Search Results (1,077)

Background: Although less frequently encountered, aortic valve stenosis is associated with complications separate from its hemodynamic burdens, such as infective endocarditis. Case Summary: We report the case of a 77-year-old female patient with regular cardiac follow-up in the setting of an asymptomatic severe aortic stenosis, who presented to the emergency department with signs and symptoms of sepsis and acute decompensated heart failure. Echocardiography revealed two vegetations attached to the tricuspid valve, an abscess of the anterior aortic ring, and a high-velocity ventricular septal defect. The patient was started on adequate antibiotic therapy. Surgical treatment in an urgent manner (within a few days) was decided by the Heart Team, in accordance with the ESC guidelines on the management of infective endocarditis. Whilst awaiting surgery, the patient presented with a sudden hemodynamic deterioration a few days after diagnosis, with cardiopulmonary arrest and subsequent death. Discussion: We hypothesize that the patient developed an infective endocarditis of the degenerated stenotic aortic valve with extension from left to right via a ventricular septal defect, the development of which was facilitated by the high trans-aortic valve gradient. Some reported cases describe a ventricular septal defect as a complication of native aortic valve endocarditis, though not all involve concomitant aortic stenosis. In conclusion, our case illustrates a very rare scenario of infective endocarditis complicating aortic stenosis with fulminant development. This case highlights a rare, albeit severe complication associated with aortic stenosis and therapeutic challenges in managing the dismal evolution of endocarditis in this setting. Full article

(1) Background and Objectives: Current risk stratification strategies for primary prevention of sudden cardiac death (SCD) have limited sensitivity and specificity. Artificial intelligence (AI) applied to electrocardiograms (ECGs) has emerged as a promising tool to predict the risk of future cardiac arrhythmias. This scoping review synthesizes evidence from original studies evaluating AI models trained on ECGs for risk stratification of SCD/malignant ventricular arrhythmias. (2) Materials and Methods: A comprehensive search of MEDLINE, Embase, Web of Science, Scopus and IEEE Xplore was conducted to identify peer-reviewed studies from inception to February 2026. Eligible studies included original investigations in which the model input was an ECG, recorded at baseline or during monitoring, and the outcome was either short-term or long-term SCD/malignant ventricular arrhythmia risk prediction. Extracted variables included study characteristics, ECG data, AI model data, model performance metrics, and the validation strategy. Risk of bias was assessed using PROBAST. (3) Results: Twenty studies met the inclusion criteria. High-risk cardiovascular subgroups (e.g., heart failure cohort, ICD cohort, etc.) or datasets from admitted patients, and conventional machine learning models or deep learning models were used in most studies. AI-ECG algorithms achieved moderate-to-high discriminative performance for identifying patients at an increased risk for imminent SCD/malignant ventricular arrhythmias (nine studies, AUROC ≈ 0.77–0.96) or future SCD/malignant ventricular arrhythmias (eleven studies, AUROC ≈ 0.66–0.94). However, multiple methodological limitations were identified, including limited sample sizes, susceptibility to overfitting, data imbalance-related bias, heterogeneity in dataset and endpoint definitions, inadequate external validation, and incomplete assessment and reporting of model calibration. (4) Conclusions: AI-ECG models demonstrate potential for risk stratification of SCD and malignant ventricular arrhythmias. However, the current evidence base is constrained by several methodological limitations, and further research is required to determine the clinical utility of AI-ECG for predicting SCD. Full article

