Background and Aims: Previous studies have highlighted the significance of RNA-binding proteins and alternative splicing (AS) in the progression of complex diseases, but the specific involvement of AS in heart failure (HF) remains unclear. This study aimed to elucidate the role of RNA-binding motif single-stranded interacting protein 1 (RBMS1), an RNA-binding protein, in the development of HF by regulating AS and its effect on cardiac fibrosis. Methods: The level of RBMS1 was investigated in the hearts of both HF patients and mice. Fibroblast-specific knockout RBMS1 mice were generated to investigate the role of RBMS1 in cardiac fibrosis and HF. Unbiased RNA sequencing and RNA immunoprecipitation combined with RNA pull-down were conducted to identify the downstream effector of RBMS1 in fibroblasts. Results: RBMS1 expression was increased in murine hearts following myocardial infarction, as well as in the hearts of patients with ischaemic cardiomyopathy and hypertrophic cardiomyopathy. Moreover, RBMS1 levels in the hearts of HF patients were positively associated with cardiac fibrosis. Furthermore, fibroblast-specific ablation of RBMS1 improved cardiac dysfunction by mitigating myocardial fibrosis. Mechanistically, RBMS1 regulated the alternative splicing of LIM domain 7 (LMO7) by binding to intron 19 and splicing out exon 20, resulting in the formation of the LMO7-Δe20 isoform, which thus activated the transforming growth factor (TGF)-β1 pathway by upregulating activator protein 1. More importantly, overexpression of LMO7-Δe20 in mice resulted in cardiac fibrosis and cardiac dysfunction, which was ablated after treatment with TGF-β1 pathway inhibitor SB431542. In addition, SB431542 attenuated the RBMS1-driven fibrogenesis in human cardiac fibroblasts. Strikingly, pharmacologically inhibiting RBMS1 by low-dose nortriptyline or antisense oligonucleotide-mediated RBMS1 deficiency alleviated myocardial fibrosis and improved cardiac function in HF mice. Conclusions: These findings unveil a critical role of RBMS1 in regulating cardiac fibrosis through controlling the splicing of LMO7 to activate the TGF-β1 pathway. Genetic ablation or pharmacological inhibition of RBMS1 improves cardiac function in mice, suggesting its potential as a therapeutic target for HF.

Background: The accurate etiology of mitral valve aneurysm (MVA) formation is not completely understood, and the most effective management approach for this condition remains controversial.Methods: We retrospectively analyzed 20 MVA patients who underwent either surgical interventions or conservative follow-ups at the Zhongnan Hospital of Wuhan University between 2017 and 2021. We examined their clinical, echocardiographic, and surgical records and tracked their long-term outcomes.Results: Of the 20 patients, 12 were diagnosed with MVA using transthoracic echocardiography, seven required additional transesophageal echocardiography for a more definitive diagnosis, and one child was diagnosed during surgery. In all these patients, the MVAs were detected in the anterior mitral leaflet. We found that 15 patients (75%) were associated with infective endocarditis (IE), whereas the remaining patients were associated with bicuspid aortic valve and moderate aortic regurgitation (AR) and mild aortic stenosis (5%), congenital heart disease (5%), elderly calcified valvular disease (5%), mitral valve prolapse (5%), and unknown reasons (5%). Of the 17 patients who underwent hospital surgical interventions, two died due to severe cardiac events. The remaining 15 patients had successful surgeries and were followed up for an average of 13.0 ± 1.8 months. We observed an improvement in their New York Heart Association functional class and mitral regurgitation and AR degrees (P-value < 0.001). During follow-up, only one infant had an increased left ventricular end-diastolic diameter and left ventricular end-systolic diameter, whereas the remaining 14 patients had decreased values (P < 0.001). In addition, none of the three conservatively managed patients experienced disease progression during the 7–24 months of follow-up.Conclusions: We recommend using echocardiography as a highly sensitive method for MVA diagnosis. Although most cases are associated with IE or AR, certain cases still require further study to determine their causes. A prompt diagnosis of MVA in patients using echocardiography can aid in its timely management.

A thrombus straddling patent foramen ovale (PFO) is rare. We present a case of timely diagnosis and surgical management of a life-threatening straddling thrombus in a PFO and pulmonary embolism, utilizing advanced imaging techniques and emergency thrombectomy. We used multimodality imaging (transthoracic echocardiography, transesophageal echocardiography, computed tomography angiography) to confirm and assess a straddling thrombus in the PFO and pulmonary artery, identifying key findings such as a snake-like thrombus crossing the PFO and pulmonary thromboembolism, and performed emergency surgical thrombectomy to remove the thrombus, prevent embolism, and reduce mortality risk. Limited literature describes PFO-straddling thrombus via advanced imaging. Sharing this case highlights timely diagnosis for risk reduction and surgical planning. Straddling thrombi in the PFO are rare but life-threatening, requiring prompt diagnosis and surgical intervention. Advanced imaging is critical for accurate diagnosis and treatment planning. Surgical thrombectomy significantly reduces mortality, emphasizing the need for timely and aggressive management.

