Background: Ischaemic heart disease (IHD) is a major cause of heart failure (HF), a condition expected to increasingly affect global health and economics. This study evaluates the global burden, trends, and disparities of HF linked to IHD, aiming to inform health policy development. Methods and results: Data from the Global Burden of Disease Study 2021 (GBD2021) are analysed using joinpoint regression, decomposition analysis, and Bayesian age–period–cohort analysis (BAPC). Health disparities are assessed through the Socio-demographic Index (SDI) via the Slope Index of Inequality and the Concentration Index, with future trends projected from 2022 to 2045. In 2021, global HF cases due to IHD were over 19.16 million, with an age-standardized prevalence rate (ASPR) of 228.31 per 100 000 [95% Uncertainty Interval (UI), 188.18–279.55] and age-standardized years lived with disability (ASYLDs) rate of 20.43 per 100 000 [95% UI, 13.55–28.7]. In 2021, there was a 2.87% increase in ASPR and ASYLDs compared with 1990, primarily driven by population growth and aging. Significant reductions in global ASPR and ASYLDs disparities are observed, though the disease burden has intensified in countries with lower SDI levels. Projections indicate that by 2045, while the prevalence and years lived with disability for HF caused by IHD will increase, the ASPR and ASYLDs are expected to decrease. Conclusion: The global burden of HF due to IHD remains a significant concern. Urgent improvements in the allocation of medical resources and the implementation of effective prevention and management strategies are necessary to address this issue.

By using the FAERS database, we aim to identify and assess risk signals of adverse drug events (ADEs) potentially causing pericardial effusion, to inform clinical drug management and promote rational drug use. We obtained reports of pericardial effusion events from the FAERS database spanning from the first quarter of 2004 to the second quarter of 2024, and identified the top 50 drugs ranked by report frequency or signal strength. Four algorithms, namely the reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed for signal detection of these drugs. Furthermore, for drugs with positive signals, we conducted sensitivity analyses and employed the Weibull shape parameter test to perform a time to onset (TTO) analysis. We identified 20,057 ADEs related to pericardial effusion, involving 19,693 patients for analysis. The patient population comprised 10,187 males (51.7%) and 7,939 females (40.3%). Adults aged 18–65 years were the largest group (7,798 cases, 39.6%). Regarding clinical outcomes, 9,924 patients (50.4%) experienced hospitalization, and 2,770 cases (14.1%) resulted in death. Ranked by the ROR risk signal strength, the top 3 drugs were hydralazine [ROR (95% CI): 27.11 (22.28–33)], dasatinib [ROR (95% CI): 15.62 (14.07–17.33)], and mesalazine [ROR (95% CI): 8.99 (6.84–11.8)]. We conducted a TTO analysis for the 26 drugs with positive signals. The median TTO and interquartile range (IQR) for the top 3 drugs causing the earliest pericardial effusion were: cytarabine 14 (7.5,38), selexipag 14.5 (4.25, 157.75), dabigatran etexilate 29 (9, 229). Most drugs exhibited an early failure type. This study systematically compiled a list of drugs with potential risks of causing pericardial effusion. There is a significant association between pericardial effusion and the use of hydralazine, dasatinib, and mesalazine. Moreover, pericardial effusion is more common in patient groups receiving treatments with antineoplastic and immunomodulating agents.

