Low troponin I levels predict the presence of arrhythmia-induced cardiomyopathy in patients with atrial fibrillation and left ventricular systolic dysfunction.

Successful atrial fibrillation (AF) ablation can improve reduced left ventricular ejection fraction (LVEF) with AF, which is defined as arrhythmia-induced cardiomyopathy (AIC). However, it is difficult to pre-procedurally predict the presence of AIC. We aimed to explore the pre-procedural predictors of AIC in patients with AF and reduced LVEF. This study included 60 patients with a reduced LVEF (LVEF < 50%; 69.1 ± 8.8 years; 45 men) who underwent successful AF ablation. Responders were defined as patients whose LVEF post-procedurally improved to the normal range (≥ 50%). Multivariate analysis revealed that the log-transformed pre-procedural troponin I (TnI) levels (odds ratio [OR] = 0.059; 95% confidence interval [CI] = 0.0052-0.42, p = 0.003) and age (OR = 0.91; 95% CI = 0.82-1.00, p = 0.044) were independent predictors of post-procedural LVEF recovery; further, low TnI levels (< 11.1 pg/ml) predicted LVEF recovery (sensitivity, 79.1%; specificity, 76.5%; positive predictive value, 89.5%; and negative predictive value, 59.1%). There were no significant differences in TnI levels between the baseline and 1 month after the procedure. However, four patients with high baseline TnI levels showed a > 50% reduction in the TnI levels post-procedurally, with three of these patients showing LVEF recovery. Low pre-procedural TnI levels can predict LVEF recovery after successful AF ablation in patients with reduced LVEF.

Synchronous ovarian and uterine mesonephric-like carcinoma that potentially arose from endometrioid adenofibroma: A case report.

Mesonephric-like carcinoma histologically resembles mesonephric adenocarcinoma (MA) of the cervix. MA arises from mesonephric duct remnants. However, the origin of mesonephric-like carcinoma is not extensively studied because of its rarity. Here, we present a case of synchronous ovarian and uterine mesonephric-like carcinoma that potentially arose from endometrioid adenofibroma. A 69-year-old woman presented with an abdominal mass with no genital bleeding. She underwent simple total abdominal hysterectomy and bilateral adnexal resection. Histological and immunohistochemical analyses were consistent with mesonephric-like carcinoma involving both ovaries and the uterus. Endometrioid adenofibroma was present in both ovaries, while adenomyosis was observed in the uterus. The glandular duct of the endometrioid adenofibroma in the right ovary had areas suggestive of precursor lesions of mesonephric-like carcinoma. All tumors exhibited the KRAS G12D mutation. These findings suggest that the origin of the mesonephric-like carcinoma was the Müllerian duct, and that the ovarian and uterine tumors were monoclonal.

Safety and durability of cavo-tricuspid isthmus linear ablation in the current era: Single-center 9-year experience from 1078 procedures.

BACKGROUND: Cavo-tricuspid isthmus (CTI) linear ablation is performed not only for atrial flutter (AFL) but empirically during atrial fibrillation (AF) ablation in real-world practice.  PURPOSE: We sought to evaluate the safety and durability of the CTI ablation.  METHODS: This retrospective study included 1078 consecutive patients who underwent a CTI ablation. AFL was documented before or during the procedure in 249 (23.1%) patients, and an empirical CTI and AF ablation were performed in 829 (76.9%) patients.  RESULTS: CTI block was successfully created in 1051 (97.5%) patients with a 10.3 ± 6.6 min total radiofrequency time. Repeat procedures were performed for recurrent arrhythmias in 187 (17.3%) patients at a median of 11.0 (5.0-30.0) months postprocedure, and conduction resumption was identified in 68/174 (39.1%). Among those undergoing a CTI ablation with an AF ablation, the durability was significantly higher in those with than without documented AFL (78.1% vs. 58.2%, p = .031).  The total radiofrequency time was significantly shorter (9.0 ± 5.3 vs. 10.0 ± 6.4 [mins], p = .024) and durability significantly higher (78.1 vs. 58.7[%], p = .043) in the large-tip than irrigated-tip catheter group. Iatrogenic AFL was observed after the empiric CTI ablation in 11 (1.3%) patients. Procedure-related complications occurred in 15 (1.4%) patients. Eight patients experienced coronary artery spasms, including one with ventricular fibrillation following ST elevation on the ward. The other six patients experienced transient atrioventricular block and one experienced cardiac tamponade requiring drainage.  CONCLUSIONS: Despite a high acute CTI ablation success, the conduction block durability was relatively low after the empiric ablation. An empiric CTI ablation at the time of the AF ablation is not recommended.

