Introduction Cardiac allograft vasculopathy (CAV) is a critical predictor of the long-term success of heart transplantation and once it is established, progression to graft dysfunction and loss is inevitable, despite adherence to immunosuppression and medications that ameliorate cardiac risk factors. Regulatory T cells (Tregs) are key for maintaining immune balance in the periphery. Studies investigating adoptive transfer of ex vivo expanded Tregs isolated from blood have been shown to be feasible and safe with good evidence for Tregs reducing CAV lesions in animal models of transplantation. Here, we describe the protocol for the ATT-Heart Study which is a phase I clinical trial investigating autologous thymus-derived Treg cell therapy in nine paediatric heart transplant recipients.Methods and analysis Patients will be recruited from the heart transplant waiting list at Great Ormond Street Hospital. Individualised autologous thymus-derived and expanded Tregs (TR006) will be injected into patients 3–6 months after transplant and follow-up will be conducted as per the post-transplant standard of care protocol with no wean of standard of care immunosuppression. Primary endpoint includes occurrence of Dose-limiting Toxicities in patients receiving TR006. Further data from blood tests, endomyocardial biopsy tissue, coronary imaging and clinical follow-up will be collected.Ethics and dissemination This article is based on the ATT-Heart study Protocol (V.1.1; dated 19 December 2024). The ATT-Heart trial has received a favourable ethical opinion from the Health Research Authority and South-Central Oxford A Research Ethics Committee (IRAS Number: 1008875/REC reference: 24/SC/0333). Clinical trials authorisation approval from UK Medicines and Healthcare products Regulatory Agency has also been received. The clinical trial will be conducted in accordance with the principles of Good Clinical Practice and following the guidelines set as part of the Research Governance Framework for Health and Social Care and all applicable necessary local policies. It is intended that the findings of the clinical trial will be presented at national/international conferences and using social media and through patient groups for dissemination among their members. The results will also be published in international peer-reviewed journals.Trial registration number ISRCTN15374803.

Heart transplantation is the only realistic therapeutic option for children with end-stage heart disease. Unlike in adults, ischaemic heart failure is rare and most paediatric transplant referrals are for cardiomyopathy and the rest for congenital heart disease. Patients with congenital heart disease pose difficulties in terms of their anatomy and the chronicity of the illness, often having had multiple surgeries and blood transfusions prior to transplantation.

Personalised 3D modelling of the heart is of increasing interest in order to better characterise pathologies and predict evolution. The personalisation consists in estimating the parameter values of an electromechanical model in order to reproduce the observed cardiac motion. However, the number of parameters in these models can be high and their estimation may not be unique. This variability can be an obstacle to further analyse the estimated parameters and for their clinical interpretation. In this paper we present a method to perform consistent estimations of electromechanical parameters with prior probabilities on the estimated values, which we apply on a large database of 84 different heartbeats. We show that the use of priors reduces considerably the variance in the estimated parameters, enabling better conditioning of the parameters for further analysis of the cardiac function. This is demonstrated by the application to longitudinal data of paediatric cardiomyopathies, where the estimated parameters provide additional information on the pathology and its evolution.

Diastolic function is an important component of left ventricular (LV) function which is often overlooked. It can cause symptoms of heart failure in patients even in the presence of normal systolic function. The parameters used to assess diastolic function often measure flow and are affected by the loading conditions of the heart. The interpretation of diastolic function in the context of congenital heart disease requires some understanding of the effects of the lesions themselves on these parameters. Individual congenital lesions will be discussed in this paper. Recently, load-independent techniques have led to more accurate measurements of ventricular compliance and remodeling in heart disease. The combination of inflow velocities and tissue Doppler measurements can be used to estimate diastolic function and LV filling pressures. This review focuses on diastolic function and assessment in congenital heart disease.

Heart failure in the paediatric setting encompasses a range of disease processes and pathophysiological mechanisms. The clinical symptoms are commonly seen in the setting of pulmonary overcirculation as well as myocardial pump failure. A significant proportion of patients with congenital heart disease present with or develop heart failure during treatment. The management of this condition differs with aetiology and it is important to understand the direct effects of hypoperfusion and those of (often maladaptive) compensatory mechanisms. The use of ventricular assist devices has heralded a new era in heart failure management and soon it will be possible to move away from transplantation and towards long-term mechanical support as a bridge to recovery and even as destination therapy in itself. This article describes the different types of heart failure seen in children, providing the reader with an improved understanding of the pathophysiology which should inform treatment decisions.

Objective Biomarkers play a pivotal role in heart failure (HF) management. Reference values and insights from studies in adults cannot be extrapolated to the paediatric population due to important differences in pathophysiology and compensatory reserve. We assessed the diagnostic utility of four novel biomarkers in paediatric HF.Methods Midregional (MR) pro-atrial natriuretic peptide (proANP), soluble ST2 (sST2), growth differentiation factor-15 (GDF-15), MR-pro-adrenomedullin (proADM) and N-terminal pro-B natriuretic peptide (NT-proBNP) were measured in 114 patients and 89 controls. HF was defined as the presence of HF symptoms and/or abnormal systolic ventricular function. Receiver-operating characteristics were plotted, and the area under the curve (AUC) was measured. This was repeated for subgroups with cardiomyopathy and congenital heart disease (CHD). Ventricular systolic function was measured by magnetic resonance or echocardiography. Reference values were calculated according to the current guidelines.Results The AUC for diagnosing HF was 0.76 for MR-proANP (CI 0.70 to 0.84) and 0.82 for NT-proBNP (CI 0.75 to 0.88). These parameters performed similarly in the subgroups with CHD and cardiomyopathy. By contrast, MR-proADM, GDF-15 and sST2 performed poorly. When used in conjunction with NT-proBNP, no parameter added significantly to its diagnostic accuracy. NT-proBNP, MR-proANP, GDF-15 and sST2 could accurately discriminate between patients with preserved and patients with poor functional status. In a subset of patients with dilated cardiomyopathy, NT-proBNP, MR-proANP, MR-proADM and GDF-15 were associated with poor LV function.Conclusions MR-proANP could accurately detect HF in children and adolescents. Its diagnostic performance was comparable with that of NT-proBNP, regardless of the underlying condition. Reference values are presented.