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. (Circ J 2013; 77: 1307–1314)
We herein report a 47-year-old man with relapsing polychondritis who developed monomorphic ventricular tachycardia (VT). His electrocardiogram in sinus rhythm showed a coved-type pattern, and there ...was no evidence of structural cardiac disease; therefore, he was diagnosed with Brugada syndrome. An electrophysiological study revealed a prolonged His-ventricular interval at the baseline. Two forms of VT were induced, which were shown to be bundle branch reentrant VT. A diagnosis of Brugada syndrome should not be ruled out in patients with monomorphic VTs, especially those with conduction abnormalities.
Gaps in the roof line have been ascribed to epicardial conduction using the septopulmonary bundle.
We sought to evaluate the frequency of septopulmonary bundle bypass during roof line ablation, to ...describe anatomical conditions favoring this epicardial gap, and to propose an alternative strategy when present.
One hundred consecutive patients underwent atrial fibrillation ablation. A de novo roof line was created between the superior pulmonary veins. In cases of residual gaps, a floor line was created between the inferior pulmonary veins. Microtomography imaging and histological analyses of 5 human donor hearts were performed: a specific focus was made on the dome and the posterior wall.
Residual gaps were more frequent in roof lines than floor lines (33% vs 15%; P = .049). Electrogram morphologies, activation sequences, and pacing maneuvers indicated an epicardial bypass of the roof line in all cases. Conduction block was obtained in 67 roof lines and 28 floor lines, resulting in a 95% success rate of linear block, without "box" isolation. Between the superior pulmonary veins, the atrial myocardium was thicker and consistently displayed adipose tissue separating the septopulmonary bundle from the septoatrial bundle.
Epicardial conduction across the roof line is common and requires careful electrogram analysis to detect. In such cases, a floor line can be an effective alternative strategy, with clear validation criteria. Myocardial thickness and fat interposition may explain difficulties in achieving lesion transmurality during roof line ablation.
Abstract
Various forms of supraventricular tachycardia (SVT) occur in patients with severe pulmonary hypertension (PH). Despite the high efficacy of radiofrequency catheter ablation (RFCA) for SVT, ...insufficient data exist regarding patients with PH. Thirty SVTs in 23 PH patients (age 47 35–60 years; mean pulmonary artery pressure 44 32–50 mmHg) were analyzed. Procedural success rate, short- and long-term clinical outcomes, were evaluated during a median follow-up of 5.1 years. Single-procedure success rate was 83%; 94% (17/18) in typical atrial flutter, 73% (8/11) in atrial tachycardia (AT), and 100% (1/1) in atrioventricular nodal reentrant tachycardia. Antiarrhythmic drugs, serum brain natriuretic peptide levels and number of hospitalizations significantly decreased after RFCA than that before (
p
= 0.002, 0.04, and 0.002, respectively). Four patients had several procedures. After last RFCA, 12 patients had SVT and 8 patients died. Kaplan–Meier curves showed that patients with SVT after the last RFCA had a lower survival rate compared to those without (
p
= 0.0297). Multivariate analysis identified any SVT after the last RFCA as significant risk factor of mortality (hazard ratio: 9.31;
p
= 0.016). RFCA for SVT in patients with PH is feasible and effective in the short-term, but SVT is common during long-term follow-up and associated with lower survival.
Abstract
Aims
Mapping data of human ventricular fibrillation (VF) are limited. We performed detailed mapping of the activities underlying the onset of VF and targeted ablation in patients with ...structural cardiac abnormalities.
Methods and results
We evaluated 54 patients (50 ± 16 years) with VF in the setting of ischaemic (n = 15), hypertrophic (n = 8) or dilated cardiomyopathy (n = 12), or Brugada syndrome (n = 19). Ventricular fibrillation was mapped using body-surface mapping to identify driver (reentrant and focal) areas and invasive Purkinje mapping. Purkinje drivers were defined as Purkinje activities faster than the local ventricular rate. Structural substrate was delineated by electrogram criteria and by imaging. Catheter ablation was performed in 41 patients with recurrent VF. Sixty-one episodes of spontaneous (n = 10) or induced (n = 51) VF were mapped. Ventricular fibrillation was organized for the initial 5.0 ± 3.4 s, exhibiting large wavefronts with similar cycle lengths (CLs) across both ventricles (197 ± 23 vs. 196 ± 22 ms, P = 0.9). Most drivers (81%) originated from areas associated with the structural substrate. The Purkinje system was implicated as a trigger or driver in 43% of patients with cardiomyopathy. The transition to disorganized VF was associated with the acceleration of initial reentrant activities (CL shortening from 187 ± 17 to 175 ± 20 ms, P < 0.001), then spatial dissemination of drivers. Purkinje and substrate ablation resulted in the reduction of VF recurrences from a pre-procedural median of seven episodes interquartile range (IQR) 4–16 to 0 episode (IQR 0–2) (P < 0.001) at 56 ± 30 months.
