Interaction of left ventricular size with the outcome of cardiac resynchronization therapy in Japanese patients.

BACKGROUND: We analyzed the influence of the QRS duration (QRSd) to LV end-diastolic volume (LVEDV) ratio on cardiac resynchronization therapy (CRT) outcomes in heart failure patients classified as III/IV per the New York Heart Association (NYHA) and with small body size. HYPOTHESIS: We proposed the hypothesis that the QRSd/LV size ratio is a better index of the CRT substrate. METHODS: We enrolled 114 patients with advanced heart failure (NYHA class III/IV, and LV ejection fraction >35%) who received a CRT device, including those with left bundle branch block (LBBB) and QRSd ≥120 milliseconds (n = 60), non-LBBB and QRSd ≥150 milliseconds (n = 30) and non-LBBB and QRSd of 120-149 milliseconds (n = 24). RESULTS: Over a mean follow-up period of 65 ± 58 months, the incidence of the primary endpoint, a composite of all-cause death and hospitalization for heart failure, showed no significant intergroup difference (43.3% vs. 50.0% vs. 37.5%, respectively, p = .72). Similarly, among 104 patients with QRSd/LVEDV ≥ 0.67 (n = 54) and QRSd/LVEDV < 0.67 (n = 52), no significant differences were observed in the incidence of the primary endpoint (35.1% vs. 51.9%, p = .49). Nevertheless, patients with QRSd/LVEDV ≥ 0.67 showed better survival than those with QRSd/LVEDV < 0.67 (14.8% vs. 34.6%, p = .0024). CONCLUSION: Advanced HF patients with a higher QRSd/LVEDV ratio showed better survival in this small-body-size population. Thus, the risk is concentrated among those with a larger QRSd, and patients with a relatively smaller left ventricular size appeared to benefit from CRT.

Right ventricular systolic function as a predictor of appropriate ICD therapy.

BACKGROUND: Recent studies have shown that right ventricular dysfunction is associated with a significantly increased risk of sudden cardiac death. The purpose of this study was to evaluate the association of the right ventricular fractional area change (RVFAC) and appropriate implantable cardioverter-defibrillator (ICD) therapy to determine the cutoff value of the RVFAC. METHODS: Consecutive patients who underwent initial ICD implantations except those with hypertrophic cardiomyopathy, Brugada syndrome, and long QT syndrome were retrospectively enrolled. The primary endpoint was defined as any appropriate ICD therapy. The right ventricular dimensions and function on transthoracic echocardiography were measured for analysis. RESULTS: In total, 172 patients (60.3 ± 13.6 years, 131 males) were enrolled. Ninety patients received an ICD as a secondary prophylaxis. The mean LV ejection fraction and RVFAC were 38.3 ± 14.3% and 35.8 ± 8.8%, respectively. Regarding appropriate ICD therapy events, the best cutoff value of the RVFAC was 34.8%, while 74 patients had an RVFAC < 34.8%. Regarding the primary endpoint, the hazard ratio of a low RVFAC was 2.73 (95% CI 1.46-5.12, P < 0.01). In the multivariate analysis, a low RVFAC was an independent predictor of appropriate ICD therapy (HR: 3.40, 95% CI 1.74-6.64, P < 0.01). The secondary prophylactic cohort with a low RVFAC had the highest incidence of appropriate ICD therapy. Among the patients with RV dysfunction, the RVFAC normalized in 39% of patients during follow-up. This recovered RVFAC group had a significantly lower incidence of appropriate ICD therapy than the unrecovered RVFAC group (P = 0.043). CONCLUSION: A low RVFAC might be associated with increased appropriate ICD therapy.

Junctional rhythm during cryoablation for typical atrioventricular nodal reentrant tachycardia.

