Details of a Researcher - SHIRAISHI Yasuyuki

Papers - SHIRAISHI Yasuyuki

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Conventional medical therapy in heart failure patients eligible for the PARADIGM-HF, DAPA-HF, and SHIFT trials.

Shoji S, Kohsaka S, Shiraishi Y, Kohno T, Sawano M, Ikemura N, Niimi N, Nagatomo Y, Tanaka TD, Takei M, Ono T, Sakamoto M, Nakano S, Nakamura I, Inoue S, Fukuda K, Yoshikawa T

International journal of cardiology (International Journal of Cardiology) 359 76 - 83 2022.04

ISSN 0167-5273

Background: Recent trials on novel heart failure (HF) treatments (angiotensin receptor-neprilysin inhibitor, sodium-glucose cotransporter 2 inhibitor, and ivabradine) emphasize the use of conventional medical therapy (angiotensin-converting enzyme inhibitors, beta-blockers [BB], and mineral corticosteroid receptor antagonists). We aimed to evaluate the prescription rate of conventional medical therapy and its association with long-term outcomes in patients eligible for recent trials. Methods: We examined 1295 consecutive patients with HF with reduced ejection fraction (HFrEF) from a multicenter registry (WET-HF registry). We assessed conventional medical therapy implementation among patients meeting the PARADIGM-HF/DAPA-HF and SHIFT enrollment criteria. We also examined the association between conventional medical therapy use and long-term outcomes within each enrollment criterion. Results: Overall, 62.2% and 35.3% of HFrEF patients met the enrollment criteria of the PARADIGM-HF/DAPA-HF and SHIFT trials. Only 33.9% and 31.9% received full conventional medical therapy within each patient subset. Notably, 84.2% of patients who met the SHIFT enrollment criteria were on BB, and only 23.0% and 4.4% were on ≥50% or the full recommended dose, respectively. Implementation of full conventional medical therapy use was associated with lower 2-year mortality and HF readmission rates in the PARADIGM-HF/ DAPA-HF eligible group (HR 0.68, 95% CI 0.50–0.92). The use of BB at ≥50% of the recommended dose was associated with lower 2-year mortality and HF readmission rates in the SHIFT-eligible group (HR 0.50, 95% CI 0.30–0.84). Conclusions: Conventional medical therapy was underutilized among patients eligible for novel trials within a Japanese HF registry. Further efforts to optimize conventional medical therapy are needed.

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Machine learning models for prediction of adverse events after percutaneous coronary intervention

Niimi N., Shiraishi Y., Sawano M., Ikemura N., Inohara T., Ueda I., Fukuda K., Kohsaka S.

Scientific Reports (Scientific Reports) 12 ( 1 ) 6262 2022.04

An accurate prediction of major adverse events after percutaneous coronary intervention (PCI) improves clinical decisions and specific interventions. To determine whether machine learning (ML) techniques predict peri-PCI adverse events [acute kidney injury (AKI), bleeding, and in-hospital mortality] with better discrimination or calibration than the National Cardiovascular Data Registry (NCDR-CathPCI) risk scores, we developed logistic regression and gradient descent boosting (XGBoost) models for each outcome using data from a prospective, all-comer, multicenter registry that enrolled consecutive coronary artery disease patients undergoing PCI in Japan between 2008 and 2020. The NCDR-CathPCI risk scores demonstrated good discrimination for each outcome (C-statistics of 0.82, 0.76, and 0.95 for AKI, bleeding, and in-hospital mortality) with considerable calibration. Compared with the NCDR-CathPCI risk scores, the XGBoost models modestly improved discrimination for AKI and bleeding (C-statistics of 0.84 in AKI, and 0.79 in bleeding) but not for in-hospital mortality (C-statistics of 0.96). The calibration plot demonstrated that the XGBoost model overestimated the risk for in-hospital mortality in low-risk patients. All of the original NCDR-CathPCI risk scores for adverse periprocedural events showed adequate discrimination and calibration within our cohort. When using the ML-based technique, however, the improvement in the overall risk prediction was minimal.

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Personalized Target Heart Rate for Patients with Heart Failure and Reduced Ejection Fraction

Yumita Y., Nagatomo Y., Takei M., Saji M., Goda A., Kohno T., Nakano S., Nishihata Y., Ikegami Y., Shiraishi Y., Kohsaka S., Adachi T., Yoshikawa T.