Mapping and ablation of left atrial roof-dependent tachycardias using an ultra-high resolution mapping system.

BACKGROUND: Left atrial roof-dependent tachycardias (LARTs) are common macroreentrant atrial tachycardias (ATs). We sought to characterize clinical LARTs using an ultra-high resolution mapping system. METHODS: This study included 22 consecutive LARTs in 21 patients who underwent AT mapping/ablation using Rhythmia systems. RESULTS: Three, 13, 4, and 2 LART patients were cardiac intervention naïve (Group-A), post-roof line ablation (Group-B), post-atrial fibrillation ablation without linear ablation (Group-C), and post-cardiac surgery (Group-D), respectively. The mean AT cycle length was 244 ± 43 ms. Coronary sinus activation was proximal-to-distal or distal-to-proximal in 16 (72.7%) ATs. The activation map revealed 13 (59.1%) clockwise and 9 (40.9%) counter-clockwise LARTs. A 12-lead synchronous isoelectric interval was observed in 10/19 (52.6%) LARTs. The slow conduction area was identified on the LA roof, anterior/septal wall, and posterior wall in 18, 6, and 2 ATs, respectively. Twenty concomitant ATs among 13 procedures were also eliminated, and peri-mitral AT coexisted in 7 of 9 non-group-B patients. In group-B, the conduction gap was predominantly located on the mid-roof. Sustained LARTs were terminated by a single application and linear ablation in 6 (27.3%) and 9 (40.9%), while converting to other ATs in 7 (31.8%) LARTs. Complete linear block was created without any complications in all, however, ablation at the mid-posterior wall was required to achieve block in 4 (18.2%) procedures. During 14.0 (6.5-28.5) months of follow-up, 17 (81.0%) and 19 (90.5%) patients were free from any atrial tachyarrhythmias after single and last procedures. CONCLUSIONS: The LART mechanisms were distinct in individual patients, and elimination of all concomitant ATs was required for the management.

Declines in serum uric acid level after catheter ablation of atrial fibrillation.

BACKGROUND: Few studies have examined whether catheter ablation for AF patients improves biomarkers other than serum levels of brain natriuretic peptide (BNP) and renal function. This study was to explore whether catheter ablation for atrial fibrillation (AF) patients affects uric acid (UA), glucose and lipid metabolism. METHODS AND RESULTS: A total of 206 patients (66.6 ± 10.4 years; 132 men) who underwent initial AF ablation without changes to oral medications were included. Baseline BNP and UA levels significantly decreased at 1 year after ablation (p < 0.05 each). Changes in UA level correlated significantly with pre-procedural UA level (r = 0.57). In multivariable logistic regression modeling, pre-procedural UA level, persistent AF, and hemoglobin A1c (p < 0.05 each) were independent predictors of post-procedural UA level decline. Significant improvements in both persistent and paroxysmal AF patients were identified, and the magnitude of post-procedural serum UA level decline after ablation (ΔUA) was significantly greater in patients with persistent AF (0.8 ± 1.0 mg/dl) than in those with paroxysmal AF (0.2 ± 0.8 mg/dl, p < 0.001). Of the 48 patients with high UA level before procedure, 28 patients showed improvement in UA level to normal range. CONCLUSIONS: Catheter ablation for AF patients significantly improved serum UA levels without obvious influences of heart failure, renal function, or inflammation, suggesting that AF ablation may be effective for AF patients with hyperuricemia. Trial registration The study was approved by the Research Ethics Committee of University of Fukui (no. 20210132) and clinical trial registration (UMIN000044669).

Oral Adrenergic Agents Produced Ventricular Fibrillation and QT Prolongation in an Elderly Patient Carrying an RYR2 Variant.

