Resting Heart Rate As a Predictor of Mortality in Patients with Hematological Diseases Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Isami Toshihiro , Nakase Koichi , Hashida Risa , Doi Yuki , Muneishi Manaka , Mori Yuki , Goto Yuki , Ueda Ryo , Itakusu Kyoko , Saeki Kyosuke , Nawa Yuichiro 
Published: December 2024

Background
Resting heart rate (RHR) has been identified as an independent predictor of mortality in patients with various solid tumors. However, in the context of hematological diseases, particularly among patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT), the prognostic value of RHR remains largely unexplored. While the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) is widely utilized for risk assessment in these patients, there is a lack of studies investigating how RHR might influence prognosis following HSCT. This study aims to address this gap by exploring the relationship between RHR and clinical outcomes in this specific patient population, thereby providing insights that could potentially enhance risk stratification.
Method
This study is a retrospective analysis of 165 adult patients with hematological diseases, including acute leukemia, myelodysplastic syndrome, malignant lymphoma, primary myelofibrosis, and aplastic anemia, who received allogeneic HSCT at our institution (the transplantation center in Chugoku-Shikoku region in Japan) between January 2015 and December 2023. Eighteen patients with unknown outcomes were excluded, resulting in a final cohort of 147 patients. The patients were categorized into two groups based on their condition at the start of conditioning therapy: complete remission (CR) or non-complete remission (non-CR). The impact of RHR on 3-year overall survival (OS) was evaluated for each group using Cox proportional hazards models.
Results
The median age of the patients was 56 years (range 18-75), with 78 males and 69 females. The disease distribution included acute leukemia (96 patients), myelodysplastic syndrome (37 patients), lymphoma (7 patients), aplastic anemia (4 patients), and primary myelofibrosis (3 patients). The median RHR before the start of conditioning therapy was 76 bpm (range 51-116). The median hemoglobin level was 9.1 g/dL (range 5.4-15.7). The median ejection fraction (EF) was 63.5% (range 43-73.5%), and 26 patients had started to take antihypertensive medications before conditioning therapy. At the start of conditioning therapy, 85 patients were in CR and 62 were in non-CR. The median follow-up period for all patients was 664 days (range 7-3407 days).
We evaluated differences in 3-year OS between the CR and non-CR groups using RHR thresholds of 60, 70, and 80 bpm. In the non-CR group, the hazard ratios for RHR ≥60, ≥70, and ≥80 bpm were 1.5645 (95% CI: 0.4524-5.411), 0.8941 (95% CI: 0.4324-1.849), and 1.102 (95% CI: 0.5696-2.132), respectively. In the CR group, the hazard ratios for RHR ≥60, ≥70, and ≥80 bpm were 2.1093 (95% CI: 0.2744-16.215), 0.7119 (95% CI: 0.29-1.748), and 1.2257 (95% CI: 0.5527-2.718), respectively. Notably, when adjusting for RHR, the hazard ratios for other covariates such as age, sex, Hb, EF, and hypertension remained largely unchanged (e.g., in the non-CR group with HR ≥60, the hazard ratios for age, sex, Hb, EF, and hypertension were 1.0357, 1.0711, 0.8024, 0.9855, and 1.1791, respectively). Similar results were observed in both the CR and non-CR groups, with a tendency for better prognosis at an RHR of approximately 70 bpm.
Conclusion
This retrospective study suggests that RHR may influence 3-year OS in patients with hematological diseases undergoing HSCT. The findings indicate that a higher RHR is not necessarily associated with poorer 3-year OS, and the OS curve for RHR exhibited a bathtub shape, with the best outcomes at approximately 70 bpm. Further studies with larger patient cohorts are needed to develop effective prophylactic and therapeutic strategies.