Conclusions
The onset of human VF is sustained by activities originating from Purkinje and structural substrate, before spreading throughout the ventricles to establish disorganized VF. Targeted ablation results in effective reduction of VF burden.
Key question
The initial phase of human ventricular fibrillation (VF) is critical as it involves the primary activities leading to sustained VF and arrhythmic sudden death. The origin of such activities is unknown.
Key finding
Body-surface mapping shows that most drivers (≈80%) during the initial VF phase originate from electrophysiologically defined structural substrates. Repetitive Purkinje activities can be elicited by programmed stimulation and are implicated as drivers in 37% of cardiomyopathy patients.
Take-home message
The onset of human VF is mostly associated with activities from the Purkinje network and structural substrate, before spreading throughout the ventricles to establish sustained VF. Targeted ablation reduces or eliminates VF recurrence.
Structured Graphical Abstract
Structured Graphical Abstract
Ventricular fibrillation (VF) onset in humans—Purkinje and structural substrate govern the transition from trigger to disorganized VF. Schematic view of initial VF activities in patients with cardiac structural abnormalities. The upper panel shows an electrocardiogram of spontaneous VF onset in a patient with a prior history of myocardial infarction. The three illustrations show the sequence of trigger, initial organized VF, and disorganized VF. The trigger is shown as a red star close to the structural substrate (mottled white area). Initial VF activities are represented as localized waves generated from the ventricular or Purkinje substrate. Then the acceleration of activities in parallel with previously described changes (reduction in action potential duration, Ca handling…) leads to dissemination of activities and VF disorganization.
Atrial tachycardia (AT) and atrial fibrillation (AF) commonly occur after cardiac surgeries (CSs). This study investigated the mechanisms and long-term outcomes of AT and AF ablation after various ...Maze procedures, particularly whether atrial tachyarrhythmias after the Maze procedure occur due to gaps in the Maze lines. We analyzed 37 consecutive cases with atrial tachyarrhythmias after the Maze procedures and concomitant CSs between 2007 and 2019. Fifty-nine atrial tachyarrhythmias were induced in 37 consecutive cases, and 49 of those atrial tachyarrhythmias were mappable ATs. Forty ATs were related to the Maze procedures in the 49 mappable ATs (81.6%). All 37 consecutive cases had residual electrical conductions (gaps) in the Maze lines (88 gaps; 2.4 ± 1.2 gaps/patient). Forty of 88 gaps (45.5%) were associated with gap-related ATs. The common ATs in this study were 1. peri-mitral atrial flutter due to gaps at pulmonary vein isolation (PVI) line to mitral valve annulus (MVA) (20 cases), and 2. peri-tricuspid atrial flutter due to gaps at right atrial incision to the tricuspid valve annulus (TVA) (10 cases). Forty-seven of 49 ATs (95.9%) were successfully ablated at the first session, and there were no complications. The mean follow-up period after ablation was 3.6 ± 3.2 (median, 2.1; interquartile range, 0.89–6.84) years. The Kaplan–Meier analysis of freedom from recurrent atrial tachyarrhythmias after Maze procedure was 82.7% at 1-year follow-up and 75.5% at 4-year follow-up after a single procedure. Reentry was the main mechanism of ATs after Maze procedures and concomitant CSs, and ATs were largely related to the gaps on the Maze lines between the PVI line and the MVA or those on the lines between right atrial incision to the TVA. Long-term follow-up data suggest that catheter ablation of atrial tachyarrhythmias after various Maze procedures is effective and safe.