Journal of Personalized Medicine (Journal of Personalized Medicine) 12 ( 1 ) 2022.01

ISSN 2075-4426

The optimal heart rate (HR) in patients with heart failure with reduced ejection fraction (HFrEF) has been ill-defined. Recently, a formula was proposed for estimating the target heart rate (THR), which eliminates the overlap between the E and A wave (E-A overlap). We aim to validate its prognostic significance in the multicenter WET-HF registry. This study used data from 647 patients with HFrEF hospitalized for acute decompensated HF (ADHF). The patients were divided into the 2 groups by THR. The primary endpoint was defined as the composite of all-cause death and ADHF readmission. The THR successfully discriminated the incidence of the primary endpoint, whereas no significant difference was observed in the primary endpoint when dividing the patients by uniform cutoff 70 bpm. HR at discharge ≤ THR was inversely associated with the primary endpoint. Restricted cubic spline analysis demonstrated the difference between HR at discharge, and THR (∆HR) from −10 to ±0 was associated with a lower risk of primary endpoint and ∆HR from ±0 to +15 was associated with a higher risk. THR discriminated long-term outcomes in patients with HFrEF more efficiently than the uniform cutoff, suggesting that it may aid in tailored HR reduction strategies.

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Sex differences in sleep and psychological disturbances among patients admitted for cardiovascular diseases

Jono Y., Kohno T., Kohsaka S., Kitakata H., Shiraishi Y., Katsumata Y., Hayashida K., Yuasa S., Takatsuki S., Fukuda K.

Sleep and Breathing (Sleep and Breathing) 26 ( 4 ) 1 - 9 2022

ISSN 15209512

Background: Understanding sex differences is critical for improving outcomes in patients with cardiovascular conditions. Sleep and psychological disturbances contribute to the development and progression of cardiovascular diseases, and important sex differences persist in their incidence and association with clinical outcomes. Methods: Sex-based variation in sleep and psychological disturbances were assessed in consecutive patients with cardiovascular diseases in a single university hospital. The prevalence of insomnia, sleep disordered breathing (SDB), anxiety, and depression was assessed using the Pittsburgh Sleep Quality Index (PSQI), nocturnal pulse oximeter, and the Hospital Anxiety and Depression Scale (HADS). The effect of sex on the prevalence of sleep and psychological disturbances as well as their associations was quantified using multivariate logistic regression models. Results: Among 1,233 patients (mean age 63.6 years, 25% women), women were significantly less likely than men to experience SDB (17.5% vs 31.5%, p < 0.001), but more likely to report an increased burden of insomnia (54.7% vs 43.3%, p = 0.001) and depression (23.9% vs 16.7%, p = 0.004). Insomnia was associated with depression, which was more remarkable among women (p value for interaction: 0.039). SDB was associated with anxiety among women but not men (p value for interaction: 0.003). There was no significant difference in the prevalence of anxiety between women and men. Conclusions: Among patients with cardiovascular disease, women reported an increased burden of insomnia and depression compared to men. The association between sleep and psychological disturbances may be more pronounced in women, suggesting that cardiologists should increase efforts for identification of such comorbidities and administer corresponding treatment, especially in women.

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Impact of Left Ventricular Chamber Size on Outcome in Heart Failure with Preserved Ejection Fraction

Ogawa S., Nagatomo Y., Takei M., Saji M., Goda A., Kohno T., Nakano S., Nishihata Y., Ikegami Y., Shoji S., Shiraishi Y., Kohsaka S., Yoshikawa T.

International Heart Journal (International Heart Journal) 63 ( 1 ) 62 - 72 2022

ISSN 13492365

Although heart failure with preserved ejection fraction (HFpEF) has a highly variable phenotype, heteroge-neity in left ventricular chamber size (LVCS) and its association with long-term outcome have not been thor-oughly investigated. The present study sought to determine the impact of LVCS on clinical outcome in HFpEF. A total of 1505 consecutive HFpEF patients admitted to hospitals in the multicenter WET-HF Registry for acute decompensated HF (ADHF) between 2006 and 2017 were analyzed. The patients (age: 80 [73-86], male: 48%) were divided into larger (L) or smaller (S) LV end-diastolic diameter (LVEDD) groups by the median value 45 mm. Younger age, male sex, higher body mass index, more favorable nutritional status, valvular etiology, and lower LVEF were associated with larger LVEDD. After propensity matching (399 pairs), the L group showed a larger left atrial diameter, E/e’, and tricuspid regurgitation pressure gradient and greater severity of mitral regur-gitation. The L group had a higher rate of composite endpoint of all-cause death and ADHF re-admission (P = 0.021) and was an independent predictor. On the other hand, in the pre-matched cohort, the S group rather showed higher in-hospital (4% versus 2%. P = 0.004) and post-discharge mortality (P = 0.009). In HFpEF, LVCS was affected by demographic and cardiac parameters. After adjustment for demographic parameters, larger LVCS was associated with worse clinical outcome. Higher mortality in the S group in the pre-matched cohort might be related to the demographic factors suggesting frailty and/or sarcopenia.

