Search Results (781)

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease and affects male patients more often than women. Prior studies, however, suggested that women are diagnosed later and at advanced stages of the disease, present with more pronounced symptoms, and experience worse outcomes. Objectives: To investigate sex-specific differences in clinical, laboratory, and comprehensive imaging characteristics in a contemporary cohort of HCM patients from a tertiary referral center in Austria. Methods: We retrospectively analyzed 321 HCM patients enrolled in a prospective registry (2018–2024). All patients underwent a comprehensive baseline evaluation, including medical history, laboratory assessment, transthoracic echocardiography, and cardiac magnetic resonance imaging. Results: At diagnosis, women were significantly older (62 vs. 53 years, p < 0.001) and presented with more advanced functional class (NYHA ≥ II: 80% vs. 49%, p < 0.001). Six-minute walking distance was lower and obstructive HCM was more prevalent in women (425 vs. 505 m, p < 0.001, and 55% vs. 32%, p < 0.001, respectively). Echocardiographic assessment revealed higher diastolic filling pressures (E/E′ 18 vs. 10, p < 0.001), larger indexed atrial volumes (29.5 vs. 26.6 mL/m², p < 0.001), a higher left ventricular ejection fraction (70% vs. 62%, p < 0.001), and a larger indexed interventricular septal thickness in women (10.2 vs. 9.3 mm/m², p = 0.004). Moreover, serum levels of NT-proBNP were significantly higher in women (760 vs. 338 pg/L, p < 0.001). Conclusions: Female patients with HCM were diagnosed at an older age, presented with more advanced symptoms, had higher rates of obstructive physiology, and a phenotype characterized by diastolic dysfunction and elevated biomarkers, closely resembling heart failure with preserved ejection fraction. Recognizing these sex-specific disparities is crucial in improving diagnostic awareness and individualized therapeutic management. Full article

Residual congestion (RC) at discharge predicts adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Its impact on the implementation of guideline-directed medical therapies (GDMT) remains unclear. N-terminal pro-B-type natriuretic peptide (NT-proBNP) trajectory during hospitalisation reflects RC and may be associated with GDMT implementation. The aim was to assess whether discharge NT-proBNP and a fall in NT-proBNP < 30% during hospitalisation (ΔNT-proBNP < 30%) predict GDMT underuse in acute HFrEF. In this prospective observational study, NT-proBNP was measured at hospital admission and 48–72 h before discharge. Provision of individual GDMT drug classes was assessed and GDMT underuse was defined as prescription of <3 key GDMT drug classes at discharge. 391 HFrEF patients (mean age, 69.9 ± 13.1years, 67.3% male) were included. ΔNT-proBNP < 30% was identified in 108 (27.6%). Higher discharge NT-proBNP was independently associated with lower likelihood of prescribing ACE-inhibitors, sacubitril/valsartan, eplerenone/spironolactone, or empagliflozin/dapagliflozin. ΔNT-proBNP < 30% was associated with 17% higher odds of GDMT underuse (95% confidence interval, 1.10–1.31, p < 0.001), regardless of clinical characteristics or in-hospital management. Patients with ΔNT-proBNP < 30% were discharged on lower doses of titratable GDMT medications. In-hospital NT-proBNP burden and trajectory, as markers of RC, are associated with GDMT underutilisation at discharge in acute HFrEF. Addressing RC may impact treatment quality in acute HFrEF. Full article

Objective: The aim of this study was to evaluate the impact of chronic kidney disease (CKD) on clinical presentation, laboratory parameters, ECG, and echocardiographic features of patients with chronic heart failure (CHF). Methods: This retrospective cross-sectional study included 2227 patients hospitalized in a tertiary care center due to CHF. Patients were divided into two groups based on the presence of CKD, defined as eGFR < 60 mL/min/1.73 m². Demographic, clinical, laboratory, and echocardiographic data were collected for all patients. Comparative analyses were performed to assess differences in cardiovascular risk factors, comorbidities, laboratory parameters, and echocardiographic findings between the two groups. Results: The proportion of men was significantly higher in the non-CKD group, whereas women predominated in the CKD group (p < 0.001). Dyspnea, orthopnea, leg swelling, claudication, and expectoration were significantly more frequent in patients with CKD, while chest pain and palpitations were more common in the non-CKD group (all p < 0.05). A significant difference in the distribution of NYHA functional classes was observed between the groups (p < 0.001), with NYHA class IV being more prevalent in the CKD group and classes II and III more frequent in the non-CKD group. Levels of CRP and NT-proBNP were significantly higher in the CKD group (p < 0.001). In-hospital mortality was 2.5-fold higher in patients with CKD (28.6% vs. 11.1%; p < 0.001). Conclusions: Coexistence of CKD was associated with a more severe clinical presentation, advanced functional limitation, and a distinct laboratory and echocardiographic profile in CHF patients. Full article

