Details of a Researcher - SHIRAISHI Yasuyuki

Papers - SHIRAISHI Yasuyuki

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Contemporary clinical characteristics and management patterns in hypertrophic cardiomyopathy: insights from baseline enrolment data in a nationwide prospective Japanese registry.

Kubo T, Sugiura K, Tokita Y, Takano H, Takamisawa I, Takayama M, Doi YL, Minami Y, Shirotani S, Ebato M, Tsujiuchi M, Nabeta T, Inomata T, Kato T, Okamoto R, Dohi K, Takei Y, Chikamori T, Watanabe E, Furugen A, Doi H, Akita K, Maekawa Y, Ogimoto A, Tada N, Yokota T, Ikeda S, Yamaguchi O, Izumiya Y, Shibata A, Takashio S, Tsujita K, Maejima Y, Fujino N, Nomura A, Akasaki Y, Higuchi K, Fujita S, Hoshiga M, Shiraishi Y, Ieda M, Miyamoto Y, Kitaoka H

Heart (British Cardiac Society) 111 ( 18 ) 885 - 892 2025.03

ISSN 1355-6037

Background The Japanese Hypertrophic Cardiomyopathy Registry Study was designed to provide comprehensive, real-world insights into the clinical characteristics and management of hypertrophic cardiomyopathy (HCM) in Japan. Methods This multicentre, prospective study enrolled consecutive patients with HCM from 24 referral hospitals across Japan starting in 2016. The baseline characteristics of 1485 patients enrolled by December 2019 are presented in this analysis. Results The median ages at registration and diagnosis were 69 and 60 years, respectively, with men accounting for 54% of the cohort. Familial HCM was confirmed in 18% of cases. Of the cohort, 36% had hypertrophic obstructive cardiomyopathy (HOCM), while 8% had mid-ventricular obstruction, 14% had apical HCM and 4% were in the end-stage phase. Atrial fibrillation was observed in 27% of patients, though the majority were asymptomatic or had mild symptoms at registration. Adverse outcomes included prior sustained ventricular tachycardia or fibrillation (6%), heart failure requiring hospitalisation (11%) and embolic events (5%). Defibrillator implantation was performed in 11% of patients. Differences in the defibrillator indications for primary prevention in the current three guidelines and status of defibrillator deployment at registration were clarified: the percentages of class IIa recommendation in the whole cohort and of patients with defibrillator implantation in class IIa were 22% and 19% in the Japanese guidelines, 4% and 39% in the European guidelines and 28% and 22% in the American guidelines, respectively. Beta blockers were prescribed to 90% of patients with HOCM, while 51% received cibenzoline. Septal reduction therapies were performed in 22% of patients with HOCM, with 6% undergoing surgical myectomy. Conclusions As the first large-scale, prospective HCM registry in Japan, this study provides valuable baseline data on the clinical characteristics and management of HCM. These findings will help address gaps between current practice and guideline recommendations, improving the care of patients with HCM.

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【がんに関連する心血管病】がん関連静脈血栓症

醍醐恭平, 白石泰之, 家田真樹

臨牀と研究 (大道学館出版部) 102 ( 3 ) 286 - 290 2025.03

ISSN 0021-4965

Cachectic biomarkers as confounders behind the obesity paradox in patients with acute decompensated heart failure.

Miura Y, Higuchi S, Kohno T, Shiraishi Y, Kitamura M, Nagatomo Y, Kawakubo Ichihara Y, Mizuno A, Nakano S, Soejima K, Goda A, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure (WET-HF) Registry Investigators

