Citations

Background: Journal editors influence the visibility and direction of scientific research and should have adequate gender and geographic representation. Research Question: Are there disparities in gender and institutional country affiliation among editors of highly cited cardiology and cardiovascular disease journals? Methods: In May 2025, we used Scimago Journal Rankings to identify the 50 top-cited cardiology and cardiovascular disease journals worldwide from 2022 to 2024. Due to the large volume of members, general editorial board listings without defined roles were excluded. Editors’ genders and country of institutional affiliation were extracted independently and in duplicate by eight sub-investigators. An additional sub-investigator resolved any discrepancies. Gender was determined using institutional profiles and publicly available pronouns on academic or professional platforms. Country affiliation was based on the editor’s primary institution and categorized by World Bank income classification 2025, which divides countries into high-income (HIC), upper-middle income (UMIC), lower-middle income (LMIC), and low-income countries (LIC). Key journal characteristics, such as country, impact factor, and article processing charges, were also extracted in duplicate. Results: All 50 top-cited cardiology and cardiovascular disease journals identified were based in HICs. A total of 1,762 editors were included. Most editorial positions were held by men (67%), with women accounting for 28%. One editor was identified as non-binary, and the gender of 91 editors (5%) could not be determined based on publicly available information (Table 1). Pronouns were identifiable for all EIC (n=52), out of which 87% were men (n=45) and 13% were women (n=7). Ninety-five percent of editors were affiliated with institutions based in HIC, while only 5% were based in UMIC (n=71), LMIC (n=16), or LIC (n=5). The most represented countries were the US (41%), Italy (8%), and the UK (7%) (Figure 2). All EICs (100%) were affiliated with institutions based in HICs, mainly the US (52%) and the UK (10%) (Figure 3). Conclusion: Editors of top-cited cardiology journals are predominantly men affiliated with HICs. Diverse editorial leadership in academic cardiology journals is needed to reflect global perspectives in research.

Introduction: Corticosteroid therapy has been demonstrated to improve prognosis and reduce mortality in patients with severe Coronavirus Disease 2019 (COVID-19) infection by attenuating the exaggerated inflammatory response that emerges in the late phase of infection. However, its impact on patients with pre-existing cardiovascular disease, who are at higher risk of complications, has not been specifically studied. The aim of this study is to evaluate the effect of corticosteroid therapy on mortality and long-term COVID-19 symptoms in this high-risk population. Methods: We analyzed the prospective registry HOPE-2. Patients with previous cardiovascular disease were selected, and 18-month all-cause death was defined as the primary endpoint. Long-term COVID-19 symptoms were considered as secondary endpoints. A total of 1188 patients with previous heart disease were included, of which 453 received corticosteroid treatment. Propensity score matching analysis in a 1:1 fashion was performed based on baseline variables that exhibited a p-value < 0.05 in the univariant analysis and outcome variables that defined corticosteroid use, with a final matched population of 796 patients. Results: In patients with pre-existing heart disease, corticosteroid treatment was not associated with differences in 18-month all-cause mortality (p = 0.52). However, a shorter duration of hospitalization (median: 8 days [IQR: 4–14] and 11 days [IQR: 7–18]; p < 0.001) was observed in patients who received corticosteroids. No significant differences in long-term COVID-19 symptoms were observed between the two groups. Conclusions: In patients with pre-existing heart disease, the absence of a clear harmful effect suggests that the positive effects of corticosteroids may be offset by their potential adverse effects which could contribute to the persistence of long COVID symptoms. This finding may reflect a differential response to corticosteroids in this high-risk subgroup, highlighting the need for further studies to clarify the role of this therapy in such patients.

