Details of a Researcher - SHIRAISHI Yasuyuki

Papers - SHIRAISHI Yasuyuki

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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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Prognostic effect of a vasopressin V<inf>2</inf> receptor antagonist in acute congestive heart failure patients with hypoperfusion, the wet–cold pattern

Matsushita K., Harada K., Miyamoto T., Iida K., Yamamoto Y., Shiraishi Y., Nagatomo Y., Yoshino H., Yamamoto T., Nagao K., Takayama M.

European Journal of Clinical Pharmacology 80 ( 11 ) 1795 - 1805 2024

ISSN 00316970

Purpose: This study investigated whether the oral vasopressin V2 receptor antagonist tolvaptan has beneficial effects on mortality in real-world congestive heart failure (CHF) patients with hypoperfusion (i.e. the wet–cold pattern), from the viewpoint of cardiorenal syndrome. Methods: Data on 5511 consecutive CHF patients were extracted from the Tokyo CCU Network data registry. Congestion and hypoperfusion were defined by Nohria–Stevenson clinical profiles at the time of hospitalization. Propensity scores for tolvaptan use were calculated for each patient and used to assemble two matched cohorts of patients receiving tolvaptan or not in the CHF with and without hypoperfusion groups. Results: Of the entire study cohort, 1073 patients (19%) had CHF with hypoperfusion (i.e. the wet–cold pattern). In-hospital mortality was significantly higher for CHF patients with than without hypoperfusion (log-rank, P < 0.001). The rate of tolvaptan use did not differ significantly between CHF patients with and without hypoperfusion (15% vs. 14%, respectively; P = 0.7848). In the propensity-matched CHF with hypoperfusion cohort, there was a significant association between the use of tolvaptan and a reduction in in-hospital mortality (log-rank, P = 0.0052). Conversely, in the matched CHF without hypoperfusion cohort, tolvaptan use was not associated with in-hospital mortality (log-rank, P = 0.4417). Conclusion: There was a significant association between the use of tolvaptan and a reduction in in-hospital mortality in CHF patients with, but not without, hypoperfusion. These findings hint at possible individualized therapies for patients with CHF.

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Effect of basic activities of daily living independence on home discharge and long-term outcomes in patients hospitalized with heart failure

Izumi K., Kohno T., Goda A., Takeuchi S., Shiraishi Y., Higuchi S., Nakamaru R., Nagatomo Y., Kitamura M., Takei M., Sakamoto M., Mizuno A., Nomoto M., Soejima K., Kohsaka S., Yoshikawa T.

Heart and Vessels 40 ( 6 ) 471 - 483 2024

ISSN 09108327

Patients hospitalized for heart failure (HF) experience impairments in functional status, primarily affecting basic activities of daily living (ADL). We investigated the independent effect of functional status for ADL on patient-centered outcomes (i.e., home discharge) and conventional clinical outcomes in HF. We analyzed 2936 consecutive hospitalized patients with HF from a prospective multicenter registry. The functional status of ADL was assessed before discharge by using the Barthel index (BI). Patients were categorized into the lower BI group (≤85; the lowest tertile) and higher BI group (>85). We evaluated the risk-adjusted association between BI and non-home discharge, as well as the two-year all-cause mortality. Exploratory subgroups included patients categorized by age, sex, HF hospitalization, left ventricular ejection fraction, body mass index, and estimated glomerular filtration rate (eGFR). Of the participants (age: 79 [69–85] years; 41.1% women), 86.3% were discharged home. A lower BI was independently associated with non-home discharge (OR: 5.12, 95% CI 3.86–6.80) and higher all-cause mortality rates (HR: 1.96, 95% CI 1.58–2.45). Two-year cardiac and non-cardiac mortality rates were higher in the lower BI group; however, the proportion of cardiac causes in two-year deaths did not differ between the lower and higher BI groups (48.8% vs. 49.5%, P = 0.891). Subgroup analyses consistently demonstrated an association between two-year mortality and lower BI; however, this association was stronger among patients with a higher eGFR (P-value for interaction = 0.004). A lower BI was independently associated with non-home discharge and higher mortality rates because of cardiac- and non-cardiac-related causes in hospitalized patients with HF.

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Discontinuation of Oral Anticoagulants in Atrial Fibrillation Patients: Impact of Treatment Strategy and on Patients' Health Status.

