Hidenori Yaku, MD, PhD

Improving the prevention, diagnosis, treatment, and prognosis of HFpEF

Overview

I am a cardiologist and physician-scientist (MD, 2009; PhD, 2019) focusing on heart failure, specifically heart failure with preserved ejection fraction (HFpEF). HFpEF is a growing global challenge, yet remains under-recognized and lacks effective therapies. My expertise spans real-world data generation, clinical trial design, and interventional cardiology. I co-led one of Japan’s largest HF registries (KCHF), shaping national practice guidelines. I also conceptualized and co-led GOREISAN-HF, a multicenter RCT evaluating a novel decongestive strategy based on traditional Japanese medicine. During my postdoctoral fellowship with Dr. Sanjiv Shah at Northwestern University, I led investigator-initiated studies on HFpEF, secured multiple peer-reviewed U.S. grants, and advanced international collaborations. Currently, I am working at the Department of Heart Failure and Transplantation at the National Cerebral and Cardiovascular Center in Japan, aiming to accelerate Asia-based innovation through precision medicine, deep phenotyping, and registry harmonization. I welcome global partnerships to advance mechanism-based research and care for HFpEF.

Contributions to Science

Yaku H, Saito N, Imai M, et al. Utility of a 3-Dimensional Printed Model to Simulate Transcatheter Aortic Valve Implantation in a Patient With an Intramural Hematoma and a Penetrating Atherosclerotic Ulcer in the Distal Aortic Arch. Circ Cardiovasc Interv. 2018 Dec;11(12):e006925.

“Patient-Specific Simulation Studies for Optimizing Structural Heart Interventions”

As an interventional cardiologist at Mitsubishi Kyoto Hospital and Kyoto University Hospital, my projects primarily focused on examining the safety of performing transcatheter aortic valve replacement (TAVR) procedures and evaluating the long-term outcomes of novel coronary interventions. In TAVR, the transfemoral approach is preferred due to its less invasive nature and fewer reported complications. However, certain conditions may prohibit its use. One of our innovative projects involved creating 3-dimensional (3D) printer models of high-risk TAVR patients to simulate procedures in advance, aiming to prevent complications. We reported on a groundbreaking pre-procedural simulation for an older woman with an intramural hematoma and a penetrating atherosclerotic ulcer in the distal aortic arch. Using the patient's multislice computed tomography data, we constructed a patient-specific 3D organ model with a 3D printer. Under fluoroscopy, we conducted in vitro experiments comparing the force applied to the distal aortic arch by different valve types. This simulation effectively determined the safest treatment strategy, representing the first case of constructing a 3D aortic model based on patient data and measuring pressure applied to the aortic wall during valve advancement.

Yaku H, Ozasa N, Morimoto T, et al. Demographics, Management, and In-Hospital Outcome of Hospitalized Acute Heart Failure Syndrome Patients in Contemporary Real Clinical Practice in Japan. Circ J. 2018 Oct 25;82(11):2811-2819.

Yaku H, Kato T, Morimoto T, et al. Association of Mineralocorticoid Receptor Antagonist Use With All-Cause Mortality and Hospital Readmission in Older Adults With ADHF. JAMA Netw Open. 2019 Jun 5;2(6):e195892.

Yaku H, Seko Y, Kato T, et al. Prognostic Implications of Residual Pleural Effusions at Discharge in Patients with Acute Decompensated Heart Failure. Eur J Intern Med. 2021;85:133-135.

“Building a National Heart Failure Registry to Advance Evidence-Based Care for an Aging Population”

During my Ph.D. program, I conducted a multicenter prospective registry called the Kyoto Congestive Heart Failure (KCHF) Registry, which enrolled 4,056 consecutive hospitalized patients with acute HF. This registry is the largest cohort of acute HF registry in Japan and has provided a great deal of knowledge to the world. First, I presented the overall picture of the registry at the Late Breaking Session of the 2017 Annual Meeting of the Japanese Society of Cardiology, highlighting the current situation where the number of patients with HFpEF, the topic of this study, has increased considerably, especially among the elderly. The results were immediately published as a scientific paper, which has been highly cited. In addition, numerous sub-analyses have been conducted, and many peer-reviewed papers have been published based on this registry, offering recommendations for improving HF care from various angles, including both medical and social issues. For example, we reported that administering mineralocorticoid receptor antagonists to older HFpEF patients was associated with a decrease in HF rehospitalization, significantly impacting actual clinical practice. In these studies, the problems that need to be solved in HF treatment in Japan, which has the world's highest aging population, have become more apparent. Notably, we need to utilize the various expertise we have accumulated to promote further clinical research focused on HFpEF, for which there is still no established treatment, despite the increasing number of patients. I believe that these findings will provide valuable information for other countries, such as the US, where the elderly population is expected to continue increasing in the future.