INTRODUCTION: Cryoablation is being used as an alternative to radiofrequency (RF) ablation for atrioventricular nodal reentrant tachycardia (AVNRT) owing to the lower risk of atrioventricular block (AVB) compared to RF ablation. Junctional rhythm often occurs during successful application of RF ablation for AVNRT. In contrast, junctional rhythm has rarely been reported to occur during cryoablation. This retrospective study evaluated the characteristics of junctional rhythm during cryoablation for typical AVNRT. METHODS AND RESULTS: This retrospective study included 127 patients in whom successful cryoablation of typical AVNRT was performed. Patients diagnosed with atypical AVNRT were excluded. Junctional rhythm appeared during cryofreezing in 22 patients (17.3%). These junctional rhythms appeared due to cryofreezing at the successful site in the early phase within 15 s of commencement of cooling. Transient complete AVB was observed in 10 of 127 patients (7.9%), and it was noted that atrioventricular conduction improved immediately after cooling was stopped in these 10 patients. No junctional rhythm was observed before the appearance of AVB. No recurrence of tachycardia was confirmed in patients in whom junctional rhythm occurred by cryofreezing at the successful site. CONCLUSION: Occurrence of junctional rhythms during cryoablation is not so rare and can be considered a criterion for successful cryofreezing. Furthermore, junctional rhythm may be associated with low risk of recurrent tachycardia.

Antithrombotic Regimen After Percutaneous Left Atrial Appendage Closure　- A Real-World Study.

BACKGROUND: Antithrombotic therapy after left atrial appendage closure (LAAC) in patients at high risk of bleeding remains controversial. We present real-world clinical outcomes of LAAC.Methods and Results: Data from 74 consecutive patients who received LAAC therapy between January 2020 and June 2022 were analyzed. Patients received 1 of 3 antithrombotic therapies according to the bleeding risk category or clinical event. Regimen 1 was based on a prior study, regimen 2 comprised a lower antiplatelet drug dose without dual antiplatelet therapy, and regimen 3 was antiplatelet drug administration for as long as possible to patients with uncontrollable bleeding who were required to stop anticoagulant drugs. Overall, 73 (98.6%) procedures were successful. Of them, 16 (21.9%) patients were selected for regimen 1, 46 (63.0%) for regimen 2, and 11 (15.1%) for regimen 3. Device-related thrombosis (13% vs. 0% vs. 0%, P=0.0257) only occurred with regimen 1. There was no difference in major bleeding event rates (6% vs. 2% vs. 9%, P=0.53). CONCLUSIONS: The post-LAAC antithrombotic regimen was modified without major concerns.

Pathophysiological background and prognosis of common atrial flutter in non-elderly patients: Comparison to Atrial Fibrillation.

BACKGROUND: It is unclear whether there is any difference in the background and prognosis between non-elderly patients who undergo catheter ablation of atrial fibrillation (AF) and common atrial flutter (CAFL). PURPOSE: To investigate the difference between the patient background of both CAFL and AF in the non-elderly. METHODS: In 526 consecutive patients who underwent catheter ablation of clinical paroxysmal/persistent CAFL or AF in our hospital, we enrolled only patients under 60 years old. Cases harboring both AFL and AF were excluded. We analyzed the patient characteristics, echocardiographic findings, electrocardiographic (ECG) abnormalities during sinus rhythm, and clinical course after ablation. RESULTS: In total, 196 patients (Cohort 1: 142 males, 156 AF cases) were analyzed. AFL patients were younger than AF patients (47.4 ± 10.6 vs. 50.2 ± 6.4years, p = 0.031) and organic heart disease (OHD) was significantly more common in AFL patients than AF patients (42.5% vs. 11.5%, p<0.001). In 161 patients excluding OHD (Cohort 2), ECG abnormalities were more frequent in AFL than in AF patients (78.3% vs. 39.1%, p = 0.001). There were no significant differences in all-cause death, onset of heart failure, and cerebral strokes. On the other hand, the number of cases that required a pacemaker was significantly higher in the CAFL group than AF group (0.0% vs. 26.1%, p-value <0.001). These results suggested that CAFL may reflect occurrence of any atrial myocardial damage, even if it does not lead to heart failure. CONCLUSIONS: Our present study suggested that CAFL may be associated with a broader atrial myocardial disorder in non-elderly patients.