Nakamaru R, Ikemura N, Kimura T, Katsumata Y, Sherrod CF, Miyama H, Shiraishi Y, Kanki H, Negishi K, Ueda I, Fukuda K, Takatsuki S, Kohsaka S

Journal of clinical medicine (Journal of Clinical Medicine) 12 ( 24 ) 2023.12

ISSN 2077-0383

Aims: The discontinuation of oral anticoagulants (OACs) remains as a significant concern in the management of atrial fibrillation (AF). The discontinuation rate may vary depending on management strategy, and physicians may also discontinue OACs due to concerns about patient satisfaction with their care. We aimed to assess the incidence of OAC discontinuation and its relationship to patients’ health in an outpatient AF registry. Methods and Results: From a multicenter registry for newly recognized AF patients (n = 3313), we extracted 1647 (49.7%) patients with OACs and a CHA2DS2-Vasc score of ≥2. Discontinuation was defined as sustained cessation of OACs within a 1-year follow-up. We examined predictors associated with discontinuation and its relations to health status defined by the AFEQT questionnaire. Of the 1647 patients, 385 (23.6%) discontinued OACs after 1 year, with discontinuation rates varying across treatment strategies (15.3% for catheter ablation, 4.9% for rhythm control with antiarrhythmic drugs, and 3.0% for rate control). Successful rhythm control was associated with discontinuation in the catheter ablation (OR 6.61, 95% CI 3.00–14.6, p < 0.001) and antiarrhythmic drugs (OR 6.47, 95% CI 2.62–15.9, p < 0.001) groups, whereas the incidence of bleeding events within 1 year was associated with discontinuation in the rate control group. One-year AFEQT scores did not significantly differ between patients who discontinued OACs and those who did not in each treatment strategy group. Conclusions: OAC discontinuation was common among AF patients with significant stroke risk but varied depending on the chosen treatment strategy. This study also found no significant association between OAC discontinuation and patients’ health status.

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バルーン肺動脈形成術後の急性肺血栓塞栓症に対して抗凝固療法の変更が有効であった慢性血栓塞栓性肺高血圧症の1例

梅井智彦, 岸野喜一, 川上崇史, 平出貴裕, 白石泰之, 猪原拓, 湯浅慎介, 福田恵一

心臓 ((公財)日本心臓財団) 55 ( 7 ) 743 - 748 2023.07

ISSN 0586-4488

症例は65歳男性で、労作時呼吸困難を主訴とした。リバーロキサバンによる抗凝固療法中の慢性血栓塞栓性肺高血圧症に対し、バルーン肺動脈形成(BPA)目的で入院した。BPA治療後、労作時息切れ症の改善を認めたが、2ヵ月後に再増悪を認めた。肺動脈造影では左A10に血栓を疑う造影欠損を認め、肺高血圧症も認めた。吸引とバルーン拡張を繰り返したが、造影欠損の完全な消失は得られなかった。赤色血栓が吸引されたため、亜急性期新鮮血栓を疑い、ヘパリン持続静注治療後にワルファリンに切り替えた。肺高血圧症にはリオシグアトを導入した。血栓は完全に消失し、血流も良好で、労作時息切れ症状も改善した。現在まで再燃なく経過良好である。

Perspectives of hospitalized heart failure patients: preferred and perceived participation roles in treatment decisions.

Sekine O, Kitakata H, Kohsaka S, Fujisawa D, Nakano N, Shiraishi Y, Kishino Y, Katsumata Y, Yuasa S, Fukuda K, Kohno T

Heart and vessels (Heart and Vessels) 38 ( 10 ) 1244 - 1255 2023.06

ISSN 0910-8327

Shared decision-making (SDM) is a pivotal process in seeking optimal individual treatment and incorporating clinical evidence and patients’ autonomous preferences. However, patients’ actual attitudes toward participation in decision-making for state-of-the-art heart failure (HF) treatment remain unclear. We conducted a questionnaire-based survey distributed by nurses and physicians specializing in HF care to assess patients’ preferred and perceived participation roles in treatment decision-making during the index hospitalization, rated on five scales (from extremely passive to purely autonomous attitudes). Simultaneously, we investigated the important factors underlying treatment decision-making from the perspective of hospitalized HF patients. Of the 202 patients who were approached by our multidisciplinary HF team between 2017 and 2020, 166 (82.2%) completed the survey. Logistic regression analyses were conducted to identify the clinical determinants of patients who reported that they left all decisions to physicians (i.e., extremely passive attitude). Of the 166 participants (male 67.5%, median age 73 years), 32.5% preferred an extremely passive attitude, while 61.4% reported that they actually chose an extremely passive attitude. A sole determinant of choosing an extremely passive decision-making role was lower educational status (odds ratio: 2.11, 95% confidence interval 1.11–4.00). The most important factor underlying the decision-making was “Physician recommendation” (89.2%). Notably, less than 50% considered “In alignment with my values and preferences” as an important factor underlying treatment decision-making. The majority of HF patients reported that they chose an extremely passive approach, and patients prioritized physician recommendation over their own values and preferences. Graphical abstract: [Figure not available: see fulltext.].