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Recurrence of myopericarditis following mRNA COVID-19 vaccination in a male adolescent.

Umei TC, Kishino Y, Shiraishi Y, Inohara T, Yuasa S, Fukuda K

CJC open (CJC Open) 4 ( 3 ) 350 - 352 2021.12

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease has spread worldwide, resulting in health and economic crises. Vaccination against SARS-CoV-2 infection is considered a valid prevention measure to control this pandemic. There have been reports of cases of myopericarditis following mRNA COVID-19 vaccination. We present a case of a 20-year-old man with recurrent myopericarditis following an initial episode of influenza virus–induced myopericarditis and after a second dose of the mRNA-1273 Moderna COVID-19 vaccine. Careful attention should be paid to patients with a history of myocarditis following COVID-19 vaccination.

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A novel device for detecting anaerobic threshold using sweat lactate during exercise

Seki Y., Nakashima D., Shiraishi Y., Ryuzaki T., Ikura H., Miura K., Suzuki M., Watanabe T., Nagura T., Matsumato M., Nakamura M., Sato K., Fukuda K., Katsumata Y.

Scientific Reports (Scientific Reports) 11 ( 1 ) 4929 2021.12

The lactate threshold (LT1), which is defined as the first rise in lactate concentration during incremental exercise, has not been non-invasively and conveniently determined in a clinical setting. We aimed to visualize changes in lactate concentration in sweat during exercise using our wearable lactate sensor and investigate the relationship between the lactate threshold (LT1) and ventilatory threshold (VT1). Twenty-three healthy subjects and 42 patients with cardiovascular diseases (CVDs) were enrolled. During exercise, the dynamic changes in lactate values in sweat were visualized in real-time with a sharp continuous increase up to volitional exhaustion and a gradual decrease during the recovery period. The LT1 in sweat was well correlated with the LT1 in blood and the VT1 (r = 0.92 and 0.71, respectively). In addition, the Bland–Altman plot described no bias between the mean values (mean differences: − 4.5 and 2.5 W, respectively). Continuous monitoring of lactate concentrations during exercise can provide additional information for detecting the VT1.

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Temporal trends in tolvaptan use after revision of national heart failure guidelines in Japan

Yamazaki Y, Shiraishi Y, Kohsaka S, Nagatomo Y, Fukuda K, Kohno T, Yoshikawa T

Scientific Reports 11 ( 1 ) 19360 2021.12

Research paper (scientific journal), Accepted

Within no definite diuretic protocol for acute heart failure (AHF) patients and its variation in regional clinical guidelines, the latest national guidelines in Japan commends use of tolvaptan in diuretic-resistant patients. This study aimed to examine trends in tolvaptan usage and associated outcomes of AHF patients requiring hospitalization. Between April, 2018 and October, 2019, 1343 consecutive AHF patients (median 78 [69–85] year-old) were enrolled in a prospective, multicenter registry in Japan. Trends over time in tolvaptan usage, along with the severity of heart failure status based on the Get With The Guideline-Heart Failure [GWTG-HF] risk score, and in-hospital outcomes were investigated. During the study period, tolvaptan usage has increased from 13.0 to 28.7% over time (p for trend = 0.07), and 49.4% started tolvaptan within 3 days after admission. The GWTG-HF risk score in the tolvaptan group has significantly decreased over time, while that in the non-tolvaptan group has unchanged. There were no differences in the in-hospital mortality rate between the patients with and without tolvaptan (6.7% vs. 5.8%). After revision of the Japanese clinical practice guidelines for AHF in March 2018, tolvaptan usage for AHF patients has steadily increased. However, in-hospital outcomes including mortality do not seem to be affected.

