Hiro Kawata

Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization

Background— Recently, we and others reported that early repolarization (J wave) is associated with idiopathic ventricular fibrillation. However, its clinical and genetic characteristics are unclear. Methods and Results— This study included 50 patients (44 men; age, 45±17 years) with idiopathic ventricular fibrillation associated with early repolarization, and 250 age- and sex-matched healthy controls. All of the patients had experienced arrhythmia events, and 8 (16%) had a family history of sudden death. Ventricular fibrillation was inducible by programmed electric stimulation in 15 of 29 patients (52%). The heart rate was slower and the PR interval and QRS duration were longer in patients with idiopathic ventricular fibrillation than in controls. We identified nonsynonymous variants in SCN5A (resulting in A226D, L846R, and R367H) in 3 unrelated patients. These variants occur at residues that are highly conserved across mammals. His-ventricular interval was prolonged in all of the patients carrying an SCN5A mutation. Sodium channel blocker challenge resulted in an augmentation of early repolarization or development of ventricular fibrillation in all of 3 patients, but none was diagnosed with Brugada syndrome. In heterologous expression studies, all of the mutant channels failed to generate any currents. Immunostaining revealed a trafficking defect in A226D channels and normal trafficking in R367H and L846R channels. Conclusions— We found reductions in heart rate and cardiac conduction and loss-of-function mutations in SCN5A in patients with idiopathic ventricular fibrillation associated with early repolarization. These findings support the hypothesis that decreased sodium current enhances ventricular fibrillation susceptibility.

Prognostic significance of early repolarization in inferolateral leads in Brugada patients with documented ventricular fibrillation: A novel risk factor for Brugada syndrome with ventricular fibrillation

BACKGROUND Little is known about the clinical and prognostic impact of early repolarization (ER) on patients with Brugada syndrome (BrS), especially those with documented ventricular fibrillation (VF). OBJECTIVE To investigate the prevalence and prognostic significance of ER in inferolateral leads in patients with BrS and documented VF. METHODS We investigated 10 different 12-lead electrocardiograms (ECGs) recorded on different days to identify the presence of ER, which was defined as J-point elevation ≥0.1 mV in inferior (II, III, aVF) or lateral leads (I, aVL, V₄-V₆), in 49 individuals (46 men; age 46 ± 13 years) with a type 1 ECG of BrS and previous history of VF. RESULTS ER was observed persistently (in all ECGs) in 15 patients (31%; P group), intermittently (in at least one but not in all ECGs) in 16 patients (33%; I group), and not observed in 18 patients (37%; N group), yielding an overall ER incidence of 63% (31/49). During the follow-up period (7.7 years), recurrence of VF was documented in all 15 patients (100%) in the P group, and less in 12 patients (75%) in the I group and in 8 patients (44%) in the N group. The P group showed a worse prognosis than N group (P = .0001) by Kaplan-Meier analysis. Either persistent or intermittent ER in an inferolateral lead was an independent predictor of fatal arrhythmic events (hazard ratio 4.88, 95% confidence interval 2.02-12.7, P = .0004; and hazard ratio 2.50, 95% confidence interval 1.03-6.43, P = .043, respectively). CONCLUSION The prevalence of ER in inferolateral leads was high and an especially persistent form of ER was associated with a worse outcome in BrS patients with documented VF.

Effect of sodium-channel blockade on early repolarization in inferior/lateral leads in patients with idiopathic ventricular fibrillation and Brugada syndrome

BACKGROUND A high incidence of early repolarization (ER) pattern in the inferolateral leads has been reported in patients with idiopathic ventricular fibrillation (IVF). Brugada syndrome (BS) is characterized by J-point or ST-segment elevation in the right precordial leads and ventricular fibrillation, and some patients with BS also have ER in the inferolateral leads. OBJECTIVE To compare the clinical characteristics and effects of sodium-channel blockade on ER between IVF patients with ER (early repolarization syndrome [ERS]) and BS patients with or without ER. METHODS Fourteen patients with ERS and 21 patients with BS were included in this study. ER was defined as an elevation of at least 0.1 mV from baseline in the QRS-T junction in the inferorolateral leads. Provocative tests with sodium-channel blockers were conducted in all patients with ERS to distinguish ERS from BS. RESULTS In the ERS group, all patients were male and most patients experienced ventricular fibrillation during sleep or low activity (79%). ER was attenuated by sodium-channel blockers in most patients with ERS (13/14, 93%) and BS (5/5, 100%), whereas ST-segment elevation was augmented in the right precordial leads in the BS group. The rates of positive late potentials were significantly higher in the BS group (60%) than in the ERS group (7%) (P <.01). CONCLUSIONS Some similarities were observed between ERS and BS, including gender, arrhythmia triggers, and response of ER to sodium-channel blockers. Unlike the ST segment in the right precordial leads in BS, ER was attenuated in patients with both ERS and BS, suggesting a differential mechanism between ER in the inferolateral leads and ST elevation in the right precordial leads.

