Differences in iron kinetics during cardiac load between patients with atrial fibrillation and those with sinus rhythm.

INTRODUCTION: The prevalence of atrial fibrillation (AF) increases with age. Although most AF cases are caused by irregular electrical impulses near the pulmonary vein, not all elderly individuals develop AF. Moreover, risk factors such as hypertension and diabetes do not always lead to AF, even in severe conditions such as pneumonia. We aimed to examine iron kinetics, including ferritin, in patients with AF and individuals in normal sinus rhythm (NSR) using peripheral blood samples. METHODS: This case-control study included 178atients who visited the outpatient clinic of a cardiovascular and arrhythmia specialist at the National Center for Geriatrics and Gerontology between August and October 2023. Patients with missing iron-related blood tests and those with pacemaker implantation were excluded. Iron parameters (ferritin, free iron, transferrin saturation) were compared between AF (n = 53) and NSR (n = 125) groups. RESULTS: The AF group had higher Log brain natriuretic peptide (BNP) levels, indicating increased cardiac load (AF 2.18 vs NSR 1.53). However, there were no significant differences in iron parameters between the AF and NSR groups. After matching for age, sex, and coronary artery disease, the AF group showed an increasing trend in ferritin and a decreasing trend in free iron with BNP elevation, suggesting chronic inflammation. In contrast, the NSR group showed no significant changes in iron parameters with BNP elevation. CONCLUSION: Patients with AF are more likely to have elevated ferritin levels and decreased free iron levels during cardiac overload. Thus, they are more likely to present with chronic inflammation associated with cardiac overload in AF. Future studies should investigate the mechanisms underlying this phenomenon and its implications for AF treatment.

Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium.

INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia associated with aging. Many known risk factors are associated with AF, but many senior individuals do not develop AF despite having multiple risk factors. This finding suggests that other factors may be involved in AF onset. This study aimed to identify upregulated genes in the peripheral blood and left atrium of patients with AF. These genes may serve as potential biomarkers to predict AF onset risk and its complications. METHODS: Gene expression data was analyzed from blood (n = 3) and left atrial samples (n = 15) of patients with AF and sinus rhythm. We evaluated the significant genes identified using p-value analysis of weighted average difference to confirm their rankings. We created figures for the genes using GeneMANIA and performed a functional analysis using Cytoscape3.10.1. Hub and bottleneck genes were identified based on degree and betweenness centrality. We used RefEx to confirm the organs in which the extracted genes were expressed. Heatmaps and Gene ontology term evaluation were performed to further elucidate the biological functions of the genes. RESULTS: We identified 12 upregulated genes (CAST, ASAH1, MAFB, VCAN, DDIT4, FTL, HEXB, PROS1, BNIP3L, PABPC1, YBX3, and S100A6) in both the blood and left atrium of patients with AF. We analyzed the gene functions using GeneMANIA and Cytoscape. The identified genes were involved in a variety of pathways, including lysosomal function and lipid and sphingolipid catabolism. Next, we investigated whether the 12 identified genes identified were systemically expressed or had high organ specificity. Finally, Reference expression (RefEx) was used to analyze the gene expression levels in various tissues. Four genes; FTL, ASAH1, S100A6, and PABPC1, were highly expressed in the normal heart tissue. Finally, we evaluated the expression levels of the 12 genes in the blood of patients with AF using a heatmap. Our findings suggest that the 12 genes identified in this study, especially the lysosome-related genes (FTL and ASAH1), may be involved in AF pathogenesis. CONCLUSION: Lysosome-related genes may be important to understand the AF pathophysiology and to develop AF-related future studies.

[Generational differences in lifestyle changes among outpatients with cardiovascular disease during the coronavirus disease pandemic].

