Results of the prospective multicenter Japanese bridge to transplant study with a continuous-flow left ventricular assist device

Abstract

Continuous-flow left ventricular assist devices (LVADs) are becoming the standard of care for patients with refractory end-stage heart failure. We present the outcomes of patients enrolled in a prospective multicenter clinical study in Japan using the HeartMate II continuous-flow LVAD for bridge to transplantation. The study evaluated 6 inotrope-dependent heart failure patients failing on medical management (3 males and 3 females, age 44.7 ± 15.8 years, BSA 1.58 ± 0.17 m²) implanted with the HMII LVAD at 5 Japanese centers. Functional status, adverse events and outcomes were determined for the first 6 months with follow-up at 2 years. After implant, functional improvement was evident in 6-min walk distance which increased from 268 ± 92 m at baseline to 399 ± 105 m at 6 months, and 100 % of patients were in NYHA class I or II at 6 months compared to 0 % at baseline. Adverse events included localized non-device-related infection (4/6), arrhythmias (3/6) and percutaneous lead infection (1/6). There were no re-thoracotomies for bleeding and no strokes or pump replacements. All patients were alive at 6 months and all were transplanted after 1.96–3.58 years of LVAD support. The results in Japan of the HMII LVAD for BTT are consistent with results from the US pivotal clinical trial. The expanded use of this technology to Japanese heart failure patients is appropriate.

Appendices

Appendix 1: Inclusion and exclusion criteria

Inclusion criteria

• 1. Patient or their legal representative has signed an informed consent.

• 2. Transplant candidates.

• 3. Body surface area (BSA) >1.3 m²

• 4. New York Heart Association class III with the history of class IV or class IV heart failure symptoms.

• 5. Female patients of childbearing potential must agree to use adequate contraceptive precautions (defined as oral contraceptives, intrauterine device, surgical contraceptive or a combination of condom and spermicide) for the duration of the study.

• 6. On inotropic support, if tolerated.

• 7. On medical therapy for heart failure.

• 8. Ages between 15 and 64 at signing an informed consent.

• 9. Sufficient supports from family and relatives.

• 10. Long-term observation should be agreed.

Exclusion criteria

• 1. Etiology of heart failure due to or associated with uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis or restrictive cardiomyopathy.

• 2. Technical obstacles, which pose an inordinately high surgical risk, in the judgment of the investigator.

• 3. Existence of any ongoing mechanical circulatory support other than intra-aortic balloon counterpulsation.

• 4. Body Mass Index (BMI) >40 kg/m².

• 5. Positive pregnancy test if of childbearing potential.

• 6. Presence of mechanical aortic cardiac valve that will not be converted to a bioprosthesis at the time of LVAD implant.

• 7. History of cardiac transplant.

• 8. Platelet count <50000/mL.

• 9. Evidence of an untreated aortic aneurysm >5 cm.

• 10. Psychiatric disease, irreversible cognitive dysfunction or psychosocial issues that are likely to impair compliance with the study protocol and LVAD management.

• 11. Presence of an active uncontrolled infection.

• 12. Intolerance to anticoagulant or antiplatelet therapies or to any operative therapies during and post surgery that will be required by the investigator due to the patient’s status.

• 13. An INR > 2.5 which is not due to anticoagulant therapy or Plavix administration within 5 days.

• 14. A total bilirubin that is >5 mg/dL, or shock liver (e.g., transaminases >2000), or biopsy proven liver cirrhosis.

• 15. History of severe COPD or severe restrictive lung disease.

• 16. Fixed pulmonary hypertension, with a most recent PVR > 6 Wood units, that is unresponsive to pharmacological intervention.

• 17. History of unresolved stroke or uncorrectable cerebrovascular disease.

• 18. Serum creatinine >3.5 mg/dL or the need for chronic renal replacement therapy (e.g., chronic dialysis).

• 19. Significant peripheral vascular disease accompanied by rest pain or extremity ulceration.

• 20. The patient has moderate to severe aortic insufficiency without plans for correction during pump implantation surgery.

• 21. Participation in any other clinical investigation that is likely to confound study results or affect study outcome.

Appendix 2: List of all contributors to this clinical trial

In addition to the authors, the following surgeons and cardiologists participated in this study: Tohoku University, Miyagi—Masatoshi Akiyama, Kiichiro Kumagai, Takumi Shibuya; The University of Tokyo—Noboru Motomura, Takeshi Nishimura, Aya Saito, Tsuyoshi Taketani, Kan Nawata, Motoyuki Hisagi, Osamu Kinoshita; Osaka University—Taichi Sakaguchi, Sigeru Miyagawa, Yasushi Yoshikawa, Takashi Yamauchi, Shunsuke Saito; Kyushu University—Atsuhiro Nakashima, Takahiro Nishida, Yoshihisa Tanoue, Yasuhisa Oishi, Hiromichi Sonoda.

Data Safety and Monitoring Board—Shinichi Takamoto, Mitsui Memorial Hospital; Motonobu Nishimura, Tottori University; Kenji Yamazaki, Tokyo Women’s Medical University; Kazuhiro Sase, Juntendo Univesity; Medical Consultant—Shunei Kyo; Mitsuaki Isobe, Tokyo Medical and Dental University.