Mutant cardiac ryanodine receptor channels (RyR2) are "leaky," and spontaneous Ca2+ release through these channels causes delayed afterdepolarizations that can deteriorate into ventricular fibrillation. Some patients carrying RYR2 mutations in type 1 catecholaminergic polymorphic ventricular tachycardia exhibit QT prolongation and are initially diagnosed with long QT syndrome. However, none have been reported to cause drug-induced ventricular fibrillation in patients with RYR2 variants. We describe the first case of an elderly woman with drug-induced QT prolongation and ventricular fibrillation who carried a novel RYR2 variant but no other mutations related to long QT syndrome. Oral adrenergic agents might induce QT prolongation and subsequent ventricular fibrillation in patients carrying an RYR2 variant. Screening for RYR2 could be valuable in patients with suspected drug-induced long QT syndrome.

Abdominal Fat Pad Fine-Needle Aspiration for Diagnosis of Cardiac Amyloidosis in Patients with Non-Ischemic Cardiomyopathy.

The diagnosis of cardiac amyloidosis is frequently delayed because histological confirmation is often challenging. Few studies have attempted to clarify the utility and safety of abdominal fat pad fine-needle aspiration (FPFNA) for an initial screening test in patients with suspected cardiac amyloidosis.This study included 77 consecutive patients with suspected non-ischemic cardiomyopathy who had left ventricular dysfunction and/or hypertrophy. All patients underwent abdominal FPFNA and an endomyocardial biopsy. In all patients, the abdominal FPFNA could be performed within less than 5 minutes with no complications; however, in 1 patient (1.3%), the obtained specimen was too small to evaluate. Among the remaining 76 patients, 5 (6.6%) were positive for amyloid (FPFNA[+]) and 7 (9.2%), including the 5 FPFNA[+], were diagnosed with cardiac amyloidosis (AL = 1, ATTR = 6) by endomyocardial biopsy. Positive abdominal FPFNAs indicated cardiac amyloidosis with high accuracy (sensitivity, 71.4%; specificity, 100%).Positive abdominal FPFNAs are directly linked to diagnoses of cardiac amyloidosis. Abdominal FPFNA is simple and useful for the initial screening test for cardiac amyloidosis in patients with non-ischemic cardiomyopathy.

The mechanisms of left septal and anterior wall reentrant atrial tachycardias analyzed with ultrahigh resolution mapping: The role of functional block in the circuit.

BACKGROUND: Low voltage areas (LVAs) are most commonly observed on the left atrial (LA) septal/anterior wall. OBJECTIVE: We explored the mechanisms of LA septal/anterior wall reentrant tachycardias (LASARTs) using ultrahigh resolution mapping. METHODS: This study included seven consecutive LASARTs in six patients (75 [62.2-82.8] years, 4 women) who underwent atrial tachycardia (AT) mapping and ablation using Rhythmia systems. RESULTS: The AT cycle length was 266 (239-321) ms. During ATs, 11.0 (9.0-12.9) cm2 of LVAs were identified in all, and 0.8 (0.7-1.7) cm2 of dense scar was identified in four patients. Five ATs rotated around dense scar, while two rotated around functional linear block, which was confirmed during atrial pacing after AT termination. The AT circuit length was 8.7 ± 2.1 cm with a conduction velocity of 30.4 ± 3.7 cm/s. A median of 3.0 (2.0-4.0) slow conduction areas per circuit were identified, and 17/23 (73.9%) areas were present in LVAs, while they were at the border of the LVA and normal voltage areas in the remaining 6/23 (26.1%). Global activation histograms facilitated the identification of the critical isthmus in all. Tailor-made ablation at critical isthmuses successfully eliminated all ATs. However, one patient with AT related to functional linear block experienced recurrent AT related to dense scar, which progressed after the procedure. During a mean 14 ± 13 month follow-up after the last procedure, no patients experienced recurrent ATs without any complications. CONCLUSION: LASARTs consist of not only fixed conduction blocks but also functional conduction blocks. Ultrahigh resolution mapping is highly useful to decide the optimal tailor-made ablation strategy based on the mechanisms.

Significance of day-to-day glucose variability in patients after acute coronary syndrome.