International journal of obesity (2005) 49 ( 5 ) 888 - 895 2025.01

ISSN 0307-0565

Background: Obesity is a risk factor for heart failure (HF) development but is associated with a lower incidence of mortality in HF patients. This obesity paradox may be confounded by unrecognized comorbidities, including cachexia. Methods: A retrospective assessment was conducted using data from a prospectively recruiting multicenter registry, which included consecutive acute heart failure patients. A low, normal, and high body mass index (BMI) was defined as <20 kg/m2, 20–25 kg/m2, and ≥25 kg/m2, respectively. Cachexia was defined as a combination of BMI < 20 kg/m2 and any biochemical abnormalities including albumin, hemoglobin, or C-reactive protein. Patients with either of the three biochemical abnormalities were categorized as those with cachectic biomarkers. Two-year all-cause, cardiac, and noncardiac mortality were evaluated. Results: This study evaluated 3314 patients (mean BMI, 22 ± 4 kg/m2 [low BMI with cachexia, 828 (25%); low BMI without cachexia, 273 (8%); normal BMI, 1584 (48%); high BMI, 629 (19%)]). Overall, an increase of 1 point in BMI was associated with a decreased incidence of all-cause mortality (adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.90–0.94; p < 0.001). Regardless of the mode of death, the low BMI with cachexia indicated the worst prognosis, while the low BMI without cachexia showed a similar prognosis to the normal BMI. Cachectic biomarkers, which were observed more frequently in the low BMI, predicted a higher incidence of 2-year all-cause mortality across the BMI categories (adjusted HR for the low BMI, 1.90; 95% CI, 1.30–2.77; p = 0.001; adjusted HR for the normal BMI, 1.94; 95% CI, 1.34–2.79; p < 0.001; adjusted HR for the high BMI, 3.60; 95% CI, 1.61–8.08; p = 0.002). Conclusions: BMI could be only a surrogate marker. The cachectic biomarkers may reflect the underlying conditions and contribute to elucidating the obesity paradox. (Figure presented.)

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Electronic Patient-Reported Outcome System Implementation in Outpatient Cardiovascular Care: A Randomized Clinical Trial.

Yamashita S, Katsumata Y, Kohsaka S, Kitakata H, Shiraishi Y, Yamaoka K, Muramoto Y, Ono T, Shoji S, Yagyu K, Oginosawa Y, Kataoka M, Hashimoto M, Ko SBH, Kitagawa Y, Jinzaki M

JAMA network open 8 ( 1 ) e2454084 2025.01

Importance: The integration of patient-reported outcome (PRO) assessments in cardiovascular care has encountered considerable obstacles despite their established clinical relevance. Objective: To assess the impact of a physician- and patient-friendly electronic PRO (ePRO) monitoring system on the quality of cardiovascular care in clinical practice. Design, Setting, and Participants: This open-label, multicenter, pilot randomized clinical trial was phase 2 of a multiphase study that was conducted from October 2022 to October 2023 and focused on the implementation and evaluation of an ePRO monitoring system in outpatient clinics in Japan. During phase 1 (conducted from December 2021 to March 2022), this ePRO monitoring system was developed at a single outpatient center using feedback from patients and physicians. Eligible patients were older than 18 years with a clinical diagnosis of heart failure (HF), atrial fibrillation (AF), or coronary artery disease (CAD). Participants were randomly assigned 1:1 to either the ePRO or control group. Statistical analysis was based on the intention-to-treat approach. Intervention: Patients in the ePRO group were asked to complete the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), Atrial Fibrillation Effect on Quality-of-Life Questionnaire (AFEQT), or Seattle Angina Questionnaire (SAQ) on smart tablets before their clinical examination. Results were reviewed by physicians at each outpatient visit. The control group received usual care consisting of medication management, lifestyle modification, and invasive procedures in accordance with clinical guidelines. Both groups had 5 monthly outpatient visits. Main Outcomes and Measures: Patient satisfaction, quality of information (QOI) provided by physicians, and disease knowledge were assessed using questionnaires (eg, Patient Satisfaction Questionnaire [PSQ]; score range: 5-25, with higher scores indicating greater patient satisfaction) at baseline and the fifth visit, over approximately 4 months. Results: Of the 50 patients included, 48 (median [SD] age, 71.0 [62.3-75.0] years; 28 males [58.3%]) completed follow-up. The prevalence was 56.2% (n = 27) for HF, 75.0% (n = 36) for AF, and 10.4% (n = 5) for CAD. The distribution of PRO measures used was 21 patients (43.8%) for KCCQ-12, 24 (50.0%) for AFEQT, and 3 (6.2%) for SAQ. Compared with the control group, the ePRO group showed significant improvements in mean (SD) PSQ score (0.16 [2.06] vs 1.61 [1.75]; P = .01) and QOI score regarding treatment (-0.12 [0.53] vs 0.35 [0.71]; P = .01). The ePRO group exhibited a greater increase in the PSQ score regarding communication (-0.12 [0.53] vs 0.43 [0.90]; P = .01). Conclusions and Relevance: In this randomized clinical trial, implementation of the ePRO monitoring system significantly enhanced patient-physician communication and the clarity of physicians' explanations about treatment. These findings suggest that the ePRO monitoring system is capable of supporting patient-centered cardiovascular care. Trial Registration: University Hospital Medical Information Network Identifier: UMIN000049251.