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Preferences on advance care planning and end-of-life care in patients hospitalized for heart failure

Kitakata H., Kohno T., Kohsaka S., Fujisawa D., Nakano N., Shiraishi Y., Katsumata Y., Nagatomo Y., Yuasa S., Fukuda K.

ESC Heart Failure (ESC Heart Failure) 8 ( 6 ) 5102 - 5111 2021.12

Aims: Early engagement in advance care planning (ACP) is recommended in heart failure (HF) management. We investigated the preferences of patients with HF regarding ACP and end-of-life (EOL) care, including their desired timing of ACP initiation. Methods and results: Data were collected using a 92-item questionnaire survey, which was directly distributed to hospitalized patients by dedicated physicians and nurses in a university hospital setting. One-hundred eighty-seven patients agreed to participate (response rate: 92.6%), and 171 completed the survey [valid response rate: 84.7%; men: 67.3%; median age: 73.0 (63.0–81.0) years]. Logistic regression analyses were conducted to identify the predictors of positive attitudes towards ACP. Most recognized ACP as important for their care (n = 127, 74.3%), 48.1% stated that ACP should be initiated after repeated HF hospitalizations in the past year, and 29.0% preferred ACP to begin during the first or second HF hospitalization. Only 21.7% of patients had previously engaged in ACP conversations during HF management. Positive attitudes towards ACP were associated with lower depressive symptoms [two-item Patient Health Questionnaire; odds ratio (OR): 0.75, 95% confidence interval (CI): 0.61–0.92, P-value: 0.006], marriage (OR: 2.53, 95% CI: 1.25–5.12, P-value: 0.010), and a high educational level (OR: 2.66, 95% CI: 1.28–5.56, P-value: 0.009), but not with severity of HF (represented by Seattle Heart Failure Model risk score). Regarding EOL care, while ‘Saying what one wants to tell loved ones’ (83.4%), ‘Dying a natural death’ (81.8%), and ‘Being able to stay at one's favorite place’ (75.6%) were the three most important factors for patients, preferences for ‘Receiving sufficient treatment’ (56.5%) and ‘Knowing what to expect about future condition’ (50.3%) were divergent. Conclusions: Despite patients' preferences for ACP conversations, there was a discrepancy between preference and engagement in ACP among patients hospitalized for HF. Patients' preferences regarding EOL care may differ; physicians need to consider the appropriate ACP approach to align with patients' care goals.

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Phenomapping in patients experiencing worsening renal function during hospitalization for acute heart failure

Yagi R., Takei M., Kohsaka S., Shiraishi Y., Ikemura N., Shoji S., Niimi N., Higuchi S., Goda A., Kohno T., Nagatomo Y., Nishihata Y., Sujino Y., Saji M., Ikegami Y., Nakano S., Takahashi T., Fukuda K., Yoshikawa T.

ESC Heart Failure (ESC Heart Failure) 8 ( 6 ) 5192 - 5203 2021.12

Aims: The impact of worsening renal function (WRF) on the prognosis of patients with acute heart failure (AHF) remains controversial. We aimed to identify phenotypically distinct subgroups among individuals with both AHF and WRF using cluster analysis. Methods and results: Overall, the data of 483 patients with both AHF and WRF enrolled in the West Tokyo Heart Failure Registry were analysed. Using cluster analysis, we identified three phenotypically distinct subgroups (phenogroups 1, 2, and 3). We assessed the impact of WRF on the prognosis of each phenogroup by comparing the incidence of composite endpoints, including all-cause death and re-hospitalization due to heart failure, with those of a propensity score-matched, non-WRF control group. Participants in phenogroup 1 (N = 122) were the youngest (69.3 ± 13.7 years), had relatively preserved estimated glomerular filtration rate (eGFR, 70.0 ± 27.7 mL/min/1.73 m2), and reduced left ventricular ejection fraction (LVEF) (41.8 ± 13.7%). Conversely, participants in phenogroup 3 (N = 122) were the oldest (81.7 ± 8.5 years), had the worst eGFR (33.0 ± 20.9 mL/min/1.73 m2), and had preserved LVEF (51.7 ± 14.8%). The characteristics of the participants in phenogroup 2 (N = 239) were between those of phenogroups 1 and 3. The propensity score matching analysis showed that WRF was associated with a higher incidence of composite endpoints in phenogroup 1, whereas this association was not observed in phenogroups 2 and 3. Conclusions: Using cluster analysis, we revealed three phenotypically distinct subgroups of patients with both AHF and WRF. WRF was associated with worse clinical outcomes in the subgroup of younger patients with reduced LVEF and preserved renal function.