Peak deflection index as a predictor of a free-wall implantation of contemporary leadless pacemakers.

BACKGROUND: Leadless pacemakers are an effective treatment for bradycardia. However, some cases exhibit pericardial effusions, presumably associated with device implantations on the right ventricular free-wall. The present study was carried out to find the ECG features during ventricular pacing with a Micra, which enabled distinguishing free-wall implantations from septal implantations without using imaging modalities. METHODS: Thirty-one consecutive patients who received Micra implantations in our facility were enrolled. The location of the device in the right ventricle was evaluated using echocardiography or computed tomography in order to determine whether the device was implanted on the septum (Sep group), apex (Apex group), or free-wall (FW group). The differences in the 12-lead ECG during ventricular pacing by the Micra were analyzed between the Sep and FW groups. RESULTS: The body of the Micra was clearly identifiable in 22 patients. The location of the device was classified into Sep in 12 patients, Apex in 4, and FW in 6. The mean age was highest in the FW and lowest in the Sep group (82.7 ± 6.6 vs. 72.8 ± 8.7 years, p = 0.027). The peak deflection index (PDI) was significantly larger in the FW group than Sep/Apex group in lead V1 (Sep: 0.505 ± 0.010, Apex: 0.402 ± 0.052, FW: 0.617 ± 0.043, p = 0.004) and lead V2 (Sep: 0.450 ± 0.066, Apex: 0.409 ± 0.037, FW: 0.521 ± 0.030, p = 0.011), whereas there was no difference in the QRS duration, transitional zone, and QRS notching. CONCLUSION: The PDI in V1 could be useful for predicting implantations of Micra devices on the free-wall and may potentially stratify the risk of postprocedural pericardial effusions.

Advanced atrioventricular block and left bundle branch block in a patient with coronary artery fistula.

Coronary artery fistulas are abnormal vascular conduits, rarely related to atrioventricular conduction abnormalities. We report the case of a 52-year-old woman who presented with dyspnoea on exertion. Her ECG revealed advanced atrioventricular block and left bundle branch block. CT scans confirmed two fistulas, from the conus branch of right coronary artery and from the left anterior descending coronary artery, into the pulmonary artery. The patient underwent pacemaker implantation. To date, only nine patients with different degrees of heart blocks associated with coronary artery fistulas have been reported. Herein, we review and summarise previously reported cases of different degrees of heart blocks associated with coronary artery fistulas.

Nutritional Therapy with Vitamin K1 Is Effective in the Improvement of Vitamin K Status and Bone Turnover Markers in Patients with Severe Motor and Intellectual Disabilities.

We have previously reported that patients with severe motor and intellectual disabilities (SMID) have a high prevalence of vitamin K deficiency both in the liver and bone. Thus, vitamin K therapy for SMID patients should be considered. In the present study, we have studied the efficacy of nutritional therapy with vitamin K1 for improving their vitamin K status and bone metabolism markers in patients with SMID. During the 3-mo period, 19 patients under enteral feeding received vitamin K1 treatment, the dose of which was determined to meet each subject's energy requirement. Biomarkers of vitamin K insufficiency; protein induced by vitamin K absence or antagonist-II (PIVKA-II), undercarboxylated osteocalcin (ucOC), intact osteocalcin (intact OC) and bone turnover markers (tartrate-resistant acid phosphatase-5b: TRACP-5b and bone alkaline phosphatase: BAP) were measured at baseline and post treatment. The ucOC/OC ratio was calculated as a more sensitive index than ucOC for vitamin K status in the bone. After treatment, the median vitamin K intake increased from 66 to 183 µg/d, and serum levels of PIVKA-II and ucOC/OC ratio were significantly decreased. Decrements of serum ucOC level and ucOC/OC ratio were significantly associated with vitamin K intake, indicating that both markers well reflect the dose-dependent vitamin K effects. Serum levels of BAP and TRACP-5b were significantly increased after vitamin K1 therapy. Nutritional therapy with vitamin K1 effectively improved the markers for vitamin K status and bone turnover, and was considered to be a good candidate for treatment in SMID patients.

