Multicenter prospective observational study to clarify the current status and clinical outcome in Japanese patients who have an indication for implantable cardioverter defibrillator (ICD) or wearable cardioverter defibrillator (WCD) (TRANSITION JAPAN-ICD/WCD study): Rationale and design of a prospective, multicenter, observational, comparative study.

Background: Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients. Methods: We are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all-cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints. Results: Not applicable. Conclusion: This study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.

Trend in Age at the Initial Pacemaker Implantation in Patients With Bradyarrhythmia　- A 50-Year Analysis (1970-2019) in Japan.

BACKGROUND: This study investigated whether the age of patients undergoing pacemaker implantation is increasing.Methods and Results: This study retrospectively reviewed the consecutive cases of 3,582 patients who underwent an initial pacemaker implantation at our hospitals because of symptomatic bradyarrhythmias between 1970 and 2019. The exclusion criteria were: patients with AV block due to cardiac surgery or AV junction ablation, and patients aged <20 years. The patients were divided into 5×10-year groups: those treated in the 1970s (1970-1979), 1980s (1980-1989), 1990s (1990-1999), 2000s (2000-2009), and 2010s (2010-2019). A total of 3,395 patients satisfied the study criteria. The average age at which the patients underwent a first pacemaker implantation increased across the 10-year periods: 63.7±13.2 years in the 1970s, 66.2±12.6 years (1980s), 69.1±12.4 years (1990s), 72.0±11.1 years (2000s), and 75.8±10.0 years (2010s) and advanced significantly in the 1990s, 2000s, and 2010s compared to the 1970s (all P<0.001). The ratio of patients aged ≥80 and ≥90 years increased from 10.6% and 0% in the 1970 s to 38.2% (P<0.001) and 5.2% (P= 0.017) in the 2010s, respectively. CONCLUSIONS: The average age at initial pacemaker implantation increased by 12.1 years over the last 50 years in Japan. In particular, the ratios of ≥80 and ≥90 years as the patients age increased significantly.

A Case of J Wave Syndrome Due to Severe Hypercalcemia with Ventricular Fibrillation Storm and Successful Treatment of Isoproterenol Infusion.

A case of J wave syndrome with ventricular fibrillation (VF) storm and severe hypercalcemia due to primary hyperparathyroidism is presented. VF storm subsided with an isoproterenol infusion. Prominent J waves and a Brugada-like electrocardiogram pattern disappeared after parathyroidectomy. Ventricular tachyarrhythmia was not induced during an electrophysiological study. The patient remained asymptomatic up to the 12-month follow-up.

Deep insight into cardiac dysfunction in children and young adults with Wolff-Parkinson-White syndrome using speckle tracking imaging.

Although ventricular pre-excitation via accessory pathways (APs) causes cardiac dysfunction in children and young adults with Wolff-Parkinson-White (WPW) syndrome, the underlying cardiac dysfunction mechanisms are unclear. This study aimed to characterize cardiac dysfunction and clarify sensitive cardiac dysfunction indicators in WPW syndrome patients classified by the APs location with a layer-specific strain analysis. Twenty-four patients with WPW syndrome with a mean age of 14.1 years (6.9-21.6 years) (11 cases: type A with a left-sided AP [WA group], 13 cases: type B with a right-sided AP [WB group]), and 37 age-matched normal controls (N group) were examined. We measured the left ventricle (LV), base-, mid-, and apical-level of circumferential strain (CS), and longitudinal strain (LS) using a layer-specific strain with speckle tracking imaging. Dyssynchrony was also measured based on the timing of the radial strain at each segment. Peak endomyocardial base- and mid-level of CS was lower in both the WA and WB groups compared to the N group. Peak mid-myocardial and epimyocardial base-level of CS and peak mid-myocardial mid-level of CS were lower only in the WB group compared to the N group. Peak LS in all three layers was lower only in the WB group compared to the N group. There was a significant difference between the patient and normal groups for the dyssynchrony index only at the base-level, and there was no significant difference between the groups for LV ejection fraction (EF). Layer-specific strain decreased in more sites in the WB group despite the normal EF value. Layer-specific strains are sensitive indicators for the detection of the early stages of cardiac dysfunction.