Background:The long-term prognosis of cardiac ryanodine receptor (RyR2) positive catecholaminergic polymorphic ventricular tachycardia (CPVT) patients after initiation of medical therapy has not been ...well investigated. This study aimed to assess the recurrence of fatal cardiac event after initiation of medical therapy inRyR2-positive CPVT patients.Methods and Results:Thirty-fourRyR2-positive CPVT patients with a history of cardiac events were enrolled. All patients had medical treatment initiated after the first symptom or diagnosis. Exercise stress tests (ESTs) were performed to evaluate the efficacy of the medical therapy. Even after the initiation of medical therapy, high-risk ventricular arrhythmias (VAs), including premature ventricular contraction couplets, bigeminy, and ventricular tachycardia, were still induced in the majority of patients (80.6%). During 7.4 years of follow-up after the diagnosis, 7 of the 34 (20.6%) patients developed fatal cardiac events. Among those 7 patients, 6 (85.7%) were not compliant with either exercise restriction or medication therapy at the time of the events.Conclusions:Even after initiation of medical treatment, high-risk VAs were induced during EST in mostRyR2-positive CPVT patients. Most fatal recurrent cardiac events occurred in patients who were noncompliant with exercise restriction and/or medical therapy. Medical management including strict exercise restriction should be emphasized to prevent recurrent cardiac event in mostRyR2-positive CPVT patients. (Circ J 2016; 80: 1907–1915)
Background:Risk stratification in patients with Brugada syndrome for primary prevention of sudden cardiac death is still an unsettled issue. A recent consensus statement suggested the indication of ...implantable cardioverter defibrillator (ICD) depending on the clinical risk factors present (spontaneous type 1 Brugada electrocardiogram (ECG) Sp1, history of syncope syncope, and ventricular fibrillation during programmed electrical stimulation PES+). The indication of ICD for the majority of patients, however, remains unclear.Methods and Results:A total of 218 consecutive patients (211 male; aged 46±13 years) with a type 1 Brugada ECG without a history of cardiac arrest who underwent evaluation for ICD including electrophysiological testing were examined retrospectively. During a mean follow-up period of 78 months, 26 patients (12%) developed arrhythmic events. On Kaplan-Meier analysis patients with each of Sp1, syncope, or PES+ suffered arrhythmic events more frequently (P=0.018, P<0.001, and P=0.003, respectively). On multivariate analysis Sp1 and syncope were independent predictors of arrhythmic events. When dividing patients according to the number of these 3 risk factors present, patients with 2 or 3 risk factors experienced arrhythmic events more frequently than those with 0 or 1 risk factor (23/93 vs. 3/125; P<0.001).Conclusions:Syncope, Sp1, and PES+ are important risk factors and the combination of these risks well stratify the risk of later arrhythmic events. (Circ J 2015; 79: 310–317)
Background: Spontaneous type 1 electrocardiogram (ECG) in the right precordial lead is a dominant predictor of ventricular fibrillation (VF) in Brugada syndrome (BrS). In some BrS patients with VF, ...however, spontaneous type 1 ECG is undetectable, even in repeated ECG and immediately after VF. This study investigated differences between BrS patients with spontaneous or drug-induced type 1 ECG. Methods and Results: We evaluated 15 BrS patients with drug-induced (D-BrS) and 29 with spontaneous type 1 ECG (SP-BrS). All patients had had a previous VF episode. In each D-BrS patient, ECG was recorded more than 15 times (mean, 46±34) during 7.2±5.1 years of follow-up. Age and family history were comparable between groups. Inferolateral early repolarization (ER) was observed in 13 D-BrS (87%) at least once but in only 3 SP-BrS (10%, P<0.01). Immediately after VF, inferolateral ER was accentuated in 9 of 10 D-BrS, while type 1 ECG was accentuated in 12 of 16 SP-BrS. Fragmented QRS in the right precordial lead and aVR sign were absent in D-BrS but present in 20 (69%, P<0.01) and 11 (38%, P<0.01) SP-BrS, respectively. There was no prognostic difference between groups. Conclusions: Although having similar clinical profiles, there are obvious ECG differences between VF-positive BrS patients with spontaneous or drug-induced type 1 ECG. The inferolateral lead rather than the right precordial lead on ECG may be particularly crucial in some BrS patients.
Background:Approximately one-third of patients with advanced heart failure (HF) do not respond to cardiac resynchronization therapy (CRT). We investigated whether the left ventricular (LV) conduction ...pattern on magnetocardiography (MCG) can predict CRT responders.Methods and Results:This retrospective study enrolled 56 patients with advanced HF (mean ±SD LV ejection fraction LVEF 23±8%; QRS duration 145±19 ms) and MCG recorded before CRT. MCG-QRS current arrow maps were classified as multidirectional (MDC; n=28) or unidirectional (UDC; n=28) conduction based on a change of either ≥35° or <35°, respectively, in the direction of the maximal current arrow after the QRS peak. Baseline New York Heart Association functional class and LVEF were comparable between the 2 groups, but QRS duration was longer and the presence of complete left bundle branch block and LV dyssynchrony was higher in the UDC than MDC group. Six months after CRT, 30 patients were defined as responders, with significantly more in the UDC than MDC group (89% vs. 14%, respectively; P<0.001). Over a 5-year follow-up, Kaplan-Meyer analysis showed that adverse cardiac events (death or implantation of an LV assist device) were less frequently observed in the UDC than MDC group (6/28 vs. 15/28, respectively; P=0.027). Multivariate analysis revealed that UDC on MCG was the most significant predictor of CRT response (odds ratio 69.8; 95% confidence interval 13.14–669.32; P<0.001).Conclusions:Preoperative non-invasive MCG may predict the CRT response and long-term outcome after CRT.
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