Background: Cardiac channelopathies are rare but potentially life-threatening disorders that may present with syncope or seizure-like episodes in children, often leading to misdiagnosis and delayed recognition. Other arrhythmia-associated cardiac conditions may also present with similar clinical manifestations and require careful cardiac evaluation. Objective: To evaluate the prevalence of cardiac channelopathies and inherited arrhythmogenic cardiac disorders in pediatric patients presenting with syncope and seizure-like events and to identify associated clinical and electrocardiographic features. Methods: This retrospective cross-sectional study included pediatric patients presenting with syncope, presyncope, seizures, or seizure-like episodes who underwent cardiac evaluation at Ankara Dr. Sami Ulus Maternity and Children’s Health and Diseases Training and Research Hospital between January 2015 and April 2019. Cardiac evaluation was performed using a standard 12-lead electrocardiogram and was complemented by additional investigations, including 24 h Holter monitoring, exercise testing, pharmacological provocation, electrophysiological studies, and genetic analysis, when clinically indicated. Demographic, clinical, and diagnostic parameters were systematically evaluated. Results: A total of 363 patients were included in the final analysis. The mean age was 12.2 ± 4.7 years, and 58.7% were female. The most common diagnosis was vasovagal syncope (n = 160, 44.1%), followed by epilepsy (n = 53, 14.6%). Cardiac channelopathies, and arrhythmogenic right ventricular dysplasia (ARVD) were identified in 18 patients, corresponding to 4.9% of the pediatric cardiology-evaluated patients and 0.82% of the initial screened population. These diagnoses included long QT syndrome (n = 8), Brugada syndrome (n = 3), short QT syndrome (n = 3), catecholaminergic polymorphic ventricular tachycardia (n = 2), ARVD (n = 1), and malignant-type early repolarization (n = 1). Compared with other patients, those with cardiac channelopathies, malignant-type early repolarization, and ARVD more frequently had exercise-related triggers (p < 0.001), ventricular extrasystoles and ventricular tachycardia (p < 0.001), and abnormal exercise test findings (p < 0.001). Conclusions: Cardiac channelopathies are not uncommon in pediatric patients presenting with syncope and seizure-like events and should be considered in the differential diagnosis. Clinical triggers, family history, and electrocardiographic abnormalities may serve as important clues for early identification. A multidisciplinary approach, including detailed cardiac evaluation, is essential to prevent misdiagnosis and reduce the risk of sudden cardiac death. Full article

Background: Genetic testing in hypertrophic cardiomyopathy (HCM) yields variable positivity rates. Identifying clinical predictors of positive genetic tests could improve pre-test counseling and refine expectations about diagnostic yield. Methods: We analyzed consecutive genotyped HCM probands from a contemporary multicenter cohort across four Italian tertiary centers. Genotype positivity was defined as the presence of ≥1 pathogenic or likely pathogenic variant (ACMG classes 4–5). Multivariable logistic regression identified predictors of genotype positivity. Sensitivity analyses assessed the incremental value of left atrial volume index (LAVI) ≥ 34 mL/m² and the mode of first clinical presentation. Results: Among 274 genotyped probands (median age at diagnosis 54 years; 62% male), 86 (31%) were genotype-positive (38% MYBPC3, 29% MYH7). Age at diagnosis <40 years (OR 2.38, 95%CI 1.26–4.51, p = 0.008), family history of sudden cardiac death/major ventricular arrhythmias (OR 2.34, 95%CI 1.16–4.84, p = 0.019) and family history of non-ischemic cardiomyopathy (OR 1.92, 95%CI 1.04–3.54, p = 0.038), were independently associated with genotype positivity whereas arterial hypertension was inversely associated (OR 0.42, 95%CI 0.23–0.77). Maximal left ventricular wall thickness > 20 mm and gender were not predictive of genotype positivity. Inclusion of LAVI modestly improved the model performance (AUC 0.769, p = 0.016, ΔAUC +0.024; DeLong p = 0.016) but without leading to meaningful patient reclassification. Conclusions: Genotype positivity in HCM links to earlier onset and family history; traditional severity markers and initial presentation may not independently suggest genetic causality. These findings may help shape a personalized approach to genetic counseling in HCM. Full article

Background/Objectives: While premature ventricular contraction (PVC) burden is clearly linked to cardiomyopathy in adults, its association with ventricular dysfunction in children remains less well established. This study investigated the myocardial effects of a PVC burden greater than 5% and its potential predictive factors in a pediatric population. Methods: The study enrolled 23 children aged 5–18 years with a PVC burden >5% on 24 h Holter monitoring, who had no chronic systemic illness, congenital or acquired heart disease, or known family history of cardiomyopathy or sudden cardiac death, along with 33 age-matched healthy controls. Data on demographic characteristics, anthropometric measures, clinical findings, and laboratory results were obtained. Twelve-lead electrocardiography, exercise testing using the Bruce protocol, 24 h Holter monitoring, and echocardiographic assessments—including conventional, tissue Doppler, and both segmental and global strain analyses—were performed and compared between the patient and control groups. Results: In the patient group, left ventricular isovolumetric relaxation time (IVRT) was prolonged, and the myocardial performance index (MPI) was higher compared with the controls (p < 0.001, p = 0.004). Longitudinal strain analysis revealed a significant reduction in global longitudinal strain (GLS) (p = 0.035). In addition, significantly lower segmental longitudinal strain values were observed in the basal anterolateral, basal inferolateral, and basal anterior segments, as well as a reduction in apical two-chamber GLS (p = 0.002, p = 0.002, p = 0.003, and p = 0.014, respectively). Circumferential strain was also significantly reduced in the basal anteroseptal, basal anterior, basal inferolateral, and mid anteroseptal segments, as well as in the basal, mid, and global averages (p = 0.003, p = 0.003, p = 0.026, p = 0.003, p = 0.006, p = 0.022, and p = 0.017, respectively). PVC burden on Holter monitoring was positively correlated with the global strain values, indicating less negative strain with increasing PVC burden. Conclusions: In children with structurally normal hearts and a PVC burden exceeding 5%, TDI and strain imaging revealed subtle alterations in diastolic function and myocardial deformation despite preserved ejection fraction. These findings suggest that frequent PVCs may be associated with early myocardial alterations and highlight the potential utility of advanced echocardiographic techniques in this population. Full article