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Which congestion presentation pattern on the physical findings is associated with future adverse events? A cluster analysis in the multicenter acute heart failure registry.

Niimi N, Kohsaka S, Shiraishi Y, Takei M, Kohno T, Nakano S, Nagatomo Y, Sakamoto M, Saji M, Ikemura N, Inohara T, Ueda I, Fukuda K, Yoshikawa T

Clinical research in cardiology : official journal of the German Cardiac Society (Clinical Research in Cardiology) 112 ( 8 ) 1108 - 1118 2023.04

ISSN 1861-0684

Background: Clinical congestion is the most frequent reason for hospital admission in patients with acute heart failure (AHF). However, few studies have investigated the patterns and prognostic implication of the physical congestion using unbiased and robust statistical methods. Methods: A hierarchical agglomerative clustering analysis was performed in the multicenter Japanese AHF registry (N = 3151) with the distance calculated by Jaccard's distance for jugular vein distention (JVD), leg edema, S3, crackles, and orthopnea. The primary outcome was a composite of cardiac death and heart failure readmission within 1-year. Results: At the time of admission, the median number of prevalent congestive signs was 2. We identified three phenogroups: ‘no physical congestions’ (N = 251); ‘congestion without JVD’ (N = 1415); and ‘congestion with JVD’ (N = 1495). Patients in ‘no physical congestion’ were the youngest (median 75 [62, 83] years) with the lowest systolic blood pressure (122 [106, 142] mmHg). Patients in ‘congestion without JVD’, and ‘congestion with JVD’ were similar in terms of age (77 [67, 84] vs. 78 [69, 84] years) and systolic blood pressure (138 [118, 160] vs. 137 [118, 158] mmHg). While 30-day mortality was similar (4.0%, 3.7%, and 4.3% in ‘no physical congestion,’ ‘congestion without JVD,’ and ‘congestion with JVD’, respectively), the patients in ‘congestion with JVD’ were at the highest risk for the primary outcome (adjusted hazard ratio 1.79, 95% CI 1.26–2.55 when ‘no physical congestion’ was a reference). Conclusions: Our clustering analysis demonstrated that congestion signs, particularly JVD, allowed identification of AHF phenogroups with distinct clinical characteristics and long-term outcomes.

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Geriatric Nutritional Risk Index at Hospital Admission or Discharge in Patients with Acute Decompensated Heart Failure.

Ono M, Mizuno A, Kohsaka S, Shiraishi Y, Kohno T, Nagatomo Y, Goda A, Nakano S, Komiyama N, Yoshikawa T

Journal of clinical medicine (Journal of Clinical Medicine) 12 ( 5 ) 2023.02

ISSN 2077-0383

Geriatric Nutritional Risk Index (GNRI) is known both as a reliable indicator of nutritional status and a predictor of long-term survival among patients with acute decompensated heart failure (ADHF). However, the optimal timing to evaluate GNRI during hospitalization remains unclear. In the present study, we retrospectively analyzed patients hospitalized with ADHF in the West Tokyo Heart Failure (WET-HF) registry. GNRI was assessed at hospital admission (a-GNRI) and discharge (d-GNRI). Out of 1474 patients included in the present study, 568 (40.1%) and 796 (57.2%) patients had lower GNRI (<92) at hospital admission and discharge, respectively. After the follow-up (median 616 days), 290 patients died. The multivariable analysis showed that all-cause mortality was independently associated with d-GNRI (per 1 unit decrease, adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04–1.09, p < 0.001), but not with a-GNRI (aHR: 0.99, 95% CI: 0.97–1.01, p = 0.341). The predictability of GNRI for long-term survival was more pronounced when evaluated at hospital discharge than at hospital admission (area under the curve 0.699 vs. 0.629, DeLong’s test p < 0.001). Our study suggested that GNRI should be evaluated at hospital discharge, regardless of the assessment at hospital admission, to predict the long-term prognosis for patients hospitalized with ADHF.

