Papers - SHIRAISHI Yasuyuki

Real-time analysis of the heart rate variability during incremental exercise for the detection of the ventilatory threshold

Shiraishi Y, Katsumata Y, Sadahiro T, Azuma K, Akita K, Isobe S, Yashima F, Miyamoto K, Nishiyama T, Tamura Y, Kimura T, Nishiyama N, Aizawa Y, Fukuda K, Takatsuki S

Journal of the American Heart Association 7 ( 1 )  2018.01

Research paper (scientific journal), Lead author, Accepted

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Background: It has never been possible to immediately evaluate heart rate variability (HRV) during exercise. We aimed to visualize the real-time changes in the power spectrum of HRV during exercise and to investigate its relationship to the ventilatory threshold (VT). Methods and Results: Thirty healthy subjects (29.1±5.7 years of age) and 35 consecutive patients (59.0±13.2 years of age) with myocardial infarctions underwent cardiopulmonary exercise tests with an RAMP protocol ergometer. The HRV was continuously assessed with power spectral analyses using the maximum entropy method and projected on a screen without delay. During exercise, a significant decrease in the high frequency (HF) was followed by a drastic shift in the power spectrum of the HRV with a periodic augmentation in the low frequency/HF (L/H) and steady low HF. When the HRV threshold (HRVT) was defined as conversion from a predominant high frequency (HF) to a predominant low frequency/HF (L/H), the VO2 at the HRVT (HRVT-VO2) was substantially correlated with the VO2 at the lactate threshold and VT) in the healthy subjects (r=0.853 and 0.921, respectively). The mean difference between each threshold (0.65 mL/kg per minute for lactate threshold and HRVT, 0.53 mL/kg per minute for VT and HRVT) was nonsignificant (P > 0.05). Furthermore, the HRVT-VO2 was also correlated with the VT-VO2 in these myocardial infarction patients (r=0.867), and the mean difference was -0.72 mL/kg per minute and was nonsignificant (P > 0.05). Conclusions: A HRV analysis with our method enabled real-time visualization of the changes in the power spectrum during exercise. This can provide additional information for detecting the VT.

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Degree of dyspnoea in patients with non-ST-elevation acute coronary syndrome: A report from Japanese multicenter registry.

Shiraishi Y, Kohsaka S, Ueda I, Inohara T, Sawano M, Numasawa Y, Hayashida K, Maekawa Y, Momiyama Y, Fukuda K

International Journal of Clinical Practice 70 ( 12 ) 978 - 987 2016.12

Research paper (scientific journal), Lead author, Accepted,  ISSN  1368-5031

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Correlation of Pre- and In-Hospital Systolic Blood Pressure in Acute Heart Failure Patients and the Prognostic Implications　- Report From the Tokyo Cardiac Care Unit Network Emergency Medical Service Database.

Shiraishi Y, Kohsaka S, Harada K, Miyamoto T, Tanimoto S, Iida K, Sakai T, Miyazaki T, Yagawa M, Matsushita K, Furihata S, Sato N, Fukuda K, Yamamoto T, Nagao K, Takayama M, Tokyo CCU Network Scientific Committee.

Circulation Journal 80 ( 12 ) 2473 - 2481 2016.11

Research paper (scientific journal), Lead author, Accepted,  ISSN  1346-9843

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Endomyocardial fibrosis: missing tricuspid valve and Fontan-like circulation.

Shiraishi Y, Kohno T, Fujii-Nishimura Y, Shimoda M, Ikeda Y, Nakajima K, Nishiyama T, Nishiyama N, Murata M, Maekawa Y, Sano M, Fukuda K

Heart and Vessels 31 ( 9 ) 1579 - 82 2016.09

Research paper (scientific journal), Lead author, Accepted,  ISSN  0910-8327

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Validation of the Seattle Heart Failure Model in Japanese heart failure patients.

Shiraishi Y, Sawano M, Kohno T, Nishiyama T, Maekawa Y, Sano M, Fukuda K, Kohsaka S

International Journal of Cardiology 203   87 - 9 2016.01

Research paper (scientific journal), Lead author, Accepted,  ISSN  0167-5273

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Validation of the Get With The Guideline-Heart Failure risk score in Japanese patients and the potential improvement of its discrimination ability by the inclusion of B-type natriuretic peptide level.

