Primary carnitine deficiency (PCD) is a treatable autosomal recessive disorder caused by SLC22A5 gene variants and included in newborn screening widely. However, its prevalence and variant spectrum vary greatly, and prenatal diagnosis for recurrence-risk families remains rare. This study assessed tandem mass spectrometry (MS/MS) combined with genetic testing in NBS and prenatal diagnosis of PCD in Yancheng, China, and described the local prevalence and variant characteristics.

From 2015 to 2024, free carnitine (C0) levels were measured in neonatal dried blood spot (DBS) samples by MS/MS for PCD screening. Newborns with persistently low C0 levels were recalled for diagnostic evaluation. At diagnosis, the C0 levels in both neonatal and maternal blood were measured, and next-generation sequencing was performed for SLC22A5 variants in the newborns. For the recurrence-risk family with a previous proband, Sanger sequencing was used to confirm the parental origin of the proband's variants, and prenatal diagnosis with amniotic fluid was performed in the subsequent pregnancy.

Combined MS/MS and genetic testing led to the diagnosis of 17 newborns with PCD (15 molecularly confirmed with biochemical results, two clinically inferred) and three newborns with maternal carnitine deficiency among the 152 newborns with persistently low C0 levels on re-screening. In these 17 PCD newborns, 10 distinct variant sites were detected, of which missense variants predominated, with c.1400C>G (p.S467C) being the most frequent (13/32, 40.63%). For the proband in this recurrence-risk family, the two pathogenic variants were inherited from each parent. The fetus carried only the maternal variant, without postnatal anomalies.

NBS using MS/MS combined with genetic testing facilitates early diagnosis and classification of PCD. The screening-detected prevalence of PCD in Yancheng was 1:25,852, with c.1400C>G (p.S467C) as the hotspot variant. Genetic testing of SLC22A5 provided effective prenatal diagnosis for the recurrence-risk family.

The long-term real-world effectiveness and safety of in-hospital initiation of sacubitril/valsartan in patients hospitalized for acute heart failure (HF) with mildly reduced or preserved left ventricular ejection fraction (HFmrEF or HFpEF) remain uncertain, particularly among patients with advanced chronic kidney disease or dialysis, who are often underrepresented in randomized trials.

We identified 9,107 patients with HFmrEF or HFpEF hospitalized for acute HF from the Chang Gung Research Database between January 1, 2016, and June 30, 2023. Propensity score weighting with overlap weights was applied to balance baseline characteristics between treatment groups. Risks of fatal and nonfatal outcomes were analyzed using Cox proportional hazards and Fine-Gray subdistribution hazard models, respectively.

After overlap weighting, the incidence rates of the composite endpoint of HF rehospitalization and cardiovascular (CV) death were 39.7 and 40.3 per 100 person-years in the angiotensin receptor neprilysin inhibitor (ARNI) and angiotensin receptor blocker (ARB) groups, respectively (Hazard ratio, 0.97; 95% confidence interval, 0.79-1.20). In analyses stratified by chronic kidney disease stage, the association between treatment group and the primary endpoint was consistent among patients with eGFR ≥60, 30-59, <30 mL/min/1.73 m², or dialysis.

In this multi-institutional real-world cohort of patients hospitalized for acute HF with left ventricular ejection fraction (LVEF) >40%, in-hospital initiation of sacubitril/valsartan was not associated with lower risks of HF rehospitalization or CV death compared with ARB therapy, despite greater NT-proBNP reduction in a biomarker subcohort. Limited sample size precludes definitive conclusions regarding therapeutic equivalence.

The aim of this study is to explore the protective effect of esmolol against sepsis-associated myocardial injury (SAMI) and its underlying molecular mechanisms.

SAMI-related differentially expressed genes were identified from the Gene Expression Omnibus database (GSE267388). Potential targets of esmolol were predicted using PharmMapper. Overlapping genes were used for enrichment and molecular docking analyses. H9C2 cells were treated with LPS to establish an injury model, followed by esmolol treatment. Cell viability, apoptosis, oxidative stress, and mitochondrial function were also assessed. The expressions of apoptotic protease activating factor 1 (APAF1) and JAK2/STAT3 pathway molecules were detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. A rat model of sepsis was used to verify cardiac function, inflammation, oxidative stress, and related protein expression.