AIM: The coronavirus disease (COVID-19) pandemic has caused significant disruptions in various aspects of daily life. The Japanese Government declared a state of emergency in April 2020, which resulted in reduced physical activity. This study investigated the impact of these lifestyle changes by generation among outpatients with cardiovascular disease (CVD). METHODS: In autumn 2020, we conducted a questionnaire survey of 1,156 CVD outpatients who visited the Department of Cardiology at our institution. The survey collected data on physical activities and changes in daily behaviors over the course of the COVID-19 pandemic. Participants were classified into 3 age groups: middle-aged (n=114, ≤64 years old), semi-old (n=330, aged 65-74 years old), and old (n=712, ≥75 years old). The number of steps per day and sedentary time per day were compared between autumn 2019 and 2020, over the course of the pandemic. RESULTS: In autumn 2020, the number of steps per day was significantly decreased and sedentary time significantly increased in all age groups compared to the pre-pandemic levels. However, there were no significant differences in the extent of changes in steps per day or sedentary time over the study period across all age groups. Regarding changes in daily behaviors, only the old-age group reported a decline in volunteering and reduced utilization of daycare services. CONCLUSIONS: The COVID-19 pandemic has resulted in changes in daily activities and lifestyles across all age groups. Because lifestyle patterns differ across generations, it may be necessary to implement age-specific interventions and procedures.

Prognostic Significance of Serum Uric Acid and Exercise Capacity in Older Adults Hospitalized for Worsening Cardiovascular Disease.

Elevated serum uric acid (sUA) is associated with the risk of developing cardiovascular disease (CVD). Here, we examined the prognostic significance of sUA and exercise capacity in 411 Japanese adults (age, ≥65; mean, 81 years) hospitalized for worsening CVD. When the patients were stratified by sUA into three groups (<5.3, 5.4-6.9, >7.0 mg/dL), the high-sUA group had a significantly worse peak VO2 and composite endpoint (rehospitalization due to worsening CVD and all-cause mortality) compared with low- and moderate-sUA groups (p < 0.001). When the patients were stratified by sUA into five groups (sUA < 3.9, 4.0-5.9, 6.0-7.9, 8.0-8.9, and >10.0 mg/dL), the incidence of the composite endpoint was significantly higher in the highest sUA group compared with that in the reference group, but only in women. Univariate Cox regression analysis, but not a multivariate analysis, indicated that sUA was significantly associated with the composite endpoint. Although sUA and exercise capacity may have some degree of prognostic significance in older patients with CVD, this significance may differ between men and women.

Exploratory bibliometric analysis and text mining to reveal research trends in cardiac aging.

Objectives: We conducted a text mining analysis of 40 years of literature on cardiac aging from PubMed to investigate the current understanding on cardiac aging and its mechanisms. This study aimed to embody what most researchers consider cardiac aging to be. Methods: We used multiple text mining and machine learning tools to extract important information from a large amount of text. Results: Analysis revealed that the terms most frequently associated with cardiac aging include "diastolic," "hypertrophy," "fibrosis," "apoptosis," "mitochondrial," "oxidative," and "autophagy." These terms suggest that cardiac aging is characterized by mitochondrial dysfunction, oxidative stress, and impairment of autophagy, especially mitophagy. We also revealed an increase in the frequency of occurrence of "autophagy" in recent years, suggesting that research on autophagy has made a breakthrough in the field of cardiac aging. Additionally, the frequency of occurrence of "mitophagy" has increased significantly since 2019, suggesting that mitophagy is an important factor in cardiac aging. Conclusions: Cardiac aging is a complex process that involves mitochondrial dysfunction, oxidative stress, and impairment of autophagy, especially mitophagy. Further research is warranted to elucidate the mechanisms of cardiac aging and develop strategies to mitigate its detrimental effects.

Evolution of a Large Language Model for Preoperative Assessment Based on the Japanese Circulation Society 2022 Guideline on Perioperative Cardiovascular Assessment and Management for Non-Cardiac Surgery.

Background: The Japanese Circulation Society 2022 Guideline on Perioperative Cardiovascular Assessment and Management for Non-Cardiac Surgery standardizes preoperative cardiovascular assessments. The present study investigated the efficacy of a large language model (LLM) in providing accurate responses meeting the JCS 2022 Guideline. Methods and Results: Data on consultation requests, physicians' cardiovascular records, and patients' response content were analyzed. Virtual scenarios were created using real-world clinical data, and a LLM was then consulted for such scenarios. Conclusions: Google BARD could accurately provide responses in accordance with the JCS 2022 Guideline in low-risk cases. Google Gemini has significantly improved its accuracy in intermediate- and high-risk cases.