Objective: To investigate the mechanism by which sphingosine-1-phosphatase 2 (SGPP2) modulates endoplasmic reticulum stress (ERS) through the SIRT1/AMPK pathway to improve ischemic cardiomyopathy-induced chronic heart failure (IHF). Methods: Key genes of IHF and ERS were identified through bioinformatics analysis, and significantly associated pathways of the key genes were obtained via single-gene enrichment analysis. In vivo, IHF was induced in Sprague–Dawley (male) rats via ligation of the left anterior descending coronary artery, with cardiac function examined through echocardiography. Myocardial tissue injury and fibrosis were evaluated utilizing hematoxylin-eosin, Masson, and TUNEL staining. Serum levels of NT-proBNP and cTnT were measured via ELISA. SGPP2 protein expression was assessed via immunohistochemistry and Western blotting (WB). In vitro, neonatal rat cardiomyocytes (NRCMs) were isolated and underwent oxygen-glucose deprivation (OGD) to establish an IHF model. SGPP2-overexpressing NRCMs were constructed and treated with the ERS inducer tunicamycin (Tu) or the SIRT1 inhibitor EX527. Cell injury was evaluated using Cell Counting Kit-8 and lactate dehydrogenase release assays, as well as flow cytometry. Endoplasmic reticulum structure was examined by transmission electron microscopy. The endoplasmic reticulum was labeled with the ER-Tracker Red molecular probe. WB was utilized to detect the expression of apoptosis- and ERS-linked proteins, and the activity of the SIRT1/AMPK signaling pathway. Results: Six key genes (CTSK, FURIN, SLC2A1, RSAD2, SGPP2, and STAT3) were identified through bioinformatics analysis, with SGPP2 showing the most significant differential expression. Additionally, SGPP2 was found to be downregulated in IHF. Single-gene enrichment analysis showed that SGPP2 exhibited a significant association with the AMPK signaling pathway. Animal experiments demonstrated that rats with IHF exhibited significantly impaired cardiac function, marked myocardial tissue injury and fibrosis, ERS in myocardial tissue, lowered SGPP2 expression, and decreased SIRT1/AMPK signaling pathway activity. In vitro experiments confirmed that SGPP2 overexpression alleviated OGD-induced cardiomyocyte injury by inhibiting ERS and simultaneously activating the SIRT1/AMPK signaling pathway. Rescue experiments further demonstrated that both Tu and EX527 significantly promoted ERS and cellular injury, thereby counteracting the protective effects of SGPP2. Conclusions: SGPP2 alleviates IHF by inhibiting ERS modulated by the SIRT1/AMPK pathway. Full article

Background/Objectives: It is unclear whether assessment of phasic atrial function could improve risk stratification for new-onset atrial fibrillation (AF) in patients with newly diagnosed cardiac sarcoidosis (CS). We aimed to investigate the prognostic value of left atrial (LA) phasic dysfunction by cardiac magnetic resonance (CMR) for new-onset AF in newly diagnosed patients with CS. Methods: 78 patients with CS, without a prior history of AF, were studied using CMR feature tracking. Over a 4-year follow-up period, AF was documented by Holter monitoring and interrogation of intracardiac devices. Clinically silent CS was defined as CS in patients with biopsy-proven extracardiac sarcoidosis, with no cardiac symptoms, but with abnormalities on CMR or positron emission tomography consistent with CS. Results: Patients with clinically manifest CS were younger (mean age 56 vs. 51 years, p = 0.018), had poorer ventricular function, higher extent of atrial late gadolinium enhancement and significantly lower LA reservoir, conduit and booster function compared to patients with clinically silent CS. Over a 4-year follow-up period, 39% of patients with clinically manifest CS and 29.7% of patients with clinically silent CS developed AF. LA reservoir strain was a strong predictor of AF in the entire cohort. In subgroup analysis, age (HR 1.30, 95% CI 1.02–1.65, p = 0.030) and LA reservoir strain (HR 0.63, 95% CI 0.44–0.90, p = 0.011) were independent predictors of AF in patients with clinically silent CS, whereas baseline NT-proBNP (HR 1.003, 95% CI 1.001–1.006, p = 0.017) predicted AF in patients with clinically manifest CS. Conclusions: Reduced LA reservoir strain on CMR predicts new-onset AF in patients with newly diagnosed CS. The predictive value of LA reservoir strain is strongest in clinically silent CS and decreases with disease progression in clinically manifest CS. Full article

Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a severe form of pulmonary hypertension with poor prognosis. It most commonly arises in systemic sclerosis (SSc), followed by systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Its pathogenesis involves a complex interplay of immune dysregulation, chronic inflammation, endothelial injury, vascular remodeling, and fibrosis. Although vasodilators targeting the endothelin, nitric oxide, and prostacyclin pathways remain the therapeutic backbone, newer agents—including the activin signal inhibitor sotatercept and inhaled treprostinil—have expanded treatment options. Immune-targeted therapies such as glucocorticoids, cyclophosphamide, mycophenolate mofetil, rituximab, and IL-6 receptor inhibitors may benefit inflammation-dominant PAH phenotypes, while fibrotic phenotypes continue to demonstrate limited responsiveness. In addition to brain natriuretic peptide (BNP), N-terminal (NT)-proBNP and disease-specific autoantibodies, emerging biomarkers show promise for early detection, risk stratification, and personalized treatment, though validation in CTD-PAH is lacking. Advances in animal models replicating immune-mediated vascular injury and fibrosis have further improved mechanistic understanding. Despite these developments, substantial unmet needs remain, including the absence of disease-specific therapeutic strategies, limited biomarker integration into clinical practice, and a scarcity of large, well-designed trials targeting individual CTD subtypes. Addressing these gaps will be essential for improving prognosis in patients with CTD-PAH. Full article

Chronic thromboembolic pulmonary disease (CTEPD) is a severe long-term complication of acute pulmonary thromboembolism (PTE). Its pathogenesis is multifactorial, involving incomplete thrombus resolution, hemodynamic burden, comorbidities, and genetic factors. However, the contribution of inherited thrombophilic mutations to CTEPD development remains controversial. This retrospective cohort study included 204 patients diagnosed with acute PTE at a tertiary referral center between December 2023 and December 2024. Baseline demographic, clinical, laboratory, and echocardiographic data were collected. Genetic analysis assessed Factor II, Factor V Leiden, MTHFR C677T, MTHFR A1298C, Factor XIII V34L, and PAI-1 4G/5G polymorphisms. Patients were followed for at least 12 months for the development of CTEPD, defined according to guideline-based hemodynamic and imaging criteria. During follow-up, 17 patients (8.3%) developed CTEPD. Patients with CTEPD were significantly older and had higher baseline and follow-up systolic pulmonary artery pressure (sPAP) (p < 0.001), elevated NT-proBNP and troponin levels (both p < 0.001), and more frequent comorbidities, including cardiac and renal disease. Multivariate logistic regression identified comorbid diseases (HR: 0.17, 95% CI: 0.039–0.80, p = 0.025) and genetic thrombophilic factors (HR: 0.30, 95% CI: 0.10–0.91, p = 0.034) as independent predictors. Among genetic variants, only the PAI-1 4G/5G polymorphism was significantly associated with CTEPD (p = 0.001). Our study demonstrates that advanced age, comorbid diseases, elevated cardiac biomarkers, and genetic predisposition are associated with the development of CTEPD after acute PTE, while the PAI-1 4G/5G polymorphism may contribute to CTEPD susceptibility within a multifactorial context. Full article

Vasculitides are a heterogeneous group of disorders characterized by inflammation of blood vessel walls, leading to tissue ischemia and organ injury. Traditional inflammatory markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are widely used but lack diagnostic specificity. This has driven the search for more informative biomarkers across vasculitis subtypes. This review summarizes current evidence for validated and emerging biomarkers in large-, medium-, small-, and variable-vessel vasculitis, as well as single-organ vasculitis. Key analytes reflect systemic inflammation, such as serum amyloid A (SAA) and interleukin-6 (IL-6), as well as endothelial activation, complement pathways, neutrophil and macrophage activation, and organ-specific damage. Promising candidates include pentraxin-3 (PTX3) and matrix metalloproteinase-9 (MMP-9) in large-vessel vasculitis; N-terminal pro-B-type natriuretic peptide (NT-proBNP) and S100 proteins in Kawasaki disease; galactose-deficient immunoglobulin A1 (Gd-IgA1) and urinary angiotensinogen (AGT) in IgA vasculitis; and tissue inhibitor of metalloproteinases-1 (TIMP-1), S100 proteins, complement C3, and PTX3 in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Although these biomarkers provide mechanistic insight, most lack disease-specificity, external validation, or standardized assays. Future progress will require multicenter studies, harmonized testing, and integrated biomarker panels combined with imaging modalities to improve diagnosis, activity assessment, and monitoring. Full article