Yaku H, Kato T, Morimoto T, et al. Rationale and study design of the GOREISAN for heart failure (GOREISAN-HF) trial: A randomized clinical trial. Am Heart J. 2023 Jun;260:18-25.

Yaku H, Kaneda K, Kitamura J, et al. Kampo medicine for the holistic approach to older adults with heart failure. J Cardiol. 2022 Oct;80(4):306-312.

Kawaji T, Shizuta S, Yaku H, et al. Efficacy and safety of Saireito (TJ-114) in patients with atrial fibrillation undergoing catheter ablation procedures: A randomized pilot study. PLoS One. 2024;19(8): e0307854.

“Integrating Traditional Medicine into Modern Heart Failure Care: The GOREISAN-HF Trial”

The decongestion strategy using loop diuretics is crucial for alleviating signs and symptoms of HF. However, chronic use of loop diuretics in HF has been linked to worsening renal function and adverse clinical outcomes in a dose-dependent manner. Goreisan, a traditional Japanese herbal medicine, has a long history of use in Japan for regulating body fluid homeostasis and has been recognized as causing fewer adverse outcomes, such as dehydration, compared to loop diuretics in clinical practice. Therefore, we designed the GOREISAN-HF trial to evaluate the long-term effects of a novel decongestion strategy, which involves adding Goreisan to usual care, in patients with HF and volume overload. The GOREISAN-HF trial is an investigator-initiated, multicenter, pragmatic, randomized, comparative effectiveness trial in which we will enroll 1,164 patients hospitalized for HF at 82 hospitals in Japan. This trial is ongoing, and I am providing leadership as the co-principal investigator. All study participants will be randomly assigned to either a decongestion strategy that includes Goreisan at a dose of 7.5 g daily in addition to usual care or usual care alone. Investigators have the flexibility to change the existing diuretic regimen in both groups. The primary endpoint is the improvement rate of cardiac edema at 12-month follow-up, and the co-primary endpoint is a composite of all-cause death or hospitalization up to the end of the planned follow-up period. Secondary endpoints include longitudinal changes in patient-reported outcomes, loop diuretic dose, and renal function. If this trial yields promising results, it may have significant implications for reducing the adverse effects of existing diuretics, such as dehydration, potentially leading to an improvement in the long-term prognosis and quality of life for patients with HF.

Yaku H, Sauer AJ, Patel S, O'Keefe EL, Borlaug BA, Kitzman DW, Windsor SL, Khumri T, Umpierrez G, Kosiborod MN, Shah SJ. Orthostatic Pulse Pressure as a Potential Indicator of Preload Insufficiency in HFpEF: Insights From PRESERVED-HF. JACC Heart Fail. 2025 Jul 25;13(9):102566.

“Orthostatic Pulse Pressure as a Potential Indicator of Preload Insufficiency in HFpEF: Insights From PRESERVED-HF”

This post-hoc analysis of the PRESERVED-HF randomized trial examined whether baseline orthostatic pulse pressure (PP)—defined as standing PP minus supine PP—modifies the effects of dapagliflozin in patients with HFpEF. Orthostatic PP was proposed as a surrogate for preload reserve, volume status, and tolerance to acute preload changes. Among 321 participants (median age 70 years, 57% female), median orthostatic PP was 0 mmHg (IQR −8.0 to +5.3 mmHg). Patients in the lowest tertile had higher supine SBP/PP and used more antihypertensives, but otherwise had similar clinical characteristics and functional status to higher tertiles. Dapagliflozin improved health status (KCCQ-CSS) and 6-minute walk distance compared with placebo across all orthostatic PP tertiles, with no statistically significant treatment-PP interaction. However, volume depletion events were numerically more frequent with dapagliflozin in the lowest orthostatic PP tertile (14.3% vs. 4.0% with placebo), whereas rates were similar in higher tertiles. The findings suggest that while dapagliflozin’s symptomatic and functional benefits in HFpEF are consistent regardless of orthostatic PP, patients with very low orthostatic PP may be more susceptible to adverse events related to preload reduction. Orthostatic PP measurement is a simple, potentially valuable bedside tool to identify HFpEF patients at higher risk for volume depletion during decongestive therapy. Further prospective studies are warranted to validate its role in guiding treatment decisions.