Six core targets were screened, and esmolol showed the strongest binding to APAF1. Esmolol increased cell viability; reduced apoptosis, ROS, and MDA; restored mitochondrial membrane potential; downregulated APAF1, Bax, cleaved-caspase-9/3; and suppressed JAK2/STAT3 phosphorylation. Esmolol reversed APAF1 overexpression-induced injury. In vivo, esmolol alleviated myocardial pathological injury, decreased the concentrations of myocardial markers and inflammatory factors, and inhibited the APAF1 and JAK2/STAT3 pathways.

Esmolol protects against SAMI by dual inhibition of the APAF1 mitochondrial apoptotic and JAK2/STAT3 inflammatory pathways, with APAF1 likely serving as a key downstream target of esmolol.

Post stroke depression is a critical barrier to recovery and rehabilitation, contributing to a higher risk of severe disability, cognitive and functional decline, greater dependence on daily activities, and poor adherence to treatment. Additionally, post-stroke depression is a leading cause of death globally. The prevalence of PSD varies significantly depending on the type of study and screening methods used. However, it remains poorly understood and inadequately explored in many parts of the world, especially in developing countries. To identify the key determinants of PSD, conducting a systematic review and meta-analysis is crucial and relevant to current clinical practices.

In conducting this review, the International Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was used. This review focused on studies examining the prevalence of post-stroke depression and its determinants in Ethiopia. Two authors conducted electronic searches in PubMed, Google Scholar, Science Direct, and African Journals Online Library, with the search period extending until April 8, 2024. Data were extracted using Microsoft Excel and exported to STATA version 11 software for analysis. Heterogeneity of studies was assessed by Cochran's Q test and I² statistics.

The analysis included the final eight studies. The pooled prevalence of post stroke depression was 40.9% (95% CI: 26.52-55.28, p < 0.001). The analysis revealed significant heterogeneity among the included studies (I² = 91.1%, p < 0.001). Being female (OR 3.51, 95% CI: 1.87-6.58), being illiterate (OR 2.02, 95% CI: 1.29-3.17), and being over 40 years old (OR = 1.59, 95% CI: 1.09, 2.32) were determinants of post stroke depression.

According to the current review, post stroke depression is highly prevalent in Ethiopia. Being female, being illiterate and being over 40 years old were factors associated with post stroke depression. Therefore, attention should be given to strengthening social support; health professionals should focus on reducing disability/physical dependency and depression, as these are vital factors for improving quality of life.

Metformin is a well-established treatment for Type 2 diabetes. Beyond its role in glycemic control, metformin has gained attention for its pleiotropic effects, including cardioprotective properties. However, its role in autoimmune myocarditis and subsequent postinflammatory dilated cardiomyopathy remains poorly understood.

To investigate the role of metformin in autoimmune-mediated cardiac disease, we employed the experimental autoimmune myocarditis mouse model. Six to eight weeks old Balb/c mice were immunized twice with an α-myosin heavy chain peptide emulsified in complete Freund's adjuvant to induce myocarditis and progression toward dilated cardiomyopathy. Metformin was administered in two approaches: a preventive (from Days 0 to 21 or 40) and a therapeutic (from Days 21 to 40). Cardiac function and disease progression were evaluated at two time points: Day 21 (inflammatory phase) and Day 40 (fibrotic phase), using echocardiography, histopathological assessment, and molecular analyses.

Treatment with metformin resulted in activation of the AMP-activated protein kinase-dependent signaling pathway during the inflammatory phase of myocarditis. This treatment was associated with activation of apoptosis-related pathways and a moderate reduction in inflammatory cell infiltration. Mice receiving metformin in the preventive approach exhibited preserved cardiac function. This was accompanied by decreased cardiomyocyte cross-sectional area and altered expression of hypertrophy-associated genes (Acta1 and Myh6). In contrast, neither preventive nor therapeutic administration of metformin significantly reduced the extent of myocardial fibrosis.