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Standard modifiable cardiovascular risk factors in patients with acute coronary syndrome: A report from multicenter percutaneous coronary intervention registry

Iwata J., Inohara T., Shiraishi Y., Nakamaru R., Niimi N., Ueda I., Suzuki M., Noma S., Numasawa Y., Fukuda K., Kohsaka S.

Journal of Cardiology (Journal of Cardiology) 81 ( 6 ) 571 - 576 2023

ISSN 09145087

Background: High mortality in patients with acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors [SMuRFs (e.g. diabetes, hypertension, smoking, and dyslipidemia)] has been reported. However, details regarding their acute presentation and reasons for the excess risk remain unclear. Method: Patient-level data were extracted from a multicenter procedure-based registry (KiCS-PCI). We analyzed consecutive patients with ACS who underwent de novo percutaneous coronary intervention (PCI) between 2009 and 2020. The primary outcome of interest was the in-hospital mortality. Results: Among the 10,523 patients with ACS, 7775 met the inclusion criteria. Patients without SMuRFs who underwent PCI [n = 529 (6.8 %)] were older [median 71 (IQR: 63–79) vs. 68 (59–76) years, p < 0.001] and more often presented with cardiogenic shock or cardiopulmonary arrest (14.6 % vs. 8.6 %, p < 0.001; 12.7 % vs. 5.3 %, p < 0.001, respectively). In patients with ST-elevation myocardial infarction (STEMI), median door-to-balloon time was significantly longer in SMuRF-less patients (90 min vs 82 min). In-hospital death was significantly higher in SMuRF-less patients [10.2 % vs. 4.1 %, p < 0.001, adjusted odds ratio, 1.81 (95%CI, 1.26–2.59); p = 0.001], whereas the rate of procedural complications showed no significant difference. When stratified by the ACS presentation pattern, the findings were consistent, although the association between SMuRF-less and the increased risk of in-hospital mortality was not statistically significant in patients with non-ST-elevation- (NSTE)-ACS. Conclusions: SMuRF-less ACS patients frequently presented with cardiopulmonary arrest and/or cardiogenic shock, leading to high in-hospital mortality. When stratified by the ACS presentation pattern, the association of SMuRF-less and the increased risk of mortality was more prominent in STEMI patients and it was not statistically significant in NSTE-ACS patients. Almost half of these patients had amendable left main trunk or left anterior descending artery disease and treating clinicians should be aware of this paradox to avoid the delay in treatment.

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Forecasting the Acute Heart Failure Admissions: Development of Deep Learning Prediction Model Incorporating the Climate Information

Jimba T., Kodera S., Kohsaka S., Otsuka T., Harada K., Shindo A., Shiraishi Y., Kohno T., Takei M., Nakano H., Matsuda J., Yamamoto T., Nagao K., Takayama M.

Journal of Cardiac Failure (Journal of Cardiac Failure) 30 ( 2 ) 404 - 409 2023

ISSN 10719164

Background: Climate is known to influence the incidence of cardiovascular events. However, their prediction with traditional statistical models remains imprecise. Methods and Results: We analyzed 27,799 acute heart failure (AHF) admissions within the Tokyo CCU Network Database from January 2014 to December 2019. High-risk AHF (HR-AHF) day was defined as a day with the upper 10th percentile of AHF admission volume. Deep neural network (DNN) and traditional regression models were developed using the admissions in 2014–2018 and tested in 2019. Explanatory variables included 17 meteorological parameters. Shapley additive explanations were used to evaluate their importance. The median number of incidences of AHF was 12 (9–16) per day in 2014–2018 and 11 (9–15) per day in 2019. The predicted AHF admissions correlated well with the observed numbers (DNN: R2 = 0.413, linear regression: R2 = 0.387). The DNN model was superior in predicting HR-AHF days compared with the logistic regression model [c-statistics: 0.888 (95% CI: 0.818–0.958) vs 0.827 (95% CI: 0.745–0.910): P = .0013]. Notably, the strongest predictive variable was the 7-day moving average of the lowest ambient temperatures. Conclusions: The DNN model had good prediction ability for incident AHF using climate information. Forecasting AHF admissions could be useful for the effective management of AHF.

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Real-time analysis of heart rate variability during aerobic exercise in patients with cardiovascular disease

Ikura H., Katsumata Y., Seki Y., Ryuzaki T., Shiraishi Y., Miura K., Sato K., Fukuda K.