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Association of non-invasive positive pressure ventilation with short-term clinical outcomes in patients hospitalized for acute decompensated heart failure

Yukino M., Nagatomo Y., Goda A., Kohno T., Takei M., Nishihata Y., Saji M., Toyosaki Y., Nakano S., Ikegami Y., Shiraishi Y., Kohsaka S., Adachi T., Yoshikawa T.

Journal of Clinical Medicine (Journal of Clinical Medicine) 10 ( 21 ) 2021.11

ISSN 2077-0383

The real-world evidence has been sparse on the impact of non-invasive positive pressure ventilation (NPPV) on the outcomes in acute decompensated heart failure (ADHF) patients. We aim to explore this issue in the prospective multicenter WET-HF registry. Among 3927 patients (77 (67–84) years, male 60%), the NPPV was used in 775 patients (19.7%). The association of NPPV use with in-hospital outcome and length of hospital stay (LOS) was examined by two methods, propensity score (PS) matching and multivariable analysis with adjustment for PS. In these analyses the NPPV group exhibited a lower endotracheal intubation (ETI) rate and a comparable in-hospital mortality, but longer LOS compared to the non-NPPV group. In the stratified analysis, the NPPV group exhibited a significantly lower ETI rate in patients with ischemic etiology, systolic blood pressure (sBP) > 140 mmHg and the Controlling Nutritional Status (CONUT) score ≤ 3, indicating better nutritional status. On the contrary, NPPV use was associated with longer LOS in patients with non-ischemic etiology, sBP < 100 mmHg and CONUT score > 3. In conclusion, NPPV use was associated with a lower incidence of ETI. Particularly, patients with ischemic etiology, high sBP, and better nutritional status might benefit from NPPV use.

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Sudden cardiac death after acute decompensation in heart failure patients: implications of discharge haemoglobin levels

Fukuoka R., Kohsaka S., Shiraishi Y., Sawano M., Abe T., Levy W.C., Nagatomo Y., Nishihata Y., Goda A., Kohno T., Kawamura A., Fukuda K., Yoshikawa T.

ESC Heart Failure (ESC Heart Failure) 8 ( 5 ) 3917 - 3928 2021.10

Aims: Heart failure (HF) patients have a high risk of mortality due to sudden cardiac death (SCD) and non-SCD, including pump failure death (PFD). Anaemia predicts more severe symptomatic burden and higher morbidity, as noted by markedly increased hospitalizations and readmission rates, and mortality, underscoring its importance in HF management. Herein, we aimed to determine whether haemoglobin (Hb) level at discharge affects the mode of death and influences SCD risk prediction. Methods: We evaluated the data of 3020 consecutive acute HF patients from a Japanese prospective multicentre registry. Patients were divided into four groups based on discharge Hb levels. SCD was defined as an unexpected and otherwise unexplained death in a previously stable patient or death due to documented or presumed cardiac arrhythmia without a clear non-cardiovascular cause. The mode of death (SCD, PFD or other cause) was adjudicated by a central committee. Finally, we investigated whether adding Hb level to the Seattle Proportional Risk Model (SPRM; established risk score utilized to estimate ‘proportion’ of SCD among death events) would affect its performance. Results: The mean age of studied patients was 74.3 ± 12.9 years, and 59.8% were male. The mean Hb level was 12.0 ± 2.1 g/dL (61.3% of patients had anaemia defined by World Health Organization criteria). During the 2-year follow-up, 474 deaths (15.7%) occurred, including 93 SCDs (3.1%), 171 PFDs (5.7%) and 210 other deaths (7.0%; predominantly non-cardiac death). Absolute risk of PFD (P < 0.001) or other death (P < 0.001) increased along with the severity of anaemia, whereas the incidence of SCD was low but remained consistent across all four groups (P = 0.440). As a proportion of total deaths in each Hb level group, the contributions from non-SCD increased and from SCD decreased along with anaemia severity (P = 0.007). Adding Hb level to the SPRM improved the overall discrimination (c-index: 0.62 [95% confidence interval (CI) 0.56–0.69] to 0.65 [95% CI 0.59–0.71]), regardless of the baseline ejection fraction (EF) (c-index: 0.64 [95% CI 0.55–0.73] to 0.67 [95% CI 0.58–0.75] for reduced EF and 0.55 [95% CI 0.45–0.66] to 0.61 [95% CI 0.52–0.70] for preserved EF). Conclusions: The discharge Hb level provides information about both absolute and proportional risks for each mode of death in acute HF patients, and the addition of Hb level improves the performance of SPRM by identifying more non-SCD cases. Future ‘proportional’ SCD risk models should incorporate Hb level as a covariate to meet this high performance.