Abstract Background and Aims Almost 36 million US adults (1 in 7, 14%) suffer from chronic kidney disease (CKD), and precision strategies to offset the progression to end-stage kidney disease are in dire need. We took advantage of a novel preclinical translational model of CKD in swine and single nucleus RNA sequencing (snRNA-seq) to identify potential therapeutic targets via characterization of the renal cell-specific transcriptomic landscape. Method Normal and CKD pigs were euthanized after 14 weeks (n = 3/group), kidneys were harvested, nuclei isolated, libraries prepared, and snRNA-seq performed. UMAP plots were generated with Seurat (v4.4.0) using default parameters. The expression profile of marker genes across single nuclei clusters was visualized to define renal cell types and ranked based on the number of differentially expressed genes (DEGs). The top cell type was subjected to subsequent analysis and DEG sorted based on their involvement in angiogenesis, inflammation, and fibrosis, which are prominent injury pathways in the pathophysiology of CKD. To mechanistically study the role of top overlapping candidate DEGs and support their potential as therapeutic targets, in vitro studies in primary renal vascular endothelial cells (RECs) were performed. Results A total of 39,935 nuclei were analyzed. Thirty clusters were identified and filtered by canonical gene markers, revealing 18 unique renal cell types (Fig. 1A). Endothelial cells exhibited the highest number of DEGs (Fig. 1B). Volcano plots (Fig. 1C) and Venn diagram (Fig. 1D) analysis of endothelial cells identified unique DEGs among three main renal injury pathways in CKD (angiogenesis, inflammation, fibrosis), with 2 overlapping DEGs (VWF, LAMA3) upregulated and participating in inflammation and fibrosis. Targeted silencing of VWF and LAMA3 (randomly selected) in RECs using siRNA ameliorated C5b9 and TGF-ẞ immunoreactivity, suggesting attenuated inflammatory and fibrogenic activity, respectively (Fig. 1E). Conclusion Our work characterized the single-nuclear renal cell transcriptomic landscape of a translational model of CKD and identified endothelial cells as the cluster with the largest number of DEGs. Our observations support the candidacy of VWF and LAMA3 as potential targets to decrease renal endothelial cell inflammation and fibrosis, which could pave the way for new therapeutic strategies in patients with CKD.

Abstract Background and Aims Almost 36 million US adults (1 in 7, 14%) suffer from chronic kidney disease (CKD), which is more prevalent in the elderly, affecting up to 34% of adults ≥ over 65. CKD has limited therapeutic options, partly due to the lack of large animal models that allow the translational study of the impact of age on CKD. This work reports the first preclinical model of CKD in naturally aged swine. Method CKD was induced in naturally aged (6-9 years old) and young (3 months old) domestic pigs (bilateral renal artery stenosis + high-cholesterol/high-carbohydrate diet), followed for 14 weeks, and compared to normal controls (n = 4–5/group). Renal hemodynamics were quantified in vivo by multidetector CT. Metabolic parameters, renal microvascular (MV) architecture (3D-micro-CT), and morphometric analysis (staining) were investigated ex vivo. Results Both young and old pigs developed CKD, but the renal and metabolic phenotype was accentuated in aging animals. We found that superimposition of aging on CKD resulted in higher triglycerides, glucose levels, insulin resistance, and adipose tissue accumulation (subcutaneous, visceral, perirenal) (Fig. 1A and B), accompanied by a more severe renal dysfunction (C), cortical MV rarefaction, and reduced peritubular capillary density (D and E), and more severe structural damage disclosed by increased glomerulosclerosis, tubule-interstitial fibrosis, and tubular injury (F). Notably, the severity of renal MV rarefaction in aging CKD correlated with functional and structural abnormalities (simple linear regression analysis, G). Conclusion Our study establishes the first large animal model of aging CKD, allowing the investigation of age as a biological variable in kidney-metabolic diseases. Age exacerbates metabolic and renal abnormalities, and our data support the critical role of renal MV disease in aging CKD and suggest that its exacerbation is a potential key player in its progression. This novel translational platform could foster new studies toward the elucidation of novel mechanisms of age-related deterioration of renal function in CKD and for developing therapeutic interventions.