BACKGROUND: Several studies have recently addressed the importance of glycemic variability (GV) in patients with acute coronary syndrome (ACS). Although daily GV measures, such as mean amplitude of glycemic excursions, are established predictors of poor prognosis in patients with ACS, the clinical significance of day-to-day GV remains to be fully elucidated. We therefore monitored day-to-day GV in patients with ACS to examine its significance. METHODS: In 25 patients with ACS, glucose levels were monitored for 14 days using a flash continuous glucose monitoring system. Mean of daily differences (MODD) was calculated as a marker of day-to-day GV. N-terminal pro-brain natriuretic peptide (NT-proBNP) was evaluated within 4 days after hospitalization. Cardiac function (left ventricular end-diastolic volume, left ventricular ejection fraction, stroke volume) was assessed by echocardiography at 3-5 days after admission and at 10-12 months after the disease onset. RESULTS: Of the 25 patients, 8 (32%) were diagnosed with diabetes, and continuous glucose monitoring (CGM)-based MODD was high (16.6 to 42.3) in 17 patients (68%). Although MODD did not correlate with max creatine kinase (CK), there was a positive correlation between J-index, high blood glucose index, and NT-proBNP (r = 0.83, p < 0.001; r = 0.85, p < 0.001; r = 0.41, p = 0.042, respectively). CONCLUSIONS: In patients with ACS, MODD was associated with elevated NT-proBNP. Future studies should investigate whether day-to-day GV in ACS patients can predict adverse clinical events such as heart failure.

Discrepancy between CARTO and Rhythmia maps for defining the left atrial low-voltage areas in atrial fibrillation ablation.

Reported mapping procedures of left atrial (LA) low-voltage areas (LVAs) vary widely. This study aimed to compare the PentaRay®/CARTO®3 (PentaRay map) and Orion™/Rhythmia™ (Orion map) systems for LA voltage mapping. This study included 15 patients who underwent successful pulmonary vein isolation (PVI) for atrial fibrillation. After PVI, PentaRay and Orion maps created for all patients were compared. LVAs were defined as sites with ≥ 3 adjacent low-voltage points < 0.5 mV. LVAs were indicated in 8 (53%) among 15 patients, and the average values of the measured LVAs was comparable between the systems (PentaRay map = 5.4 ± 8.7 cm2; Orion map = 4.3 ± 6.4 cm2, p = 0.69). However, in 2 of 8 patients with LVAs, the Orion map indicated LVAs at the septum and posterolateral sites of the LA, respectively, whereas the PentaRay map indicated no LVAs. In those patients, sharp electrograms of > 0.5 mV were properly recorded at the septum and posterolateral sites during appropriate beats in the PentaRay map. The PentaRay map had a shorter procedure time than the Orion map (12 ± 3 min vs. 23 ± 8 min, respectively; p < 0.01). Our study results showed a discrepancy in the LVA evaluation between the PentaRay and Orion maps. In 2 of 15 patients, the Orion map indicated LVAs at the sites where > 0.5-mV electrograms were properly recorded in the PentaRay map.

Cardiac rehabilitation after catheter ablation of atrial fibrillation in patients with left ventricular dysfunction.

Few studies have examined the efficacy and safety of cardiac rehabilitation in patients with atrial fibrillation (AF) who underwent AF ablation. We explored the feasibility of additional cardiac rehabilitation after AF ablation in patients with a reduced left ventricular ejection fraction (LVEF). Fifty-four patients with heart failure (HF) and a reduced LVEF (HFrEF) (LVEF < 50%; 67.1 ± 11.6 years; 43 men) who underwent initial AF ablation procedures were included. Fourteen (25.9%) patients underwent cardiac rehabilitation (rehabilitation-group) and the remaining 40 (74.1%) did not (non-rehabilitation-group) after the procedure. The rehabilitation-group patients were relatively older, more likely female (p = 0.024), and had more likely a history of an HF hospitalization (p < 0.01) and cardiac device implantation (p = 0.041). The baseline LVEF was significantly lower (p = 0.043) and brain natriuretic peptide (BNP) (p < 0.01) and C-reactive protein (CRP) (p < 0.01) values were significantly higher in the rehabilitation-group. The 6-min walk distance significantly improved after 21.4 ± 11.5 days of cardiac rehabilitation during hospitalization (226.1 ± 155.9 vs. 398.1 ± 77.5 m, p = 0.016) without any adverse events. During an 18.9 ± 6.3 month follow-up period, the freedom from AF recurrence (p = 0.52) and re-hospitalizations due to HF (p = 0.63) were similar between the 2 groups. No death or strokes were observed. During the follow-up period, the LVEF significantly improved similarly in both groups, and the change in the BNP and CRP values significantly decreased in the rehabilitation-group. Despite the rehabilitation-group patients having a more severe HF status, the clinical outcomes and AF freedom were similar between the 2 groups, suggesting the favorable impact of cardiac rehabilitation after AF ablation in HFrEF patients.