Our findings suggest that metformin provides cardioprotective effects during the early inflammatory stages of autoimmune myocarditis and, to a lesser extent, during the later fibrotic remodeling phase.

Untreated acute myocarditis can lead to functional decline and postinflammatory dilated cardiomyopathy. Using an autoimmune myocarditis mouse model, we demonstrate that preventive metformin treatment reduces cardiac inflammation and preserves cardiac function. These findings suggest that metformin, in addition to its applications in diabetes, could be used to prevent inflammatory heart disease.

Inherited cardiovascular diseases (ICVDs) are a broad category of hereditary disorders resulting from pathogenic mutations that alter cardiac anatomy, electrical conduction, and metabolic pathways. The main types include hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), cardiac channelopathies, and familial hypercholesterolemia (FH) and are associated with heart failure, malignant arrhythmias, and sudden cardiac death, particularly in young people. Current treatments, such as pharmacological therapies, implantable cardioverter-defibrillators, and heart transplantation, have significantly improved outcomes; however, these treatments are mainly targeted toward symptom control and the prevention of complications without correcting the underlying genetic defects. Recent advancements in genome editing have transformed precision cardiovascular care, with clustered regularly interspaced short palindromic repeats (CRISPR)-based technologies emerging as potential methods for targeting and modifying disease-causing variants. Emerging platforms, such as base editing, prime editing, and epigenome editing, have widened the therapeutic potential of genome engineering by enhancing editing precision and reducing some of the constraints of the traditional CRISPR-Cas9 strategy. In the setting of inherited cardiovascular disorders, promising early results have been obtained in preclinical studies using human induced pluripotent stem cell and animal models, including correction of MYBPC3 and MYH7 mutations in HCM; targeting of TTN-, RBM20-, and LMNA-associated mechanisms in DCM; restoration of ion channel function in inherited arrhythmia syndromes; and modulation of lipid-related genes such as PCSK9, LDLR, and ANGPTL3 in FH. However, major challenges remain, including off-target effects, effective delivery to cardiac tissues, immunological responses, interpretation of genetic variants, and ethical concerns. This review provides a translational, integrated view of the evolution of CRISPR-based genome editing technologies, their application to ICVDs, current preclinical and clinical advances, and the challenges that need to be addressed to achieve safe and effective translation into cardiovascular therapeutics.

Infection is a significant cause of morbidity and mortality among patients with cardiac implantable electronic devices (CIEDs). Over 400,000 CIEDs are placed annually in the United States with an infection rate of approximately 1-2% in the first 12 months after implantation. In 2010, the American Heart Association provided a class I recommendation for complete system removal in all cases of endovascular CIED-I or pocket infection. Retrospective studies have shown that CIED removal is associated with improved outcomes, and prompt CIED removal within 7 days of confirmed infection is associated with lower mortality at 1-year compared to extraction after 7 days. Despite these strong recommendations and existing evidence, data demonstrates that ∼80% of patients with CIED-I do not undergo device extraction. To address this gap, we advocate for creation of an electronic clinical quality measure (eCQM) that would create incentives for hospitals to provide efficient, guideline-concordant care, analogous to existing eCQMs for other conditions, such as ST elevation myocardial infarctions. At present, patients with CIED-Is are dying unnecessarily due to non-adherence with evidence-based, guideline recommended care. Healthcare providers and professional societies, working alongside government agencies, have an opportunity to significantly improve outcomes by developing a sustainable, accountable care model for CIED-Is.

Data on estimation of cardiovascular (CV) risk by physicians and perceptions of hypertension and dyslipidemia control are lacking in Eastern Europe. Therefore, in patients with hypertension and dyslipidemia, during the COVID-19 pandemic and post-pandemic periods, we compared CV risk, blood pressure (BP) and low-density lipoprotein-cholesterol (LDL-C) control, as assessed by physicians, with the recommendations of the European guidelines.

Two observational, cross-sectional, epidemiological studies with similar designs were conducted in Romania during the pandemic (SNAPSHOT-1, June 2021) and post-pandemic (SNAPSHOT-2, June 2022).