Sudden cardiac death (SCD) remains a major challenge in forensic medicine, representing a leading cause of natural mortality and frequently occurring in individuals without antecedent symptoms. Although conventional autopsy and histology remain the cornerstones of investigation, up to 10–15% of cases are classified as “autopsy-negative sudden unexplained death,” underscoring the need for complementary diagnostic tools. In recent years, post-mortem biochemistry and molecular approaches have become essential to narrowing this gap. Classical protein markers of myocardial necrosis (cardiac troponins, CK-MB, H-FABP, GPBB) continue to play a fundamental role, though their interpretation is influenced by post-mortem interval and sampling site. Peptide biomarkers reflecting hemodynamic stress (BNP, NT-proBNP, copeptin, sST2) offer additional insight into cardiac dysfunction and ischemic burden, while inflammatory and immunohistochemical markers (CRP, IL-6, fibronectin, desmin, C5b-9, S100A1) assist in detecting early ischemia and myocarditis when routine histology is inconclusive. Beyond these traditional markers, molecular signatures—including cardiac-specific microRNAs, exosomal RNA, proteomic alterations, and metabolomic fingerprints—provide innovative perspectives on metabolic collapse and arrhythmic mechanisms. Molecular autopsy through next-generation sequencing has further expanded diagnostic capability by identifying pathogenic variants associated with channelopathies and cardiomyopathies, enabling both cause-of-death clarification and cascade screening in families. Emerging multi-omics and artificial intelligence frameworks promise to integrate these heterogeneous data into standardized and robust interpretive models. Pre- and post-analytical considerations, together with medico-legal implications ranging from malpractice evaluation to the management of genetic information, remain essential components of this evolving field. Overall, the incorporation of validated biomarkers into harmonized international protocols, increasingly supported by AI, represents the next frontier in forensic cardiology. Full article

Background/Objectives: Hypertensive disorders of pregnancy (HDP) remain a significant cause of maternal and perinatal morbidity worldwide. In some healthcare settings, access to angiogenic testing is limited, underscoring the need for affordable biomarkers to guide risk assessment. NT-proBNP, a marker of myocardial wall stress and cardio-renal dysfunction, may offer complementary prognostic value to the angiogenic sFlt-1/PlGF ratio. Methods: In this prospective multicenter observational study, we enrolled 180 pregnant women and categorized them into preeclampsia (PE, n = 95), non-PE HDP (gestational or chronic hypertension, n = 25), and healthy controls (n = 60). NT-proBNP and sFlt-1/PlGF levels were measured at enrollment, after 20 weeks of gestation, predominantly during the second and third trimesters. Associations with proteinuria, uric acid, creatinine, and maternal–fetal complications were examined using multivariable logistic regression adjusted for maternal age, BMI, and gestational age. Discrimination was assessed using receiver operating characteristic (ROC) curve analysis, and the incremental value of NT-proBNP beyond the sFlt-1/PlGF ratio was evaluated using ΔAUC and net reclassification improvement (NRI). Results: Median NT-proBNP levels were significantly higher in PE compared with non-PE HDP and controls (p < 0.01). NT-proBNP ≥200 pg/mL independently predicted maternal–fetal complications (adjusted OR 3.12, 95% CI 1.41–6.90, p = 0.005) and correlated with proteinuria (r = 0.47), creatinine (r = 0.43), and uric acid (r = 0.40) (all p < 0.001). sFlt-1/PlGF alone yielded an AUC of 0.84 (95% CI 0.77–0.89), while NT-proBNP alone demonstrated an AUC of 0.78 (0.71–0.84). Combining both biomarkers improved discrimination (AUC 0.88, 95% CI 0.82–0.92), with a ΔAUC of 0.04 (p = 0.02) and a continuous NRI of 0.21 (p = 0.03). The 200 pg/mL threshold for NT-proBNP achieved 80% sensitivity and 71% specificity (p < 0.001). Conclusions: NT-proBNP provides independent and complementary prognostic value to the sFlt-1/PlGF ratio in predicting maternal–fetal complications in HDP. A practical threshold of 200 pg/mL aids risk assessment, and integrating NT-proBNP into angiogenic models improves prediction. Further multicenter studies are needed to validate multimarker strategies and their cost-effectiveness. Full article

