Quantitative comparison of the isolation lesions between conventional- and larger-sized visually guided laser balloon ablation.

BACKGROUND: The importance of a wider circumferential isolation of the pulmonary veins (PV), which includes a large portion of the left atrial posterior wall (LAPW), has been suggested in several studies. However, the extended isolation area using a larger inflated visually guided laser balloon (VGLB) ablation remains to be elucidated. METHODS: Seventy-eight patients with atrial fibrillation (AF) who underwent VGLB ablation were enrolled in this prospective study. An electroanatomic map of the left atrium was obtained before and after PV isolation (PVI) using a conventional-sized VGLB. The isolation areas were extended by the largest-sized VGLB ablation and remapped in the same manner. After the ablation, isolation areas were calculated with CARTO-3 system. The one-year atrial arrhythmia (Ata) recurrence was assessed.  RESULTS: The largest-sized VGLB ablation yielded statistically greater areas of isolation in left-sided PV antrum (PVA) (11.5 ± 2.3 cm2 vs. 15.9 ± 3.5 cm2, P < .001) and right-sided PVA (14.2 ± 3.3 cm2 vs. 20.6 ± 4.4 cm2, P < .001) than the conventional-sized VGLB. Further, non-ablated LAPW (12.3 ± 4.4 cm2 vs. 7.8 ± 3.9 cm2, P < .001) was significantly reduced after largest-sized VGLB ablation, compared to the conventional-sized VGLB ablation. The one-year Ata freedom was 83.7% in patients with paroxysmal AF and 96.4% in those with persistent AF. CONCLUSION: The largest-sized VGLB ablation technique can create a significantly wider isolation area of PVA and debulk a large amount of LAPW than the conventional-sized VGLB ablation. The one-year outcome was similarly high in paroxysmal and persistent AF.

Left atrial roof region ablation using a visually guided laser balloon.

Balloon-based catheter ablation including visually guided laser balloon (VGLB) has been adopted a first line therapeutic strategy for the patients with atrial fibrillation (AF). Recently, the roof area ablation beyond pulmonary vein (PV) isolation (PVI) using cryoballoon has been described as an effective therapy for the patients with persistent AF. However, the roof area ablation performed with a VGLB remains unknown. In this case, we report the case of roof area ablation for the patient with persistent AF using a VGLB.

The impact of home electrocardiograph measurement rate on the detection of atrial fibrillation recurrence after ablation: A prospective multicenter observational study.

Background: This multicenter prospective observational study examined the impact of additionally using a home electrocardiograph (ECG) to detect atrial fibrillation (AF) recurrence after ablation. Methods: Between May 2019 and December 2020, 128 patients undergoing ablation were enrolled in the study. After performing ablation, they were instructed to measure their ECGs at home using Complete (ECG paired with a blood pressure monitor; Omron Healthcare, Japan) every day and to visit the hospital every 3 months until after 12 months for 24-hour Holter ECG and 12-lead ECG as usual care (UC). Results: After ablation, 94 patients were followed up, and AF recurrence at 12 months was detected more commonly in adjudicators-interpreted Complete (31 [33 %]) than in UC (18 [9 %]) (hazard ratio 1.95, 95 % confidence interval [95 %CI] 1.35-2.81, P < 0.001). In patients with recurrent AF found via both modalities (n = 16), the time to first AF detection by Complete was 40.9 ± 73.9 days faster than that in UC (P = 0.04). Notably, when the adherence to Complete measurement was divided by 80 %, the add-on effect of Complete on the detection of recurrent AF in UC indicated the hazard ratio (HR) of 1.71 (95 %CI 0.92-3.18, P = 0.09) for the low adherence (<80 %) group, but it was significant for the high adherence (≥80 %) group, with HR of 2.19 (95 %CI 1.43-3.36, P < 0.001). Conclusions: Despite a shorter measurement time, Complete detected recurrent AF more frequently and faster compared with UC after AF ablation. A significant adherence-dependent difference of Complete was found in detecting AF recurrence.

