Abstract Background Cardiovascular imaging is commonly used for assessment of surrogate endpoints in early phase clinical trials in heart failure (HF). Treatment-induced change in left ventricular (LV) volumes and ejection fraction (EF) were validated against change in outcomes in a meta-analysis from 2011 [1]. However, cardiovascular imaging has evolved significantly since then with new modalities and endpoints introduced in interventional trials. Purpose To analyse temporal trends in implementation of cardiovascular imaging modalities and endpoints in HF trials in the last 15 years and identify endpoints with existing data on relationship between short-term change in imaging endpoint and long-term change in hard outcomes. Methods Firstly, we performed a systematic review of cardiovascular outcome trials (CVOTs) evaluating treatment effects on outcomes in HF. Secondly, we reviewed remodelling trials (RTs) evaluating effect of drugs identified in CVOTs search on imaging parameters. Results The CVOTs search yielded 64 records. Seventeen CVOTs evaluating effect of 10 different interventions on cardiovascular outcomes were considered eligible and included in the final analysis. The RTs search yielded 80 records, 34 publications were considered eligible (Fig.1). Out of 34 RTs, 29 trials employed transthoracic echocardiography (Echo), 1– low dose Dobutamine stress-Echo, 5– cardiac magnetic resonance (CMR), 1– Dobutamine stress-CMR, 1– Phosphorus CMR spectroscopy, and 1– PET. With exception of one study, Echo was the only imaging modality used in selected RTs until 2020. Four studies utilised >1 imaging modality. Data on relationship between therapy-induced changes in remodelling parameters and changes in clinical outcomes are mostly available for conventional markers of the LV and left atrium (LA) (LV EF, volumes, mass, E/e’, e’, LA volume), followed by LV global longitudinal strain. Data on how the therapy-induced changes in other novel endpoints (LV global circumferential strain, right ventricular function, or surrogates of myocardial fibrosis), can translate into change in clinical outcomes in HF has been investigated for single interventions only (Fig.2). Conclusions While Echo had been dominating the field in interventional HF trials, new imaging modalities and endpoints have been introduced in trials recently. Conventional parameters of LV remodelling and function remain the most validated regarding relationship between change in surrogate endpoint in response to treatment and change in clinical outcomes. More evidence on translatability of changes in imaging markers of LV and LA myocardial deformation, right ventricular function and myocardial tissue characterisation with clinical outcomes need to be generated in future trials. Fig.1. PRISMA Flow chart diagram Fig. 2. Imaging endpoints in HF trials
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