Estimation of the accessory pathway location of the manifest Wolf-Parkinson-White syndrome using synthesized right-sided chest leads.

PURPOSE: The classification using QRS morphology of V1 lead is a useful simple predictor of accessory pathway location (type A, R or Rs pattern; type B, rS pattern; type C, QS or Qr pattern), but often leads to misdiagnosis of accessory pathway location, especially in types B and C. The synthesized 18-lead electrocardiography (ECG) derived from standard 12-lead ECG can provide virtual waveforms of right-sided chest leads. This study aimed to evaluate the usefulness of the right-sided chest lead ECG for prediction of accessory pathway location. METHODS: This retrospective study included 44 patients in whom successful ablation of manifest Wolff-Parkinson-White (WPW) syndrome was performed. Synthesized ECG waveforms were automatically generated, and ECG data obtained before the procedure. RESULTS: There were 26, 4, and 14 patients with left, right, and septal accessory pathways, respectively. All left accessory pathway cases have type A in V1 and syn-V4R leads. Of the 4 right accessory pathway cases, 2 have type B in V1 and syn-V4R leads. Other 2 of 4 cases have type C. In V1 lead, 5 of 14 septal accessory pathway cases have type C, 7 of 14 cases have type B, and 2 of 14cases have type A. In syn-V4R lead, all 14 septal accessory pathway cases have type C. The QRS morphology of V1 and syn-V4 leads could predict the site of accessory pathway with overall accuracy of 79% and 95%, respectively. CONCLUSIONS: QRS morphology of syn-V4R lead may be useful for predicting accessory pathway location of manifest WPW syndrome.

Gastric and Jejunal Enteral Feeding Differently Affect Vitamin B12 Status in Subjects with Severe Motor and Intellectual Disabilities.

The absorption of vitamin B12 is a complex process involving gastric acid and intrinsic factor as the indispensable components. In this study, we have investigated the effects of the administration site in enteral feeding on vitamin B12 status in subjects with severe motor and intellectual disabilities (SMID). This is a cross-sectional study conducted from January to June 2016. Blood concentrations of vitamin B12, folate, vitamin B6, and homocysteine (Hcy) were measured in a total of 82 subjects (38 men, 44 women). Also, nutrients intake was assessed. Subjects with enteral feeding (EF) had significantly higher intakes of vitamin B12, folate, and vitamin B6 than those with oral ingestion (OI). Serum folate and vitamin B6 concentrations in subjects with EF were significantly higher than those with OI. Among the EF subjects, serum vitamin B12 concentration was significantly higher in those fed with gastric tube than those fed with jejunal tube in spite of similar vitamin B12 intakes. No significant difference was observed between the two groups regarding the circulating concentrations of folate, vitamin B6, or Hcy. Although each administration route has its own benefit, gastric tube is advantageous in the absorption of vitamin B12.

The lysosomal signaling anchor p18/LAMTOR1 controls epidermal development by regulating lysosome-mediated catabolic processes.

The lysosomal adaptor protein p18 is an essential anchor of a scaffolding complex for the mTORC1 and MAPK pathways, which play crucial roles in controlling cell growth and energy homeostasis. To elucidate the in vivo function of the p18-mediated pathway, we conditionally ablated p18 in the mouse epidermis. Mutant mice were born with severe defects in formation of the stratum corneum and died within 12 h after birth due to dehydration caused by loss of skin barrier function. Mutant epidermal cells can grow and differentiate into granular cells, but exhibit functional defects in corneocyte maturation. Electron microscopy identified abnormal immature cells, overlying the mutant granular cells, which accumulated autophagosomes, glycogen granules and dead nuclei. Cell culture analysis showed that loss of p18 attenuated lysosome function, resulting in accumulation of immature lysosomes and autophagosomes. Analyses of lysosome behavior revealed that p18 is required for functional interaction between lysosomes and target organelles including autophagosomes. These findings suggest that p18-mediated pathways control lysosome-mediated catabolic processes, which are crucial for the development of mouse epidermis.