV, P < 0.0001) and thick LA wall (2.52 ± 1.15 vs. 1.42 ± 0.44 mm, P < 0.0001). A modified AI ≤ 199 AU/mV, bipolar voltage ≥ 2.64 mV, wall thickness ≥ 2.04 mm, and roof ablation line ≥ 43.4 mm well predicted gaps (AUCs: 0.783, 0.787, 0.858, and 0.752, respectively). A high-voltage zone, thick LAPW, and long roof ablation line appeared to be determinants of gaps, and a modified AI ≥ 199 AU/mV along the ablation lines appeared to predict an acute durable LAPWI.

Formation of low-voltage zones on the anterior left atrial wall due to mechanical compression by the ascending aorta.

BACKGROUND: Although low-voltage zones (LVZs) in the left atrium (LA) are considered arrhythmogenic substrates in some patients with atrial fibrillation (AF), the pathophysiologic factors responsible for LVZ formations remain unclear. OBJECTIVE: To elucidate the anatomical relationship between the LA and ascending aorta responsible for anterior LA wall remodeling. METHODS: We assessed the relationship between existence of LVZs on the anterior LA wall and the three-dimensional computed tomography image measurements in 102 patients who underwent AF ablation. RESULTS: Twenty-nine patients (28%) had LVZs grearer than 1.0 cm2 on the LA wall in the LA-ascending aorta contact area (LVZ group); no LVZs were seen in the other 73 patients (no-LVZ group). The LVZ group (vs. no-LVZ group) had a smaller aorta-LA angle (21.0 ± 7.7° vs. 24.9 ± 7.1°, p = .015), greater aorta-left-ventricle (LV) angle (131.3 ± 8.8° vs. 126.0 ± 7.9°; p = .005), greater diameter of the noncoronary cusp (NCC; 20.4 ± 2.2 vs. 19.3 ± 2.5 mm; p = .036), thinner LA wall-thickness adjacent to the NCC (2.3 ± 0.7 vs. 2.8 ± 0.8 mm; p = .006), and greater cardiothoracic ratio (percentage of the area in the thoracic area, 40.1 ± 7.1% vs. 35.4 ± 5.7%, p < .001). The aorta-LA angle correlated positively with the patients' body mass index (BMI), and the aorta-LV angle correlated negatively with the body weight and BMI. CONCLUSION: Deviation of the ascending aorta's course and distention of the NCC appear to be related to the development of LA anterior wall LVZs in the LA-ascending aorta contact area. Mechanical pressure exerted by extracardiac structures on the LA along with the limited thoracic space may contribute to the development of LVZs associated with AF.

Three-dimensional visualization of bidirectional preferential pathway conduction of premature ventricular contractions originating from the outflow tract.

INTRODUCTION: Preferential pathway conduction is mostly detected as fractionated presystolic-potentials preceding the QRS during premature ventricular contractions (PVCs) and late-potentials during sinus rhythm (SR), but the electrophysiologic mechanisms and significance of these potentials have not been fully clarified. We describe a PVC case series in which the preferential pathway conduction was three-dimensionally visualized. METHODS: Five PVCs (two from the left coronary cusp, two from the commissure of the left and right coronary cusps, and one from the pulmonary artery) in four patients for which a fractionated presystolic-potential during the PVCs and late-potential during SR were recorded at the successful ablation site were reviewed, and three-dimensional coherent activation maps with the conduction velocity vector during the PVCs and SR were reconstructed. RESULTS: At the successful ablation site, an "M"-shaped discrete presystolic-potential and "W"-shaped discrete late-potential were recorded in all patients. The configuration of the inverted electrogram of the presystolic-potential was similar to that of the electrogram exhibiting the late-potential. We created coherent activation maps annotating the onset of the presystolic-potentials during the PVCs and offset of the late-potentials during SR, which suggested bidirectional conduction of the preferential pathway connecting the PVC origin to the myocardium. CONCLUSION: Detailed activation mapping of these PVCs is consistent with the presence of fibers along the aortic or pulmonic valve ring that have preferential directions for conduction. PVCs produce a presystolic-potential. In SR, the fiber is activated late and from the opposite direction, producing an inverted potential inscribed on the end of the QRS.