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Bleeding risk in East Asian patients with atrial fibrillation: Validation of the DOAC score in a Japanese multicenter registry

Nishiyama T., Kohsaka S., Nakamaru R., Katsumata Y., Kimura T., Ueda I., Shiraishi Y., Ono T., Tanimoto K., Takatsuki S., Ieda M.

Heart Rhythm O2 6 ( 9 ) 1289 - 1295 2025

Background: Bleeding events remain relatively frequent in patients with atrial fibrillation (AF), posing significant clinical challenges in routine patient management. The recently developed direct oral anticoagulant (DOAC) score shows promise in predicting bleeding risk; however, its performance in East Asian patients is not well characterized. Objective: This study aimed to assess the performance of the DOAC score in a contemporary outpatient-based registry of Japanese patients with AF and evaluate potential modifications to enhance its predictive accuracy. Methods: The Keio Interhospital Cardiovascular Studies-Atrial Fibrillation registry is a multicenter prospective database designed according to international standards for newly diagnosed AF. Adjudicated bleeding events were prospectively collected, and we assessed each bleeding risk score's predictive capacity using the C-index and calibration analysis. Performance was evaluated at 1- and 5-year intervals. Results: Among 2101 patients (median age of 70 years; 67.9% men), the overall 1- and 5-year bleeding incidence was 2.1% and 4.7%, respectively. The DOAC score demonstrated acceptable discrimination at 1 year (C-index 0.704, 95% confidence interval [CI] 0.634–0.774), which was maintained over the extended 5-year follow-up (C-index 0.690, 95% CI 0.640–0.741). Calibration analysis showed acceptable performance across validation datasets. Notably, modifying antiplatelet scoring by distinguishing aspirin (2 points) from other antiplatelets (1 point) improved the performance (C-index 0.707, 95% CI 0.637–0.777). Conclusion: The DOAC score proved valuable for long-term bleeding risk assessment in Japanese patients with AF, with enhanced performance through antiplatelet stratification. These findings support its implementation in East Asian populations for individualized clinical decision making.

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Tropheryma whipplei Endocarditis Diagnosed by Tissue 16S rRNA Gene Sequencing: A Case Report

Maeda T., Kohsaka S., Niimi N., Uno S., Uwamino Y., Nagata M., Shiraishi Y., Kishino Y., Ieda M.

Cjc Open 2025

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Global longitudinal strain decline after anthracyclines in a relatively low-risk Japanese breast cancer cohort

Daigo K., Shiraishi Y., Ko S., Katsumata Y., Hayashida T., Hiraide T., Kitakata H., Tsuruta H., Yokoe T., Nagayama A., Seki T., Takahashi M., Kitagawa Y., Itabashi Y., Ieda M., Kataoka M.

