Ikutaro Nakajima

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.

Risk stratification in patients with brugada syndrome without previous cardiac arrest – Prognostic value of combined risk factors

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.

Evaluation of the Necessity for Cardioverter-Defibrillator Implantation in Elderly Patients With Brugada Syndrome

Background—The clinical characteristics and prognosis of elderly patients with Brugada syndrome (BrS) are largely unknown. The purpose of this study was to evaluate the risks and benefits of implantable cardioverter defibrillator (ICD) in elderly patients with BrS based on a long follow-up. Methods and Results—A total of 120 BrS patients with ICD (90 for aborted sudden cardiac arrest or syncope, mean age, 46.6±12.2 years; 50 with age ≥60 years at the last follow-up) were included in this study. During 102±68 months of follow-up, 31 patients (26%) experienced appropriate shocks. Age at the first attack of ventricular fibrillation (VF) was <70 years in all patients (mean, 45.0±12.1 years), the incidence of VF decreased with age, and VF did not recur after 70 years of age except in 2 patients with ischemic heart disease. Eleven of 28 patients with supraventricular tachycardia experienced inappropriate shocks. These inappropriate shocks increased with age and reached a peak in patients who were in their sixties. Lead failures occurred in later stages after implantation in 10 of 120 patients (8%). Conclusions—Long-term follow-up of high-risk BrS patients with ICD showed a low incidence of VF in those aged >70 years. Considering the increasing risk of inappropriate shocks because of the relatively late onset of supraventricular tachycardia and lead failures, avoidance of ICD implantation, or replacement may be considered in elderly BrS patients who remain free from VF until 70 years of age.

Initial experience using Excimer laser for the extraction of chronically implanted pacemaker and implantable cardioverter defibrillator leads in Japanese patients

BACKGROUND Given the exponential growth in cardiac device implantations, the need for less invasive lead extraction is increasing. The Excimer laser was approved for lead removal in Japan in 2010. The present study reports the initial experience using this novel technique to extract chronically implanted pacemaker and implantable cardioverter defibrillator (ICD) leads from Japanese patients. METHODS AND RESULTS We performed a retrospective study of consecutive patients undergoing lead extraction using the laser sheath at a single Japanese center. Patient and lead characteristics, indications, and outcomes were analyzed. From August 2010 to September 2012, a total of 70 leads, including 14 ICD leads, were removed using the laser sheath from 40 patients (26 male, 14 female; age 65.5±18.3 [mean±SD] years; body mass index 21.8±3.5 kg/m2). The median implant duration was 87 months (range 13-328 months). Indications were infection (n=35), venous occlusion (n=4), and pain (n=1). The femoral approach was used in combination with the laser technique in five cases. Complete procedural success was achieved with 68 leads (97.1%). Although the electrode tip was left behind in the remaining two leads, the desired clinical outcomes could be achieved; which were defined as clinical success. No cases resulted in failure. There were no major complications, including death and bleeding requiring open-chest surgery. CONCLUSIONS Laser sheaths appear to provide a feasible and effective means of extracting chronically implanted pacemaker and ICD leads in Japanese patients.

Significance of electrocardiogram recording in high intercostal spaces in patients with early repolarization syndrome

AIMS Published reports regarding inferolateral early repolarization (ER) syndrome (ERS) before 2013 possibly included patients with Brugada-pattern electrocardiogram (BrP-ECG) recorded only in the high intercostal spaces (HICS). We investigated the significance of HICS ECG recording in ERS patients. METHODS AND RESULTS Fifty-six patients showing inferolateral ER in the standard ECG and spontaneous ventricular fibrillation (VF) not linked to structural heart disease underwent drug provocation tests by sodium channel blockade with right precordial ECG (V1-V3) recording in the 2nd-4th intercostal spaces. The prevalence and long-term outcome of ERS patients with and without BrP-ECG in HICS were investigated. After 18 patients showing type 1 BrP-ECG in the standard ECG were excluded, 38 patients (34 males, mean age; 40.4 ± 13.6 years) were classified into four groups [group A (n = 6;16%):patients with ER and type 1 BrP-ECG only in HICS, group B (n = 5;13%):ERS with non-type 1 BrP-ECG only in HICS, group C (n = 8;21%):ERS with non-type 1 BrP-ECG in the standard ECG, and group D (n = 19;50%):ERS only, spontaneously or after drug provocation test]. During follow-up of 110.0 ± 55.4 months, the rate of VF recurrence including electrical storm was significantly higher in groups A (4/6:67%), B (4/5:80%), and C (4/8:50%) compared with D (2/19:11%) (A, B, and C vs. D, P < 0.05). CONCLUSIONS Approximately 30% of the patients with ERS who had been diagnosed with the previous criteria showed BrP-ECG only in HICS. Ventricular fibrillation mostly recurred in patients showing BrP-ECG in any precordial lead including HICS; these comprised 50% of the ERS cohort.