Idiopathic right ventricular arrhythmias requiring additional ablation from the left-sided outflow tract: ECG characteristics and efficacy of an anatomical approach.

INTRODUCTION: Despite the characteristic electrocardiogram (ECG) findings of early activation during ventricular tachyarrhythmias (VAs) and/or excellent pacemapping in the right ventricular outflow tract (RVOT), some VAs may require additional, left-sided ablation for a cure. METHODS AND RESULTS: This study included five patients with idiopathic VAs whose QRS morphologies were highly suggestive of an RVOT origin. The ECG characteristics and intracardiac electrocardiograms during catheter ablation were assessed. In all patients, the clinical VAs had an LBBB QRS morphology and inferior axis with a precordial R/S transition through leads V3-V5, and negative components in lead I. The earliest activation during the VAs (local electrogram-QRS interval = -34 ± 6.8 ms) and excellent pacemapping were obtained at the posterior portion of the RVOT just beneath the pulmonary valve. However, ablation at those sites failed, and the QRS morphology of the VAs changed. During left-sided OT mapping, the earliest activation was found at sites just contralateral to the initially ablated sites of the RVOT (junction of the left and right coronary cusps = 2, left coronary cusp = 3). In spite of the late activation time and poor pacemapping scores, catheter ablation at those sites cured the VAs. Those successful sites were also near the transitional zone from the great cardiac vein to the anterior interventricular vein (GCV-AIV). CONCLUSIONS: Some VAs, highly suggestive of having RVOT origins, require catheter ablation in the left-sided OT near the initially ablated RVOT site. Those VAs have the same ECG characteristics and might have intramural origins in the superobasal LV surrounded by the RVOT, LVOT, and GCV-AIV.

Femoral vascular complications after catheter ablation in the current era: The utility of computed tomography imaging.

BACKGROUND: Few studies have examined the characteristics of catheter ablation vascular complications, and recently physicians increasingly use computed tomography angiography (CTA) for diagnosing. OBJECTIVE: We sought to investigate the incidence of femoral vascular complications in catheter ablation and factors associated with complications in the current era. METHODS: This single-center observational study consisted of 311 consecutive (atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, and ventricular arrhythmias in 222 [71.4%], 7 [2.3%], 43 [13.8%], and 39 [12.5%]) patients who underwent catheter ablation. The detailed patient data and clinical outcomes were obtained from the medical records. RESULTS: Emergent CTA was performed in a total of 8 (2.6%) patients at a median of 4.5 (2.0-12.5) days postprocedure, and the precise diagnosis was obtained in all. Among them, pseudoaneurysms, arteriovenous fistulae (AVF), and actively bleeding hematomas were identified in two, one, and one patient, respectively, and all required readmissions after discharge. AVF was diagnosed by a Doppler ultrasound examination in another patient. In total, 5 (1.6%) patients exhibited major femoral vascular complications including two pseudoaneurysms, two AVFs, and one active bleeding hematoma. The pseudoaneurysms and AVFs were successfully eliminated by direct compression, and extravasation from the femoral circumflex artery required coil embolization. Antiplatelet therapy and the use of larger arterial sheaths (≥7-Fr) increased the major femoral arterial complications, but atrial fibrillation ablation under uninterrupted anticoagulation therapy or the use of larger venous sheaths did not. CONCLUSION: Vascular complications are still not negligible procedure-related complications during catheter ablation in the current era. CTA provides a rapid and precise diagnosis for optimal treatment strategies.

Cryothermal atrial linear ablation in patients with atrial fibrillation: An insight from the comparison with radiofrequency atrial linear ablation.