Clinical impact of the number of extrastimuli in programmed electrical stimulation in patients with Brugada type 1 electrocardiogram

BACKGROUND Use of programmed electrical stimulation (PES) for risk stratification of Brugada syndrome (BrS) is controversial. OBJECTIVE To elucidate the role of the number of extrastimuli during PES in patients with BrS. METHODS Consecutive 108 patients with type 1 electrocardiogram (104 men, mean age 46 ± 12 years; 26 with ventricular fibrillation [VF], 40 with syncope, and 42 asymptomatic) underwent PES with a maximum of 3 extrastimuli from the right ventricular apex and the right ventricular outflow tract. Ventricular arrhythmia (VA) was defined as VF or nonsustained polymorphic ventricular tachycardia >15 beats. Patients with VA induced by a single extrastimulus or double extrastimuli were assigned to group SD (Single/Double), by triple extrastimuli to group T (Triple), and the remaining patients to group N. RESULTS VA was induced in 81 patients (VF in 71 and polymorphic ventricular tachycardia in 10), in 4 by a single extrastimulus, in 41 by double extrastimuli, and in 36 by triple extrastimuli. During 79 ± 48 months of follow-up, 24 patients had VF events. Although the overall inducibility of VA was not associated with an increased risk of VF (log-rank P = .78), group SD had worse prognosis than did group T (P = .004). Kaplan-Meier analysis in patients without prior VF also showed that group SD had poorer outcome than did group T and group N (P = .001). Positive and negative predictive values of VA induction with up to 2 extrastimuli were, respectively, 36% and 87%, better than those with up to 3 (23% and 81%, respectively). CONCLUSIONS The number of extrastimuli that induced VA served as a prognostic indicator for patients with Brugada type 1 electrocardiogram. Single extrastimulus or double extrastimuli were adequate for PES of patients with BrS.

Significance of Non-Type 1 Anterior Early Repolarization in Patients With Inferolateral Early Repolarization Syndrome

OBJECTIVES The aim of this study was to investigate the significance of non-type 1 anterior early repolarization (NT1-AER) combined with inferolateral early repolarization syndrome (ERS). BACKGROUND Inferolateral ERS might be a heterogeneous entity, although it excludes type 1 Brugada syndrome (BS). METHODS Of 84 patients with spontaneous ventricular fibrillation, 31 ERS patients were divided into 2 groups. The ERS(A)-group consisted of inferolateral ER and NT1-AER--that is, notching or slurring with J-wave ≥ 1 mm at the end of QRS to early ST segment in any of V1 to V3 leads, in which the ST-T segment did not change to a coved pattern in the standard and high costal (second and third) electrocardiographic recordings even after drug provocation tests (n = 12). The other, ERS(B)-group, showed only inferolateral ER (n = 19). Clinical characteristics and outcomes were compared between the ERS groups, 40 patients with type-1 BS (BS-group), and 13 patients with idiopathic ventricular fibrillation lacking J-wave (IVF-group). RESULTS Ventricular fibrillation occurred during sleep or near sleep in 10 of 12 patients in ERS(A)-group and in 22 of 40 patients in BS-group but in 2 of 19 patients in ERS(B)-group and in 1 of 13 patients in IVF-group (ERS[A] vs. ERS[B], p < 0.0001). Ventricular fibrillation recurrence was significantly higher in ERS(A)-group (58%), particularly in patients with J waves in the high lateral lead, and BS-group (55%), compared with ERS(B)-group (11%) and IVF-group (15%) (ERS[A] vs. ERS[B], p = 0.012). CONCLUSIONS Inferolateral ERS comprises heterogeneous ER subtypes with and without NT1-AER. Coexistence of NT1-AER was a key predictor of poor outcome in patients with ERS.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Associated With Ryanodine Receptor (RyR2) Gene Mutations – Long-Term Prognosis After Initiation of Medical Treatment –

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. METHODSANDRESULTS 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).