Effect of obesity and epicardial fat/fatty infiltration on electrical and structural remodeling associated with atrial fibrillation in a novel canine model of obesity and atrial fibrillation: A comparative study.

BACKGROUND: How obesity and epicardial fat influence atrial fibrillation (AF) is unknown. METHODS: To investigate the effect of obesity/epicardial fat on the AF substrate, we divided 20 beagle dogs of normal weight into four groups (n = 5 each): one of the four groups (Obese-rapid atrial pacing [RAP] group) served as a novel canine model of obesity and AF. The other three groups comprised dogs fed a standard diet without RAP (Control group), dogs fed a high-fat diet without RAP (Obese group), or dogs fed a standard diet with RAP (RAP group). All underwent electrophysiology study, and hearts were excised for histopathologic and fibrosis-related gene expression analyses. RESULTS: Left atrial (LA) pressure was significantly higher in the Obese group than in the Control, RAP, and Obese-RAP groups (23.4 ± 6.9 vs. 11.4 ± 2.1, 11.9 ± 6.4, and 13.5 ± 2.9 mmHg; p = .005). The effective refractory period of the inferior PV was significantly shorter in the RAP and Obese-RAP groups than in the Control group (p = .043). Short-duration AF was induced at greatest frequency in the Obese-RAP and Obese groups (p < .05). Epicardial fat/Fatty infiltration was greatest in the Obese-RAP group, and greater in the Obese and RAP groups than in the Control group. %interstitial fibrosis/fibrosis-related gene expression was significantly greater in the Obese-RAP and RAP groups (p < .05). CONCLUSIONS: Vulnerability to AF was associated with increased LA pressure and increased epicardial fat/fatty infiltration in our Obese group, and with increased epicardial fat/fibrofatty infiltration in the RAP and Obese-RAP groups. These may explain the role of obesity/epicardial fat in the pathogenesis of AF.

Impact of the combined use of intracardiac ultrasound and a steerable sheath visualized by a 3D mapping system on pulmonary vein isolation.

BACKGROUND: A novel steerable sheath visualized on a three-dimensional mapping system has become available in this era in which a durable pulmonary vein (PV) isolation (PVI) with reduced fluoroscopy is required. METHODS: In 60 patients who underwent a PVI with a visualized sheath (n = 30) and non-visualized conventional sheath (n = 30), the fluoroscopic time and catheter stability during the PVI were analyzed. RESULTS: The fluoroscopic time during the transseptal access (0 [0, 0.1] vs. 1.4 [0.8, 2.3] minutes, P < .001) and PVI (0 [0, 0.1] vs. 0.4 [0.2, 1.1] minutes, P < .001) were shorter in the visualized sheath group than conventional sheath group. The procedure time during the PVI (32.0 [26.8, 36.3] vs. 41.0 [31.8, 47.3] minutes, P = .01), particularly during the right PVI (15.0 [12.8, 18.0] vs. 23.0 [15.8, 26.3] minutes, P = .009), was shorter in the visualized sheath group than conventional sheath group, however, that during the other steps was equivalent. The standard deviation of the catheter contact force during each radiofrequency application was smaller in the visualized sheath group than conventional sheath group (4.5 ± 2.7 vs. 4.9 ± 3.1 g, P = .001). The impedance drop for each lesion was larger in the visualized sheath group than conventional sheath group (10.7 ± 6.5 vs. 9.8 ± 5.5 ohms, P < .001). The incidence of acute PV reconnections per patient (30% vs. 23%, P = .56) and per PV segment (2.5% vs. 2.3%, P = .83) were similar between the two groups. No major complications occurred in either sheath group. CONCLUSIONS: The use of visualized sheaths may reduce the fluoroscopic time and improve the catheter stability during the PVI.

