Prognostic impact of resting heart rate on outcomes after allogeneic hematopoietic cell transplantation

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for patients with hematologic malignancies, but is associated with life-threatening toxicities which contribute to prolonged hospitalization and chronic comorbidities. The presence of life-threatening toxicities results in variable length of survival. In this context, identifying appropriate prognostic biomarkers of HCT response is of clinical importance. Pre-treatment elevated resting heart rate (RHR) has been associated with increased risk of toxicities and worse survival in patients with solid tumors, but this has not been studies in patients undergoing HCT. Purpose To examine the association between pre-HCT RHR and outcomes after allogeneic HCT. Methods This was a retrospective cohort study of patients who underwent allogeneic HCT for acute leukemia or myelodysplastic syndrome as adults (≥18 years old). RHR was obtained from pre-HCT screening electrocardiogram or echocardiogram after a 5-minute rest in the supine position. RHR was first divided into quartiles: 50-66 beat per minutes (bpm), 67-75 bpm, 76-85 bpm, 86-163 bpm. There was no significant association between RHR and 2-year mortality among the three lowest quartiles, and they were combined in our analyses (lower RHR [<86 bpm] vs. elevated RHR [≥86 bpm]). Outcomes of interest included length of hospitalization, major adverse cardiovascular events (MACE: myocardial infarction, coronary artery stenosis, congestive heart failure), and cause-specific (relapse, non-relapse) and all-cause mortality, at 2 years. Results There were 792 consecutive patients who underwent HCT between 2007-2014. Median age was 51 years (range 18–74 years); 53.8% were male and 57.1% were non-Hispanic white. Average length of hospitalization was significantly longer in patients with elevated RHR compared to those with lower RHR (35.6 [21.2] vs 32.0 [18.7] days; P = 0.003). However, there was no association between RHR and the development of MACE after HCT. Patients with elevated RHR had significantly worse 2-year overall survival (50.2% vs. 66.1%, p<0.001; Figure 1) compared to those with lower RHR. In the multivariable model (adjusted for age at HCT, sex, diagnosis, stem cell donor source, risk of relapse, HCT conditioning intensity, hypertensive medication, and hemoglobin), elevated RHR was associated with increased risk of all-cause (HR:1.41, 95% CI 1.11–1.79; P=0.005), relapse related (HR: 1.60 95% CI 1.11–2.31; P= 0.012), and non-relapse-related (HR:1.58, 95% CI 1.13–2.21; P = 0.007) mortality. Conclusion This study is the first to demonstrate the association between pre-treatment RHR and clinically important outcomes in patients with acute leukemia or myelodysplastic syndrome undergoing HCT. This information may be used to facilitate treatment decisions prior to HCT and guide interventions to decrease the risk of treatment-related complications after HCT.