Comparison of maximum-sized visually guided laser balloon and cryoballoon ablation.

Balloon ablation therapy has recently been used for atrial fibrillation (AF) ablation. Laser balloons possess the property in which the balloon size can be changed. Standard laser balloon ablation (Standard LBA) was followed by additional ablation using a maximally extended balloon (Extended LBA) and its lesion characteristics were compared to cryoballoon ablation (CBA), another balloon technology. From June 2020 to July 2021, patients with paroxysmal AF who underwent an initial pulmonary vein (PV) isolation were enrolled. Sixty-five patients with paroxysmal AF were included, 32 in the LBA and 33 in the CBA group. To measure the isolated surface area after the ablation procedures, left atrial voltage mapping was performed after Standard LBA, Extended LBA, and CBA. The baseline patient characteristics did not differ between LBA and CBA. Extended LBA could successfully increase the isolated area more than Standard LBA for all four PVs. Compared to CBA, the isolated area of both superior PVs was significantly greater with Extended LBA (left superior PV: 8.5 ± 2.1 vs 7.3 ± 2.4, p = 0.04, right superior PV: 11.4 ± 3.7 vs 8.7 ± 2.7, p < 0.01), and thus the non-isolated posterior wall (PW) was smaller (8.5 ± 3.4 vs 12.4 ± 3.3, p < 0.01). Nevertheless, changes in the cardiac injury markers were significantly lower with LBA than CBA. There was no significant correlation between the cardiac injury level and isolated area in both groups. In conclusion, Extended LBA exhibited a significantly greater isolation of both superior PVs and resulted in a smaller non-isolated PW, but the cardiac injury markers were significantly suppressed as compared to CBA.

Diagnostic Value of Atrial Fibrillation by Built-in Electrocardiogram Technology in a Blood Pressure Monitor.

Background: Hypertension in patients with atrial fibrillation (AF) is a known independent risk factor for stroke. The Complete blood pressure (BP) monitor (Omron Healthcare, Kyoto, Japan) was developed as the first BP monitor with electrocardiogram (ECG) capability in a single device to simultaneously monitor ECG and BP readings. This study investigated whether the Complete can accurately differentiate sinus rhythm (SR) from AF during BP measurement. Methods and Results: Fifty-six consecutive patients with persistent AF admitted for catheter ablation were enrolled in the study (mean age 65.8 years; 83.9% male). In all patients, 12-lead ECGs and simultaneous Complete recordings were acquired before and after ablation. The Complete interpretations were compared with physician-reviewed ECGs, whereas Complete recordings were reviewed by cardiologists in a blinded manner and compared with ECG interpretations. Sensitivity, specificity, and κ coefficient were also determined. In all, 164 Complete and ECG recordings were simultaneously acquired from the 56 patients. After excluding unclassified recordings, the Complete automated algorithm performed well, with 100% sensitivity, 86% specificity, and a κ coefficient of 0.87 compared with physician-interpreted ECGs. Physician-interpreted Complete recordings performed well, with 99% sensitivity, 85% specificity, and a κ coefficient of 0.85 compared with physician-interpreted ECGs. Conclusions: The Complete, which combines BP and ECG monitoring, can accurately differentiate SR from AF during BP measurement.

Copy number variations of SCN5A in Brugada syndrome.

