Shinya Kowase

Automated Template Matching to Pinpoint the Origin of Right Ventricular Outflow Tract Tachycardia

Background: Template matching, a technique that examines the similarity between two QRS complexes, has not been broadly applied clinically.

Novel Mutation in the α-Myosin Heavy Chain Gene Is Associated With Sick Sinus Syndrome

Background—Recent genome-wide association studies have demonstrated an association between MYH6, the gene encoding &agr;-myosin heavy chain (&agr;-MHC), and sinus node function in the general population. Moreover, a rare MYH6 variant, R721W, predisposing susceptibility to sick sinus syndrome has been identified. However, the existence of disease-causing MYH6 mutations for familial sick sinus syndrome and their underlying mechanisms remain unknown. Methods and Results—We screened 9 genotype-negative probands with sick sinus syndrome families for mutations in MYH6 and identified an in-frame 3-bp deletion predicted to delete one residue (delE933) at the highly conserved coiled-coil structure within the binding motif to myosin-binding protein C in one patient. Co-immunoprecipitation analysis revealed enhanced binding of delE933 &agr;-MHC to myosin-binding protein C. Irregular fluorescent speckles retained in the cytoplasm with substantially disrupted sarcomere striation were observed in neonatal rat cardiomyocytes transfected with &agr;-MHC mutants carrying delE933 or R721W. In addition to the sarcomere impairments, delE933 &agr;-MHC exhibited electrophysiological abnormalities both in vitro and in vivo. The atrial cardiomyocyte cell line HL-1 stably expressing delE933 &agr;-MHC showed a significantly slower conduction velocity on multielectrode array than those of wild-type &agr;-MHC or control plasmid transfected cells. Furthermore, targeted morpholino knockdown of MYH6 in zebrafish significantly reduced the heart rate, which was rescued by coexpressed wild-type human &agr;-MHC but not by delE933 &agr;-MHC. Conclusions—The novel MYH6 mutation delE933 causes both structural damage of the sarcomere and functional impairments on atrial action propagation. This report reinforces the relevance of MYH6 for sinus node function and identifies a novel pathophysiology underlying familial sick sinus syndrome.

Non-Reentrant Fascicular Tachycardia: Clinical and Electrophysiological Characteristics of a Distinct Type of Idiopathic Ventricular Tachycardia.

Background—The most common form of idiopathic Purkinje-related ventricular tachycardia (VT) is the reentrant type. We describe the clinical and electrophysiological characteristics of focal non-reentrant fascicular tachycardia. Methods and Results—Among 530 idiopathic VT patients who were referred for ablation, we identified 15 (2.8%) with non-reentrant fascicular tachycardia (11 men, 45±21 years). Sinus rhythm ECG showed normal conduction intervals with a His–ventricular interval of 41±4 ms. All patients had monomorphic VT (cycle length: 337±88 ms) with a relatively narrow QRS (123±12 ms), and they did not respond to verapamil during the initial presentation. VT exhibited right bundle-branch block/superior axis configuration in 11 patients (73%) and inferior axis in 3 (20%). In 1 patient (7%), VT exhibited left bundle-branch block/superior axis configuration. During ablation, spontaneous VT occurred in 3 patients (20%) and nonentraintable VT or identical premature ventricular complex was induced in 9 (60%). A high-frequency presystolic Purkinje potential was recorded during VT/premature ventricular complex, preceding the QRS by 25±16 ms. VT recurrence was observed in 4 patients (27%), and among them, 3 underwent pacemap-guided ablation during the first session. A second ablation with activation mapping guidance eliminated the VT during the 88±8-month follow-up. Conclusions—Among idiopathic VT cases referred for ablation, 2.8% were focal non-reentrant fascicular tachycardia, which had distinct clinical characteristics and usually originated from the left posterior fascicle, and less commonly from the left anterior fascicle and right ventricular Purkinje network. Catheter ablation is effective, whereas pacemap-guided approach is less efficacious.