Optimal diameter of the pulmonary vein ostium for second-generation 28-mm cryoballoon ablation of atrial fibrillation.

BACKGROUND: Large pulmonary veins (PVs) have the risk of excessive cooling when the cryoballoon is moved into them, whereas smaller PVs may not be isolated because of insufficient balloon-tissue contact. We previously reported that the effective nadir balloon temperature (NBT) was <- 44°C for predicting early PV reconnections. However, the ideal PV and left atrial (LA) diameters for cooling temperatures during cryoballoon ablation (CBA) are unknown. METHODS: We measured the PV ostium (PVos) and LA diameters on computed tomography images in 71 atrial fibrillation patients who underwent a 28-mm CBA. We defined -60°C ≤ NBT <- 44°C as the optimal NBT. The optimal PVos diameters and elliptical area were determined using the receiver operating characteristic curve cutoff values for the optimal NBT. RESULTS: The maximum PVos diameter (PVmax), minimum PVos diameter (PVmin), and PV elliptical area correlated negatively with the NBT (PVmax: r = -.34, P < .0001; PVmin: r = -.41, P < .0001; PV elliptical area: r = -.41, P < .0001). Based on the NBT-derived definition, the optimal PVmax, PVmin, and PV elliptical area were 19 < PVmax ≤ 21 mm, 14 < PVmin ≤ 16 mm, and 186.83 < PV elliptical area ≤ 254.34 mm2 , respectively. In addition, a positive correlation between the LA longitudinal diameter and NBT was observed in the right superior PV (r = .34, P = .004), and the LA transverse diameter correlated inversely with the NBT in the left inferior PV (r = -.34, P = .004). CONCLUSIONS: We identified the optimal PV diameters and elliptical area to establish the optimal NBT during the second-generation 28-mm CBA. These data will help for the preclinical judgment for a successful CBA.

Is Vagal Response During Left Atrial Ganglionated Plexi Stimulation a Normal Phenomenon?: Comparison Between Patients With and Without Atrial Fibrillation.

BACKGROUND: Ganglionated plexi (GPs) play an important role in both the initiation and maintenance of atrial fibrillation (AF). GPs can be located by using continuous high-frequency stimulation (HFS) to elicit a vagal response, but whether the vagal response phenomenon is common to patients without AF is unknown. METHODS: HFS of the left atrial GPs was performed in 42 patients (aged 58.0±10.2 years) undergoing ablation for AF and 21 patients (aged 53.2±12.8 years) undergoing ablation for a left-sided accessory pathway. The HFS (20 Hz, 25 mA, 10-ms pulse duration) was applied for 5 seconds at 3 sites within the presumed anatomic area of each of the 5 major left atrial GPs (for a total of 15 sites per patient). We defined vagal response to HFS as prolongation of the R-R interval by >50% in comparison to the mean pre-HFS R-R interval averaged over 10 beats and active-GP areas as areas in which a vagal response was elicited. RESULTS: Overall, more active-GP areas were found in the AF group patients than in the non-AF group patients, and at all 5 major GPs, the maximum R-R interval during HFS was significantly prolonged in the AF patients. After multivariate adjustment, association was established between the total number of vagal response sites and the presence of AF. Conclusions The significant increase in vagal responses elicited in patients with AF compared with responses in non-AF patients suggests that vagal responses to HFS reflect abnormally increased GP activity specific to AF substrates.

Adverse Clinical Events during Long-Term Follow-Up After Catheter Ablation of Atrial Fibrillation.