Heart and Vessels 2025

ISSN 09108327

Background: Anthracyclines are known to exhibit dose-dependent cardiotoxicity, leading to cancer therapy-related cardiac dysfunction (CTRCD). The significance of routine global longitudinal strain (GLS) measurements remains uncertain in patients at low or moderate risk for cardiotoxicity. This study aimed to investigate the appropriateness of the contemporary CTRCD surveillance strategy in this population. Methods: We prospectively enrolled women with breast cancer undergoing anthracycline-based chemotherapy at Keio University Hospital from April 2018 to November 2023. Cardiotoxicity risk was assessed using the Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) tool. GLS was measured by echocardiography at baseline (T0), completion of anthracyclines (T1), and 6 months (T2) and 12 months (T3) after initiating chemotherapy. CTRCD was defined as a > 15% relative decline in GLS from baseline. Repeated GLS measurements were analyzed using linear mixed models with post-hoc Tukey testing. Results: Fifty-eight patients (mean age 53.8 ± 9.3 years) were included, with 53 (91.3%) classified as low or moderate risk. GLS significantly declined at T2 and returned toward baseline at T3. GLS-based CTRCD was observed in 4 (6.9%), 14 (24.1%), and 4 (6.9%) patients at T1, T2, and T3, respectively. The majority of CTRCD cases showed spontaneous recovery by T3. Persistent CTRCD at T3 was limited to a small number of patients and was significantly associated with higher high-sensitivity cardiac troponin T levels at T1 (area under curve = 0.836; 95% CI, 0.674–0.997), with a Youden index-derived cutoff of 0.016 ng/mL by receiver operating characteristic analysis. Conclusions: In breast cancer patients with low to moderate cardiotoxicity risk, early GLS decline following anthracycline exposure was mostly transient. These findings support current surveillance recommendations and suggest a potential role for troponin in identifying patients at risk for persistent dysfunction.

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Sweat lactate sensor for detecting anaerobic threshold in heart failure: a prospective clinical trial (LacS-001)

Katsumata Y, Muramoto Y, Ishida N, Takemura R, Nagashima K, Ikoma T, Kawamatsu N, Araki M, Goda A, Okawara H, Sawada T, Ichihara Y, Hattori O, Yamaoka K, Seki Y, Ryuzaki T, Ikura H, Nakashima D, Nagura T, Nakamura M, Sato K, Shiraishi Y

Scientific Reports 14 ( 1 ) 18985 2024.12

Research paper (scientific journal), Last author, Accepted

A simple method for determining the anaerobic threshold in patients with heart failure (HF) is needed. This prospective clinical trial (LacS-001) aimed to investigate the safety of a sweat lactate-monitoring sensor and the correlation between lactate threshold in sweat (sLT) and ventilatory threshold (VT). To this end, we recruited 50 patients with HF and New York Heart Association functional classification I–II (mean age: 63.5 years, interquartile range: 58.0–72.0). Incremental exercise tests were conducted while monitoring sweat lactate levels using our sensor. sLT was defined as the first steep increase in lactate levels from baseline. Primary outcome measures were a correlation coefficient of ≥ 0.6 between sLT and VT, similarities as assessed by the Bland–Altman analysis, and standard deviation of the difference within 15 W. A correlation coefficient of 0.651 (95% confidence interval, 0.391–0.815) was achieved in 32/50 cases. The difference between sLT and VT was −4.9 ± 15.0 W. No comparative error was noted in the Bland–Altman plot. No device-related adverse events were reported among the registered patients. Our sweat lactate sensor is safe and accurate for detecting VT in patients with HF in clinical settings, thereby offering valuable additional information for treatment.

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Rapid Reversal of Pulmonary Hypertension by High-Dose Thiamine Supplementation: A Case Report

Moriizumi T., Hiraide T., Momoi M., Shinya Y., Kishino Y., Shiraishi Y., Iai W., Matsumura K., Kohsaka S., Ieda M.

CJC Open 6 ( 12 ) 1534 - 1537 2024.12

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Pulmonary arterial hypertension therapies in patients with obesity hypoventilation syndrome: a case series.

Daigo K, Hiraide T, Momoi M, Shinya Y, Katsumata Y, Kishino Y, Shiraishi Y, Nishiyama T, Kohsaka S, Ieda M