BACKGROUND: Atrial linear lesions are generally created with radiofrequency energy. We sought to evaluate the feasibility of cryothermal atrial linear ablation. METHODS AND RESULTS: Twenty-one atrial fibrillation (AF) patients underwent linear ablation on the left atrial (LA) roof, mitral isthmus (MI), and cavotricuspid isthmus (CTI) with 8-mm-tip cryocatheters following pulmonary vein isolation. The data were compared with those of 31 patients undergoing linear ablation with irrigated-tip radiofrequency catheters. Conduction block was successfully created in 18 of 20 (90%), 9 of 21 (43%), and 20 of 20 (100%) on the LA roof, MI, and CTI by endocardial cryoablation alone with 19.0 (12.0-24.0), 30.0 (23.0-34.0), and 14.0 (14.0-16.0) minute cryo applications, respectively. The presence of either an interposed circumflex artery or pouch at the MI was significantly associated with failed MI block (P = .04). Conduction block was created in 25 of 31 (83.9%), 27 of 31 (87.1%), and 30 of 31 (96.8%) on the roof, MI, and CTI, respectively, by radiofrequency ablation. During the 17.5 (13.0-31.7) months of follow-up, freedom from AF/atrial tachycardia (AT) was significantly higher in the cryo group (P = .05); especially, recurrent AT was more frequent in the RF group (8/31 vs 1/21; P = .03). Conduction block across the roof, MI, and CTI was durable in 6 of 12 (50.0%), 4 of 12 (33.3%), and 9 of 12 (75.0%) patients during second procedures. All nine patients (except one) with recurrent ATs had at least one roof or MI conduction resumption. CONCLUSIONS: Cryoablation is effective for creating a roof and CTI linear block, however, creating MI block by endocardial ablation alone was often challenging. Conduction resumption of LA linear block is common and recurrent arrhythmias, especially iatrogenic ATs, are more frequently observed after radiofrequency linear ablation.

The P wave morphology in lead V7 on the synthesized 18-lead ECG is a useful parameter for identifying arrhythmias originating from the right inferior pulmonary vein.

Atrial tachyarrhythmias often originate from the superior vena cava (SVC), and right superior (RSPV) and inferior pulmonary veins (RIPV). However, a precise differentiation of those origins is challenging using the standard 12-lead electrocardiogram (ECG) P-wave morphology due to the anatomical proximity. The recently developed synthesized 18-lead ECG provides virtual waveforms of the right-sided chest and back leads. This study evaluated the utility of the synthesized 18-lead ECG to differentiate atrial arrhythmias originating from 3 adjacent structures. Synthesized 18-lead ECGs were obtained during SVC-, RSPV-, and RIPV-pacing in 20 patients with lone paroxysmal atrial fibrillation to develop an algorithm. The P-wave morphologies were classified into 4 patterns: positive, negative, biphasic, and isoelectric. Subsequently, the algorithm's accuracy was validated prospectively in another 40 patients. In retrospective analyses, isoelectric P-waves in synthesized V7 distinguished RIPV-pacing from the others (sensitivity = 81%, specificity = 92%) (first criteria). The P wave morphologies in Leads II (sensitivity = 83%, specificity = 94%) and V1 (sensitivity = 84%, specificity = 80%) distinguished SVC- and RSPV-pacing (second criteria). In a prospective evaluation, the sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], and accuracy of the first criteria for identifying RIPV-pacing was 97%, 90%, 78%, 99%, and 92%, respectively. The sensitivity, specificity, RPV, NPV, and accuracy of the second criteria (amplitudes > 1 mV in lead II or biphasic P-waves in lead V1) for discriminating SVC- and RSPV-pacing was 66%, 95%, 98%, 50%, and 74%, respectively. The P wave morphology pattern in lead V7 in synthesized 18-lead ECGs is useful for differentiating RIPV origins from RSPV/SVC origins.

Pressure-guided second-generation cryoballoon pulmonary vein isolation: Prospective comparison of the procedural and clinical outcomes with the conventional strategy.