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Different impact of beta-blockers on long-term mortality in heart failure patients with and without chronic obstructive pulmonary disease

Higuchi S., Kohno T., Kohsaka S., Shiraishi Y., Takei M., Goda A., Shoji S., Nagatomo Y., Yoshikawa T.

Journal of Clinical Medicine (Journal of Clinical Medicine) 10 ( 19 ) 2021.10

ISSN 2077-0383

The administration of beta-blockers is challenging and their efficacy is unclear in heart failure (HF) patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the association of beta-blockers with mortality in such patients. This multicenter observational cohort study included hospitalized HF patients with a left ventricular ejection fraction <50% and evaluated them retrospectively. COPD was diagnosed based on medical records and/or the clinical judgment of each investigator. The study endpoints were two-year all-cause, cardiac, and non-cardiac mortality. This study included 83 patients with COPD and 1760 patients without. Two-year all-cause, cardiac, and non-cardiac mortality were observed in 315 (17%), 149 (8%), and 166 (9%) patients, respectively. Beta-blockers were associated with lower all-cause mortality regardless of COPD (COPD: hazard ratio [HR] 0.39, 95% CI 0.16–0.98, p = 0.044; non-COPD: HR 0.62, 95% CI 0.46–0.83, p = 0.001). This association in HF patients with COPD persisted after multivariate analysis and inverse probability weighting and was due to lower non-cardiac mortality (HR 0.40, 95% CI 0.14–1.18. p = 0.098), not cardiac mortality (HR 0.37, 95% CI 0.07–2.01, p = 0.248). Beta-blockers were associated with lower all-cause mortality in HF patients with COPD due to lower non-cardiac mortality. This may reflect selection biases in beta-blocker prescription.

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Assessment of physical activity using waist-worn accelerometers in hospitalized heart failure patients and its relationship with Kansas City Cardiomyopathy Questionnaire

Shiraishi Y, Niimi N, Goda A, Takei M, Kimura T, Kohno T, Kawana M, Fukuda K, Kohsaka S

Journal of Clinical Medicine (Journal of Clinical Medicine) 10 ( 18 ) 2021.09

Research paper (scientific journal), Lead author, Corresponding author, Accepted, ISSN 2077-0383

The health benefits of physical activity have been widely recognized, yet there is limited information on associations between accelerometer-related parameters and established patient-re-ported health status. This study investigated the association between the waist-worn accelerometer measurements, cardiopulmonary exercise testing (CPX), and results of the Kansas City Cardiomy-opathy Questionnaire (KCCQ) in heart failure (HF) patients hospitalized for acute decompensation. A total of 31 patients were enrolled and wore a validated three-axis accelerometer for 2 weeks and completed the short version of the KCCQ after removing the device. Daily step counts, exercise time (metabolic equivalents × hours), and %sedentary time (sedentary time/device-equipped time) were measured. Among the measured parameters, the best correlation was observed between %seden-tary time and the KCCQ overall and clinical summary scores (r = −0.65 and −0.65, each p < 0.001). All of the individual domains of the KCCQ (physical limitation, symptom frequency, and quality of life), with the exception of the social limitation domain, showed moderate correlations with %sed-entary time. Finally, oxygen consumption assessed by CPX demonstrated only weak associations with the accelerometer-measured parameters. An accelerometer could complement the KCCQ results in accurately assessing the physical activity in HF patients immediately after hospitalization, albeit its correlation with CPX was at most moderate.

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Exercise tolerance and quality of life in hemodynamically partially improved patients with chronic thromboembolic pulmonary hypertension treated with balloon pulmonary angioplasty

Miura K., Katsumata Y., Kawakami T., Ikura H., Ryuzaki T., Shiraishi Y., Fukui S., Kawakami M., Kohno T., Sato K., Fukuda K.