The association between impairment of HDL cholesterol efflux capacity and atrial remodeling in atrial fibrillation.

This cross-sectional study enrolled 202 patients with atrial fibrillation (AF) who had undergone catheter ablation and evaluated the association between high-density lipoprotein (HDL) functionality, cholesterol efflux capacity (CEC) of HDL, and the pathophysiology of left atrial structural remodeling. Participants were divided into two groups, based on their left atrial volume index (LAVI) (< 34 mL/m2, n = 60 vs. LAVI ≥ 34 mL/m2, n = 142). We quantified three types of HDL CECs by the presence or absence of cyclic-AMP, as entire, and CEC dependent or not dependent on ATP binding cassette transporter A1 (ABCA1) and termed them Global CEC, ABCA1 CEC, and Non-ABCA1 CEC, respectively. Consequently, Global and Non-ABCA1 CECs were significantly impaired in patients with an enlarged LA (Global CEC: p = 0.039, Non-ABCA1 CEC: p = 0.022). Logistic regression analyses demonstrated that Non-ABCA1 CEC was significantly associated with an enlarged LA after adjusting for the conventional risk factors of AF. Furthermore, the association of higher Non-ABCA1 CEC with an enlarged LA was independent of serum levels of HDL cholesterol and serum myeloperoxidase (Odds ratio of 1 standard deviation higher: 0.64, 95% confidence interval: 0.43-0.95, p = 0.027). The findings of this study indicate the potential contribution of reduced Non-ABCA1 CEC in HDL to the pathophysiology in left atrial structural remodeling of patients with AF.

Enhanced monocyte migratory activity in the pathogenesis of structural remodeling in atrial fibrillation.

BACKGROUND AND AIMS: Pathophysiological roles of monocytes in atrial fibrillation (AF), particularly for the progression of structural remodeling of the left atrium (LA), remain elusive. This study examined the association between the characteristics of circulating and local monocytes and extent of structural remodeling in LA, gauged by LA size, in AF patients. METHODS: First, 161 AF patients who were referred for catheter ablation were enrolled and divided into two groups according to the median of LA diameter (≤39 mm: normal LA group, >39 mm: enlarged LA group). As a control group, 22 patients underwent catheter ablation for paroxysmal supraventricular tachycardia (PSVT) without history of AF were analyzed. Blood samples were collected for flow cytometric analyses to evaluate monocyte subsets based on the levels of CD14 and CD16. Moreover, monocytes were isolated from blood to measure CC chemokine receptor 2 (CCR2) transcripts and protein levels, and migratory activity toward monocyte chemoattractant protein 1 (MCP-1). Second, to characterize the local monocytes in the atrial wall in AF, the resected left atrial appendages (LAA) in AF patients underwent cardiac surgery were histologically evaluated (n = 20). RESULTS: The proportions of monocyte subsets based on CD14 and CD16 expressions were not significantly different between the normal and enlarged LA group. Both transcripts and total protein levels of CCR2 in monocytes were higher in the enlarged LA group compared to those in the normal LA group. In the enlarged LA group, monocytes exhibited more enhanced migratory activity than the normal LA group. Moreover, we found a significantly higher number of CCR2-positive monocytes/macrophages in the LAA in the enlarged LA group. CONCLUSION: Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.

Stability of intrinsic rhythm in pacemaker-dependent patients during pacemaker replacement: Can we predict the need for temporary pacing?