BACKGROUND: The utility of pressure waveform analyses to assess pulmonary vein (PV) occlusions has been reported in cryoballoon PV isolation (CB-PVI) using first-generation CBs. This prospective randomized study compared the procedural and clinical outcomes of pressure-guided and conventional CB-PVI. METHODS AND RESULTS: Sixty patients with paroxysmal atrial fibrillation underwent CB-PVI with 28-mm second-generation CBs. PV occlusions were assessed either by real-time pressure waveforms without contrast utilization (pressure-guided group) or contrast injections (conventional group) and randomly assigned. Before the randomization, 24 patients underwent pressure-guided CB-PVIs. In the derivation study, a vein occlusion was obtained in 88/96 (91.7%) PVs among which 86 (97.7%) were successfully isolated by the application. In the validation study, the nadir balloon temperature and total freezing time did not significantly differ per PV between the two groups. The positive predictive value of the vein occlusion for predicting successful acute isolations was similar (93 of 103 [90.2%] and 89 of 98 [90.8%] PVs; P = 1.000), but the negative predictive value was significantly higher in pressure-guided than angiographical occlusions (14 of 17 [82.3%] vs 7 of 22 [31.8%]; P = .003). Both the procedure (57.7 ± 14.2 vs 62.6 ± 15.8 minutes; P = .526) and fluoroscopic times (16.3 ± 6.4 vs 20.1 ± 6.1; P = .732) were similar between the two groups, however, the fluoroscopy dose (130.6 ± 97.7 vs 353.2 ± 231.4 mGy; P < .001) and contrast volume used (0 vs 17.5 ± 7.7 mL; P < .001) were significantly smaller in the pressure-guided than conventional group. During 27.8 (5-39) months of follow-up, the single procedure arrhythmia freedom was similar between the two groups (P = .438). CONCLUSIONS: Pressure-guided second-generation CB-PVIs were similarly effective and as safe as conventional CB-PVIs. This technique required no contrast utilization and significantly reduced radiation exposure more than conventional CB-PVIs.

Involvement of selective epithelial cell death in the formation of feather buds on a bioengineered skin.

Selective cell death by apoptosis plays important roles in organogenesis. Apoptotic cells are observed in the developmental and homeostatic processes of several ectodermal organs, such as hairs, feathers, and mammary glands. In chick feather development, apoptotic events have been observed during feather morphogenesis, but have not been investigated during early feather bud formation. Previously, we have reported a method for generating feather buds on a bioengineered skin from dissociated skin epithelial and mesenchymal cells in three-dimensional culture. During the development of the bioengineered skin, epithelial cavity formation by apoptosis was observed in the epithelial tissue. In this study, we examined the selective epithelial cell death during the bioengineered skin development. Histological analyses suggest that the selective epithelial cell death in the bioengineered skin was induced by caspase-3-related apoptosis. The formation of feather buds of the bioengineered skin was disturbed by the treatment with a pan-caspase inhibitor. The pan-caspase inhibitor treatment suppressed the rearrangement of the epithelial layer and the formation of dermal condensation, which are thought to be essential step to form feather buds. The suppression of the formation of feather buds on the pan-caspase inhibitor-treated skin was partially compensated by the addition of a GSK-3ß inhibitor, which activates Wnt/ß-catenin signaling. These results suggest that the epithelial cell death is involved in the formation of feather buds of the bioengineered skin. These observations also suggest that caspase activities and Wnt/ß-catenin signaling may contribute to the formation of epithelial and mesenchymal components in the bioengineered skin.

Endothelial damage and thromboembolic risk after pulmonary vein isolation using the latest ablation technologies: a comparison of the second-generation cryoballoon vs. contact force-sensing radiofrequency ablation.

Experimental data suggest that cryoenergy is associated with less endothelial damage and thrombus formation than radiofrequency energy. This study aimed to compare the impact of pulmonary vein isolation (PVI) on the endothelial damage, myocardial damage, inflammatory response, and prothrombotic state between the two latest technologies, second-generation cryoballoon (CB2) and contact force-sensing radiofrequency catheter (CFRF) ablation. Eighty-six paroxysmal atrial fibrillation (AF) patients (55 men; 65 ± 12 years) underwent PVI with either the CB2 (n = 64) or CFRF (n = 22). Markers of the endothelial damage (L-arginine/asymmetric dimethylarginine [ADMA]), myocardial injury (creatine kinase-MB [CK-MB], troponin-T, and troponin-I), inflammatory response (high-sensitive C-reactive protein), and prothrombotic state (D-dimer, soluble fibrin monomer complex, and thrombin-antithrombin complex) were determined before and up to 24-h post-procedure. The total application time was shorter (1,460 ± 287 vs. 2,395 ± 571 [sec], p < 0.01) and total procedure time tended to be shorter (199 ± 37 vs. 218 ± 38 [min], p = 0.06) with CB2 than CFRF ablation. The amount of myocardial injury was greater (CK-MB: 45 ± 17 vs. 11 ± 3 [IU/l], p < 0.01) with CB2 than CFRF ablation. The L-arginine/ADMA ratio was lower (160 ± 51 vs. 194 ± 38, p = 0.028) after CB2 than CFRF ablation. Inflammatory and all prothrombotic markers were significantly elevated post-ablation; however, the magnitude was similar between the two groups. During a mean follow-up of 20 ± 6 months, the single-procedure AF freedom was similar between the CB2 and CFRF groups (60/64 vs. 20/22, p = 0.82). CB2-PVI produces significantly lesser endothelial damage with greater myocardial injury than CFRF-PVI; however, similar anticoagulant regimens are required during the peri-procedural periods in both technologies.