Abstract Background and Aims Patients with chronic kidney disease (CKD) have a higher risk of developing heart failure with preserved ejection fraction (HFpEF). Growing evidence supports that changes in cardiac microcirculation are a major pathophysiological driver of HFpEF. We created a model of CKD stage 3 that subsequently developed a cardiac phenotype with numerous traits of HFpEF (CKD-HFpEF), including microvascular (MV) rarefaction and decreased availability of the pro-angiogenic growth factor vascular endothelial growth factor (VEGF) in the heart. We hypothesize that cardiac VEGF therapy will attenuate MV injury and improve cardiac function in CKD-HFpEF. Method CKD and normal pigs (n = 6 each, 3 males/3 females) were studied for 14 weeks. In addition, CKD-HFpEF pigs (n = 6, 3 males/3 females) were treated after 6 weeks of disease with a single intracoronary (IC) administration of VEGF attached to a drug-delivery vector (ELP-VEGF) that increases cardiac targeting, and effects quantified 8 weeks later. Renal (multi-detector CT) and cardiac (echocardiography, PV loops) morphology and function were quantified in vivo, microvascular (MV) density (3D micro-CT) ex vivo, and cardiac expression of VEGF was quantified by qPCR and western blot, as VEGF-related genes by bulk mRNA-sequencing (n = 3/group). Results A single IC administration of ELP-VEGF improved MV density and rescued cardiac function compared to placebo similarly in male and female pigs and independent of hypertension (Fig. 1A–C). These improvements were accompanied by improved mRNA and protein expression of VEGF and restored expression of VEGF-related pro- and anti-angiogenic genes (Fig. 1D and E). Conclusion Our study supports the prominent role of cardiac MV disease in the development of HFpEF in CKD, supports the critical need for healthy VEGF signaling to preserve the heart in CKD, and shows the feasibility of a potential new therapeutic strategy via a targeted mechanistic intervention.

Chronic kidney disease (CKD), heart failure with preserved ejection fraction (HFpEF), and the recently defined cardiovascular-kidney-metabolic (CKM) syndrome are important challenges for the health care system, associated with a staggering increase in morbidity and mortality rates. Unfortunately, the complex pathophysiology of these processes remains to be fully elucidated, imposing hurdles to prevent their development and decelerate their progression. Large animal models are critical for understanding cardio-renal pathophysiology and for the discovery of new therapies. Among them, pig models offer significant translational power to grasp cardio-renal pathophysiology and to test the feasibility and efficacy of new strategies. We recently developed and characterized swine models of CKD, HFpEF, and CKM syndrome that closely recapitulate human disease and allow for the study of the impact of biological variables, such as sex or age, on these conditions. Furthermore, data from these studies revealed key mechanisms implicated in the pathogenesis of CKD, HFpEF, and CKM syndrome and identified potential targets for intervention. This focused mini review highlights the main features of these novel swine models and discusses ongoing and future research aimed at developing novel therapies.

Abstract Aims Our aim was to assess the clinical and prognostic significance of the left ventricular (LV) hypercontractile phenotype (HP) in hypertrophic cardiomyopathy (HCM), which until now remains unclear. Methods and results We enrolled 1533 HCM patients (age 51 ± 15 years, 965 males, 63%) with ejection fraction (EF) ≥ 50%, referred for rest transthoracic echocardiography (TTE) in 27 laboratories from 13 countries. Two-dimensional volumetric TTE assessment included LV outflow tract gradient (LVOTG), LV EF, and LV force (systolic blood pressure + LVOTG/ESV, mmHg/mL). HP was defined as the highest quartile of the force (&gt; 7.32 mmHg/mL). Survival analysis was performed in a subset of 1200 patients with follow-up information. Compared with non-HP patients, HP showed higher heart rate (72 ± 14 vs. 67 ± 14 beats per minute, P &lt; 0.001), lower stroke volume (50 ± 22 vs. 67 ± 22 mL, P &lt; 0.001), larger left atrial volume index (44 ± 16 vs. 40 ± 16 mL/m2, P = 0.011) and higher coronary flow velocity in the mid-distal left anterior descending artery (n = 325, 41 ± 12 vs. 37 ± 14 cm/s, P = 0.021). Force was moderately related to LV EF (r = 0.48, P &lt; 0.001) and weakly to LVOTG (r = 0.36, P &lt; 0.001). During a median follow-up of 87 months (interquartile range 45–143 months), 131 all-cause deaths occurred. At multivariable Cox analysis, a force &gt; 7.32 mmHg (the fourth quartile for analyzed patients) was associated with a hazard ratio of 1.44 (95% Confidence intervals 1.00–2.07) for all-cause death, independently of LVOTG and LV EF. Conclusion HP in HCM is associated with a disadvantageous systemic, cardiac and coronary hemodynamic profile as well as lower survival in the long-term.