European Journal of Clinical Investigation最新文献

Background and Aims

Chest radiography (CXR) is the gold standard tool for early mechanical complications' detection after cardiac implantable electronic devices (CIED) procedures, along with CIED electrical parameters control for the diagnosis of early catheter dislodgement. However, the detection of thoracic complications using CXR is limited, and it requires radiation exposure. Thoracic ultrasound (TUS) is a more versatile and quicker alternative for the diagnosis of thoracic pathologies, although its use in cardiac electrophysiology is not yet validated.

Aim of this study was to compare the diagnostic power of CXR and TUS in the diagnosis of non-infective early complications of CIED implantation.

Methods

A total of 397 patients who underwent CIED implantation were prospectively enrolled from 1 November 2021, to 30 September 2022. Following surgery, all patients underwent CXR and TUS at the patient's bed and the electrical parameters were tested before discharge.

Results

21 patients experienced mechanical complications (5.3%), of which the most common were pneumothorax (3.3%) and pericardial effusion (2%). TUS demonstrated non-inferior accuracy in diagnosing early mechanical complications, with increased sensitivity when compared to CXR. When associated with device interrogation, TUS was at least as accurate as CXR and device control in diagnosing lead dislodgment.

Conclusions

TUS has a non-inferior diagnostic power compared to the CXR to detect early mechanical complications of CIED implantation, avoiding x-ray exposure. Our results suggest that TUS could be employed as a primary technique in association with standard electrical control to diagnose postoperative complications.

Background

Obesity and atherogenic dyslipidemias are interrelated disorders that substantially contribute to the development of atherosclerotic cardiovascular disease (ASCVD) and the broader cardiovascular–kidney–metabolic (CKM) syndrome. The heterogeneity of obesity, particularly the role of visceral, ectopic and dysfunctional adipose tissue, drives the dyslipidemia phenotype characterized by hypertriglyceridemia, reduced high-density lipoprotein cholesterol and elevated apolipoprotein B–containing lipoproteins.

Methods

We review the epidemiological studies, imaging analyses, genetic data and clinical trial evidence linking obesity phenotypes with dyslipidemias and cardiovascular outcomes. We further evaluated lifestyle, pharmacological and surgical strategies targeting obesity-related lipid abnormalities.

Results

Visceral and ectopic fat accumulation, rather than body mass index alone, strongly predicts adverse lipid patterns, insulin resistance and cardiovascular events. Atherogenic dyslipidemias contribute to substantial residual ASCVD risk despite low-density lipoprotein cholesterol lowering. Lifestyle interventions—including diet modification, physical activity and improved cardiorespiratory fitness—demonstrate favourable effects on lipid metabolism independent of weight loss. Traditional pharmacotherapies such as statins, fibrates and omega-3 fatty acids offer partial benefits, while novel incretin-based agents and dual or triple receptor agonists provide robust weight loss and metabolic improvements. Metabolic and bariatric surgery remains an effective approach for sustained weight reduction and remission of dyslipidemias in the appropriate patient and is increasingly integrated with pharmacotherapy.

Conclusions

Atherogenic dyslipidemias are a hallmark of high-risk obesity phenotypes and a major contributor to ASCVD within the CKM framework. Precision medicine approaches that incorporate obesity phenotyping, targeted treatment strategies and population-level interventions are needed to reduce the burden of dyslipidemias and their cardiovascular sequelae.

Background

Epicardial adipose tissue (EAT) exhibits brown-like features, including the expression of uncoupling protein 1 (UCP1). EAT interacts dynamically with cardiac cells to modulate local cardiac tissue physiology and metabolic function. No studies have evaluated the impact of UCP1 inhibition on oxidative phosphorylation (OXPHOS) in fresh EAT explants. This study aimed to determine the unique bioenergetic characteristics of fresh EAT explants by comparing it to subcutaneous adipose tissue (SAT). Furthermore, the key impact of UCP1 inhibition on EAT respiration and how this process is influenced by the presence of type 2 diabetes mellitus (DM) or coronary artery disease (CAD), was also evaluated.

Methods

EAT and SAT biopsies were collected from 205 (151 male and 51 female) study participants, undergoing cardiac surgery. Participants were stratified according to the presence/absence of DM or CAD. Markers of mitochondrial content and bioenergetics were evaluated.

Results

EAT demonstrated a higher bioenergetic activity compared to SAT, in both nicotinamide adenine dinucleotide (NADH)-linked and fatty acid oxidation (FAO)-linked OXPHOS. Importantly, UCP1 inhibition with guanosine 5′-diphosphate (GDP), flattens the differences between the tissues in the NADH-linked OXPHOS; in contrast these differences were potentiated in the FAO-linked OXPHOS. Minor differences in mitochondrial content and respiration were observed when subjects were stratified according to either DM or CAD.