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 21 ( 4 ) 723 - 732 2024.11

ISSN 1550-9389

Obesity hypoventilation syndrome is caused by complex interactions between multiple pathological processes, including diminished respiratory drive and sleep-related breathing alterations, leading to structural and functional respiratory impairment and ultimately, pulmonary hypertension. Because pulmonary hypertension is closely associated with obesity hypoventilation syndrome, thoroughly evaluating its etiology is essential, and individualized treatments must be considered. We describe 2 patients with obesity hypoventilation syndrome exhibiting severe pulmonary hypertension with pulmonary vascular resistance exceeding 5 Wood units; both were classified as Group 1 pulmonary hypertension, ie, pulmonary arterial hypertension. Initially admitted to our hospital complaining of dyspnea, both patients commenced pulmonary arterial hypertension therapies in addition to positive airway pressure therapy and diuretics, improving their hemodynamic status, dyspnea, and exercise capacity, and finally enabling their discharge. These findings suggest that pulmonary arterial hypertension can coexist with obesity hypoventilation syndrome, and pulmonary arterial hypertension therapies, introduced with careful consideration, may provide substantial benefits for select patients.

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Post-Discharge Self-Care Confidence and Performance Levels in Hospitalized Heart Failure Patients.

Himeno Y, Kitakata H, Kohno T, Hashimoto S, Fujisawa D, Shiraishi Y, Nakano N, Hiraide T, Kishino Y, Katsumata Y, Yuasa S, Kohsaka S, Ieda M

Journal of cardiac failure 31 ( 8 ) 1103 - 1114 2024.11

ISSN 1071-9164

Background: Multidisciplinary self-care education plays a critical role in ensuring the high-quality transitional care of patients hospitalized due to heart failure (HF). However, whether confidence concerning self-care during their index hospitalizations would influence their post-discharge self-care performances and long-term outcomes remains uncertain. Methods: We conducted an assessment of 100 consecutive patients with HF who completed self-care questionnaires both during their hospitalizations and 1 year after discharge. Among these patients hospitalized due to HF, self-care confidence was assessed immediately after they completed their pre-discharge education program. One year after the index hospitalization, we evaluated self-care performance by using the European Heart Failure Self-care Behavior Scale. Logistic regression analysis was employed to identify determinants of poor self-care behavior 1 year after the hospitalization. Additionally, the Cox proportional hazards model with adjustment for the Seattle Heart Failure Model was applied to assess their association with 2-year mortality and readmission risk. Results: The enrolled patients predominantly had HF with reduced ejection fraction (43.0%), and approximately half of the patients had experienced a previous hospitalization due to HF (47.0%). The 3 worst-performing aspects of post-discharge self-care behavior (among the 12 items) were appropriate consultation for fatigue (40.0%), weight gain (52.0%) and application of regular exercise (57.0%). After adjustment, low self-care confidence during the index hospitalization was associated with poor post-discharge self-care performance (OR: 1.11, CI: 1.00–1.21). Poor post-discharge self-care behavior was not associated with worse prognoses over a 2-year follow-up (hazard ratio [HR]: 1.82, CI: 0.85–3.86); however, the association was significant in patients with reduced ejection fraction (HR: 4.04, CI: 1.17–13.89) and previous HF hospitalization (HR: 3.66, CI: 1.46–9.13). Conclusions: Post-discharge self-care performance was associated with self-care confidence during the index HF hospitalization. Effective measures that improve pre-discharge confidence levels in self-care should be considered to enhance the quality of transitional care.

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橈骨動脈のシース留置後に血栓性閉塞を起こし抗リン脂質抗体症候群の診断に至った1例

平松卓, 平出貴裕, 白石泰之, 小平真幸, 香坂俊, 家田真樹

日本内科学会関東地方会 (日本内科学会-関東地方会) 699回 7 - 7 2024.10

骨盤内巨大動静脈奇形を合併したCowden症候群の1例

山中隼, 平出貴裕, 白石泰之, 小平真幸, 香坂俊, 家田真樹

日本内科学会関東地方会 (日本内科学会-関東地方会) 699回 6 - 6 2024.10

Time to intravenous diuretic administration in patients hospitalized with heart failure: An observational study.