Background/Objectives: Frailty, a syndrome characterized by diminished physiological reserves and increased vulnerability to stressors, is a strong predictor of adverse outcomes in heart failure. The MECKI (Metabolic Exercise Cardiac Kidney Index) score, derived from cardiopulmonary exercise testing and renal function parameters, has demonstrated prognostic value in HF patients. This study aimed to evaluate the prognostic value of physical frailty on mortality in patients with advanced heart failure and to compare it directly with the MECKI score. Methods: A total of 104 patients with advanced HF receiving optimized guideline-directed medical therapy were prospectively enrolled. At baseline, all patients underwent clinical, echocardiographic, and laboratory assessment and CPET for MECKI score calculation. Physical frailty was assessed using a modified Fried phenotype tailored for HF. The composite endpoint comprised all-cause mortality, urgent heart transplantation, or LVAD implantation. Results: Over a mean follow-up of 30.0 ± 15.3 months, there were 25 deaths, 5 urgent heart transplants, and 1 LVAD implantation. Patients who experienced the composite outcome had significantly worse NYHA class, higher NT-proBNP, lower VO₂max, higher VE/VCO₂ slope, higher frailty, and higher MECKI score (all p < 0.001). Frailty was significantly correlated with all MECKI score components, as demonstrated by Spearman’s rank correlation analysis. Both frailty (HR = 1.89; 95% CI 1.22–2.93; p = 0.005) and MECKI score (HR = 1.04; 95% CI 1.00–1.08; p = 0.037) independently predicted outcomes. ROC analysis showed high and comparable discriminative performance (AUC = 0.86 for frailty; AUC = 0.88 for MECKI). Conclusions: Physical frailty and MECKI scores independently predict mortality and adverse events in advanced HF. Physical frailty, despite its simplicity and low cost, provides prognostic insight comparable to the MECKI score and may represent a practical alternative when CPET is unavailable. Full article

To help assess the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and feline cardiogenic arterial thromboembolism (ATE), the objective of this retrospective study was to compare plasma NT-proBNP concentrations between cats with cardiomyopathy that developed ATE (ATE group) and cats with occult cardiomyopathy that did not develop ATE within 1 year of testing (occult cardiomyopathy [OCM] group). Cats with cardiomyopathy and congestive heart failure (CHF) but no ATE (CHF group) were included for comparison. Cats with cardiomyopathy that had NT-proBNP testing were classified into ATE, OCM, or CHF groups. Clinical, echocardiographic, treatment, and NT-proBNP data from medical records were reviewed and compared among groups. A receiver operating characteristic curve was generated to develop a cutoff point for NT-proBNP. Cats were then compared based on this cutoff point. The ATE group (n = 25) had significantly higher NT-proBNP concentrations than the OCM group (n = 31; p < 0.001); there was no significant difference in NT-proBNP concentrations between the ATE and CHF groups (p = 0.92). The estimated optimal NT-proBNP cutoff point to separate OCM and ATE groups was 491 pmol/L (sensitivity = 96.0%, specificity = 93.5%). Cats with NT-proBNP > 491 pmol/L had a larger left atrium, thicker left ventricle, lower fractional shortening, and higher prevalence of spontaneous echogenic contrast and left atrial thrombi on echocardiography. These preliminary, hypothesis-generating findings suggest that NT-proBNP concentrations > 491 pmol/L may help detect cats with OCM at risk for ATE, but given the limitations of this retrospective study, prospective studies are needed to evaluate the potential utility of this measurement. Full article