Conclusions

This study emphasizes the important bioenergetic differences between EAT and SAT, which are crucial in the context of the local cardiomyocyte metabolism, as well as the impact of UCP1 inhibition in EAT. A deeper understanding of the unique characteristics of EAT and its metabolic micro-environment may provide valuable insights into the cardiovascular disease pathologies.

Background

Calcific aortic valve disease (CAVD) is the predominant valvular pathology in older adults, advancing from aortic sclerosis to life-threatening stenosis. Without effective medical therapies, intervention mainly relies on timely valve replacement, although silent myocardial and valvular damage may progress before symptoms arise. Early, non-invasive detection of disease activity is a crucial unmet need.

Aims

To review circulating and mechanistic biomarkers reflecting the core pathogenic pathways of CAVD and asses their potential for early detection and patient-specific risk stratification.

Methods

Narrative review of literature focusing on traditional protein biomarkers, emerging non-coding RNAs, and extracellular vesicles (EVs) associated with lipid oxidation and inflammation, bone and mineral metabolism, extracellular matrix (ECM) remodelling, endothelial dysfunction and non-coding RNA regulation.

Results

Traditional protein biomarkers—such as lipoprotein(a), osteopontin, fetuin-A, galectin-3 and matrix metalloproteinases—offer insights into the disease and correlate with disease burden but lack sensitivity for detecting early-stage CAVD. Emerging non-coding RNA markers, including long non-coding RNAs (lncRNAs) and microRNAs (like miR-30b and miR-125b), show promise as predictive and diagnostic tools by mediating key molecular pathways involved in calcification and inflammation. EVs, which carry proteins, lipids and nucleic acids across all pathogenic pathways, provide stable and comprehensive signatures that enhance risk stratification compared to conventional markers. Notably, no single biomarker has demonstrated sufficient sensitivity or specificity across all stages of the disease. Combining proteins, RNAs and EV cargo into integrative, multimodal panels—supported by proteomics and transcriptomics—provides the greatest potential for early detection and patient-specific management. However, further validation in prospective cohorts and standardization of assays are necessary before clinical implementation.

Conclusion

Biomarker-guided approaches could revolutionize CAVD management by enabling early detection and patient stratification before irreversible valvular damage occurs.

Background

Overweight and obesity are highly prevalent in atrial fibrillation (AF) patients, yet the best anticoagulant strategy for this group is still unclear. We evaluated the risk of all-cause mortality and cardiovascular events (CVEs) in overweight and obese AF patients treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs).

Methods

We analysed 10,259 AF patients on anticoagulants from the prospective nationwide START registry. Overweight was defined as BMI 25–29.9 kg/m² and obesity as BMI ≥30 kg/m². Mortality risk was assessed with Cox proportional hazards models, and CVEs with Fine–Grey models accounting for competing risks. Additional modelling strategies, subgroup analyses, and propensity score matching were performed to explore data and ensure robustness.

Results

Overall, 6534 (63.7%) patients had BMI >25 kg/m² (65.7% overweight, 34.3% obese). Over a median follow-up of 17.4 months, 408 deaths and 481 CVEs occurred. DOACs' use was associated with a lower risk of all-cause mortality (HR 0.57, 95% CI 0.46–0.70, p < 0.001) and CVEs (sHR 0.71, 95% CI 0.59–0.86, p < 0.001) versus VKAs. The inverse association of DOACs with mortality was evident in both overweight (HR 0.52, 95% CI 0.39–0.68, p < 0.001) and obese patients (HR 0.69, 95% CI 0.48–0.98, p = 0.040), while the reduction in CVEs reached significance only in the overweight group.

Conclusions

In this nationwide registry, DOACs were associated with lower risks of mortality and CVEs compared with VKAs across BMI groups, though the CVE effect was not evident in obese patients. These findings suggest a potential mortality advantage of DOACs irrespective of BMI, warranting further confirmation.

Background

Venous outflow (VO) is a promising prognostic imaging biomarker in acute ischemic stroke (AIS) patients selected for endovascular treatment (EVT). However, the best score for properly assessing VO profiles on multi-phase CT-Angiography (mCTA) remains to be identified.