Pulmonary vein isolation (PVI) of atrial fibrillation (AF) can reduce the AF burden and, potentially, reduce the long-term risk of strokes and death. However, it remains unclear whether anticoagulants can be stopped after PVI because of post-ablation AF recurrence in some patients. This study aimed to investigate the discontinuation rate of anticoagulants and long-term incidence of strokes after PVI.We enrolled 512 consecutive Japanese patients with AF (mean age, 63.4 ± 10.4 years; 123 women; 234 with non-paroxysmal AF; CHADS2 score/CHA2DS2-VASC score, 1.32 ± 1.12/2.21 ± 1.54) who underwent PVI between 2012 and 2015. During a 28.0 ± 17.1 -month follow-up, anticoagulants were terminated in 230 (44.9%) of the 512 patients, AF recurred in 200 (39.1%), and 10 (1.95%) suffered from a stroke. Death occurred in 5 (0.98%) patients. Although the incidence of strokes, by a Kaplan-Meier analysis, was similar, the incidence of death was lower (Hazard ratio 0.37, 95% confidence interval 0.12-0.93, P = 0.041) in the AF ablation group than the control group without ablation after 1:1 propensity score matching (the control data was derived from 2,986 patients in the SAKURA AF Registry, a large-cohort AF registry).Anticoagulants were discontinued in nearly half the patients who underwent AF ablation; of these, 39.1% experienced AF recurrences, 1.95% suffered from strokes, and 0.98% died, but the risk of death after AF ablation appeared to be lower than that in a propensity score-matched control group without ablation during long-term follow-up.

Electrophysiologic and anatomic factors predictive of a need for touch-up radiofrequency application for complete pulmonary vein isolation: Comparison between hot balloon- and cryoballoon-based ablation.

INTRODUCTION: Although electrophysiologic and anatomic factors associated with the need for touch-up radiofrequency (RF) applications after cryoballoon ablation (CBA) for atrial fibrillation (AF) have been well described, those associated with the need for such touch-up after hot balloon ablation (HBA) have not. We aimed to identify factors predictive of the need for touch-up applications following HBA. METHODS: Anatomic and electrophysiologic factors predictive of the need for touch-up RF ablation were compared between 46 propensity score-matched pairs of patients who underwent HBA or CBA for AF. RESULTS: Touch-up RF ablation was more frequently required after HBA than after CBA (57% vs 30%, respectively; P = .01), and mostly at the anterior aspect of the left superior pulmonary vein (LSPV) carina after HBA (35%) but at the inferior aspect of the right inferior PV (RIPV) after CBA (71%). Post HBA touch-up was associated with male gender, a CHA 2 DS 2 -VASc score ≤ 2, PV-left atrial bipolar voltage ≥ 1.35 mV, and PV trunk length ≥ 24.0 mm; post CBA touch-up associated with a history of heart failure. CONCLUSION: Following balloon ablation for AF, there may be a need for touch-up applications, especially at the LSPV ridge after HBA but at the RIPV after CBA. It may behoove operators to expect a need for touch-up following HBA when patients are male, have a CHA2 DS 2 -VASc score ≤ 2 points, when PV-LA bipolar voltage is ≥ 1.35 mV, or when the PV trunk is ≥ 24.0 mm or following CBA when there is a history of heart failure.

The modified ablation index: a novel determinant of acute pulmonary vein reconnections after pulmonary vein isolation.

