Kenji Sakata

Pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). While it is known to affect the autonomic nervous system, the relationship between left atrial (LA) remodeling and PVI-mediated neuromodulation remains unclear. We aimed to assess the neuromodulatory effects of PVI using skin sympathetic nerve activity (SKNA). SKNA was recorded one day before and 2–3 days after PVI in 28 paroxysmal AF (PAF) and 33 persistent AF (PerAF) groups. Baseline low frequency to high frequency (LF/HF) ratio was higher in the PAF group (1.23 [interquartile range {IQR}: 0.79–1.76] vs. 0.74 [IQR: 0.49–1.38], p = 0.017). After PVI, the PAF group demonstrated significant reductions in burst amplitude (1.46 [IQR: 1.04–2.84] vs. 1.09 [IQR: 0.78–2.17] μV, p = 0.015) and LF/HF ratio (0.91 [IQR: 0.73–1.52] vs. 0.71 [IQR: 0.48–1.21], p = 0.012), whereas the PerAF group exhibited no such changes. A weak positive correlation was observed between the percentage change in LF/HF ratio and LA volume index in the PAF group (r = 0.572, p = 0.002). PVI significantly decreased SKNA in PAF patients but not in PerAF. LA remodeling may hinder the effectiveness of PVI-mediated neuromodulation.

Tada H, et al. J Lipid Atheroscler. 2025 Jan;14(1):120-127. https://doi.org/10.12997/jla.2025.14.1.120

Kojima N, et al. J Lipid Atheroscler. 2024 Jan;13(1):53-60. https://doi.org/10.12997/jla.2024.13.1.53

Pulmonary arterial hypertension (PAH) remains a disease with poor prognosis; thus, a new mechanism for PAH treatment is necessary. Circulating nerve growth factor receptor (Ngfr)-positive cells in peripheral blood mononuclear cells are associated with disease severity and the prognosis of PAH patients; however, the role of Ngfr in PAH is unknown. In this study, we evaluated the function of Ngfr using Ngfr gene-deletion (Ngfr^−/−) mice. To elucidate the role of Ngfr in pulmonary hypertension (PH), we used Ngfr^−/− mice that were exposed to chronic hypoxic conditions (10% O₂) for 3 weeks. The development of hypoxia-induced PH was accelerated in Ngfr^−/− mice compared to littermate controls. In contrast, the reconstitution of bone marrow (BM) in Ngfr^−/− mice transplanted with wild-type BM cells improved PH. Notably, the exacerbation of PH in Ngfr^−/− mice was accompanied by the upregulation of pulmonary vascular remodeling-related genes in lung tissue. In a hypoxia-induced PH model, Ngfr gene deletion resulted in PH exacerbation. This suggests that Ngfr may be a key molecule involved in the pathogenesis of PAH.

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Pulmonary arterial hypertension (PAH) causes congestive liver due to right heart failure. There are few cases of PAH that lead to liver cirrhosis, and little attention is paid to liver function in PAH patients. However, it is certain that long-term congestion due to right heart failure in PAH causes a gradual exacerbation of liver dysfunction and affects metabolic function. The purpose of this study is to investigate liver fibrosis associated with the severity and prognosis of PAH. This retrospective observational study was included 57 PAH patients and 22 control subjects. PAH patients were assigned to three risk variables according to the simplified risk stratification proposed at the 6thWSPH 2018 after measuring hemodynamic parameters using right heart catheterization, WHO functional class, 6- minutes walking distance (6MWD), and BNP plasma levels. The Fibrosis-4 (FIB4)-index, a liver fibrosis marker, was calculated using the formula: FIB-4 = Age (years) × AST (U/L) / [PLT (10⁹/L) × ALT1/2 (U/L)], and assessed for association with severity of PAH. PAH patients were followed up for 12 years to assess the occurrence of major adverse event, such as death or lung transplantation. Next, adult 8-week-old C57BL/6 mice were exposed to chronic hypoxia (10% O2) or normoxia for 6 weeks. Then, mice were anesthetized and performed right heart catheterization. Liver tissue was collected for histological assessment by Hematoxylin and eosin and Azan staining, and evaluated RNA expression involved in liver fibrosis by real-time PCR. The levels of FIB4-index in intermediate and high risk groups of PAH patients had significantly increased compared to those in control group. In PAH patients, FIB4-index was not obviously correlated with hemodynamic parameters, BNP, or 6MWD. Major adverse events occurred in 18 PAH patients (32%): death in 18 (100%) and lung transplant in none (0%). Kaplan-Meier curves for PAH patients with and without major adverse events were constructed based on a cut-off frequency of 2.001 for FIB4-index. During the 12-years follow-up period, major-event-free survival was significantly better in PAH patients with FIB4-index 2.001 (hazard ratio, 3.3; P=0.038). In a PAH model mice, hemodynamic parameters showed that chronic hypoxia significantly increased the right ventricular systolic pressure. In histological analysis, there was no significantly difference in liver fibrosis in hypoxia or normoxia group. However, the RNA expression such as αSMA and TGFβ1 associated with liver fibrosis in PAH model mice was increased compared to control mice. This study showed that the liver fibrosis gradually progressed subsurfacely with severity of PAH. Even the slight liver dysfunction may affect metabolism and cause exacerbation of PAH, so it might be necessary to pay attention to liver fibrosis as one of the risk factors of PAH. Type of funding sources: None.