Methods

A series of consecutive AIS patients undergoing EVT for large vessel occlusion within 24 h from symptom onset were investigated. The following scores were rated: cortical vein score difference in stroke (PRECISE, range 0–8), cortical vein opacification score (COVES, range 0–6), comprehensive venous outflow (CVO, range 0–8) and internal cerebral vein (ICV) asymmetry. Receiver operating characteristic curves and multivariable logistic regression analyses were performed to explore the performance of the different VO scores for prediction of a good outcome (modified Rankin Scale 0–2 at 3 months).

Results

Three hundred and thirty-six subjects (56.2% females, mean age 74.8) were included, of whom 145 (43.1%) had good outcomes. In multivariable logistic analysis, the CVO score (odds ratio = 2.51, 95% CI = 1.49–4.18, p = .001) was the only independent predictor of good functional outcomes. The AUC of the CVO score was .75 (95% CI = .70–.80), with an optimal cut-off of ≥4 (sensitivity 56%, specificity 69%). Patients with favourable CVO profiles had better pial arterial (70.7%, p < .001) and hypoperfusion intensity ratio (HIR) tissue-related collaterals (HIR = .35, p = .005), higher rates of successful recanalization (95.7%, p < .001) and lower symptomatic intracranial haemorrhage occurrence (6%, p = .020) than those with unfavourable CVO profiles.

Conclusion

The CVO score measured on mCTA had the best discriminative performance and was independently associated with functional outcome in AIS patients undergoing EVT within 24 h from onset.

Background

Epilepsy is a common neurological disease that heavily impacts children and adolescents and carries serious physical, cognitive, psychological, social and economic consequences for patients and their caregivers.

Methods

Data was obtained via the Global Burden of Disease Study 2021. We reported numbers, rates and percentage changes of prevalence, mortality and disability-adjusted life years (DALYs).

Results

In 2021, there were 18.15 million [95% UI: 14.61–21.85] prevalent cases of epilepsy in children and adolescents worldwide, 8.24 million [5.77–11.13] of which were idiopathic epilepsy and 9.91 million [8.72–11.06] of which were secondary epilepsy. While mortality and DALY rates of idiopathic epilepsy declined between 1990 and 2021, the burden of secondary epilepsy remained substantial and, in some cases, increased—particularly in low-SDI regions. The prevalence rate of secondary epilepsy increased by 16.14% [4.28–29.24], driven by increases in epilepsy attributable to neonatal encephalopathy (82.02%), neonatal jaundice (18.45%) and malaria (77.03%). There were notable geographic variations in the burden of epilepsy, with the burden generally concentrated in Sub-Saharan Africa, Latin America and the Caribbean and Southeast Asia.

Conclusions

While efforts to reduce premature mortality of epilepsy have been successful, the burden on children and adolescents living with epilepsy is still significant. A healthcare gap remains for vulnerable populations with increased risk of infectious diseases, perinatal insults, poor sanitation and limited access to healthcare. Global and national action is needed to improve access to specialist care and medication, manage comorbidities, address stigma and discrimination and strengthen primary prevention initiatives.

Background

We present the final report from the Fabry Outcome Survey (FOS) on long-term effectiveness and safety of agalsidase alfa in adults (≥18 years old).

Methods

FOS was an international, multicentre, observational registry (NCT03289065), designed to enhance the understanding of Fabry disease and improve clinical management. Primary effectiveness endpoints were annualized change in estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMI), and time to and age at composite morbidity event (comprising renal, cardiac or stroke events) and death. Safety outcomes were also assessed.

Results

FOS included data for 1864 adults (female/male, n = 907/957) who received agalsidase alfa only for a median (minimum, maximum) of 6.0 (0, 21.6) years, and 1613 untreated adults (female/male, n = 1235/378). At baseline, mean (standard deviation [SD]) eGFR was 94.01 (27.60) mL/min/1.73 m² in treated adults; annualized changes in eGFR (slope [standard error; SE]) remained relatively stable in females and declined slightly in males (−1.07 [.12] vs. −2.17 [.12] mL/min/1.73 m²). At baseline, mean (SD) LVMI was 58.25 (25.01) g/m^2.7 and LVMI (slope [SE]) remained stable (.34 [.16] vs. .38 [.15] g/m^2.7/year in females and males, respectively). Time (median [95% confidence interval]) from treatment initiation to first composite event was longer for females than males (83.4 [65.7–98.0] vs. 56.3 [45.6–66.7] months); age (median [minimum, maximum]) at death was also higher for treated females than males (69.9 [32.5, 87.7] vs. 59.1 [26.2, 79.6] years). Agalsidase alfa was generally well tolerated.

Conclusions

This report further supports the long-term effectiveness and safety of agalsidase alfa in adults with Fabry disease.