Randomized Controlled Trial of Cardiac Rehabilitation Using the Balance Exercise Assist Robot in Older Adults with Cardiovascular Disease.

BACKGROUND: Recent studies have investigated the effects of exercise on the functional capacity of older adults; training with a balance exercise assist robot (BEAR) effectively improves posture. This study compared the clinical safety and efficacy of training using BEAR video games to conventional resistance training in older adults with cardiovascular disease (CVD). METHODS: Ninety patients (mean age: 78 years) hospitalized due to worsening CVD were randomized to cardiac rehabilitation (CR) Group R (conventional resistance training) or Group B (training using BEAR). After appropriate therapy, patients underwent laboratory testing and functional evaluation using the timed up-and-go test (TUG), short physical performance battery (SPPB), and functional independence measure (FIM) just before discharge and 4 months after CR. The rates of CVD readmission, cardiac death, and fall-related fractures were monitored. RESULTS: BEAR had no adverse effects during exercise. At 4 months, TUG and SPPB improved significantly in both groups, with no significant difference between them. FIM motor and the Geriatric Nutritional Risk Index were significantly improved in Group B versus Group R. There was no significant difference in cardiac events and fall-related fractures between the two groups. CONCLUSION: CR with BEAR is safe and comparable to conventional resistance training for improving balance in older adults with CVD.

Transcriptome Discovery of Genes in the Three Phases of Autophagy That Are Upregulated During Atrial Fibrillation.

Background: Autophagy may contribute to the maintenance of atrial fibrillation (AF), but no previous study has concurrently surveyed all 3 phases of autophagy, namely autophagosome formation, lysosome formation, and autophagosome-lysosome fusion. Here we aimed to identify disorders involving various phases of autophagy during AF. Methods and Results: We used bioinformatic techniques to analyze publicly available DNA microarray datasets from the left atrium (LA) and right atrium (RA) of 7 patients with AF and 6 patients with normal sinus rhythm who underwent valvular surgeries. We compared gene expression levels in the LA (AF-LA) and RA of patients with AF with those in the LA and RA of patients with normal sinus rhythm. Several differentially expressed genes in the AF-LA sample were significantly associated with the Gene Ontogeny term 'Autophagy', indicating that the expression of autophagic genes was specifically altered in this dataset. In particular, the expression of genes known or suspected to be involved in autophagosome formation (autophagy related 5 [ATG5], autophagy related 10 [ATG10], autophagy related 12 [ATG12], and light chain 3B [LC3B]), lysosome formation (lysosomal associated membrane protein 1 [LAMP1] and lysosomal associated membrane protein 2 [LAMP2]), and autophagosome-lysosome fusion (synaptosome associated protein 29 [SNAP29], SNAP associated protein [SNAPIN], and syntaxin 17 [STX17]) was significantly upregulated in the LA-AF dataset. Conclusions: Autophagy is activated excessively in, and may perpetuate, AF.

Septal E/e' Ratio Is Associated With Cerebral White Matter Hyperintensity Progression in Young-Old Hypertensive Patients.

Background: The incidence of hypertension increases with age, as does that of brain abnormalities associated with cerebral pathologic and functional degeneration. Little is known about the relationship between hypertension-related cardiac changes and cerebral pathologic degeneration. We examined the relationship between left ventricular (LV) diastolic dysfunction and cerebral white matter hyperintensity (WMH) progression in young-old hypertensive patients. Methods and Results: This single-center prospective longitudinal observational study included 156 individuals aged 65-75 years with well-controlled hypertension, normal LV contraction, and no history of symptomatic heart failure. WMH was quantified on brain magnetic resonance imaging (MRI). The primary outcome was the rate of WMH volume progression between the baseline and follow-up MRI (∆WMH). Participants were classified into tertiles on the basis of ∆WMH (small, medium, and large ∆WMH). The mean (±SD) age at recruitment was 69.6±2.8 years, and the mean follow-up period was 4.6 years. The ratio of early diastolic mitral inflow velocity to early diastolic septal mitral annulus velocity (septal E/e') was significantly higher in the large ∆WMH group than in the small and medium ∆WMH groups. On multiple regression analysis, septal E/e' was significantly positively associated with square-root-transformed ∆WMH (ß=0.457, P<0.001). Conclusions: Septal E/e' was significantly positively associated with the rate of progression of WMH volume, suggesting that LV diastolic dysfunction is associated with the progression of abnormal brain aging.

