Clinical Outcomes of Autologous Stem Cell–Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy
Background Clinical effectiveness of autologous skeletal cell‐patch implantation for nonischemic dilated cardiomyopathy has not been clearly elucidated in clinical settings. This clinical study aimed to determine the feasibility, safety, therapeutic efficacy, and the predictor of responders of this...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-07-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.117.008649 |
| _version_ | 1797936120680415232 |
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| author | Keitaro Domae Shigeru Miyagawa Yasushi Yoshikawa Satsuki Fukushima Hiroki Hata Shunsuke Saito Satoshi Kainuma Noriyuki Kashiyama Hiroko Iseoka Emiko Ito Akima Harada Maki Takeda Yasushi Sakata Koichi Toda Kyongsun Pak Tomomi Yamada Yoshiki Sawa |
| author_facet | Keitaro Domae Shigeru Miyagawa Yasushi Yoshikawa Satsuki Fukushima Hiroki Hata Shunsuke Saito Satoshi Kainuma Noriyuki Kashiyama Hiroko Iseoka Emiko Ito Akima Harada Maki Takeda Yasushi Sakata Koichi Toda Kyongsun Pak Tomomi Yamada Yoshiki Sawa |
| author_sort | Keitaro Domae |
| collection | DOAJ |
| description | Background Clinical effectiveness of autologous skeletal cell‐patch implantation for nonischemic dilated cardiomyopathy has not been clearly elucidated in clinical settings. This clinical study aimed to determine the feasibility, safety, therapeutic efficacy, and the predictor of responders of this treatment in patients with nonischemic dilated cardiomyopathy. Methods and Results Twenty‐four nonischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% on optimal medical therapy were enrolled. Autologous cell patches were implanted over the surface of the left ventricle through left minithoracotomy without procedure‐related complications and lethal arrhythmia. We identified 13 responders and 11 nonresponders using the combined indicator of a major cardiac adverse event and incidence of heart failure event. In the responders, symptoms, exercise capacity, and cardiac performance were improved postoperatively (New York Heart Association class II 7 [54%] and III 6 [46%] to New York Heart Association class II 12 [92%] and I 1 [8%], P<0.05, 6‐minute walk test; 471 m [370–541 m] to 525 m [425–555 m], P<0.05, left ventricular stroke work index; 31.1 g·m2·beat [22.7–35.5 g·m2·beat] to 32.8 g·m2·beat [28–38.5 g·m2·beat], P=0.21). However, such improvement was not observed in the nonresponders. In responders, the actuarial survival rate was 90.9±8.7% at 5 years, which was superior to the estimated survival rate of 70.9±5.4% using the Seattle Heart Failure Model. However, they were similar in nonresponders (47.7±21.6% and 56.3±8.1%, respectively). Multivariate regression model with B‐type natriuretic peptide, pulmonary capillary wedge pressure, and expression of histone H3K4me3 (H3 lysine 4 trimethylation) strongly predicted the responder of this treatment (B‐type natriuretic peptide: odds ratio [OR], 0.96; pulmonary capillary wedge pressure: OR, 0.58; H3K4me3: OR, 1.35, receiver operating characteristic–area under the curve, 0.96, P<0.001). Conclusions This clinical trial demonstrated that autologous skeletal stem cell–patch implantation might promise functional recovery and good clinical outcome in selected patients with nonischemic dilated cardiomyopathy, in addition to safety and feasibility. Registration URL: http://www.umin.ac.jp/english/. Unique identifiers: UMIN000003273, UMIN0000012906 and UMIN000015892. |
| first_indexed | 2024-04-10T18:24:48Z |
| format | Article |
| id | doaj.art-a53220ff04544c758184aee3f0e3ad32 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-10T18:24:48Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-a53220ff04544c758184aee3f0e3ad322023-02-02T06:18:05ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802021-07-01101310.1161/JAHA.117.008649Clinical Outcomes of Autologous Stem Cell–Patch Implantation for Patients With Heart Failure With Nonischemic Dilated CardiomyopathyKeitaro Domae0Shigeru Miyagawa1Yasushi Yoshikawa2Satsuki Fukushima3Hiroki Hata4Shunsuke Saito5Satoshi Kainuma6Noriyuki Kashiyama7Hiroko Iseoka8Emiko Ito9Akima Harada10Maki Takeda11Yasushi Sakata12Koichi Toda13Kyongsun Pak14Tomomi Yamada15Yoshiki