PLoS ONE (PLoS ONE) 16 ( July ) e0255180 2021.07

The efficacy of extensive balloon pulmonary angioplasty (BPA) beyond hemodynamic improvement in chronic thromboembolic pulmonary hypertension (CTEPH) patients has been verified. However, the relationship between extensive BPA in CTEPH patients after partial hemodynamic improvement and exercise tolerance or quality of life (QOL) remains unclear. We prospectively enrolled 22 CTEPH patients (66±10 years, females: 59%) when their mean pulmonary artery pressure initially decreased to <30 mmHg during BPA sessions. Hemodynamic and echocardiographic data, cardiopulmonary exercise testing, and QOL scores using the 36-item short form questionnaire (SF-36) were evaluated at enrollment (entry), just after the final BPA session (finish), and at the 6-month follow-up (followup). We analyzed whether extensive BPA improves exercise capacity and QOL scores over time. Moreover, the clinical characteristics leading to improvement were elucidated. The peak oxygen uptake (VO2) showed significant improvement at entry, finish, and follow-up (17.3±5.5, 18.4±5.9, and 18.9±5.3 mL/kg/min, respectively; P<0.001). Regarding the QOL, the physical component summary (PCS) scores significantly improved (32±11, 38±13, and 43±13, respectively; P<0.001), but the mental component summary scores remained unchanged. Linear regression analysis revealed that age and a low peak VO2 at entry were predictors of improvement in peak VO2, while low PCS scores and low TAPSE at entry were predictors of improvement in PCS scores. In conclusion, extensive BPA led to improved exercise tolerance and physical QOL scores, even in CTEPH patients with partially improved hemodynamics.

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Transcatheter Mitral Valve Repair Effective and Safe Refractory Eclipsed Mitral Regurgitation-Induced Cardiogenic Shock: A Case Report

Umei T.C, Shiraishi Y, Tsuruta H, Hayashida K, Imaeda S, Ryuzaki T, Myojin S, Kobari Y, Saito T, Yoshijima N, Itabashi Y, Kishino Y, Katsumata Y, Yuasa S, Fukuda K

Circulation: Cardiovascular Imaging 14 ( 7 ) 681 - 684 2021.06

Research paper (scientific journal), Corresponding author, Accepted

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Abnormal liver function tests and long-term outcomes in patients discharged after acute heart failure

Miyama H, Shiraishi Y, Kohsaka S, Goda A, Nishihata Y, Nagatomo Y, Takei M, Fukuda K, Kohno T, Yoshikawa T

Journal of Clinical Medicine (Journal of Clinical Medicine) 10 ( 8 ) 2021.04

Research paper (scientific journal), Accepted, ISSN 2077-0383

Abnormal liver function tests (LFTs) are known to be associated with impaired clinical outcomes in heart failure (HF) patients. However, this implication varies with each single LFT panel. We aim to evaluate the long-term outcomes of acute HF (AHF) patients by assessing multiple LFT panels in combination. From a prospective multicenter registry in Japan, 1158 AHF patients who were successfully discharged were analyzed (mean age, 73.9 ± 13.5 years; men, 58%). LFTs (i.e., total bilirubin, aspartate aminotransferase or alanine aminotransferase, and alkaline phosphatase) at discharge were assessed; borderline and abnormal LFTs were defined as 1 and ≥2 parameter values above the normal range, respectively. The primary endpoint was composite of all-cause death or HF readmission. At the time of discharge, 28.7% and 8.6% of patients showed borderline and abnormal LFTs, respectively. There were 196 (16.9%) deaths and 298 (25.7%) HF readmissions during a median 12.4-month follow-up period. The abnormal LFTs group had a significantly higher risk of experiencing the composite outcome (adjusted hazard ratio: 1.51, 95% confidence interval: 1.08–2.12, p = 0.017), whereas the borderline LFTs group was not associated with higher risk of adverse events when referenced to the normal LFTs group. Among AHF patients, the combined elevation of ≥2 LFT panels at discharge was associated with long-term adverse outcomes.

