ALT Study outline for investigating the efficacy of intravenous administration TY1 in a mouse two-hit model of HFpEF. Wildtype c57BL/6 mice were placed on a high-fat diet and the nitric oxide synthase inhibitor Nω-Nitro-L-arginine methyl ester (L-NAME) for five weeks whereafter they were randomized to receive intravenous (retro-orbital) infusions of vehicle (saline; negative control) or TY1 (0.15 mg/kg) at frequencies of every other week, weekly, or biweekly (total of 10 weeks). TY1 administration reduced diastolic dysfunction as indicated by echocardiographic E/e´(n = 4–10 animals per group).

ALT Venn diagram illustrating relative proportion and overlap of DMPs within HFpEF and HFrEF relative to CON, and X–Y plot of overlapping DMPs revealing a strong positive correlation irrespective of disease etiology.

ALT Different treatments can recruit interorgan protective afferent (blue), and efferent PNS (red) signalling pathways. Sympathetic signalling pathways are shown in green.

ALT Schematic overview of immune checkpoint-inhibitor-related myocarditis. Modified from: Seidel JA, Otsuka A, Kabashima K (2018) Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations. Front Oncol 8:86. https:// doi. org/ 10. 3389/ fonc.2018. 00086

ALT Effect of ventricular fibrillation on infarct size in patients with STEMI The area under the curve (AUC) of 48-h troponin I was significantly lower in the VF group than in the CTRL group (right panel). Data are expressed as median (first-to-third quartiles). The circles represent individual data.

ALT The current study aimed to assess the effects of sex and obesity on immune checkpoint inhibition-related cardiac systolic dysfunction in aged mice. Anti-PD-1 treatment caused systolic dysfunction in the lean, normocholesterolemic mice, nevertheless, systolic dysfunction was not observed in the obese, hypercholesterolemic mice. This effect was independent of the sexes.

ALT Single-cell landscapes of ECs across 24 organs in human. Heatmap showing the scaled expression levels of top 10 tissues-specific marker genes (left). Expression patterns of 49 marker genes conserved in two or more tissues are shown on the right (z-score, Poisson mixed model; corresponding P value calculated from two-sided Wilcoxon rank-sum test, FDR < 0.01). PFC, prefrontal cortex; ACC, anterior cingulate cortex; EC, entorhinal cortex; OC, occipital cortex; OTC, occipitotemporal cortex; HIP, hippocampus; RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle; AX, apex; SP, septum; MG, mammary gland; SAT, subcutaneus adipose tissue; VAT, visceral adipose tissue; PIT, pituitary; SC, spinal cord.

ALT Response to ischemia–reperfusion injury. Differences in cardiac infarct size (n = 11 for control and n = 10 for adenine, **P < 0.01, Student’s t test). (Data are expressed as mean ± SD)

ALT Early molecular and functional changes Post CKD in the heart.

ALT The field of cardio-oncology presents both chances and challenges. Currently, many of the existing recommendations are based on expert consensus, which highlights the need for further research to better understand the interactions between cancer, cancer treatments and cardiovascular health. The simultaneous management of cancer and cardiovascular disease requires seamless multidisciplinary team coordination. It is therefore essential to implement comprehensive cardio-oncology programmes based on personalised risk scores to optimise resource investment. Ensuring equitable access to cardiooncology care remains a challenge. Integrating cardiovascular care into oncology is an effective strategy for improving overall patient outcomes.

ALT Integrated atlas of cardiac fibroblasts from different disease models. UMAP embeddings, showing the integrated fibroblast atlas colored by cell clusters, i.e. the integrated fibroblast states (IFS). Labels indicate possible fibroblast differentiations based on functional characterization.

ALT Mechanisms and proposed therapies for anthracycline cardiotoxicity. This figure summarizes the complex interactions between the mechanisms of cardiotoxicity and the potential therapeutic interventions that could ameliorate these effects. Left Panel: Various mechanisms contributing to anthracycline cardiotoxicity are depicted. Right Panel: Proposed cardioprotective therapies than can target the mechanisms of anthracycline cardiotoxicity (AC).

ALT MRI-analysis of global LV function in the Phase 1 pilot study. Global LV function analysis using MRI. After rhPlGF-2 infusion, the mean EF of all treatment groups tended to improve from 4 to 8 weeks compared to CON (P = 0.056) .

ALT Inhibition of SGLT2 and SGLT1 in 11 and 22 mmol/L glucose at reperfusion. Mizagliflozin, abrogates the excess injury associated with elevated glucose. Representative mid-ventricular myocardial slices shown. *p < 0.05 versus respective control

ALT Overview of cellular effects of ICI administration in preclinical models on cardiovascular integrity and functioning. ICI immune checkpoint inhibitor.

ALT Molecular mechanisms of anthracycline-induced cardiomyocyte death. Anthracyclines, in particular doxorubicin, treatment initiates multiple pathways including upregulation of death receptors, calcium overload, disruption in iron homeostasis with lipid peroxidation, generation of ROS with final DNA damage and cell death. AMPK 5ʹ adenosine monophosphate-activated protein kinase, DNA deoxyribonucleic acid, Fe2+ iron, GLC glucose, MyD88 Myeloid differentiation primary response 88, IL-1β R Interleukin-1 beta receptor, NF-kB Nuclear factor kappa-light-chain-enhancer of activated B cells, ROS reactive oxygen species, TLR toll-like receptor.

ALT Polar map imaging of the cMRI infarct transmurality (upper panel) and [18F]FDG PET tracer uptake (bottom panel). Note the high [18F]FDG PET uptake in the infarcted area at 3 days and lower tracer uptake with higher transmurality and larger infarction at 30 days after reperfused myocardial infarction in the Mismatch group.

ALT Cardiac mechano-energetic coupling. In the healthy heart, oxidative phosphorylation produces 95% of the adenosine triphosphate (ATP) required to fuel excitation–contraction coupling.

ALT Schematic of malonate inhibition of IRI in MI. Ischemia-accumulated succinate is rapidly oxidized on reperfusion by SDH upon reperfusion. This drives the ROS burst at reperfusion via RET at complex I, which subsequently primes cardiomyocytes for cell death and leads to post-MI HF. Malonate inhibits SDH, slowing down succinate oxidation and ROS production on reperfusion, reducing cell death. Malonate entry into cardiomyocytes can be enhanced by ischemia or low pH, driving the entry of monocarboxylate malonate via MCT1. Whether malonate can prevent post-MI HF by preventing RET-ROS on reperfusion is currently unknown. (MCT1 monocarboxylate transporter 1, DIC dicarboxylate carrier, SDH succinate dehydrogenase, CxI complex I, RET reverse electron transport, ROS reactive oxygen species, TCA tricarboxylic acid cycle, EF ejection fraction)