Successful Slow Pathway Ablation in a Patient with a Rare Unroofed Type Coronary Sinus

We report a case of atrioventricular nodal reentrant tachycardia coexistent with a coronary sinus (CS) anomaly. During a standard electrophysiological study, the CS could not be cannulated despite several attempts. A persistent left superior vena cava angiogram through the left brachial vein confirmed an unroofed type CS. Successful slow pathway ablation from the right posterior paraseptum lesion was achieved using an anatomical approach.

Flecainide reduces ventricular arrhythmias via a mechanism that differs from that of β-blockers in catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by episodic ventricular tachycardia induced by adrenergic stress. Although β‐blockers are used as first‐line therapy, their therapeutic effects are largely incomplete. Flecainide has recently been shown to modify the molecular defects in CPVT. The aim of this study was to investigate the effects of flecainide as an add‐on to conventional therapy on exercise‐induced ventricular arrhythmia and compare them with those of conventional therapy alone.

Different responses to exercise between Andersen–Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia

Aims Andersen-Tawil Syndrome (ATS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are both inherited arrhythmic disorders characterized by bidirectional ventricular tachycardia (VT). The aim of this study was to evaluate the diagnostic value of exercise stress tests for differentiating between ATS and CPVT. Methods and results We included 26 ATS patients with KCNJ2 mutations from 22 families and 25 CPVT patients with RyR2 mutations from 22 families. We compared the clinical and electrocardiographic (ECG) characteristics, responses of ventricular arrhythmias (VAs) to exercise testing, and the morphology of VAs between ATS and CPVT patients. Ventricular arrhythmias were more frequently observed at baseline in ATS patients compared with CPVT patients [the ratio of ventricular premature beats (VPBs)/sinus: 0.83 ± 1.87 vs. 0.06 ± 0.30, P = 0.01]. At peak exercise, VAs were suppressed in ATS patients, whereas they were increased in CPVT patients (0.14 ± 0.40 vs. 1.94 ± 2.71, P < 0.001). Twelve-lead ECG showed that all 25 VPBs and 15 (94%) of 16 bidirectional VTs were right bundle branch block (RBBB) morphology in ATS patients, whereas 19 (86%) of 22 VPBs had left bundle branch block (LBBB), and 12 (71%) of 17 bidirectional VT had LBBB and RBBB morphologies in CPVT patients. Conclusion In patients with ATS, VAs with RBBB morphology were frequently observed at baseline and suppressed at peak exercise. In contrast, exercise provoked VAs with mainly LBBB morphology in patients with CPVT. In adjunct to clinical and baseline ECG assessments, exercise testing might be useful for making the diagnosis of ATS vs. CPVT, both characterized by bidirectional VT.

Persistent tachycardia within isolated pulmonary veins during atrial fibrillation ablation

During circumferential pulmonary vein (PV) isolation for ongoing atrial fibrillation (AF), distinguishing passive conduction to the pulmonary vein (PV) from rapid PV arrhythmia in the isolated PV is difficult. Hence, the purpose of this study is to investigate both the feasibility of distinguishing the PV tachycardia after circumferential PV isolation and the electrophysiological characteristics of these tachycardia. Among 178 consecutive patients who underwent circumferential PV isolation during ongoing AF, fibrillatory PV converted to a regular cycle length PV tachycardia independent of the atrial rhythm (=independent PV tachycardia) in 13 PVs among 12 (7%) patients. We classified independent PV tachycardia according to 3 different atrial rhythms: sinus rhythm (type 1, n = 2), atrial tachycardia (type 2, n = 4), and AF (type 3, n = 6). independent PV tachycardia was observed in 3 right PV and 10 left PV (P = 0.0864). There were 10 mappable independent PV tachycardia, in which 8 were focal and 2 were macroreentrant tachycardia. i-PVT can be diagnosed in a small number of patients who underwent circumferential PV isolation during AF. The main mechanism or independent PV tachycardia was focal tachycardia mainly in the left PV.