IJC Heart and Vasculature (IJC Heart and Vasculature) 43 101147 2022.12

ISSN 23529067

Background: Exercise therapy for cardiovascular disease (CVD) is mainly evaluated based on the heart rate (HR) or Borg scale. However, these indices can be unreliable depending on the patient's medication or their subjective decisions; thus, alternative methods are required for easier and safer implementation of aerobic exercise. Here, we examined whether real-time analysis of HR variability (HRV) can help maintain exercise intensity at the ventilatory threshold (VT) during exercise. Methods: Twenty-eight patients with CVD treated at Keio University Hospital between August 2018 and March 2020 were enrolled. Initially, oxygen uptake (VO2) and HR at the VT were determined using the cardiopulmonary exercise test. Patients then performed aerobic exercise on a stationary bicycle for 30 min while a parameter of HRV, the high-frequency (HF) component, was monitored in real time using an electrocardiograph. The work rate during exercise was adjusted every 2 min to maintain the HF range between 5 and 10. The VO2 and HR values, recorded every 2 min during exercise, were compared with those at VT. The Bland–Altman method was used to confirm similarity. Results: VO2 and HR during exercise were closely correlated with those at VT (e.g., 19 min after exercise initiation; VO2: r = 0.647, HR: r = 0.534). The Bland–Altman plot revealed no bias between the mean values (e.g., 19 min; VO2: −0.22 mL/kg/min; HR: −0.07/min). Conclusion: Real-time HRV analysis with electrocardiograph alone during exercise can provide continuous and non-invasive exercise intensity measurements at VT, promoting safer and effective exercise strategies.

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Association of Potassium Level at Discharge with Long-Term Mortality in Hospitalized Patients with Heart Failure

Miura Y., Higuchi S., Kohno T., Shiraishi Y., Kitamura M., Nagatomo Y., Takei M., Nakano S., Goda A., Soejima K., Kohsaka S., Yoshikawa T.

Journal of Clinical Medicine (Journal of Clinical Medicine) 11 ( 24 ) 2022.12

ISSN 2077-0383

Dyskalemia (hypokalemia and hyperkalemia) is a common comorbidity of heart failure (HF). Although dyskalemia is associated with poor prognosis, different prognostic impacts of hypo- and hyperkalemia remain vastly unclear. This study investigated the association of dyskalemia with prognosis in HF patients, especially the mode of death and left ventricular ejection fraction (LVEF). The multicenter study included 3398 patients hospitalized for HF. Patients were divided into three groups based on serum potassium levels at discharge: hypokalemia (<3.5 mEq/L; n = 115 (3.4%)), normokalemia (3.5–5.0 mEq/L; n = 2960 (87.1%)), and hyperkalemia (≥5.0 mEq/L; n = 323 (9.5%)). Two-year all-cause, cardiac, and non-cardiac mortality was evaluated. Association of serum potassium with two-year mortality demonstrated a U-shaped curve, with a worse prognosis for patients with hypokalemia. All-cause mortality at two-years did not differ among the three groups. Hypokalemia was associated with 2-year cardiac death (adjusted hazard ratio (HR), 2.60; 95% confidence interval (CI), 1.20–5.64) in HF with reduced ejection fraction (HFrEF; LVEF < 40%), but not in non-HFrEF. Regardless of LVEF, hyperkalemia was not independently associated with any mortality. Hypokalemia was independently associated with cardiac death, particularly in HFrEF patients. Such an association was not observed in hyperkalemia regardless of LVEF.

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画像情報と深層学習を応用した心疾患患者の予後予測

白石泰之

上原記念生命科学財団研究報告集 ((公財)上原記念生命科学財団) 36 1 - 6 2022.12

Social Isolation and Implementation of Advanced Care Planning Among Hospitalized Patients With Heart Failure

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

Journal of the American Heart Association (Journal of the American Heart Association) 11 ( 21 ) e026645 2022.11

