Cardiovascular screening prior to stem cell transplantation in the United Kingdom

Haematopoietic cell transplantation (HCT) recipients experience an increased risk of cardiovascular disease compared to the general population[1, 2]. Although transplant-related mortality has decreased over the last decades, this has not been through a reduction in death due to cardiovascular disease [3, 4]. Improving cardiovascular outcomes post-transplant is a focus of the International Cardio-Oncology Society [5], and the European Society of Cardiology has recently produced guidelines for risk assessment and surveillance [6]. Given this background, we aimed to investigate the current United Kingdom (UK) and Republic of Ireland (ROI) pre-transplant cardiovascular screening practice. We wanted to understand if screening was performed,which investigationswereusedand if a left ventricular ejection fraction (LVEF) cut-off was an exclusion criterion for HCT.We also wanted to investigate what cardiology support was available to transplant centres, and if there were dedicated cardio-oncology services. This study surveyed adult and paediatric units. A 23-item survey was created with three introductory questions and 13 adult and seven paediatric-specific questions (Supplementary Material). Centres could answer both sections, and they had the option to skip questions. The survey was distributed as an internetbased questionnaire (surveymonkey.com) through the British Society of Blood and Marrow Transplantation and Cellular Therapy to transplant directors at the 52UK and ROI transplant centres. The studywas open from March 2022 to June 2022, and three reminders were sent out to non-respondents before the survey closed. A total of 26 centres responded (50% response rate) without duplicates. One adult centre erroneously answered the paediatric section giving 25 complete responses. Response rates were equal across England, Wales and Scotland; however there were no responses from either Northern Ireland or the ROI. Fifty-five percent (18/33) of the centres that perform both autologous and allogeneic transplants and 42% (8/19) of the centres that perform autologous only transplants responded. From the responding centres, 21 only performed adult transplants, three exclusively performed paediatric transplants, and two performed combined adult and paediatric transplants. Over three quarters of the adult centres (76%) recorded a comorbidity score prior to transplant; the majority used the hematopoietic cell transplantation co-morbidity index [7]. This score has 17

cular screening practice. We wanted to understand if screening was performed, which investigations were used and if a left ventricular ejection fraction (LVEF) cut-off was an exclusion criterion for HCT. We also wanted to investigate what cardiology support was available to transplant centres, and if there were dedicated cardio-oncology services.
This study surveyed adult and paediatric units.  Over three quarters of the adult centres (76%) recorded a comorbidity score prior to transplant; the majority used the hematopoietic cell transplantation co-morbidity index [7]. This score has 17 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. sections, with three corresponding to cardiac disease. Despite not all centres using a co-morbidity score, they all performed some form of cardiovascular screening. One centre only preformed routine screening for patients prior to allogeneic transplants, not autografts (Table 1a).
A variety of investigations were used for adults with most centres using trans-thoracic echocardiography (TTE; 90%) and a 12-lead electrocardiogram (ECG; 86%). There was infrequent use of serum biomarkers (19%), more advanced cardiac imaging techniques (33%), and cardio-pulmonary exercise testing (CPEX; 19%). One centre that had used CPEX stopped at the start of the COVID-19 pandemic.
Most adult centres (81%) used an LVEF measurement to exclude patients from transplantation. There was heterogeneity in the value used for exclusion, ranging from ≤50% to ≤30% with no justification for the difference. Only one centre that used ≤40% as an exclusion criterion specified that they use reduced intensity conditioning (RIC) if the LVEF is ≤50% (Figure 1).
Post-transplantation, 32% of adult centres referred select patients for cardio-oncology review, and a quarter of centres had specific referral criteria. In general, patients were referred on a case-by-case basis if there were clinical concerns or a low LVEF. There was substantial  The heterogeneity in the LVEF boundary for adults was surprising ( Figure 1). The majority of assessment was performed using TTE, which is associated with significant intra-and inter-observer variability [8]. Previous studies do not support a LVEF boundary cut-off and suggest patients with a moderately impaired LVEF can safely undergo HCT, particularly with reduced toxicity regimens [9,10]. There is limited data for patients with severely impaired LVEF (≤35%). The number of centres selectively using RIC may be higher than that captured by this survey. Given the effects of HCT on the haematological and pulmonary systems, a more global assessment of cardiovascular fitness pre-transplant with CPEX may have a greater ability to predict adverse outcomes post-transplant, although this needs further research [11,12].
Other significant knowledge gaps include the utility of blood and imaging biomarkers on long-term risk stratification. Although recommendations on cardiovascular risk assessment and ongoing surveillance exist, the majority are formed from expert consensus [6,13,14] . A cardiovascular risk score for the prediction of heart failure and coronary artery disease 10 years post-transplant has been generated using variables available one year after transplant (history of anthracycline exposure, chest radiation, hypertension, age, diabetes, and smoking) [15]. Despite this, the optimal approach to monitoring and treating patients at different levels of risk is unknown, and there are little data to help us predict short term complications arising 100 days to 6 months after HCT in both adult and paediatric patients.