Epicardial Catheter Ablation of Ventricular Tachycardia in "No Entry" Left Ventricle: Mechanical Aortic and Mitral Valves

Background—In patients with mechanical aortic and mitral valves and left ventricular tachycardia, catheter ablation may be prevented by limited access to the left ventricle. Methods and Results—In our series of 6 patients, 2 patients underwent direct surgical ablation and 4 underwent epicardial catheter ablation via a pericardial window. All patients had abnormal low voltage areas with fractionated or delayed isolated potentials on the apical epicardium. Most of the ventricular tachycardias were targeted by pace mapping. Sites with a good pace match or abnormal electrograms were ablated using an irrigated radiofrequency ablation catheter. A microscopic pathological evaluation of the resected tissue from 2 of the open-heart ablation patients revealed dense fibrosis on the epicardium compared with the endocardium, supporting the feasibility of an epicardial ablation for the ventricular tachycardia. Conclusions—Epicardial catheter ablation of ventricular tachycardia is a potentially useful therapy in patients who have mechanical aortic and mitral valves.

Implications of right ventricular septal pacing for medium-term prognosis: Propensity-matched analysis

BACKGROUND The effect of right ventricular (RV) septal pacing as opposed to RV apical pacing on prognosis in patients undergoing pacemaker implantation remains controversial. This study was performed to examine the clinical efficacy of RV septal pacing in a large cohort with medium-term follow-up and propensity-matched analysis. METHODS A total of 982 consecutive patients with first pacemaker implantation between 2008 and 2013 at two centers in Japan (51.4% male, age 76.1±10.6years, 64.3% septal pacing, 94% preserved ejection fraction [EF]) were enrolled. Propensity matching successfully matched 446 patients into RV septal and apical pacing groups. The primary endpoint, a combination of all-cause death and hospitalization due to heart failure, was compared between the two groups. RESULTS In the propensity-matched cohort, the primary endpoint was observed in 61 patients (13.7%) over a median follow-up period of 2.1years (interquartile range, 1.1-3.5years). The effects of septal pacing on prognosis were not statistically significant (hazard ratio [HR]=1.10, 95% confidence interval [CI]=0.60-2.04, P=0.752). No significant benefit of septal pacing was observed on all-cause death (HR=1.86, 95%CI=0.74-4.66, P=0.187) and heart failure hospitalization (HR=0.93, 95%CI=0.44-1.98, P=0.847) when assessed separately. CONCLUSION Septal pacing did not show medium-term advantages in prognosis in this large-scale retrospective cohort study with propensity matching of patients with predominantly preserved EF.

Fascicular Ventricular Tachycardia Originating From Papillary Muscles

Background— Verapamil-sensitive fascicular ventricular tachycardia (FVT) has been demonstrated to be a reentrant mechanism using the Purkinje network as a part of its reentrant circuit. Although the papillary muscles (PMs) are implicated in arrhythmogenic structure, reentrant FVT originating from the PMs has not been well defined. Methods and Results— We studied 13 patients in whom FVT was successfully eliminated by ablation at the posterior PMs (n=8; PPM-FVT) and anterior PMs (n=5; APM-FVT). Although intravenous administration of verapamil (5 mg) terminated ventricular tachycardia (VT) in 6 patients, VT was only slowed in the remaining 7 patients. PPM-FVT exhibited right bundle branch block and superior right axis (extreme right axis) or horizontal axis deviation. APM-FVT exhibited right bundle branch block configuration and right axis deviation with deep S wave in leads I, V5, and V6. VT was reproducibly induced by programmed atrial or ventricular stimulation. His-ventricular interval during VT was shorter than that during sinus rhythm. Ablation at the left posterior or anterior fascicular regions often changed the QRS morphology but did not completely eliminate it. Mid-diastolic Purkinje potentials were recorded during VT around the PMs, where ablation successfully eliminated the tachycardia. All patients have been free from recurrent VT after ablation. Conclusions— Reentrant circuit of verapamil-sensitive FVT can involve the Purkinje network lying around the PMs. PM-FVT is a distinct entity that is characterized by distinctive electrocardiographic characteristics and less sensitivity to verapamil administration compared with common type FVT. Ablation targeting the mid-diastolic Purkinje potentials around the PMs during tachycardia can be effective in suppressing this arrhythmia.

Kaplan-Meier survival analysis and Cox regression analyses regarding right ventricular septal pacing: Data from Japanese pacemaker cohort.

The presented data were obtained from 982 consecutive patients receiving their first pacemaker implantation with right ventricular (RV) lead placement between January 2008 and December 2013 at two centers in Japan. Patients were divided into RV apical and septal pacing groups. Data of Kaplan–Meier survival analysis and Cox regression analysis are presented. Refer to the research article “Implications of right ventricular septal pacing for medium-term prognosis: propensity-matched analysis” (Mizukami et al., in press) [1] for further interpretation and discussion.