Shiraishi Y, Kurita Y, Mori H, Ooishi K, Matsukawa M

ESC Heart Failure 11 ( 6 ) 4061 - 4070 2024.08

Research paper (scientific journal), Lead author, Corresponding author, Accepted

Aims: To help establish optimized treatment strategies for congestion in patients with acute heart failure, this study aimed to provide a detailed summary of real-world diuretic use in hospitalized patients with heart failure requiring urgent therapy in Japan. Methods and results: This observational study used a Japanese medical records database to extract data of patients admitted to hospital with a heart failure diagnosis and an intravenous diuretic prescription from the day before admission to 2 days after. Time from hospital visit to first dose, second dose, and maximum dose of intravenous diuretics were determined. Patients were grouped according to whether they received diuretic modification, defined as an intravenous diuretic dose increase or concomitant use of other diuretics. Results: Overall, 1577 patients were included in the study (without diuretic modification, n = 1140 [72.3%]; with diuretic modification, n = 437 [27.7%]). The study population was 49.5% female (n = 780) and the mean age ± standard deviation was 80.1 ± 12.7 years. Intravenous diuretic treatment was received within 1 h of their hospital visit in 43.5% of patients (686/1577) and ≤2 h in 16.4% of patients (258/1577). Among 437 patients with an inadequate response following their first dose, 42.1% received an intravenous dose titration, 56.5% received combination diuretics, and 1.4% received both. Over half of the patients (59.0% [258/437]) with diuretic modification received it after the first 24 h of the hospital visit. The median time from hospital visit to first dose titration was similar to time to first combination diuretic use (18.6 h and 17.0 h, respectively). The mean ± standard deviation duration of intravenous diuretic use was significantly longer for patients with versus without diuretic modification (6.3 ± 5.2 vs. 3.7 ± 3.2 days), and a significantly greater proportion of patients (44.6% [195/437] vs. 35.0% [399/1140]) received repeated intravenous diuretic administration. Other characteristics/outcomes of intravenous diuretic use were similar with versus without diuretic modification, including in-hospital death (15.6% [68/437] vs. 13.9% [159/1140]) and mean ± standard deviation length of hospitalization (21.9 ± 14.7 days vs. 22.1 ± 21.2 days). Conclusions: In Japan, real-world patterns of intravenous diuretic administration for patients with heart failure remains far from the time-sensitive approach recommended in Japanese, European, and United States guidelines.

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Renin-angiotensin system inhibitors for patients with mild or moderate chronic kidney disease and heart failure with mildly reduced or preserved ejection fraction.

Takeuchi S, Kohno T, Goda A, Shiraishi Y, Kitamura M, Nagatomo Y, Takei M, Nomoto M, Soejima K, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure Registry Investigators

International journal of cardiology (International Journal of Cardiology) 409 132190 2024.05

ISSN 0167-5273

Background: Renin-angiotensin system inhibitors (RASI) reduce adverse cardiovascular events in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤40% and mild or moderate chronic kidney disease (CKD). However, RASI administration rate and its association with long-term outcomes in patients with CKD complicated by HF with LVEF >40% remain unclear. Methods: We analyzed 1923 consecutive patients with LVEF >40% registered within the multicenter database for hospitalized HF. We assessed RASI administration rate and its association with all-cause mortality among patients with mild or moderate CKD (estimated glomerular filtration rate [eGFR]: 30–60 mL/min/1.73 m2). Exploratory subgroups included patients grouped by age (<80, ≥80 years), sex, previous HF hospitalization, B-type natriuretic peptide (higher, lower than median), eGFR (30–44, 45–59 mL/min/1.73 m2), systolic blood pressure (<120, ≥120 mmHg), LVEF (41–49, ≥50%), and mineralocorticoid receptor antagonists (MRA) use. Results: Among patients with LVEF >40%, 980 (51.0%) had mild or moderate CKD (age: 81 [74–86] years; male, 52.6%; hypertension, 69.7%; diabetes, 25.9%), and 370 (37.8%) did not receive RASI. RASI use was associated with hypertension, absence of atrial fibrillation, and MRA use. After multivariable adjustments, RASI use was independently associated with lower all-cause mortality over a 2-year median follow-up (hazard ratio: 0.58, 95% confidence interval: 0.43–0.79, P = 0.001), and the mortality rate difference was predominantly due to cardiac death, consistent in all subgroups. Conclusions: Approximately one-third of HF patients with mild or moderate CKD and LVEF >40% were discharged without RASI administration and demonstrated relatively guarded outcomes.