Bioinformatics analysis of autophagy-lysosomal degradation in cardiac aging.

AIM: Cardiac aging, which causes cardiac diastolic dysfunction, frequently occurs in older people. The role of autophagy in cardiac aging is the subject of intensive research. Autophagy comprises steps called the autophagosome formation and autophagosome-lysosome fusion. Caloric restriction (CR) is the gold standard used to induce autophagosome formation, and autophagosome-lysosome fusion is reduced by aging. However, few studies are available that survey and compare signaling during CR (autophagosome formation induced status) and old (potentially autophagosome-lysosome fusion-reduced status). Here we aimed to identify the rate-limiting step of autophagic disorders during cardiac aging. METHODS: We employed bioinformatics to analyze publicly available DNA microarray datasets. The first dataset compared the hearts of young and old C57BL6 mice (OLD). The second dataset compared the hearts of young C57BL6 mice fed a normal diet with those of young C57BL6 mice subjected to CR. RESULTS: We analyzed OLD-upregulated genes that were significantly associated with the Gene Ontogeny term "Autophagy," indicating that autophagic genes were upregulated in OLD mice. The autophagy-related gene Atg5 and Atg5-related genes were upregulated in OLD and CR mice. The identified hub and bottleneck genes are autophagic autophagosome formation suppressors such as Sirt2, Ilk and Islr, as well as the autophagosome-lysosome fusion inducer Snapin. CONCLUSIONS: Autophagosome formation genes were upregulated in aging mice subjected to CR, indicating that an upregulated autophagosome formation is not a change specific to cardiac aging. However, autophagosome-lysosome fusion genes, particularly the lysosome transportation-related gene Snapin, were downregulated in aging, indicating that autophagosome-lysosome fusion may cause autophagic disorders in cardiac aging. Geriatr Gerontol Int 2021; 21: 108-115.

Nonsustained ventricular tachycardia does not affect the prognosis of neuromuscular diseases: A preliminary and retrospective study.

BACKGROUND: Nonsustained ventricular tachycardia (NSVT) is sometimes observed in patients with neuromuscular diseases (NMDs). The aim of this study was to assess the role of NSVT in the survival prognosis of NMD patients. METHODS: We retrospectively analyzed the patients with NMDs who had undergone Holter ECG recordings at a single center between February and August 2012. Sixty-eight patients were enrolled in this study. The 5 year follow-up was assessed according to the cumulative event-free rate. RESULTS: Twenty-one patients died during the follow-up, seven of whom died by cardiac death. The Kaplan-Meier survival curve that compared the patients with NSVT and those without NSVT indicated the NSVT was not related to the rate of all causes of death or cardiac death in those patients with NMDs. The survival curve was not significantly changed after the adjustment by age and ejection fraction. CONCLUSION: No significant correlations between NSVT and the prognosis in patients with NMDs were found.

Development and Validation of a Novel Cuff-Less Blood Pressure Monitoring Device.

Ordinary cuff-based blood pressure-monitoring devices remain a technical limitation that disturbs activities of daily life. Here we report a novel system for the cuff-less blood pressure estimation (CLB) that requires only 1 sensor for photoplethysmography. The present study is the first report to validate and assess the clinical application of the CLB in accordance with the latest wearable device standard (issued by the Institute of Electrical and Electronics Engineers, standard 1708-2014). Our CLB is expected to offer a flexible and wearable device that permits blood pressure monitoring in more continuous and stress-free settings.

A case of extensive encircling pulmonary vein isolation in a patient with severe scoliosis.

The patient was a 62-year-old man with atrial fibrillation and severe scoliosis. Scoliosis may impair cardiorespiratory function. Enhanced computed tomography (CT) was helpful for the Brockenbrough method. Three-dimensional (3D) mapping also demonstrated clockwise rotation of the heart. We successfully isolated extensive encircling pulmonary vein in this patient using enhanced CT and 3D mapping. The CT venous images revealed appropriate localization of the vein and heart. CT and 3D mapping may ensure a more stable and safer procedure.