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Clinical trajectories and outcomes of patients with heart failure with preserved ejection fraction with normal or indeterminate diastolic function

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Abstract

Background

We recently reported that nearly half of patients with heart failure with preserved ejection fraction (HFpEF) did not show echocardiographic diastolic dysfunction (DD), but had normal diastolic function (ND) or indeterminate diastolic function (ID). However, the clinical course and outcomes of patients with HFpEF with ND or ID (ND/ID) remain unknown.

Methods

From the PURSUIT–HFpEF registry, we extracted 289 patients with HFpEF with ND/ID at discharge who had echocardiographic data at 1-year follow-up. Patients were classified according to the status of progression from ND/ID to DD at 1 year. Primary endpoint was a composite of all-cause death or HF rehospitalization.

Results

Median age was 81 years, and 138 (47.8%) patients were female. At 1 year, 107 (37%) patients had progressed to DD. The composite endpoint occurred in 90 (31.1%) patients. Compared to patients without progression to DD, those with progression had a significantly higher cumulative rate of the composite endpoint (P < 0.001) and HF rehospitalization (P < 0.001) after discharge and at the 1-year landmark (P = 0.030 and P = 0.001, respectively). Progression to DD was independently associated with the composite endpoint (hazard ratio (HR): 2.014, 95%CI 1.239–3.273, P = 0.005) and HF rehospitalization (HR: 2.362, 95%CI 1.402–3.978) after discharge. Age (odds ratio (OR): 1.043, 95%CI 1.004–1.083, P = 0.031), body mass index (BMI) (OR: 1.110, 95%CI 1.031–1.195, P = 0.006), and albumin (OR: 0.452, 95%CI 0.211–0.969, P = 0.041) were independently associated with progression from ND/ID to DD.

Conclusions

More than one-third of HFpEF patients with ND/ID progressed to DD at 1 year and had poor outcomes. Age, BMI and albumin were independently associated with this progression.

UMIN-CTR ID: UMIN000021831.

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Acknowledgements

The authors would like to thank Sugako Mitsuoka, Nagisa Yoshioka, Satomi Kishimoto, Kyoko Tatsumi and Noriko Murakami for their excellent assistance in data collection, data management and secretarial work. The OCVC-Heart Failure Investigators: Masahiro Seo, Tetsuya Watanabe, and Takahisa Yamada, Osaka General Medical Center, Osaka, Japan; Takaharu Hayashi and Yoshiharu Higuchi, Osaka Police Hospital, Osaka, Japan; Masaharu Masuda, Mitsutoshi Asai, and Toshiaki Mano, Kansai Rosai Hospital, Amagasaki, Japan; Hisakazu Fuji, Kobe Ekisaikai Hospital, Kobe, Japan; Shunsuke Tamaki, Daisaku Masuda, Ryu Shutta, and Shizuya Yamashita, Rinku General Medical Center, Izumisano, Japan; Masami Sairyo and Yusuke Nakagawa, Kawanishi City Hospital, Kawanishi, Japan; Haruhiko Abe, Yasunori Ueda, and Yasushi Matsumura, National Hospital Organization Osaka National Hospital, Osaka, Japan; Kunihiko Nagai, Ikeda Municipal Hospital, Ikeda, Japan; Masamichi Yano, Masami Nishino, and Jun Tanouchi, Osaka Rosai Hospital, Sakai, Japan; Yoh Arita and, Nobuyuki Ogasawara, Japan Community Health Care Organization Osaka Hospital, Osaka, Japan; Takamaru Ishizu, Minoru Ichikawa and Yuzuru Takano, Higashiosaka City Medical Center, Higashiosaka, Japan; Eisai Rin, Kawachi General Hospital, Higashiosaka, Japan; Yukinori Shinoda, Koichi Tachibana and Shiro Hoshida, Yao Municipal Hospital, Yao, Japan; Masahiro Izumi, Kinki Central Hospital, Itami, Japan; Hiroyoshi Yamamoto and Hiroyasu Kato, Japan Community Health Care Organization, Osaka Minato Central Hospital, Osaka, Japan; Kazuhiro Nakatani and Yuji Yasuga, Sumitomo Hospital, Osaka, Japan; Mayu Nishio and Keiji Hirooka, Saiseikai Senri Hospital, Suita, Japan; Takahiro Yoshimura, Kazunori Kashiwase and Shinji Hasegawa, National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Japan; Akihiro Tani, Kano General Hospital, Osaka, Japan; Yasushi Okumoto, Kinan Hospital, Tanabe, Japan; Yasunaka Makino, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan; Toshinari Onishi and Katsuomi Iwakura, Sakurabashi Watanabe Hospital, Osaka, Japan; Yoshiyuki Kijima, Japan Community Health Care Organization, Hoshigaoka Medical Center, Hirakata, Japan; Takashi Kitao, Minoh City Hospital, Minoh, Japan; Masashi Fujita, Osaka International Cancer Institute, Osaka, Japan; Koichiro Harada, Suita Municipal Hospital, Suita, Japan; Masahiro Kumada and Osamu Nakagawa, Toyonaka Municipal Hospital, Toyonaka, Japan; Ryo Araki and Takayuki Yamada, Otemae Hospital, Osaka, Japan; Akito Nakagawa and Yoshio Yasumura, Amagasaki Chuo Hospital, Amagasaki, Japan; and Yuki Matsuoka, Taiki Sato, Akihiro Sunaga, Bolrathanak Oeun, Hirota Kida, Yohei Sotomi, Tomoharu Dohi, Yasuhiro Akazawa, Kei Nakamoto, Katsuki Okada, Fusako Sera, Hidetaka Kioka, Tomohito Ohtani, Toshihiro Takeda, Daisaku Nakatani, Hiroya Mizuno, Shungo Hikoso, and Yasushi Sakata, Osaka University Graduate School of Medicine, Suita, Japan.