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Time-sensitive approach in the management of acute heart failure

Shiraishi Y, Kawana M, Nakata J, Sato N, Fukuda K, Kohsaka S

ESC Heart Failure 8 ( 1 ) 204 - 221 2021.02

Research paper (scientific journal), Lead author, Accepted

Acute heart failure (AHF) has become a global public health burden largely because of the associated high morbidity, mortality, and cost. The treatment options for AHF have remained relatively unchanged over the past decades. Historically, clinical congestion alone has been considered the main target for treatment of acute decompensation in patients with AHF; however, this is an oversimplification of the complex pathophysiology. Within the similar clinical presentation of congestion, significant differences in pathophysiological mechanisms exist between the fluid accumulation and redistribution. Tissue hypoperfusion is another vital characteristic of AHF and should be promptly treated with appropriate interventions. In addition, recent clinical trials of novel therapeutic strategies have shown that heart failure management is ‘time sensitive’ and suggested that treatment selection based on individual aetiologies, triggers, and risk factor profiles could lead to better outcomes. In this review, we aim to describe the specifics of the ‘time-sensitive’ approach by the clinical phenotypes, for example, pulmonary/systemic congestion and tissue hypoperfusion, wherein patients are classified based on pathophysiological conditions. This mechanistic classification, in parallel with the comprehensive risk assessment, has become a cornerstone in the management of patients with AHF and thus supports effective decision making by clinicians. We will also highlight how therapeutic modalities should be individualized according to each clinical phenotype.

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Psychological disturbances and their association with sleep disturbances in patients admitted for cardiovascular diseases

Matsuda R., Kohno T., Kohsaka S., Shiraishi Y., Katsumata Y., Hayashida K., Yuasa S., Takatsuki S., Fukuda K.

PLoS ONE (PLoS ONE) 16 ( 1 January ) e0244484 2021.01

Copyright: © 2021 Matsuda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Depression and anxiety are common mental health problems that are strongly associated with sleep disturbances, according to community-based researches. However, this association has not been investigated among patients admitted for cardiovascular diseases (CVDs). We examined the prevalence of depression and anxiety in inpatients with various CVDs and their association with sleep disturbances. Materials and methods This cross-sectional study included 1294 patients hospitalized for CVDs in a Japanese university hospital were evaluated for their mental status using the Hospital Anxiety and Depression Scale (HADS), for sleep-disordered breathing (SDB) using pulse oximetry, and for sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Results Patient characteristics were as below: mean age, 63.9±14.7 years; 25.7% female. Overall, 18.9% had depression (HADS-depression>8) and 17.1% had anxiety (HADS-anxiety>8). The presence of depression was associated with female sex, older age, higher plasma brain natriuretic peptide level, lower estimated glomerular filtration rate, and the prevalence of heart failure. Overall, 46.5% patients were categorized as having a poor sleep quality (PSQI>5), and 28.5% patients had SDB (3% oxygen desaturation index>15). Although depression and anxiety were not associated with SDB, they were independently associated with poor sleep quality (OR = 3.09, 95% CI 2.19–4.36; OR = 3.93, 95% CI 2.71–5.69, respectively). Conclusions Depression and anxiety were not uncommon in patients with CVDs. Poor sleep quality could be an important risk factor linked to psychological disturbances.

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Sleep-disordered breathing is independently associated with elevated natriuretic peptide levels in patients with cardiovascular diseases

Sugiura K., Kohno T., Kohsaka S., Shiraishi Y., Katsumata Y., Hayashida K., Yuasa S., Takatsuki S., Fukuda K.

Heart and Vessels (Heart and Vessels) 37 ( 6 ) 994 - 1002 2021

ISSN 09108327

Sleep disorders and sleep duration have attracted considerable attention as potential modifiable risk factors for the development and progression of heart failure (HF). However, whether these sleep behaviors could aggravate the underlying cardiac condition remains ambiguous. We evaluated the associations between the levels of plasma B-type natriuretic peptide (BNP) and sleep-disordered breathing (SDB), sleep quality and quantity, or daytime sleepiness in cardiovascular diseases (CVD) patients. A total of 1717 consecutive patients with CVD [median age, 66 years (55–74 years); female, 27.5%] were enrolled. SDB was screened by nocturnal pulse oximetry; sleep quality and quantity were determined by Pittsburg Sleep Quality Index, and daytime sleepiness was examined by Epworth Sleepiness Scale. The median plasma BNP level was 54.9 pg/ml (23.5–146.4 pg/ml). Multiple regression analyses showed that the BNP level in the highest quintile (BNP > 181.8 pg/ml) was associated with SDB (severe: OR, 5.88; 95% CI 3.17–10.88; moderate: OR, 3.62; 95% CI 2.17–6.02; mild: OR, 2.22: 95% CI 1.42–3.47). There were no significant associations between other sleep parameters and higher BNP levels. The relationship between SDB and BNP levels was unchanged regardless of the previous history of symptomatic HF. SDB was independently associated with the elevated plasma BNP level in patients with a variety of CVD.

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