We included 5004 patients with hypertension and dyslipidemia: 2469 in SNAPSHOT-1 and 2535 in SNAPSHOT-2. In SNAPSHOT-1, the CV risk estimated by investigators was "high" or "very high" for 34.3% and 35.4% of patients, respectively, whereas the CV risk based on guidelines recommendations was "high" or "very high" for 12.6% and 81.8% of patients; 41.5% of investigators estimated the CV risk accurately, whereas 54.2% underestimated it. BP and LDL-C were considered to be controlled by investigators in 71.2% and 46.1% of patients, respectively, whereas control rates based on guideline recommendations were achieved in 25.0% and 8.8% of patients. Both targets were considered controlled together by investigators in 39.6% of patients versus 3.3% based on guideline recommendations. The SNAPSHOT-2 results were similar.

SNAPSHOT studies have shown that the estimation of CV risk by physicians is accurate in fewer than half of patients, being markedly underestimated. BP and LDL-C control is overestimated by physicians, whereas control rates, as recommended by the guidelines, are very low. The results were similar when a similar population was assessed during the COVID-19 pandemic and post-pandemic.

Systemic arterial hypertension (SAH) remains a leading global cause of premature death, significantly increasing the risk of cardiovascular, cerebrovascular, and renal diseases. While non-modifiable factors, such as age and genetics, contribute to its development, lifestyle changes are crucial for prevention and management. Dietary modifications, such as reducing sodium intake, increasing potassium, and adopting a diet rich in fruits and vegetables, combined with regular physical activity, weight management, smoking cessation, and reduced alcohol intake are effective strategies for lowering blood pressure. Recent research has increasingly focused on bioactive compounds with antioxidant and anti-inflammatory properties for the management of SAH. Substances such as polyphenols, curcumin, and other plant-derived compounds, as well as live microorganisms such as probiotics, are being actively studied for their potential to improve endothelial function, modulate nitric oxide production, and reduce oxidative stress. This narrative review summarizes the current evidence on dietary interventions and bioactive compounds as complementary approaches to traditional treatments, examining their mechanisms of action.

Remote ischaemic preconditioning (RIPC) protects against renal ischaemia-reperfusion injury (IRI), yet its precise mechanism remains incompletely understood, particularly regarding the role of mitochondrial quality control. This study investigated whether SIRT3-dependent mitophagy mediates the protective effects of RIPC against acute kidney injury (AKI) induced by IRI and further examined the integrity of mitophagic flux and involvement of the classic Parkin-mediated mitophagic pathway. We used a murine bilateral renal ischaemia-reperfusion injury (IRI) model, including RIPC pretreatment, 3-methyladenine (3-MA) intervention and SIRT3 knockout intervention, and a HK-2 cell hypoxia/reoxygenation (H/R) model, including SIRT3 siRNA knockdown, SIRT3 overexpression and chloroquine (CQ) intervention. Renal function, histopathological changes, apoptosis, mitochondrial membrane potential and mitophagy were assessed using biochemical analysis, histological and TUNEL staining, JC-1 staining, transmission electron microscopy, mitochondrial protein analysis and immunofluorescence colocalization of Parkin and LC3B. RIPC improved renal function, alleviated tubular injury and apoptosis, and enhanced mitophagy in mice, which was attenuated by SIRT3 knockout or 3-MA. In HK-2 cells, RIPC plasma protected against H/R injury and activated mitophagic flux, as verified by CQ treatment, while SIRT3 knockdown abolished these effects and SIRT3 overexpression maintained protective mitophagy levels. RIPC pretreatment restored the IRI-induced reduction in Parkin and LC3B colocalization in renal tubular epithelial mitochondria, and this effect was attenuated by 3-MA. RIPC alone had no detectable cytotoxicity or effect on basal mitophagy. In conclusion, RIPC mitigates renal IRI by activating SIRT3-dependent mitophagy, with involvement of the Parkin-mediated mitophagic pathway. Our in vivo and in vitro data support the central role of SIRT3 in RIPC-induced renoprotection and provide evidence for an intact mitophagic flux mechanism.