Shiraishi Y, Kohsaka S, Abe T, Mizuno A, Goda A, Izumi Y, Yagawa M, Akita K, Sawano M, Inohara T, Takei M, Kohno T, Higuchi S, Yamazoe M, Mahara K, Fukuda K, Yoshikawa T, West Tokyo Heart Failure Registry Investigators.

American Heart Journal 171 ( 1 ) 33 - 9 2016.01

Research paper (scientific journal), Lead author, Accepted,  ISSN  0002-8703

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Thrombus in acute aortic dissection with atrial fibrillation: a treatment dilemma.

Shiraishi Y, Kohno T, Egashira T, Maekawa Y, Yamada Y, Yoshitake A, Shimizu H, Sano M, Jinzaki M, Fukuda K

American Journal of Emergency Medicine 33 ( 2 ) 308.e3 - 4 2015.02

Research paper (scientific journal), Lead author, Accepted,  ISSN  0735-6757

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Time Interval from Symptom Onset to Hospital Care in Patients with Acute Heart Failure: A Report from the Tokyo Cardiac Care Unit Network Emergency Medical Service Database.

Shiraishi Y, Kohsaka S, Harada K, Sakai T, Takagi A, Miyamoto T, Iida K, Tanimoto S, Fukuda K, Nagao K, Sato N, Takayama M, Scientific Committee of Tokyo CCU Network.

PloS One 10 ( 11 ) e0142017 2015

Research paper (scientific journal), Lead author, Accepted

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Comments on "the role of the emergency department in acute heart failure clinical trials-Enriching patient identification and enrollment" by Collins et al.

Shiraishi Y, Kohsaka S, Sakai T, Harada K, Sato N, Takagi A, Miyamoto T, Fukuda K, Nagao K, Takayama M

American Heart Journal 166 ( 6 ) e45 - 6 2013.12

Research paper (scientific journal), Lead author, Accepted,  ISSN  0002-8703

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Primary aldosteronism associated with a giant coronary aneurysm after drug-eluting stent implantation.

Shiraishi Y, Tanaka H, Hayashi T, Inui Y, Takayama E, Ikegami Y, Fuse J, Sakamoto M, Chong T, Momiyama Y

Journal of Cardiology Cases 7 ( 1 ) e11 - e14 2013.01

Research paper (scientific journal), Lead author, Accepted

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Association of Tricuspid Regurgitation With Mortality in Heart Failure With Left-Sided Heart Disease

Kitamura M., Amami K., Yaguchi T., Okabe K., Shiraishi Y., Nakamaru R., Nagatomo Y., Goda A., Nomoto M., Mizuno A., Sakamoto M., Ichihara Y.K., Kohno T., Kohsaka S., Yoshikawa T.

Jacc Advances 4 ( 6P1 ) 101832 2025.06

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Background: Left-sided heart disease is the leading etiology of tricuspid regurgitation (TR) in heart failure (HF); however, the association between different HF phenotypes and the adverse effects of TR remains unclear. Objectives: The authors aimed to elucidate the association between TR and outcomes across the subtypes of left-sided heart disease in patients hospitalized for HF. Methods: We analyzed data from the multicenter West Tokyo Heart Failure registry between January 2006 and December 2021. Moderate or severe mitral or aortic valve disease was defined as left-sided valve dysfunction (LVD). Patients with congenital heart disease, secondary cardiomyopathy, systemic conditions related to HF, or those with incomplete datasets were excluded. Using a multivariable Cox hazard model, the survival effect of TR on mortality in patients with LVD was examined. Results: Overall, 3,040 presented with LVD (median age, 80 years; 45.9% female), and 2,438 had no LVD (median age, 74 years; 27.8% female). The prevalence of moderate and severe TR was 27.6% and 6.5% in patients with LVD and 9.2% and 1.5% in those without LVD, respectively. The adjusted HRs of moderate and severe TR for mortality were 1.25 (95% CI: 1.03-1.52) and 1.72 (95% CI: 1.30-2.29) in those with LVD, respectively, and 2.15 (95% CI: 1.62-2.84) and 3.09 (95% CI: 1.87-5.09) in those without LVD, respectively. Significant interactions between the subtypes were observed (P = 0.005). Conclusions: TR severity stratified mortality after acute decompensated HF better in patients without LVD than in those with LVD.