Background The implementation of advance care planning (ACP) in heart failure management is insufficient. Social isolation (SI) could be a barrier to ACP initiation, albeit the relationship between SI and patients' preference for ACP or end-of-life care remains unknown. Methods and Results We conducted a questionnaire survey, including assessments of SI using the 6-item Lubben Social Network Scale as well as patients' perspectives on ACP and end-of-life care. Of the 160 patients approached by our multidisciplinary heart failure team during admission, 120 patients (75.0%) completed the survey (median age, 73.0 years; men, 74.2%). A Cox proportional hazard model was constructed to elucidate the short-term (180-day) prognostic impact of SI. Overall, 28.3% of participants were at high risk for SI (6-item Lubben Social Network Scale score <12). High-risk patients had more negative attitudes toward ACP than those without (61.8% versus 80.2%; P=0.035). The actual performance of ACP conversation in patients with and without high risk were 20.6% and 30.2%, respectively. Regarding preference in end-of-life care, "Saying what one wants to tell loved ones" (73.5% versus 90.6%; P=0.016) and "Spending enough time with family" (58.8% versus 77.9%; P=0.035) were less important in high-risk patients. High risk for SI was associated with higher 180-day risk-adjusted all-cause mortality (hazard ratio, 7.89 [95% CI, 1.53-40.75]). Conclusions In hospitalized patients with heart failure, high risk for SI was frequently observed. High-risk patients were associated with a negative attitude toward ACP, despite higher mortality. Further research is required to establish an ideal approach to provide ACP in socially vulnerable patients.

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Low blood pressure and guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.

Izumi K, Kohno T, Goda A, Takeuchi S, Shiraishi Y, Saji M, Nagatomo Y, Tanaka TD, Takei M, Nakano S, Soejima K, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure Registry Investigators.

International journal of cardiology (International Journal of Cardiology) 370 255 - 262 2022.10

ISSN 0167-5273

Background: Patients with heart failure (HF) presenting with low blood pressure (BP) have been underrepresented in large-scale clinical trials. We investigated the characteristics and implementation of conventional guideline-directed medical therapy (GDMT; renin-angiotensin system inhibitors and β-blockers) in patients with low BP hospitalized for HF with systolic dysfunction. Methods: Conventional GDMT was evaluated by discharge BP among 2043 consecutive patients with HF and left ventricular ejection fraction (LVEF) < 50% in the WET-HF registry. Among the 708 (34.7%) patients with lower discharge BP (≤ 100 mmHg; the lower tertiles), exploratory subgroups included patients with previous HF hospitalization, inotrope use, New York Heart Association (NYHA) III–IV class, and lower estimated glomerular filtration rate (eGFR) and LVEF (lower than median value). We evaluated the risk-adjusted association between GDMT implementation and 2-year adverse events (all-cause mortality or HF rehospitalization). Results: Among the 2043 patients (age 74 [63–82] years), the median systolic BP was 108 (98–120) mmHg. Among patients with lower BP, GDMT prescription rate was 62.7%, and GDMT use was associated with decreased adverse events (HR:0.74, 95%CI:0.58–0.94). GDMT prescription rates were lower among higher-NYHA class and lower-eGFR subgroups compared with their reference subgroups, and directionally similar outcomes were noted in all subgroups (favoring GDMT use); however, this association was somewhat attenuated in the lower-eGFR group (HR:0.87, 95%CI:0.64–1.17). Conclusions: Conventional GDMT use was associated with decreased adverse outcomes in most patients with HF compounded by systolic dysfunction and low BP, albeit caution is warranted in patients with renal dysfunction.

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Malnutrition in real-world patients hospitalized for heart failure with preserved ejection fraction and its potential impact on generalizability of EMPEROR-Preserved trial.

Takeuchi S, Kohno T, Goda A, Shiraishi Y, Saji M, Nagatomo Y, Tanaka TD, Takei M, Nakano S, Soejima K, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure Registry Investigators.

International journal of cardiology (International Journal of Cardiology) 370 263 - 270 2022.10

ISSN 0167-5273

Background: Despite the benefits of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin, its suitability for patients with heart failure (HF) in the real-world setting remains unclear. Considering the unique pharmacological profile of SGLT2i (e.g., glucose excretion leading to calorie loss) and increasingly aging patients with HF, applicability of trials' finding in patients with malnutrition is important. Methods: We examined 1633 consecutive patients with a preserved left ventricular ejection fraction (LVEF; >40%) enrolled in a multicenter-based acute HF registry. After applying the EMPEROR-Preserved eligibility criteria, we compared the baseline characteristics of trial-eligible and actual trial participants, and patients with and without malnutrition among the trial-eligible group. Malnutrition was assessed by the geriatric nutritional risk index (GNRI). The trial-eligible patients were divided into high (GNRI≥92) and low (GNRI<92) nutritional groups, and a composite endpoint comprising all-cause death and HF rehospitalization was evaluated. Results: Majority (70.2%) of the analyzed patients were eligible for the EMPEROR-Preserved trial (age: 77 ± 12 years and body mass index [BMI]: 22.0 ± 4.1 kg/m2), but were older and had lower BMIs than the actual trial participants. Notably, 51.9% of the eligible patients were at high risk for malnutrition and had a higher rate of the composite endpoint than non-malnourished counterparts (HR 1.27, 95%CI 1.04–1.56, P = 0.020). The difference in outcomes was predominantly due to mortality from non-cardiac causes. Conclusions: Mostly patients with HF in a real-world setting met the EMPEROR-Preserved criteria; however, approximately half were at high risk for malnutrition with poorer outcomes owing to non-cardiac-related causes.