BACKGROUND: Although pulmonary vein isolation (PVI) guided by the ablation index (AI) has been well-developed, acute PV reconnections (PVRs) still occur. This study aimed to compare the prognostic performance of the modified AI and its optimal cut-off value for the prediction of acute PVRs to ensure durable PVI. METHODS: Three-dimensional left atrium (LA) voltage maps created before an extensive encircling PVI in 64 patients with atrial fibrillation (AF) (45 men, 62 ± 10 years) were examined for an association between electrogram voltage amplitude recorded from the PV-LA junction and acute post-PVI PVRs (spontaneous PVRs and/or ATP-provoked dormant PV conduction). RESULTS: Acute PVRs were observed in 22 patients (34%) and 33 (3%) of the 1012 PV segments. Acute PVRs were significantly associated with segments with higher bipolar voltage zones (3.23 ± 1.17 vs. 1.97 ± 1.20 mV, P < 0.0001), lower mean AI values (449 [428-450] vs. 460 [437-486], P = 0.05), and radiofrequency lesion gaps ≥ 6 mm (48 vs. 32%, P = 0.04), but not with contact force, force-time integral, or power. We created the modified AI calculated as AI/LA bipolar voltage, and found it to be significantly lower in areas with acute PVRs than in those without (152 [109-185] vs. 256 [176-413] AU/mV, P < 0.0001). Univariate analysis showed the prognostic performance of the modified AI, with an area under the curve of 0.801 (0.775-0.825), to be the highest of all the significant parameters. CONCLUSIONS: Low values of the novel modified AI on the PV-encircling ablation line were strongly associated with acute PVRs.

Decreased coronary blood flow velocity in two patients with coronary microvascular spasm: case series†.

INTRODUCTION: Diagnostic criteria for coronary microvascular spasm (CMS) have not yet been fully established. CASE PRESENTATION: We present two cases of CMS in which decreased coronary blood flow velocities were observed during acetylcholine (ACH) provocation tests. The first patient suffered from chest pain occurring while at rest. The patient underwent coronary angiography (CAG), which revealed a decrease in the average peak velocity (APV) from 29 cm/s to 14 cm/s and a slow flow phenomenon following ACH injection. The second patient suffered from chest pain occurring during the night. The patient underwent CAG, which revealed a decrease in the APV from 17 cm/s to 7 cm/s with no significant epicardial coronary artery spasm following ACH injection. Both patients complained of chest pain, and electrocardiogram changes were observed in leads equivalent to the distal area of the vessel during an ACH provocation test. These findings were consistent with CMS, and their conditions improved under medical treatment. DISCUSSION: A transient decrease in coronary blood flow velocity following ACH administration might be a phenomenon specific to CMS. These cases may provide some insight into the underlying pathophysiology of CMS.

OVA-bound nanoparticles induce OVA-specific IgG1, IgG2a, and IgG2b responses with low IgE synthesis.

There is an urgent requirement for a novel vaccine that can stimulate immune responses without unwanted toxicity, including IgE elevation. We examined whether antigen ovalbumin (OVA) conjugated to the surface of nanoparticles (NPs) (OVA-NPs) with average diameter of 110nm would serve as an immune adjuvant. When BALB/c mice were immunized with OVA-NPs, they developed sufficient levels of OVA-specific IgG1 antibody responses with low levels of IgE synthesis, representing helper T (Th)2-mediated humoral immunity. OVA-specific IgG2a and IgG2b responses (i.e., Th1-mediated immunity) were also induced by secondary immunization with OVA-NPs. As expected, immunization with OVA in alum (OVA-alum) stimulated humoral immune responses, including IgG1 and IgE antibodies, with only low levels of IgG2a/IgG2b antibodies. CD4-positive T cells from mice primed with OVA-NPs produced substantial levels of IL-21 and IL-4, comparable to those from OVA-alum group. The irradiated mice receiving OVA-NPs-primed B cells together with OVA-alum-primed T cells exhibited enhanced anti-OVA IgG2b responses relative to OVA-alum-primed B cells and T cells following stimulation with OVA-NPs. Moreover, when OVA-NPs-primed, but not OVA-alum-primed, B cells were cultured in the presence of anti-CD40 monoclonal antibody, IL-4, and IL-21, or LPS plus TGF-ß in vitro, OVA-specific IgG1 or IgG2b antibody responses were elicited, suggesting that immunization with OVA-NPs modulates B cells to generate IgG1 and IgG2b responses. Thus, OVA-NPs might exert their adjuvant action on B cells, and they represent a promising potential vaccine for generating both IgG1 and IgG2a/IgG2b antibody responses with low IgE synthesis.