BACKGROUND: In pacemaker-dependent patients, the risk of asystole must be managed during device replacement. This study aimed to examine whether we could predict the indication for temporary pacing (TP) during the generator replacement. METHODS: We studied 105 consecutive patients who underwent pacemaker replacement due to battery depletion at Juntendo Nerima Hospital between September 2005 and December 2016. We examined the relationship between the stability of the intrinsic rhythm (IR) during pacemaker replacement and several clinical factors including age, gender, sick sinus syndrome or atrioventricular (AV) block, duration of pacing, structural heart disease, use of anti-arrhythmic drugs, and the presence/absence of a stable IR (>40 bpm) at the outpatient clinic (OPC) just before pacemaker replacement. RESULTS: Of the 105 patients, we excluded 1 patient who required TP because of bradycardia-dependent torsades de points. Therefore, we evaluated 104 patients for the indication for TP. TP was underwent in 19 patients (18%) because of an absence or instability of the IR during pacemaker replacement. The indication for TP was significantly correlated with AV block (84% vs 48%, P = .0044) and the absence of a stable IR at the last OPC visit (89% vs 24%, P < .0001). For predicting the indication for TP, the following values of no stable IR at the last OPC visit were obtained: 89% sensitivity, 77% specificity, 46% positive predictive value, and 97% negative predictive value. CONCLUSIONS: The presence of a stable IR at the last OPC visit was a good predictor (97%) of no indication for TP during pacemaker replacement.

Left Atrial Appendage Volume and Plasma Docosahexaenoic Acid Levels Are Associated With Atrial Fibrillation Recurrence After Catheter Ablation.

BACKGROUND: Risk factors for atrial fibrillation (AF) recurrence in patients who have undergone AF catheter ablation have not been fully clarified. The objective of this study was to assess whether the left atrium (LA) and LA appendage (LAA) volumes, and cardio-metabolic markers such as polyunsaturated fatty acids (PUFAs) levels were associated with AF recurrence. METHODS: Seventy-seven consecutive patients with AF (mean age, 59 ± 8 years; male, 81%; paroxysmal AF, 64%) undergoing catheter ablation were enrolled. Using contrast-enhanced cardiac multi-detector computed tomography (MDCT) scan, the LA and LAA volume and orifice area were assessed. Radiofrequency ablation was performed by an irrigation catheter, initially targeting the pulmonary veins with a wide area circumferential ablation. RESULTS: Patients with AF recurrence (36%) exhibited both larger LAA volumes and an LAA orifice area than those without AF recurrence, whereas the LA diameter and LA volumes were not significantly different. Notably, AF recurrence occurred in all patients with a large LAA (≥ 25 mL), and the LAA volume was significantly and negatively associated with docosahexaenoic acid (DHA) levels (ß = -0.33, P = 0.003). A multiple regression analysis revealed that the log N-terminal proB-type natriuretic peptide and plasma DHA levels were independent factors for the LAA volume when adjusted for age, AF detected age, left ventricular (LV) ejection fraction, end-systolic LV diameter. CONCLUSIONS: These results suggest that the association between LAA volume and low plasma DHA levels may be an important factor for post-ablation AF recurrence.

A proposal of clinical ECG index "vagal score" for determining the mechanism of paroxysmal atrioventricular block.

BACKGROUND: Paroxysmal atrioventricular block (P-AVB) is a well-known cause of syncope; however, its underlying mechanism is difficult to determine. This study aimed to evaluate a new ECG index, the "vagal score (VS)," to determine the mechanism of P-AVB. METHODS: We evaluated the VS in 20 patients with P-AVB (13 men, 7 women; aged 25-78 years [mean, 59.3 years]). The VS was developed by assigning 1 point each for the following: (1) no AVB or intraventricular conduction disturbance on the baseline ECG, (2) PR prolongation immediately before P-AVB, (3) sinus slowing immediately before P-AVB, (4) initiation of P-AVB by PP prolongation, (5) sinus slowing during ventricular asystole, and (6) resumption of AV conduction with PP shortening, and by assigning -1 point each for (7) the initiation of P-AVB by a premature beat, and (8) resumption of AV conduction by an escape beat. Based on the clinical situations and electrophysiologic findings, we considered the mechanism of P-AVB as vagally mediated or intrinsic conduction disease (ICD). RESULTS: The VS ranged from 5 to -2 points for each patient. Five patients with a definite vagally mediated P-AVB had high VSs (3-5 points). We observed characteristic ECG findings of ICD consisting of changes in AV conduction by an extrasystole and/or escape beat in only 5 of the 6 patients (83%) with a low VS (1 to -2). CONCLUSIONS: The VS is simple and potentially useful for determining the mechanism of P-AVB. P-AVB with a VS ≥3 strongly suggested a vagally mediated mechanism.