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Supra-normal and mildly reduced ejection fraction in women -An overlooked vulnerable subpopulation in heart failure.

Kawai A, Nagatomo Y, Yukino-Iwashita M, Ikegami Y, Takei M, Goda A, Kohno T, Mizuno A, Kitamura M, Nakano S, Sakamoto M, Shiraishi Y, Kohsaka S, Adachi T, Yoshikawa T, as WET-HF investigators

International journal of cardiology (International Journal of Cardiology) 409 132166 2024.05

ISSN 0167-5273

Background: Recently, patients with supra-normal left ventricular ejection fraction (snEF) are reported to have high risk of adverse outcomes, especially in women. We sought to evaluate sex-related differences in the association between LVEF and long-term outcomes in heart failure (HF) patients. Methods: The multicenter WET-HF Registry enrolled all patients hospitalized for acute decompensated HF (ADHF). We analyzed 3943 patients (age 77 years; 40.1% female) registered from 2006 to 2017. According to LVEF the patients were divided into the 3 groups: HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF) and preserved EF. The primary endpoint was defined as the composite of cardiac death and ADHF rehospitalization after discharge. Results: In HFmrEF, implementation of guideline-directed medical therapy (GDMT) such as the combination of renin-angiotensin-system inhibitor (RASi) and β-blocker at discharge was significantly lower in women than men even after adjustment for covariates (p = 0.007). There were no such sex-related differences in HFrEF. Female sex was associated with higher incidence of the primary endpoint and ADHF rehospitalization after adjustment for covariates exclusively in HFmrEF. Restricted cubic spline analysis demonstrated a U-shaped relationship between LVEF and the hazard ratio of the primary endpoint showing higher event rate in HFmrEF and HFsnEF in women, but such relationship was not observed in men (p for interaction = 0.037). Conclusions: In women, mrEF and snEF were associated with worse long-term outcomes. Additionally, sex-related differences in the GDMT implementation for HFmrEF highlight the need for further exploration, which might lead to creation of sex-specific guidelines to optimize HF management.

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【腫瘍循環器学-新しい学際領域の最新知見-】CTR-CVTの病態と機序　アントラサイクリン心筋症の病態と機序

白石泰之, 北方博規, 家田真樹

日本臨床 ((株)日本臨床社) 82 ( 増刊2 腫瘍循環器学 ) 60 - 66 2024.04

ISSN 0047-1852

Myocardial Injury by COVID-19 Infection Assessed by Cardiovascular Magnetic Resonance Imaging　- A Prospective Multicenter Study.

Kato S, Kitai T, Utsunomiya D, Azuma M, Fukui K, Hagiwara E, Ogura T, Ishibashi Y, Okada T, Kitakata H, Shiraishi Y, Torii S, Ohashi K, Takamatsu K, Yokoyama A, Hirata KI, Matsue Y, Node K

Circulation journal : official journal of the Japanese Circulation Society 88 ( 9 ) 1450 - 1458 2024.03

ISSN 1346-9843

Background: This prospective multicenter study assessed the prevalence of myocardial injury in patients with COVID-19 using cardiac magnetic resonance imaging (CMR). Methods and Results: We prospectively screened 505 patients with moderate to severe COVID-19 disease from 7 hospitals in Japan. Of these patients, 31 (mean [±SD] age 63.5±10.4 years, 23 [74%] male) suspected of myocardial injury, based on elevated serum troponin or B-type natriuretic peptide concentrations either upon admission or 3 months after discharge, underwent CMR 3 months after discharge. The primary endpoint was the presence of myocardial injury, defined by any of the following: (1) contrast enhancement in the left or right ventricle myocardium on late gadolinium enhancement CMR; (2) left or right ventricular dysfunction (defined as <50% and <45%, respectively); and (3) pericardial thickening on contrast enhancement. The mean (±SD) duration between diagnosis and CMR was 117±16 days. The primary endpoint was observed in 13 of 31 individuals (42%), with 8 (26%) satisfying the modified Lake Louise Criteria for the diagnosis of acute myocarditis. Conclusions: This study revealed a high incidence of myocardial injury identified by CMR in patients with moderate to severe COVID-19 and abnormal findings for cardiac biomarkers.