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Exercise hemodynamic evaluation in the management of dasatinib-related pulmonary arterial hypertension: a case report.

Yamashita S, Hiraide T, Shiraishi Y, Katsumata Y, Kataoka M, Fukui S, Kawakami M, Yuasa S, Okamoto S, Fukuda K, Ieda M

Journal of medical case reports 19 ( 1 ) 209 2025.05

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Background: Dasatinib-related pulmonary arterial hypertension is a rare complication of chronic therapy for hematological malignancies. Pulmonary hypertension often persists despite drug discontinuation and might require vasodilators. Normalizing pulmonary hemodynamics and avoiding the long-term use of vasodilators is challenging. Case presentation: Patient was a 55-year-old Japanese man complaining of progressive dyspnea on effort and fatigue. He had a history of hypertension and chronic myeloid leukemia treated with dasatinib. He was diagnosed with dasatinib-related pulmonary arterial hypertension by a right heart catheterization at rest, demonstrating a mean pulmonary artery pressure of 31 mmHg and a normal pulmonary arterial wedge pressure of 6 mmHg. Symptoms and hemodynamics significantly improved after the discontinuation of dasatinib and the initiation of upfront combination therapy of vasodilators. An exercise right heart catheterization, performed more than 2 years after the initiation of vasodilators, showed a mean pulmonary artery pressure of 15 mmHg at rest and 29 mmHg at peak exercise (normal reference value, < 30 mmHg), suggesting normal pulmonary microcirculation. On the basis of these findings, pulmonary vasodilators were discontinued. Notably, a repeat exercise right heart catheterization demonstrated preserved pulmonary microcirculation, and the patient has remained asymptomatic for more than 2 years after discontinuing pulmonary-arterial-hypertension-targeted therapy. Conclusions: The evaluation of pulmonary microcirculation by exercise right heart catheterization can be useful for withdrawing pulmonary vasodilators safely in the management of patients with dasatinib-related pulmonary arterial hypertension.

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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)  2025.03

ISSN  1355-6037

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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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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

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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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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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COVID-19パンデミックが急性心不全診療における呼吸器管理に与える影響

中野 宏己, 山下 淳, 河野 隆志, 北野 大輔, 木庭 新治, 白石 泰之, 進藤 彰人, 神馬 崇宏, 武井 眞, 塚本 茂人, 松下 健一, 松田 淳也, 原田 和昌, 香坂 俊, 長尾 建, 山本 剛, 高山 守正, 東京都CCUネットワーク学術委員会

ICUとCCU (医学図書出版(株))  48 ( 別冊 ) S43 - S46 2024.12

ISSN  0389-1194

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【背景】COVID-19パンデミック下では急性心不全患者における非侵襲的陽圧換気(NPPV)の使用制限が予想され,患者予後への悪影響が懸念される。【方法】多施設共同前向きコホートである東京都CCUネットワークに登録された急性心不全患者を対象にCOVID-19流行前の2019年に登録された5,233人とCOVID-19パンデミック下2020年に登録された4,499人の2群間で比較検討した。【結果】COVID-19流行前後でNPPVの使用率は有意に減少し(41.4% vs.32.3%,P<0.001),気管挿管の施行率は上昇した(4.2% vs.6.9%,P<0.001)。一方で患者背景や院内死亡率に有意差を認めなかった(9.5% vs.9.3%,P=0.842)。気管挿管を施行された患者はCOVID-19流行前と比較してCOVID-19パンデミック下では若年で搬送時血圧が高い患者に使用され(145±44 vs.136±43,P=0.021),院内死亡率は低かった(18.3% vs.26.4%,P=0.028)。【結論】COVID-19パンデミック下における急性心不全診療において全体の予後への悪影響は認めなかったが,NPPV使用率が減少し,気管挿管施行率が上昇した。エアロゾル拡散が制御できるNPPV方法の導入が望まれる。(著者抄録)

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

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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  2024.11

ISSN  1071-9164

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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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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

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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

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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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