Background: Several genes and genomic regions have been implicated in COVID-19 susceptibility and severity, but their clinical relevance remains uncertain. We comprehensively assessed both copy number variants (CNVs) and single-nucleotide variants (SNVs) disrupting genes implicated in COVID-19 in a Swedish cohort of ICU-treated COVID-19 patients with detailed phenotype data. Methods: Patients (n = 301) with severe COVID-19 treated in intensive care units (ICU) between March 2020 and January 2021 at two large Swedish university hospitals were included. Whole exome sequencing (WES) was performed to identify both large copy number variations (CNVs) and single-nucleotide variants (SNVs), including small indels, using the Genome Analysis Toolkit (GATK) pipelines. We focused our analyses on variants disrupting coding genes implicated in severe COVID-19, but also assessed variants known to cause human disease. Results: We identified 11 rare CNVs and several SNVs potentially linked to severe COVID-19. Patients carrying a CNV spanning a COVID-19-implicated gene had higher levels of the heart failure marker NT-proBNP (median 4440 [1558–8160] vs. 1170 [329–3152], p = 0.017), worse renal function at ICU admission (p = 0.0026), and a higher need for continuous renal replacement therapy (CRRT) (28% vs. 10%, p = 0.045) compared to patients without a potentially damaging CNV. Conclusions: Although patients with a potentially damaging CNV or SNV exhibited some differences in cardiac and renal markers, our findings do not support broad genetic screening as a predictive tool for COVID-19 severity. Full article

Background and Objectives: The conflicting findings in existing studies and insufficient evidence highlight the necessity for additional research on the relationship between sleep quality and coronary artery disease (CAD) in elderly acute coronary syndrome (ACS) patients. We aimed to investigate the association between sleep quality and the CAD severity of in geriatric patients with ACS. Materials and Methods: This retrospective observational cohort study analyzed data from 308 patients aged 65 years and older admitted with ACS who had undergone coronary angiography between May 2022 and June 2025 at a tertiary cardiology department. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) at the 6-month follow-up, with scores > 5 indicating poor quality. CAD severity was quantified by SYNTAX score from angiograms. The primary endpoint was the relationship between PSQI and SYNTAX score, with secondary analyses concerning factors associated with clinical outcomes. Results: Poor sleep quality (PSQI > 5) was associated with higher SYNTAX scores (p < 0.001), lower ejection fraction (p < 0.001), higher CRP (median 5.1 vs. 4.05, p = 0.029), NT-proBNP (median 748.5 vs. 595, p = 0.034), lower glomerular filtration rate (p = 0.025), and higher hypertension prevalence (p = 0.034). ST-elevation myocardial infarction was more common in subjects with poor sleep. Multivariable logistic regression identified hypertension (p = 0.011), reduced ejection fraction (p = 0.030), STEMI (p = 0.045), intermediate SYNTAX (p = 0.003), and high SYNTAX (p = 0.009) as associated factors of poor sleep. Conclusions: Poor sleep quality is independently linked to greater CAD severity in geriatric ACS patients. This is a modifiable risk factor that can reduce morbidity and mortality in this high-risk group. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) remains a major global health problem, affecting over 300 million people worldwide. Its high morbidity and mortality rates impose substantial psychosocial and financial burdens on patients and healthcare systems. In the emergency setting, managing acute exacerbations of COPD (AECOPD) poses a major clinical challenge, as these patients often present with multi-organ dysfunction secondary to hypoxia and hypercapnia. Identifying reliable prognostic biomarkers could improve early risk stratification, guide therapeutic decisions, and enhance patient outcomes. Methods: This multicenter, prospective, observational study aims to evaluate the prognostic significance of several novel biomarkers—resistin, club cell secretory protein 16 (CC16), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), S100β protein—alongside conventional markers such as N-terminal-pro–B-type-Natriuretic-Peptide (NT-proBNP), D-dimer, high-sensitivity troponin I (hs-cTnI), C-reactive protein (CRP), and procalcitonin in patients with AECOPD admitted to the Emergency Department (ED). Blood samples will be collected at admission. The novel biomarkers (resistin, CC16, IL-6, TNF-α, S100β) will be measured using standardized ELISA kits, while conventional biomarkers (NT-proBNP, troponin I, CRP, procalcitonin) will be analyzed using routine automated clinical laboratory methods. Correlations between biomarker levels, clinical and imaging data, severity scores (GCS, SOFA, CFS, Ottawa COPD Risk Scale, DECAF, BAP-65), and short-term outcomes (hospital discharge status and 28-day survival) will be assessed. The study has received approval from the Ethics Committee of the “Iuliu-Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, and all participating hospitals. Written informed consent will be obtained from all participants or their legal representatives. Results: This study protocol does not report results, as data collection and analysis are ongoing. Conclusions /Expected Impact: By identifying novel biomarkers with prognostic and pathophysiological relevance, this research aims to inform the development of early risk stratification tools and support future evidence-based approaches to the management of critically ill COPD patients in the ED. Full article