Background: Heart failure (HF) is the final stage of various cardiac diseases with poor prognosis. The integrated traditional Chinese medicine (TCM) and western medicine therapy has been considered as a prospective therapeutic strategy for chronic heart failure (CHF). There have been small clinical trials and experimental studies to demonstrate the efficacy of Shenfu Qiangxin Pills (SFQX) for treating CHF, however, there is still a lack of further high-quality trial. This paper describes the protocol for the clinical assessment of SFQX in CHF (heart-kidney Yang deficiency syndrome) patients. Methods: A randomized, double-blind, parallel-group, placebo-controlled, multi-center trial will assess the efficacy and safety of SFQX in the treatment of CHF. 352 patients with CHF (heart-kidney Yang deficiency syndrome) from 22 hospitals in China will be enrolled. Besides their standardized western medicine, patients will be randomized to receive treatment of either SFQX or placebo for 12 weeks. The primary outcome is the plasma N-terminal pro-B-type natriuretic peptide levels, which will be measured uniformly by the central laboratory. The secondary outcomes include composite endpoint events (hospitalization due to worsening HF, all-cause mortality, other serious cardiovascular events), echocardiography indicators, grades of the New York Heart Association (NYHA) functional classification, the 6-minute walk test (6MWT) results, Minnesota Living With Heart Failure Questionnaire and TCM syndrome scores. Discussion: The integrated TCM and western medicine therapy has developed into a treatment model in China. The rigorous design of the trial will assure an objective and scientific assessment of the efficacy and safety of SFQX in the treatment of CHF. Trial registration: Chinese Clinical Trial Registry: ChiCTR2000028777 (registered on January 3, 2020).

Purpose: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have cardiorenal protective effects regardless of whether they are combined with type 2 diabetes mellitus, but their specific pharmacological mechanisms remain undetermined. Materials and Methods: We used databases to obtain information on the disease targets of “Chronic Kidney Disease,” “Heart Failure,” and “Type 2 Diabetes Mellitus” as well as the targets of SGLT2 inhibitors. After screening the common targets, we used Cytoscape 3.8.2 software to construct SGLT2 inhibitors' regulatory network and protein-protein interaction network. The clusterProfiler R package was used to perform gene ontology functional analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analyses on the target genes. Molecular docking was utilized to verify the relationship between SGLT2 inhibitors and core targets. Results: Seven different SGLT2 inhibitors were found to have cardiorenal protective effects on 146 targets. The main mechanisms of action may be associated with lipid and atherosclerosis, MAPK signaling pathway, Rap1 signaling pathway, endocrine resistance, fluid shear stress, atherosclerosis, TNF signaling pathway, relaxin signaling pathway, neurotrophin signaling pathway, and AGEs-RAGE signaling pathway in diabetic complications were related. Docking of SGLT2 inhibitors with key targets such as GAPDH, MAPK3, MMP9, MAPK1, and NRAS revealed that these compounds bind to proteins spontaneously. Conclusion: Based on pharmacological networks, this study elucidates the potential mechanisms of action of SGLT2 inhibitors from a systemic and holistic perspective. These key targets and pathways will provide new ideas for future studies on the pharmacological mechanisms of cardiorenal protection by SGLT2 inhibitors.

Aims: Heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) are related conditions with an increasing incidence. The mechanism of their relationship remains undefined. Here, we aimed to explore the potential mechanisms, diagnostic markers, and therapeutic options for HFpEF and NAFLD. Methods and results: HFpEF and NAFLD datasets were downloaded from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (DEGs) were screened for functional annotation. A protein–protein interaction network was constructed based on the STRING database, and hub genes were analysed using GeneMANIA annotation. ImmuCellAI (Immune Cell Abundance Identifier) was employed for analysis of immune infiltration. We also used validation datasets to validate the expression levels of hub genes and the correlation of immune cells. To screen for diagnostic biomarkers, we employed the least absolute shrinkage and selection operator and support vector machine-recursive feature elimination. Drug signature database was used to predict potential therapeutic drugs. Our analyses identified a total of 33 DEGs. Inflammation and immune infiltration played important roles in the development of both diseases. The data showed a close relationship between chemokine signalling pathway, cytokine–cytokine receptor interaction, calcium signalling pathway, neuroactive ligand–receptor interaction, osteoclast differentiation, and cyclic guanosine monophosphate-protein kinase G signalling pathway. We demonstrated that PRF1 (perforin 1) and IL2RB (interleukin-2 receptor subunit beta) proteins were perturbed by the diseases and may be the hub genes. The analysis showed that miR-375 may be a potential diagnostic marker for both diseases. Our drug prediction analysis showed that bosentan, eldecalcitol, ramipril, and probucol could be potential therapeutic options for the diseases. Conclusions: Our findings revealed common pathogenesis, diagnostic markers, and therapeutic agents for HFpEF and NAFLD. There is need for further experimental studies to validate our findings.