BACKGROUND: Loss-of-function mutations in SCN5A are associated in ∼20% of Brugada syndrome (BrS) patients. Copy number variations (CNVs) have been shown to be associated with several inherited arrhythmia syndromes. OBJECTIVE: The purpose of this study was to investigate SCN5A CNVs among BrS probands. METHODS: The study cohort consisted of 151 BrS probands who were symptomatic or had a family history of BrS, sudden death, syncope, or arrhythmic diseases. We performed sequence analysis of SCN5A by the Sanger method. For detecting CNVs in SCN5A, we performed multiplex ligation-dependent probe amplification analysis of the 151 BrS probands. RESULTS: We identified pathogenic SCN5A mutations in 20 probands by the Sanger method. In 140 probands in whom multiplex ligation-dependent probe amplification was successfully performed, 4 probands were found to present different CNVs (deletion in 3 and duplication in 1). Three of them had fatal arrhythmia events; the remaining 1 was asymptomatic but had a family history. Mean age at diagnosis was 23 ± 14 years. All of the baseline 12-lead electrocardiograms showed PQ-interval prolongation. The characteristics of these 4 probands with CNVs were similar to those of the probands with mutations leading to premature truncation of the protein or missense mutations causing peak INa reduction >90%. CONCLUSION: We identified SCN5A CNVs in 2.9% of BrS probands who were symptomatic or had a family history.

Flecainide ameliorates arrhythmogenicity through NCX flux in Andersen-Tawil syndrome-iPS cell-derived cardiomyocytes.

Andersen-Tawil syndrome (ATS) is a rare inherited channelopathy. The cardiac phenotype in ATS is typified by a prominent U wave and ventricular arrhythmia. An effective treatment for this disease remains to be established. We reprogrammed somatic cells from three ATS patients to generate induced pluripotent stem cells (iPSCs). Multi-electrode arrays (MEAs) were used to record extracellular electrograms of iPSC-derived cardiomyocytes, revealing strong arrhythmic events in the ATS-iPSC-derived cardiomyocytes. Ca2+ imaging of cells loaded with the Ca2+ indicator Fluo-4 enabled us to examine intracellular Ca2+ handling properties, and we found a significantly higher incidence of irregular Ca2+ release in the ATS-iPSC-derived cardiomyocytes than in control-iPSC-derived cardiomyocytes. Drug testing using ATS-iPSC-derived cardiomyocytes further revealed that antiarrhythmic agent, flecainide, but not the sodium channel blocker, pilsicainide, significantly suppressed these irregular Ca2+ release and arrhythmic events, suggesting that flecainide's effect in these cardiac cells was not via sodium channels blocking. A reverse-mode Na+/Ca2+exchanger (NCX) inhibitor, KB-R7943, was also found to suppress the irregular Ca2+ release, and whole-cell voltage clamping of isolated guinea-pig cardiac ventricular myocytes confirmed that flecainide could directly affect the NCX current (INCX). ATS-iPSC-derived cardiomyocytes recapitulate abnormal electrophysiological phenotypes and flecainide suppresses the arrhythmic events through the modulation of INCX.

Ultrastructural maturation of human-induced pluripotent stem cell-derived cardiomyocytes in a long-term culture.

BACKGROUND: In the short- to mid-term, cardiomyocytes generated from human-induced pluripotent stem cells (hiPSC-CMs) have been reported to be less mature than those of adult hearts. However, the maturation process in a long-term culture remains unknown. METHODS AND RESULTS: A hiPSC clone generated from a healthy control was differentiated into CMs through embryoid body (EB) formation. The ultrastructural characteristics and gene expressions of spontaneously contracting EBs were analyzed through 1-year of culture after cardiac differentiation was initiated. The 14-day-old EBs contained a low number of myofibrils, which lacked alignment, and immature high-density Z-bands lacking A-, H-, I-, and M-bands. Through the long-term culture up to 180 days, the myofibrils became more tightly packed and formed parallel arrays accompanied by the appearance of mature Z-, A-, H-, and I-bands, but not M-bands. Notably, M-bands were finally detected in 360-day-old EBs. The expression levels of the M-band-specific genes in hiPSC-CMs remained lower in comparison with those in the adult heart. Immunocytochemistry indicated increasing number of MLC2v-positive/MLC2a-negative cells with decreasing number of MLC2v/MLC2a double-positive cells, indicating maturing of ventricular-type CMs. CONCLUSIONS: The structural maturation process of hiPSC-CMs through 1-year of culture revealed ultrastructural sarcomeric changes accompanied by delayed formation of M-bands. Our study provides new insight into the maturation process of hiPSC-CMs.