Sawa16Department of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiology Osaka University Graduate School of Medicine Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanDivision of Biostatistics Clinical Research Center National Center for Child Health and Development Tokyo JapanDepartment of Medical Innovation Data Coordinating Center Osaka University Hospital Osaka JapanDepartment of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka JapanBackground Clinical effectiveness of autologous skeletal cell‐patch implantation for nonischemic dilated cardiomyopathy has not been clearly elucidated in clinical settings. This clinical study aimed to determine the feasibility, safety, therapeutic efficacy, and the predictor of responders of this treatment in patients with nonischemic dilated cardiomyopathy. Methods and Results Twenty‐four nonischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% on optimal medical therapy were enrolled. Autologous cell patches were implanted over the surface of the left ventricle through left minithoracotomy without procedure‐related complications and lethal arrhythmia. We identified 13 responders and 11 nonresponders using the combined indicator of a major cardiac adverse event and incidence of heart failure event. In the responders, symptoms, exercise capacity, and cardiac performance were improved postoperatively (New York Heart Association class II 7 [54%] and III 6 [46%] to New York Heart Association class II 12 [92%] and I 1 [8%], P<0.05, 6‐minute walk test; 471 m [370–541 m] to 525 m [425–555 m], P<0.05, left ventricular stroke work index; 31.1 g·m2·beat [22.7–35.5 g·m2·beat] to 32.8 g·m2·beat [28–38.5 g·m2·beat], P=0.21). However, such improvement was not observed in the nonresponders. In responders, the actuarial survival rate was 90.9±8.7% at 5 years, which was superior to the estimated survival rate of 70.9±5.4% using the Seattle Heart Failure Model. However, they were similar in nonresponders (47.7±21.6% and 56.3±8.1%, respectively). Multivariate regression model with B‐type natriuretic peptide, pulmonary capillary wedge pressure, and expression of histone H3K4me3 (H3 lysine 4 trimethylation) strongly predicted the responder of this treatment (B‐type natriuretic peptide: odds ratio [OR], 0.96; pulmonary capillary wedge pressure: OR, 0.58; H3K4me3: OR, 1.35, receiver operating characteristic–area under the curve, 0.96, P<0.001). Conclusions This clinical trial demonstrated that autologous skeletal stem cell–patch implantation might promise functional recovery and good clinical outcome in selected patients with nonischemic dilated cardiomyopathy, in addition to safety and feasibility. Registration URL: http://www.umin.ac.jp/english/. Unique identifiers: UMIN000003273, UMIN0000012906 and UMIN000015892.https://www.ahajournals.org/doi/10.1161/JAHA.117.008649cardiac regenerative therapyheart failurenonischemic dilated cardiomyopathy |
| spellingShingle | Keitaro Domae Shigeru Miyagawa Yasushi Yoshikawa Satsuki Fukushima Hiroki Hata Shunsuke Saito Satoshi Kainuma Noriyuki Kashiyama Hiroko Iseoka Emiko Ito Akima Harada Maki Takeda Yasushi Sakata Koichi Toda Kyongsun Pak Tomomi Yamada Yoshiki Sawa Clinical Outcomes of Autologous Stem Cell–Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiac regenerative therapy heart failure nonischemic dilated cardiomyopathy |
| title | Clinical Outcomes of Autologous Stem Cell–Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy |
| title_full | Clinical Outcomes of Autologous Stem Cell–Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy |
| title_fullStr | Clinical Outcomes of Autologous Stem Cell–Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy |
| title_full_unstemmed | Clinical Outcomes of Autologous Stem Cell–Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy |
| title_short | Clinical Outcomes of Autologous Stem Cell–Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy |
| title_sort | clinical outcomes of autologous stem cell patch implantation for patients with heart failure with nonischemic dilated cardiomyopathy |
| topic | cardiac regenerative therapy heart failure nonischemic dilated cardiomyopathy |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.117.008649 |
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