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Background: This study aimed to identify heart failure (HF) subphenotypes using 92 repeatedly measured circulating proteins in 250 patients with heart failure with reduced ejection fraction, and to investigate their clinical characteristics and prognosis., Methods: Clinical data and blood samples were collected tri-monthly until the primary endpoint (PEP) or censoring occurred, with a maximum of 11 visits. The Olink Cardiovascular III panel was measured in baseline samples and the last two samples before the PEP (in 66 PEP cases), or the last sample before censoring (in 184 PEP-free patients). The PEP comprised cardiovascular death, heart transplantation, Left Ventricular Assist Device implantation, and hospitalization for HF. Cluster analysis was performed on individual biomarker trajectories to identify subphenotypes. Then biomarker profiles and clinical characteristics were investigated, and survival analysis was conducted., Results: Clustering revealed three clinically diverse subphenotypes. Cluster 3 was older, with a longer duration of, and more advanced HF, and most comorbidities. Cluster 2 showed increasing levels over time of most biomarkers. In cluster 3, there were elevated baseline levels and increasing levels over time of 16 remaining biomarkers. Median follow-up was 2.2 (1.4-2.5) years. Cluster 3 had a significantly poorer prognosis compared to cluster 1 (adjusted event-free survival time ratio 0.25 (95%CI:0.12-0.50), p < 0.001). Repeated measurements clusters showed incremental prognostic value compared to clusters using single measurements, or clinical characteristics only., Conclusions: Clustering based on repeated biomarker measurements revealed three clinically diverse subphenotypes, of which one has a significantly worse prognosis, therefore contributing to improved (individualized) prognostication., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

In this prospective cohort study of 250 stable heart failure patients with trimonthly blood sampling, we investigated associations of 17 repeatedly measured cytokines and cytokine receptors with clinical outcome during a median follow-up of 2.2 (25th-75th percentile, 1.4-2.5) years. Sixty-six patients reached the primary end point (composite of cardiovascular mortality, heart failure hospitalization, heart transplantation, left ventricular assist device implantation). Repeatedly measured levels of 8 biomarkers correlated with clinical outcomes independent of clinical characteristics. Rates of change over time (slopes of biomarker evolutions) remained independently associated with outcome for 15 biomarkers. Thus, temporal patterns of cytokines and cytokine receptors, in particular tumour necrosis factor ligand superfamily member 13B and interleukin-1 receptor type 1, might contribute to personalized risk assessment., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Cardiovascular magnetic resonance (CMR) is considered the standard imaging modality in clinical trials to monitor patients after acute myocardial infarction (AMI). However, limited data is available with respect to infarct size, presence, and extent of microvascular injury (MVO), and changes over time, in relation to cardiac function in these optimally treated patients. In this study, we prospectively investigate the change of infarct size over time, and the incidence and significance of MVO in a uniform, optimally treated patient group after AMI., Methods: Forty patients underwent cine and late gadolinium-enhanced CMR within 9 days and at 4 months after primary stenting. Left ventricular ejection fraction (LVEF), infarct size (IS) and MVO size were calculated., Results: IS decreased with 19.0% at follow-up (p<0.01). The 23 (57.5%) patients with MVO had larger infarct size, higher left ventricular volumes and lower LVEF and more involution of IS at follow-up. Overall, LVEF improved from 42.3+/-9.8% to 44.0+/-9.8% (p=0.06), irrespective of presence or size of MVO., Conclusion: Infarct size reduces over time by 19.0% in optimally treated patients after AMI. Despite optimal reperfusion, MVO was found in the majority of patients. Although patients with MVO had larger infarcts and worse indices of left ventricular remodelling, functional change at follow-up was comparable to patients without MVO.