Yaku H,

“Towards Precision Medicine in HFpEF: Ongoing International Cohort Studies and Their Potential Impact”

Despite the growing recognition of HFpEF as a heterogeneous syndrome, optimal approaches for patient phenotyping and risk stratification remain insufficiently defined. In response to these challenges, multiple international cohort initiatives have emerged to advance our understanding of HFpEF pathophysiology through diverse deep phenotyping strategies. This white paper reviews five key international HFpEF cohort studies: HeartShare (US), CRC 1470 (Germany), UK HFpEF (UK), PACIFIC-PRESERVED (France), and the Canadian Cardiomyopathy Collaborative AID-HF study (Canada). These initiatives employ distinct yet complementary methodologies, ranging from molecular characterization and multi-omics profiling to continuous physiological monitoring and artificial intelligence-driven risk prediction. Collectively, they offer a unique opportunity to refine HFpEF phenotyping, enhance risk stratification, and inform targeted therapeutic development. However, representation remains a critical gap, not only geographically with most efforts concentrated in North America and Europe, but also concerning the inclusion of underrepresented groups such as women and racial/ethnic minorities within these regions. Expanding these initiatives globally and ensuring diverse participation are essential for the applicability of findings. Additionally, effective data integration and open-sharing frameworks are necessary to maximize scientific collaboration while addressing ethical, regulatory, and methodological challenges. By leveraging the strengths of these international efforts, HFpEF research can transition from being viewed as a broadly defined syndrome to a collection of well-characterized subtypes, each with tailored therapeutic strategies. Here, we outline key considerations for ongoing and future collaboration, emphasizing the need for standardized analytical frameworks, robust data integration, and interdisciplinary partnerships. Achieving true precision medicine in HFpEF demands a concerted, global commitment from dedicated researchers and collaborators prepared to tackle these complex challenges

Education/Work

Education

2015-2019 PhD, Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University

2003-2009 MD, University of Fukui School of Medicine

Professional experience

2025-present Senior Cardiologist, Division of Heart Failure and Structural Heart Disease, Department of Heart Failure and Transplantation, National Cerebral and Cardiovascular Center, Osaka, Japan

2022-2025 Postdoctoral Fellow, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

2019-2022 Staff Cardiologist, Department of Cardiology, Mitsubishi Kyoto Hospital, Kyoto, Japan

2019-present Visiting Researcher, Kyoto University Graduate School of Medicine

2019 Staff Cardiologist, Department of Cardiology, Kyoto University Hospital, Kyoto, Japan

2015-2019 Graduate Student Researcher, Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University

2011-2015 Senior Resident in Cardiology, Mitsubishi Kyoto Hospital, Kyoto, Japan

2009-2011 Junior Resident in Internal Medicine, Rakuwakai Otowa Hospital, Kyoto, Japan

Borad certification and professional memberships

2025-present Elected Fellow, Heart Failure Society of America

2022-present Professional Member, American Heart Association

2022-present Professional Member, Heart Failure Society of America

2021-present ESC, HFA certification for professionals specializing in heart failure

2019-present Board Certified Member, Japan Transcatheter Valve Therapies

2017-present Professional Member, Japanese Heart Failure Society

2017-present Professional Member, European Society of Cardiology

2015-present Board Certified Specialist, Japanese Circulation Society

2015-present Board Certified Member, Japanese Association of Cardiovascular Intervention and Therapeutics

2015-present International Associate, American College of Cardiology

2009-present Board Certified Member, Japanese Society of Internal Medicine

Hidenori Yaku, MD, PhD/ 夜久　英憲

〒564-8565 大阪府吹田市岸部新町6番1号

E-mail: hide.yaku[at]ncvc.go.jp

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