Long-term reliability of sweet-tip type screw-in leads.

BACKGROUND: Active fixation leads have provided stable atrial and ventricular pacing; however, long-term follow-up data have not been satisfactory. The purpose of this study was to investigate the long-term reliability of active fixation leads and their electrical characteristic stability. METHODS: A total of 1196 pacing leads were implanted in 830 patients consecutively between 2002 and 2013. In this retrospective study, we were able to trace 1092 leads in 750 patients to investigate the prognosis of implanted leads. The measurement values (including pacing thresholds, sensing amplitudes, and lead impedances of both the atrial and ventricular leads) were obtained from medical records at the time of implantation and during follow up at the outpatient device clinic. All pacing leads were FINELINE II Sterox EZ Leads (Boston Scientific, MN, USA), which are sweet-tip type screw-in active fixation leads, except for the shock leads in patients with implantable cardioverter defibrillator. RESULTS: The mean follow-up period was 51.3±29.2 months (median, 48 months). A total of 1092 leads were implanted in either the atrium (682 leads) or the ventricle (410 leads). Venous access was achieved through cephalic vein cut down (CVC) method (914 leads) or the subclavian vein puncture (SVP) method (178 leads). The overall lead survival rate was 99.6% at both 5 and 10 years. Lead fracture was observed in 4 of 1092 leads (0.37%), all of which were implanted by the SVP method. No lead fracture occurred among patients wherein CVC method was applied (p<0.01). Device-related infection was observed in four patients (0.53%). CONCLUSIONS: The overall reliability and stability of sweet-tip type screw-in leads were satisfactory throughout the long-term follow-up period (median, 4 years). Because it was associated with less lead fractures, cut-down access from the cephalic vein may be recommended as the first-line approach when considering the importance of long-term durability of pacing leads.

Non-uniform distribution of the contraction/extension (C-E) in the left ventricular myocardium related to the myocardial function.

OBJECTIVE: We attempted to disclose the microscopic characteristics of the non-uniform distribution of the contraction and extension (C-E) of the left ventricular (LV) myocardium using a new methodology (echo-dynamography). METHODS: The distributions of the "axial strain rate" (aSR) and the intra-mural velocity in the local areas of the free wall including the posterior wall (PW) and interventricular septum (IVS) were microscopically obtained using echo-dynamography with a high accuracy of 821 µm in the spatial resolution. The results were shown by the color M-mode echocardiogram or curvilinear graph. Subjects were 10 presumably normal volunteers. RESULTS: (1) Both the C-E in the pulsating LV wall showed non-uniformity spatially and time-sequentially. (2) The C-E property was better evaluated by the aSR distribution method rather than the intra-mural velocity distribution method. (3) Two types of non-uniformity of the aSR distribution were observed: i.e. (i) the difference of its (+)SR (contraction: C) or (−)SR (extension: E) was solely the "magnitude"; (ii) the coexistence of both the (+) SR and (−)SR at the same time. (4) The aSR distribution during systole was either "spotted," or "multi-layered," or "toned" distribution, whereas "stratified," "toned," or "alternating" distributions were observed during diastole. (5) The aSR distribution in the longitudinal section plane was varied in the individual areas of the wall even during the same timing. (6) To the mechanical function of the LV, there was a different behavior between the IVS and PW. . CONCLUSIONS: The aSR and its distribution were the major determinants of the C-E property of the LV myocardium. Spatial as well as time-sequential uniformity of either contraction or extension did not exist. The myocardial function changed depending on the assemblage of the aSR distribution, and by the synergistic effect of (+)SR and (-)SR, the non-uniformity itself potentially served to hold the smooth LV mechanical function.