Intra-procedural evaluation of the cavo-tricuspid isthmus anatomy with different techniques: comparison of angiography and intracardiac echocardiography.

Cavo-tricuspid isthmus (CTI) anatomies are highly variable, and specific anatomies lead to a difficult CTI ablation. This study aimed to compare the clinical utility of angiography and intracardiac echocardiography (ICE) in evaluating CTI anatomies, and to investigate the impact of the CTI anatomy on the procedure when the ablation tactic was adjusted to the anatomy. This study included 92 consecutive patients who underwent a CTI ablation. The CTI morphology was assessed with both right atrial angiography and ICE before the ablation, and the ablation tactic was adjusted to the anatomy. The mean CTI length was 34 ± 9 mm. On ICE imaging, 21 (23%) patients had a flat CTI, while 41 (45%) had a concave CTI with a mean depth of 5.6 ± 2.7 mm. The remaining 30 (32%) had a distinct pouch with a mean depth of 6.4 ± 2.3 mm, located at the posterior, middle, and anterior isthmus in 15, 14, and 1 patients, respectively. The Eustachian ridge (ER) was visualized in 46 (50%) patients. On angiography, a pouch and ER were detected in 22 and 15 patients, but not in the remaining 8 and 31, respectively. A complete CTI block line was created in all patients without any complications. The CTI anatomy did not significantly impact any procedural parameters. ICE was superior to angiography in evaluating the detailed CTI anatomy, especially pouches and the ER. An adjustment of the ablation tactic to the anatomy could overcome the procedural difficulties of the CTI ablation in cases with specific anatomies.

Feasibility of Uninterrupted Direct Oral Anticoagulants with Temporary Switching to Dabigatran ("Dabigatran Bridge") for Catheter Ablation of Atrial Fibrillation.

Uninterrupted anticoagulation therapy during atrial fibrillation (AF) ablation minimizes the risk of periprocedural thromboembolic events. Although the use of direct oral anticoagulants (DOACs) has rapidly developed in patients undergoing AF ablation, no antidote is available for factor Xa inhibitors. We sought to investigate the feasibility of an uninterrupted DOAC protocol with temporary switching to dabigatran ("dabigatran bridge") for AF ablation.The study consisted of consecutive 137 patients in whom DOACs were interrupted on the procedural day with heparin bridging (interrupted group) and 135 in whom DOACs were uninterrupted with temporary switching to dabigatran during the periprocedural hospitalization period ("dabigatran bridge" group). The coagulation markers were measured just before and after the ablation procedure. The adverse events during and up to 8 weeks after the procedure were compared according to the definition of the International Society on Thrombosis and Hemostasis.The patients were significantly older in the "dabigatran bridge" group; however, the other baseline patient characteristics were similar between the two groups. The incidence of all adverse events was comparable between the two groups (8/137 versus 8/135, P = 0.96); however, one patient from the interrupted group experienced stroke, and another from the "dabigatran bridge" group experienced cardiac tamponade, which was safely managed with an antidote. In the "dabigatran bridge" group, the activated partial thromboplastin time was significantly longer, and coagulation markers (soluble fibrin monomer and thrombin-antithrombin complexes) were significantly lower than in the interrupted group before ablation.The "dabigatran bridge" seems to be a reasonable anticoagulation protocol to minimize the thromboembolic risk while ensuring safety in patients undergoing AF ablation and taking factor Xa inhibitors.