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).

Clinical and Pathological Impact of Tissue Fibrosis on Lethal Arrhythmic Events in Hypertrophic Cardiomyopathy Patients With Impaired Systolic Function

BACKGROUND The natural history of hypertrophic cardiomyopathy (HCM) varies from an asymptomatic benign course to a poor prognosis. Myocardial fibrosis may play a critical role in ventricular tachyarrhythmias (VT/VF); however, the clinical significance of tissue fibrosis by right ventricular (RV) biopsy in the long-term prognosis of HCM patients remains unclear. METHODS AND RESULTS We enrolled 185 HCM patients (mean age, 57±14 years). The amount of fibrosis (%area) was quantified using a digital microscope. Hemodynamic, echocardiographic, and electrophysiologic parameters were also evaluated. Patients with severe fibrosis had longer QRS duration and positive late potential (LP) on signal-averaged ECG, resulting in a higher incidence of VT/VF. At the 5±4 year follow-up, VT/VF occurred in 31 (17%) patients. Multivariate Cox regression analysis revealed that tissue fibrosis (hazard ratio (HR): 1.65; P=0.003 per 10% increase), lower left ventricular ejection fraction (HR: 0.64; P=0.001 per 10% increase), and positive SAECG (HR: 3.14; P=0.04) led to a greater risk of VT/VF. The combination of tissue fibrosis severity and lower left ventricular ejection fraction could be used to stratify the risk of lethal arrhythmic events in HCM patients. CONCLUSIONS Myocardial fibrosis in RV biopsy samples may contribute to abnormal conduction delay and spontaneous VT/VF, leading to a poor prognosis in HCM patients.

Efficacy and safety of flecainide for ventricular arrhythmias in patients with Andersen-Tawil syndrome with KCNJ2 mutations

BACKGROUND Andersen-Tawil syndrome (ATS) is an autosomal dominant genetic or sporadic disorder characterized by ventricular arrhythmias (VAs), periodic paralyses, and dysmorphic features. The optimal pharmacological treatment of VAs in patients with ATS remains unknown. OBJECTIVE We evaluated the efficacy and safety of flecainide for VAs in patients with ATS with KCNJ2 mutations. METHODS Ten ATS probands (7 females; mean age 27 ± 11 years) were enrolled from 6 institutions. All of them had bidirectional VAs in spite of treatment with β-blockers (n = 6), but none of them had either aborted cardiac arrest or family history of sudden cardiac death. Twenty-four-hour Holter recording and treadmill exercise test (TMT) were performed before (baseline) and after oral flecainide therapy (150 ± 46 mg/d). RESULTS Twenty-four-hour Holter recordings demonstrated that oral flecainide treatment significantly reduced the total number of VAs (from 38,407 ± 19,956 to 11,196 ± 14,773 per day; P = .003) and the number of the longest ventricular salvos (23 ± 19 to 5 ± 5; P = .01). At baseline, TMT induced nonsustained ventricular tachycardia (n = 7) or couplets of premature ventricular complex (n = 2); treatment with flecainide completely (n = 7) or partially (n = 2) suppressed these exercise-induced VAs (P = .008). In contrast, the QRS duration, QT interval, and U-wave amplitude of the electrocardiogram were not altered by flecainide therapy. During a mean follow-up of 23 ± 11 months, no patients developed syncope or cardiac arrest after oral flecainide treatment. CONCLUSION This multicenter study suggests that oral flecainide therapy is an effective and safe means of suppressing VAs in patients with ATS with KCNJ2 mutations, though the U-wave amplitude remained unchanged by flecainide.

Cardiac resynchronization therapy to prevent life-threatening arrhythmias in patients with congestive heart failure

Various clinical data demonstrate that cardiac resynchronization therapy (CRT) provides a favorable structural as well as electrical remodeling. The CArdiac Resynchronization-Heart Failure study, which tested the pure effect of CRT (using CRT devices without the capability of defibrillation) clearly showed a significant reduction in the total mortality by partly preventing sudden cardiac death. The antiarrhythmic effects of CRT are explained, at least in part, by ionic and genetic modulation of ventricular myocytes. It has been revealed in animal experiments to mimic disorganized ventricular contraction that CRT reverses down-regulation of certain K(+) channels and abnormal Ca(2+) homeostasis in the failing heart. However, CRT can be proarrhythmic in some particular cases especially in the early phase of this therapy. According to our study, proarrhythmic effects after CRT can be observed in approximately 10% of patients. The relatively high incidence of the proarrhythmic effects of CRT may promote a trend toward selecting CRT-D rather than CRT-P.