Dilated cardiomyopathy (DCM) was the most prevalent cardiomyopathy worldwide. Although ferroptosis has been implicated in cardiac pathogenesis, its regulatory mechanism in DCM remained poorly defined. In this study, we found that GIPC1 (GAIP/RGS19-interacting protein), a scaffolding protein, was significantly downregulated in cardiac tissues from DCM patients and doxorubicin (DOX)-induced DCM models. Integrated proteomic and lipidomic analysis revealed that cardiac-specific knockout of GIPC1 disrupted mitochondrial fatty acid metabolism, increased the abundance of polyunsaturated fatty acid-containing phospholipids (PUFA-PLs), and ultimately promoted ferroptosis in cardiomyocytes. Both in vitro and in vivo experiments demonstrated that GIPC1 deficiency exacerbated ferroptosis and cardiac dysfunction in DOX-induced cardiomyopathy, whereas GIPC1 overexpression conferred protection against ferroptosis in DOX-induced cardiomyopathy. Mechanistically, co-immunoprecipitation mass spectrometry (Co-IP/MS) and molecular docking demonstrated that GIPC1 interacted with mitochondrial 2,4-dienoyl-CoA reductase (DECR1) via its PDZ domain. Surface plasmon resonance (SPR) analysis further confirmed a high-affinity direct binding between GIPC1 and DECR1 (KD = 16.3 nM). Co-IP and immunofluorescence (IF) demonstrated that GIPC1 facilitated actin-dependent transport of DECR1 into mitochondria, thereby maintaining redox homeostasis and suppressing ferroptosis. Consistently, DECR1 overexpression rescued GIPC1 ablation-induced ferroptosis by balancing redox homeostasis. Together, these results demonstrated that GIPC1 reduced cardiomyocyte susceptibility to ferroptosis by promoting mitochondrial translocation of DECR1 and remodeling lipid homeostasis, highlighting GIPC1/DECR1 axis as a potential therapeutic strategy for DCM.

A 56-year-old female patient presented to our hospital with a ‘heavy ball’ mass adjacent to the right ventricle accompanied by chest congestion. Her medical history revealed oedema in the lower limbs. Echocardiography on admission demonstrated a 6.3 cm × 5.4 cm circular occupying lesion, resembling a bulky hypoechoic ball originating from the right coronary artery and casing compression on the right ventricle (Panel A and B; Supplementary data online, Videos S1 and S2). Electrocardiogram-gated cardiac computed tomography and 3D reconstruction further confirmed the mass as a hypodense shadow, linked to the right coronary artery (Panel C–E). Coronary angiography depicted a normal left coronary artery but an isolated proximal right coronary artery aneurysm (CAA; Panel F). Subsequent surgical intervention and pathological analysis verified the existence of this mass, aligning with the previous diagnostic findings (Panel G–I). A CAA is a rare condition characterized by localized dilation of the coronary vasculature, with an incidence rate ranging from 0.3% to 5.3%. Large size tumour can oppress adjacent cardiac chambers. Surgery remains the primary treatment potion. This particular case represented a rare instance of a giant CAA with thrombosis and emphasized the crucial role of a multimodality imaging approach in accurate diagnosis and comprehensive assessment.

Background: Unruptured sinus of Valsalva aneurysm (SVA) is a rare congenital or acquired cardiac lesion. It may remain asymptomatic or present with various clinical manifestations due to its ‘mass effect’ on the coronary arteries, valves, atria, and other adjacent structures. Unruptured SVA also carries the risk of secondary complications such as infection, thrombosis, and rupture, posing a serious threat to patient health. Case summary: A 55-year-old male from the central region of China, who presented with chest tightness following COVID-19 infection, underwent transthoracic echocardiography (TTE) one year before, which revealed an unruptured non-coronary SVA. Recent follow-up TTE showed findings consistent with the previous examination. Coronary computed tomography angiography (CCTA) subsequently demonstrated a non-coronary SVA complicated by a large thrombus and atherosclerotic changes in the aortic sinus wall. Due to the significant risk of thrombus dislodgement and subsequent systemic embolism, the patient underwent surgical thrombectomy and plasty of the non-coronary SVA. Intraoperative transoesophageal echocardiography (TEE) and surgical exploration confirmed the presence of a mural thrombus; while the potential association between COVID-19 infection and aneurysm formation remains to be fully elucidated. At the 6-month postoperative follow-up, the patient demonstrated favourable physical recovery, with no reported thrombo-embolic events (e.g. stroke or systemic embolism), recurrent symptoms, or other adverse clinical outcomes. A repeat TTE during follow-up revealed a well-preserved aortic root morphology, with normal dimensions and no signs of residual aneurysm or valvular dysfunction. Discussion: We report a unique instance of a massive thrombosed non-coronary SVA. Considering the limitations of TTE and its low sensitivity to SVA secondary lesions, it is recommended to further perform TEE or CCTA to comprehensively evaluate the morphology and structure of SVA.