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Confidence in self-care after heart failure hospitalization.

Hashimoto S, Kitakata H, Kohsaka S, Fujisawa D, Shiraishi Y, Nakano N, Sekine O, Kishino Y, Katsumata Y, Yuasa S, Fukuda K, Kohno T

Journal of cardiology (Journal of Cardiology) 81 ( 1 ) 42 - 48 2022.10

ISSN 0914-5087

Background: Understanding patient perspectives of self-care is critical for improving multidisciplinary education programs and adherence to such programs. However, perspectives of self-care for patients with heart failure (HF) as well as the association between patient perspectives and patient-physician communication remain unclear. Methods: Confidence levels regarding self-care behaviors (eight lifestyle behaviors and four consulting behaviors) and self-monitoring were assessed using a self-administered questionnaire survey, which was directly distributed by dedicated physicians and nurses to consecutive patients hospitalized with HF in a tertiary-level hospital. Patient-physician communication was evaluated according to the quality of physician-provided information regarding “treatment and treatment choices” and “prognosis” using the Prognosis and Treatment Perception Questionnaire. Out of 202 patients, 187 (92.6 %) agreed to participate, and 176 completed the survey [valid response rate, 87.1 %; male, 67.0 %; median age, 73 (63–81) years]. Multivariate logistic regression analyses were conducted to predict low confidence in self-care (score in the lowest quartile). Results: High confidence (confident or completely confident >75 % of patients) was observed for all self-care behavior categories except low-salt diet (63.1 %), regular exercise (63.1 %), and flu vaccination (65.9 %). Lower confidence in self-care behavior was associated with low quality of patient-physician communication. With regard to self-monitoring, 62.5 % of patients were not confident in distinguishing worsening symptoms of HF from other diseases; non-confidence was also associated with low quality of patient-physician communication. Conclusions: Hospitalized patients with HF had low confidence regarding regular exercise, salt restriction, and flu vaccination. The results also suggest patient-physician communication affects patient confidence.

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Association between class of foundational medication for heart failure and prognosis in heart failure with reduced/mildly reduced ejection fraction.

Ito M, Maeda D, Matsue Y, Shiraishi Y, Dotare T, Sunayama T, Nogi K, Takei M, Ueda T, Nogi M, Ishihara S, Nakada Y, Kawakami R, Kagiyama N, Kitai T, Oishi S, Akiyama E, Suzuki S, Yamamoto M, Kida K, Okumura T, Nagatomo Y, Kohno T, Nakano S, Kohsaka S, Yoshikawa T, Saito Y, Minamino T

Scientific reports (Scientific Reports) 12 ( 1 ) 16611 2022.10

We clarified the association between changes in the number of foundational medications for heart failure (FMHF) during hospitalization for worsening heart failure (HF) and post-discharge prognosis. We retrospectively analyzed a combined dataset from three large-scale registries of hospitalized patients with HF in Japan (NARA-HF, WET-HF, and REALITY-AHF) and patients diagnosed with HF with reduced or mildly reduced left ventricular ejection fraction (HFr/mrEF) before admission. Patients were stratified by changes in the number of prescribed FMHF classes from admission to discharge: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor blockers. Primary endpoint was the combined endpoint of HF rehospitalization and all-cause death within 1 year of discharge. The cohort comprised 1113 patients, and 482 combined endpoints were observed. Overall, FMHF prescriptions increased in 413 (37.1%) patients (increased group), remained unchanged in 607 (54.5%) (unchanged group), and decreased in 93 (8.4%) (decreased group) at discharge compared with that during admission. In the multivariable analysis, the increased group had a significantly lower incidence of the primary endpoint than the unchanged group (hazard ratio 0.56, 95% confidence interval 0.45–0.60; P < 0.001). In conclusion, increase in FMHF classes during HF hospitalization is associated with a better prognosis in patients with HFr/mrEF.

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Divergent effect of blood glucose dysregulation on long-term clinical outcome in acute decompensated heart failure: A reappraisal in contemporary practice.