New concept of the contraction-extension property of the left ventricular myocardium.

OBJECTIVES: Using newly developed ultrasonic technology, we attempted to disclose the characteristics of the left ventricular (LV) contraction-extension (C-E) property, which has an important relationship to LV function. METHODS: Strain rate (SR) distribution within the posterior wall and interventricular septum was microscopically measured with a high accuracy of 821µm in spatial resolution by using the phase difference tracking method. The subjects were 10 healthy men (aged 30-50 years). RESULTS: The time course of the SR distribution disclosed the characteristic C-E property, i.e. the contraction started from the apex and propagated toward the base on one hand, and from the epicardial side toward the endocardial side on the other hand. Therefore, the contraction of one area and the extension of another area simultaneously appeared through nearly the whole cardiac cycle, with the contracting part positively extending the latter part and vice versa. The time course of these propagations gave rise to the peristalsis and the bellows action of the LV wall, and both contributed to effective LV function. The LV contraction started coinciding in time with the P wave of the electrocardiogram, and the cardiac cycle was composed of 4 phases, including 2 types of transitional phase, as well as the ejection phase and slow filling phase. The sum of the measurement time duration of either the contraction or the extension process occupied nearly equal duration in normal conditions. CONCLUSION: The newly developed ultrasonic technology revealed that the SR distribution was important in evaluating the C-E property of the LV myocardium. The harmonious succession of the 4 cardiac phases newly identified seemed to be helpful in understanding the mechanism to keep long-lasting pump function of the LV.

Physiological basis and clinical significance of left ventricular suction studied using echo-dynamography.

BACKGROUND: The existence as well as the exact genesis of left ventricular suction during rapid filling phase have been controversial. In the present study, we aimed at resolution of this problem using noninvasive and sophisticated ultrasonic methods. The clinical meaning was also documented. METHODS: Ten healthy male volunteers were examined by 2D echocardiography and echo-dynamography which enables us to obtain detailed instantaneous data of blood flow and wall motion simultaneously from the wide range of the left ventricle. The correlation of blood flow and wall motion was also studied. RESULTS: Rapid ventricular filling was divided into 2 phases which had different physiology. The early half (early rapid filling: ERF) showed the effect which was alike drawing a piston. This was proved by the shape of the velocity of inflow and the basal muscle contraction which actively assisted extension of the relaxed apical and central parts of the left ventricle, giving the negative pressure which causes the ventricular suction. The later half (late rapid filling: LRF) showed the turning of the fundamental flow and the squeezed basal part just like the sphincter in addition to the expansion of the apical and central portions of the left ventricle, and all of these cooperatively augmented the suction effect. CONCLUSION: Ventricular suction does exist to help ventricular filling. Simultaneous appearance of the contraction in the basal part and the relaxation or extension in the apical part during the post-ejection transitional period was made to occur the suction in the LV. And it can be said that the suction appeared in the late stage of systole as the one of the serial systolic phenomena.

Location of flow axis line in the left ventricle and its interaction with local myocardial motion.

BACKGROUND: The interaction between local myocardial motion and blood flow dynamics should be assessed to evaluate left ventricular pump function. METHODS: The contour map of the absolute value of blood flow velocity in the left ventricle (LV) was drawn. The ridgeline of the contour was defined as the "flow axis line". LV wall motion was assessed by the tracing endocardial border in consecutive B-mode images and by myocardial tissue velocity distribution obtained by the optical flow method. RESULTS: The location of the main flow axis line was affected by the local myocardial movement in the short axis direction. The flow axis line method is superior to the previous investigations on two-dimensional blood flow analysis because it considered three-dimensional blood flow. CONCLUSIONS: The flow axis line represents not only intracardiac blood flow structure but also its interaction with the cardiac wall motion.