Funding

This work was funded by Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.

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Contributions

All authors made substantial contributions to the study conception and design. BO: conceptualization, methodology, formal analysis, investigation, writing—original draft, visualization; SH: conceptualization, methodology, investigation, writing—original draft, supervision, project administration; DN, HM, TK, KO, TD, and YS: methodology, investigation, supervision, writing—review and editing; HK, AS, TS, and YM: methodology, investigation, validation, writing—review and editing; HK and TY: data curation, supervision, validation, writing—review and editing; ST, MS, MY, TH, AN, and YN: investigation, writing—review and editing; TY and YY: supervision, investigation, writing—review and editing; YS: funding acquisition, supervision, project administration, investigation, writing—review and editing. All authors read and approved the final manuscript to be published.

Corresponding author

Correspondence to Shungo Hikoso.

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Conflict of interest

Shungo Hikoso reports a relationship with Daiichi Sankyo Company, Bayer, Astellas Pharma, Pfizer Pharmaceuticals, Novartis Pharmaceuticals, Kowa Company, Otsuka Pharmaceutical, AstraZeneca, Eli Lilly Japan, and Boehringer Ingelheim Japan that includes speaking and lecture fees. Shungo Hikoso reports a relationship with Roche Diagnostics, FUJIFILM Toyama Chemical that includes funding grants. Daisaku Nakatani reports a relationship with Roche Diagnostics that includes speaking and lecture fees. Hiroya Mizuno reports a relationship with Daiichi Sankyo Company, Kowa Company, Bayer and Pfizer Pharmaceuticals that includes speaking and lecture fees. Hiroya Mizuno reports a relationship with Terumo that includes funding grants. Yohei Sotomi reports a relationship with Abbott Vascular Japan, Boston Scientific Japan, TERUMO, Japan Lifeline, Biosensors, Medtronic, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, and Bristol-Myers Squibb that includes funding grants and speaking and lecture fees. Yohei Sotomi reports a relationship with TERUMO, Asahi Intecc, NIPRO, and Shimadzu Corporation that includes consulting or advisory fees. Yasushi Sakata reports a relationship with Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation and Actelion Pharmaceuticals that includes speaking and lecture fees. Yasushi Sakata reports a relationship with Roche Diagnostic, FUJIFILM Toyama Chemical, Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation and Biotronik that includes funding grants. Yasushi Sakata reports that financial support was provided by the Japan Society for the Promotion of Science and Japan Agency for Medical Research and Development. The other authors have no conflicts of interest to declare.

Ethics approval

The protocol of this study was reviewed and approved by the institutional review board (IRB) of Osaka University Hospital (approval ID: 15471) and the IRBs of each participating hospital in compliance with the principles of the Declaration of Helsinki of the World Medical Association. Informed consent was obtained from all individual participants included in the study.

Additional information

The OCVC-Heart Failure Investigators are listed in acknowledgements section.

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Oeun, B., Hikoso, S., Nakatani, D. et al. Clinical trajectories and outcomes of patients with heart failure with preserved ejection fraction with normal or indeterminate diastolic function. Clin Res Cardiol 112, 145–157 (2023). https://doi.org/10.1007/s00392-022-02121-z

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