A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents.

AIMS: Short-QT syndrome (SQTS) is a recently recognized disorder associated with atrial fibrillation (AF) and sudden death due to ventricular arrhythmias. Mutations in several ion channel genes have been linked to SQTS; however, the mechanism remains unclear. This study describes a novel heterozygous gain-of-function mutation in the inward rectifier potassium channel gene, KCNJ2, identified in SQTS. METHODS AND RESULTS: We studied an 8-year-old girl with a markedly short-QT interval (QT = 172 ms, QTc = 194 ms) who suffered from paroxysmal AF. Mutational analysis identified a novel heterozygous KCNJ2 mutation, M301K. Functional assays displayed no Kir2.1 currents when M301K channels were expressed alone. However, co-expression of wild-type (WT) with M301K resulted in larger outward currents than the WT at more than -30 mV. These results suggest a gain-of-function type modulation due to decreased inward rectification. Furthermore, we analysed the functional significance of the amino acid charge at M301 (neutral) by changing the residue. As with M301K, in M301R (positive), the homozygous channels were non-functional, whereas the heterozygous channels demonstrated decreased inward rectification. Meanwhile, the currents recorded in M301A (neutral) showed normal inward rectification under both homo- and heterozygous conditions. Heterozygous overexpression of WT and M301K in neonatal rat ventricular myocytes exhibited markedly shorter action potential durations than the WT alone. CONCLUSION: In this study, we identified a novel KCNJ2 gain-of-function mutation, M301K, associated with SQTS. Functional assays revealed no functional currents in the homozygous channels, whereas impaired inward rectification demonstrated under the heterozygous condition resulted in larger outward currents, which is a novel mechanism predisposing SQTS.

KCNE5 (KCNE1L) variants are novel modulators of Brugada syndrome and idiopathic ventricular fibrillation.

BACKGROUND: Brugada syndrome (BrS) has a significantly higher incidence among the male sex. Among genes coding ion channels and their modulatory proteins, KCNE5 (KCNE1L) is located in the X chromosome and encodes an auxiliary ß-subunit for K channels. KCNE5 has been shown to modify the transient outward current (I(to)), which plays a key role in determining the repolarization process in the myocardium. This study investigated whether KCNE5 mutations could be responsible for BrS and other idiopathic ventricular fibrillation (IVF). METHODS AND RESULTS: In 205 Japanese patients with BrS or IVF who tested negative for SCN5A mutation, we conducted a genetic screen for KCNE5 variants. We identified 2 novel KCNE5 variants: p.Y81H in 3 probands and p.[D92E;E93X] in 1 proband from 4 unrelated families. Y81H was identified in 1 man and 2 women; D92E;E93X was found in a 59-year-old man. All probands received implantable cardioverter-defibrillators. Functional consequences of the KCNE5 variants were determined through biophysical assay using cotransfection with KCND3 or KCNQ1. In the experiments with KCND3, which encodes Kv4.3, I(to) was significantly increased for both KCNE5 variants compared to wild type. In contrast, there were no significant changes in current properties reconstructed by KCNQ1+ wild type KCNE5 and the 2 variants. With the simulation model, both variants demonstrated notch-and-dome or loss-of-dome patterns. CONCLUSIONS: KCNE5 modulates I(to), and its novel variants appeared to cause IVF, especially BrS, in male patients through gain-of-function effects on I(to). Screening for KCNE5 variants is relevant for BrS or IVF.

Venous thrombus formation following percutaneous cardiopulmonary support.

It is considered that percutaneous cardiopulmonary support (PCPS)-associated thrombosis is rare on antithrombotic coated PCPS if anticoagulation therapy is appropriately performed. We experienced two cases in which the association between antithrombotic coated PCPS and venous thrombus formation was highly suspected. These cases suggest that PCPS-associated venous thrombus formation should be checked frequently during and after PCPS even if anticoagulation was appropriately performed.