Background/Purpose: Autologous Haematopoietic Stem Cell Transplantation (AHSCT) is an effective treatment for severe systemic sclerosis (SSc), with demonstrated benefit for pulmonary and cutaneous outcomes and survival. Cardiac involvement from SSc is highly prevalent and is a potential contributor to transplant-related toxicity. The purpose of this study was to evaluate the trajectory of circulating cardiac biomarkers pre and post AHSCT and to determine if cardiac biomarkers predict treatment-related mortality (TRM) and cardiorespiratory toxicity.

Methods: NTproBNP and troponin I were analysed on biobanked plasma in SSc patients undergoing AHSCT at baseline, day +8 and 12-months post AHSCT. Patients received either standard (200mg/kg) or attenuated cyclophosphamide conditioning depending on the presence of cardiorespiratory risk factors. Clinical outcomes of interest were TRM and cardiac and/or respiratory adverse events during conditioning. Longitudinal biomarker data were analysed with Wilcoxon’s test, mixed-effects modelling or Chi-square testing. Cox regression and logistic regression were used to investigate the association of baseline biomarkers and clinical events. Data are presented as median (IQR).

Results: Of n=49 patients consented for AHSCT, 16/49 (32.65%) had an elevated troponin I and 28/49 (57.14%) had an elevated NTproBNP. 43 patients proceeded with conditioning; baseline NTproBNP was 125 ng/L (66-241) and was significantly elevated at day +8, 205 ng/L (93-1458) p< 0.01, and significantly decreased at 12 months post AHSCT, 80 ng/L (50-240) p=0.03. Compared to pre-AHSCT, there was a significant decline in troponin I at 12 months, 3.60 ng/L (2.28-5.25) vs 6.30 ng/L (2.60-26.00), p< 0.01; at baseline 14/43 (32.56%) had an elevated troponin I compared to 1/30 (3.33%) at 12 months (p=0.01). Neither marker at baseline was associated with treatment-related mortality or significant cardiorespiratory events. Both markers were elevated at day +8 in patients who had a cardiac event (p< 0.05). Baseline NTproBNP was elevated in those patients with increased cardiorespiratory risk factors, an abnormal cardiac MRI or right heart catheter (p< 0.05).

Conclusion: Elevated cardiac biomarkers are highly prevalent in this cohort of SSc patients undergoing standard and attenuated cyclophosphamide conditioning AHSCT, however these alone did not predict adverse outcomes. Elevated NTproBNP in the whole cohort at day +8 may reflect increased haemodynamic and inflammatory stimuli during AHSCT. Long-term improvement of NTproBNP and troponin I suggests AHSCT may positively impact underlying SSc-cardiac disease, particularly myocardial inflammation.  Future studies incorporating longitudinal sensitive cardiac imaging (eg cardiac MRI) and/or myocardial biopsy are planned to confirm these observations.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cardiac-biomarkers-for-predicting-cardiopulmonary-toxicity-of-autologous-haematopoietic-stem-cell-transplantation-for-systemic-sclerosis/