Chishiki T, Nagatomo Y, Saji M, Takei M, Goda A, Kohno T, Nakano S, Nishihata Y, Ikegami Y, Shiraishi Y, Kohsaka S, Adachi T, Yoshikawa T, for WET-HF Investigators.

International journal of cardiology (International Journal of Cardiology) 365 91 - 99 2022.07

ISSN 0167-5273

Background: The prognostic implication of elevated or decreased blood glucose (BG) level in acute decompensated heart failure (ADHF) has been still controversial. Indices of stress hyperglycemia, expressed by the ratio of BG and chronic BG control, has been reported to be associated with poor outcome in different disease population. We sought to assess BG at admission and %ΔBG, an index of BG deviation from estimated average BG calculated from glycated hemoglobin (HbA1c), on the long-term outcome in ADHF patients. Methods and results: The West Tokyo Heart Failure (WET-HF) Registry is a prospective multicenter registry enrolling consecutive hospitalized ADHF patients. Among the patients (N = 3078, 77 [67–84] years, male 59%), BG at admission discriminated the long-term (1000 days) incidence of ADHF rehospitalization, but not cardiac death. BG at admission showed a U-shape relationship with the long-term incidence of ADHF rehospitalization after adjustment for covariates. Especially, in patients with HbA1c ≥ 6.5%, the lowest quartile showed the highest risk of ADHF rehospitalization. On the contrary, %ΔBG showed U-shape relationship with the long-term incidence of cardiac death after discharge, rather than ADHF rehospitalization after adjustment for covariates. In addition, elevated %ΔBG was associated with the long-term risk of sudden cardiac death (SCD) even after adjustment for covariates. Conclusions: For ADHF patients, BG at admission and %ΔBG might be a simple, useful tool for predicting and stratifying long-term risk of cardiac events. Especially, elevated %ΔBG might be an important in predicting hard events such as cardiac death or SCD.

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Association of ambient temperature and acute heart failure with preserved and reduced ejection fraction.

Jimba T, Kohsaka S, Yamasaki M, Otsuka T, Harada K, Shiraishi Y, Koba S, Takei M, Kohno T, Matsushita K, Miyazaki T, Kodera S, Tsukamoto S, Iida K, Shindo A, Kitano D, Yamamoto T, Nagao K, Takayama M, Tokyo CCU Network Scientific Committee.

ESC heart failure (ESC Heart Failure) 9 ( 5 ) 2899 - 2908 2022.06

Aims: Evidence on the association between ambient temperature and the onset of acute heart failure (AHF) is scarce and mixed. We sought to investigate the incidence of AHF admissions based on ambient temperature change, with particular interest in detecting the difference between AHF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). Methods and results: Individualized AHF admission data from January 2015 to December 2016 were obtained from a multicentre registry (Tokyo CCU Network Database). The primary event was the daily number of admissions. A linear regression model, using the lowest ambient temperature as the explanatory variable, was selected for the best-estimate model. We also applied the cubic spline model using five knots according to the percentiles of the distribution of the lowest ambient temperature. We divided the entire population into HFpEF + HFmrEF and HFrEF for comparison. In addition, the in-hospital treatment and mortality rates were obtained according to the interquartile ranges (IQRs) of the lowest ambient temperature (IQR1 <5.5°C; IQR25.5–13.3°C; IQR3 13.3–19.7°C; and IQR4 >19.7°C). The number of admissions for HFpEF, HFmrEF and HFrEF were 2736 (36%), 1539 (20%), and 3354 (44%), respectively. The lowest ambient temperature on the admission day was inversely correlated with the admission frequency for both HFpEF + HFmrEF and HFrEF patients, with a stronger correlation in patients with HFpEF + HFmrEF (R2 = 0.25 vs. 0.05, P < 0.001). In the sensitivity analysis, the decrease in the ambient temperature was associated with the greatest incremental increases in HFpEF, followed by HFmrEF and HFrEF patients (3.5% vs. 2.8% vs. 1.5% per −1°C, P < 0.001), with marked increase in admissions of hypertensive patients (systolic blood pressure >140 mmHg vs. 140–100 mmHg vs. <100 mmHg, 3.0% vs. 2.0% vs. 0.8% per −1°C, P for interaction <0.001). A mediator analysis indicated the presence of the mediator effect of systolic blood pressure. The in-hospital mortality rate (7.5%) did not significantly change according to ambient temperature (P = 0.62). Conclusions: Lower ambient temperature was associated with higher frequency of AHF admissions, and the effect was more pronounced in HFpEF and HFmrEF patients than in those with HFrEF.

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