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Rationale and protocol of the LAQUA-HF trial: a factorial randomised controlled trial evaluating the effects of neurohormonal and diuretic agents on health-status reported outcomes in heart failure patients

Shiraishi Y, Ikemura N, Urashima M, Kohno T, Nakano S, Tanaka T, Nagatomo Y, Ikoma T, Ono T, Numasawa Y, Sakamoto M, Nishikawa K, Takei M, Hakuno D, Nakamaru R, Ueda I, Kohsaka S

BMJ open (BMJ Open) 14 ( 2 ) e076519 2024.02

Research paper (scientific journal), Lead author, Accepted

Introduction The current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction to improve prognosis and health status. However, evidence on the optimal sequencing of approved drugs is scarce, highlighting the importance of individualised treatment plans. Registry data indicate that only a portion of these patients can tolerate all four recommended classes, underscoring the need to establish the favoured sequence when using these drugs. Additionally, the choice between long-acting and short-acting loop diuretics in the present era remains uncertain. This is particularly relevant given the frequent use of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor, both of which potentiate natriuretic effects. Methods and analysis In a prospective, randomised, open-label, blinded endpoint method, LAQUA-HF (Long-acting vs short-acting diuretics and neurohormonal Agents on patients' QUAlity-of-life in Heart Failure patients) will be a 2×2 factorial design, with a total of 240 patients randomised to sacubitril/valsartan versus dapagliflozin and torsemide versus furosemide in a 1:1 ratio. Most enrolment sites have participated in an ongoing observational registry for consecutive patients hospitalised for heart failure involved dedicated study coordinators, and used the same framework to enrol patients. The primary endpoint is the change in patients' health status over 6 months, defined by the Kansas City Cardiomyopathy Questionnaire. Additionally, clinical benefit at 6 months defined as a hierarchical composite endpoint will be assessed by the win ratio as the secondary endpoint. Ethics and dissemination The medical ethics committee Keio University in Japan has approved this trial. All participants provide written informed consent prior to study entry. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses. Trial registration number UMIN000045229

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Visually assessing work performance using a smartwatch via day-to-day fluctuations in heart rate variability.

Okawara H, Shiraishi Y, Sato K, Nakamura M, Katsumata Y

Digital health (Digital Health) 10 20552076241239240 2024.01

ISSN 2055-2076

Objective: To optimize workplace health promotion, a simple method for quantifying allostatic load response is needed. This study examines the feasibility of optimizing objective anxiety and presenteeism monitoring using daily smartwatch-measured ultra-short heart rate variability (HRV). Methods: Office workers without diagnosed disease prospectively performed 30 s HRV self-measurement each morning for two months and responded to the State-Trait Anxiety Inventory (STAI) and Work Limitation Questionnaire (WLQ). Logistic regression analysis examined daily HRV parameters in the high-trait anxiety group (HTA, STAI ≥ 40) using mean and variance HRV, age, self-reported gender, and body mass index (BMI). The ideal cutoff value enabled comparison of WLQ using the Mann–Whitney U test. Heart rate variability data were collected for 279 participants (male ratio, 83.9%; age, 42 ± 10 years) who completed questionnaires and monitored HRV for 30+ days. Results: Compared to the low-trait anxiety group, HTA exhibited higher variance of the log-transformed coefficient of component variance of high-frequency component (LnccvHF) and low-frequency per HF (Lnccv L/H), in addition to differences in the means of these HRV parameters. In addition to BMI (odds ratio [OR] = 0.92, p = 0.02) and mean LnccvL/H (OR = 10.75, p < 0.01), the variance of Lnccv L/H was an independent predictor of HTA (OR = 2.39E + 8, p = 0.011). The daily Lnccv L/H dispersion group had a lower WLQ productivity loss score (p = 0.02, r = 0.17). Conclusions: By focusing on HRV dispersion status, this simple and instantly applicable daily HRV monitoring system enables optimized quantitative monitoring of anxiety and productivity.

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