Background: Some patients with COVID-19 experienced sudden death due to rapid symptom deterioration. Thus, it is important to predict COVID-19 symptom exacerbation at an early stage prior to increasing severity in patients. Patients with COVID-19 could experience a unique “silent hypoxia” at an early stage of the infection when they are apparently asymptomatic, but with rather low SpO2 (oxygen saturation) levels. In order to continuously monitor SpO2 in daily life, a high-performance wearable device, such as the Apple Watch or Fitbit, has become commercially available to monitor several biometric data including steps, resting heart rate (RHR), physical activity, sleep quality, and estimated oxygen variation (EOV). Objective: This study aimed to test whether EOV measured by the wearable device Fitbit can predict COVID-19 symptom exacerbation. Methods: We recruited patients with COVID-19 from August to November 2020. Patients were asked to wear the Fitbit for 30 days, and biometric data including EOV and RHR were extracted. EOV is a relative physiological measure that reflects users’ SpO2 levels during sleep. We defined a high EOV signal as a patient’s oxygen level exhibiting a significant dip and recovery within the index period, and a high RHR signal as daily RHR exceeding 5 beats per day compared with the minimum RHR of each patient in the study period. We defined successful prediction as the appearance of those signals within 2 days before the onset of the primary outcome. The primary outcome was the composite of deaths of all causes, use of extracorporeal membrane oxygenation, use of mechanical ventilation, oxygenation, and exacerbation of COVID-19 symptoms, irrespective of readmission. We also assessed each outcome individually as secondary outcomes. We made weekly phone calls to discharged patients to check on their symptoms. Results: We enrolled 23 patients with COVID-19 diagnosed by a positive SARS-CoV-2 polymerase chain reaction test. The patients had a mean age of 50.9 (SD 20) years, and 70% (n=16) were female. Each patient wore the Fitbit for 30 days. COVID-19 symptom exacerbation occurred in 6 (26%) patients. We were successful in predicting exacerbation using EOV signals in 4 out of 5 cases (sensitivity=80%, specificity=90%), whereas the sensitivity and specificity of high RHR signals were 50% and 80%, respectively, both lower than those of high EOV signals. Coincidental obstructive sleep apnea syndrome confirmed by polysomnography was detected in 1 patient via consistently high EOV signals. Conclusions: This pilot study successfully detected early COVID-19 symptom exacerbation by measuring EOV, which may help to identify the early signs of COVID-19 exacerbation. Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000041421; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047290

This study explores the association between lifestyle behavior and incident atrial fibrillation (AF) in the general Japanese population. Japanese residents aged ≥40 years undergoing a national health checkup in Kanazawa City were included. We hypothesized that better lifestyle behavior is associated with lower incidence of AF. Lifestyle behavior was evaluated by the total cardiovascular health (CVH) score (0 = poor to 14 = ideal), calculated as the sum of the individual scores on seven modifiable risk factors: smoking status, physical activity, obesity, patterns of eating schedule, blood pressure, total cholesterol, and blood glucose. The association between CVH and incident AF was assessed, adjusting for other factors. A total of 37,523 participants (mean age 72.3 ± 9.6 years, 36.8% men, and mean total CVH score 9 ± 1) were analyzed. During the median follow-up period of 5 years, 703 cases of incident AF were observed. Using a low CVH score as a reference, the upper group (ideal CVH group) had a significantly lower risk of incident AF (hazard ratio [HR] = 0.79, 95% confidence interval 0.65–0.96, p = 0.02), especially among those aged p = 0.02). Thus, ideal CVH is independently associated with a lower risk for incident AF, particularly in younger Japanese individuals (<75 years).

We herein report a case of nonbacterial thrombotic endocarditis (NBTE) in a patient with previously undiagnosed lung cancer. A 62-year-old woman presented to our hospital with multiple cerebral infarctions. There was no evidence of valvular heart disease or vegetations. Whole-leg ultrasonography revealed deep vein thrombosis of the left peroneal vein. We administered direct oral anticoagulants (DOACs) for a presumed diagnosis of paradoxical embolisms caused by patent foramen ovale. Unfortunately, she experienced further embolization and died. At a postmortem examination, she was diagnosed with NBTE and metastatic adenocarcinoma of the lung. Our experience with this patient suggests that DOACs may be an insufficient treatment for NBTE.