Conversion to Purkinje-Related Monomorphic Ventricular Tachycardia After Ablation of Ventricular Fibrillation in Ischemic Heart Disease

Background—Catheter ablation is an effective therapy for ventricular fibrillation (VF) arising from the Purkinje system in ischemic heart disease. However, some patients experience newly emergent monomorphic ventricular tachycardia (VT) after the ablation of VF. We evaluated the prevalence and mechanism of monomorphic VT after VF ablation. Methods and Results—Twenty-one consecutive patients with primary VF because of ischemic heart disease who underwent catheter ablation were retrospectively analyzed. Twenty of 21 patients were in electrical storm. Ventricular premature contractions triggering VF arose from the left Purkinje system and were targeted for ablation. Before the ablation, 14 of 21 patients had only VF, and the other 7 had VF and concomitant monomorphic VT. Four of the 14 patients with only VF (29%) exhibited newly emergent monomorphic VT after VF ablation. Three of these patients had Purkinje-related VTs, which were successfully eliminated by the ablation of a Purkinje network located in the same low-voltage area as the site of prior successful VF ablation. During a median follow-up of 28 months (interquartile range, 16–68 months), VF recurred in 6 of 21 patients (29%); however, there were neither electrical storms nor monomorphic VT, and all recurring arrhythmias were controlled by medical therapy alone. Conclusions—Over one fifth of patients with primary ischemic VF experienced newly emergent Purkinje-related monomorphic VT after VF ablation. The circuit of the monomorphic VT associated with the Purkinje network was located in the same low-voltage area as the Purkinje tissue that triggered VF and could be suppressed by additional ablation.

New Substrate-Guided Method of Predicting Slow Conducting Isthmuses of Ventricular Tachycardia: Preliminary Analysis to the Combined Use of Voltage Limit Adjustment and Fast-Fourier Transform Analysis

Background: Several conducting channels of ventricular tachycardia (VT) can be identified using voltage limit adjustment (VLA) of substrate mapping. However, the sensitivity or specificity to predict a VT isthmus is not high by using VLA alone. This study aimed to evaluate the efficacy of the combined use of VLA and fast-Fourier transform analysis to predict VT isthmuses. Methods and Results: VLA and fast-Fourier transform analyses of local ventricular bipolar electrograms during sinus rhythm were performed in 9 postinfarction patients who underwent catheter ablation for a total of 13 monomorphic VTs. Relatively higher voltage areas on an electroanatomical map were defined as high voltage channels (HVCs), and relatively higher fast-Fourier transform areas were defined as high-frequency channels (HFCs). HVCs were classified into full or partial HVCs (the entire or >30% of HVC can be detectable, respectively). Twelve full HVCs were identified in 7 of 9 patients. HFCs were located on 7 of 12 full HVCs. Five VT isthmuses (71%) were included in the 7 full HVC+/HFC+ sites, whereas no VT isthmus was found in the 5 full HVC+/HFC− sites. HFCs were identical to 9 of 16 partial HVCs. Eight VT isthmuses (89%) were included in the 9 partial HVC+/HFC+ sites, whereas no VT isthmus was found in the 7 partial HVC+/HFC− sites. All HVC+/HFC+ sites predicted VT isthmus with a sensitivity of 100% and a specificity of 80%. Conclusions: Combined use of VLA and fast-Fourier transform analysis may be a useful method to detect VT isthmuses.

Nonreentrant proximal fascicular ventricular tachycardia, with normal QRS duration and normal axis, originating from a region remote from the His bundle

Introduction Nonreentrant fascicular ventricular tachycardia (VT) is a rare type of idiopathic VT that often presents with relatively narrow QRS and left (LBBB) or right (RBBB) bundle branch block patterns. Unlike reentrant fascicular VT, it is usually not responsive to verapamil; however, it is responsive to lidocaine and b-blocker treatment. Catheter ablation, targeting the earliest Purkinje potential, is often effective at eliminating the VT. In the present case, tachycardia with a normal QRS duration and a normal axis was proven to be nonreentrant fascicular VT. The VT was successfully suppressed using catheter ablation at a site remote from the His bundle.