Arrhythmogenic cardiomyopathy (ACM) is a genetic myocardial disorder marked by progressive cardiomyocyte loss, fibro-fatty replacement, ventricular arrhythmias, and risk of sudden cardiac death. Traditionally considered a structural and electrical disease driven by desmosomal dysfunction, emerging evidence redefines ACM as an inflammatory cardiomyopathy in which immune activation plays a central role. This review integrates genetic, molecular, experimental, and clinical data to highlight inflammation as a unifying feature of ACM. Desmosomal gene variants impair cell adhesion and also activate cardiomyocyte-intrinsic inflammatory pathways, including nuclear factor of kappa B (NFκB) and glycogen synthase kinase 3β (GSK3β) signaling, promoting cytokine release, immune cell recruitment, and fibrotic remodeling. Preclinical studies suggest inflammation precedes structural changes, indicating it may be an initiating event rather than a secondary response. Clinical and pathological findings support this model, with inflammatory infiltrates, circulating cytokines, and autoantibodies observed across disease stages. These processes often present as episodic “hot phases” resembling myocarditis, thus complicating diagnosis. The inflammatory landscape involves both innate and adaptive immunity, along with stromal and neuronal remodeling, contributing to arrhythmogenesis through gap junction disruption, calcium-handling abnormalities, and fibrosis. Environmental factors such as exercise, stress, and metabolic disturbances further modulate inflammatory pathways and disease expression. Therapeutically, this evolving perspective supports immunomodulatory approaches, including inhibition of NFκB, GSK3β, and cytokine signaling. Early clinical data on immunosuppressive and cytokine-directed therapies are promising, especially during active inflammatory phases, while gene-based strategies specifically address the underlying genetic defects. In conclusion, ACM should be recognized as an inflammatory cardiomyopathy shaped by interactions between genetic susceptibility and immune dysregulation. Integrating genetic and immunologic profiling may improve diagnosis, risk stratification, and treatment, ultimately leading to refined personalized therapeutic strategies. Full article

Background/Objectives: Excessive trabeculation of the left ventricle, previously known as left ventricular non-compaction (LVNC), is a rare phenotypic trait whose mechanisms and pathogenesis still remain conflictual. Its presentations may range from heart failure to embolism and, most importantly, ventricular arrhythmias (VAs). This study aims to find novel predictive factors for the occurrence of potentially fatal VAs in patients with left ventricular hypertrabeculation. Methods: All consecutive patients meeting the echocardiographic (Chin, Jenny or Stöllberger) and/or MRI criteria (Petersen) for hypertrabeculation were prospectively enrolled from October 2009 to December 2023. The primary outcome was a composite of sudden cardiac death, sustained ventricular tachycardias (sVTs), ventricular fibrillation (VF) or appropriate implantable cardioverter defibrillator (ICD) interventions. The secondary outcome was a composite of cardiovascular death and cardiovascular hospitalizations. Results: Overall, 64 patients (41 males, mean age 46 ± 19 years old) were enrolled and followed for a median time of 2.2 years. Six patients (9.4%) experienced a composite outcome at eight years, three with previous sVTs and three with previous non-sustained VTs (nsVTs). The strongest predictor of the primary endpoint was the anamnesis of nsVTs and sVTs before LVNC diagnosis. In addition, nsVTs and sVTs were significantly associated with the secondary outcome. Conclusions: Hypertrabeculation of the left ventricle is a complex and poorly understood condition whose status of cardiomyopathy is currently challenged. In our population, patients with a trabecular pattern experienced a high incidence of VAs, cardiovascular death and hospitalizations. VAs before LVNC diagnosis were predictive of the outcome independently from systolic function. Full article

Background: Short QT syndrome (SQTS) is a rare inherited cardiac channelopathy associated with high risk of atrial and ventricular arrhythmias and sudden cardiac death (SCD). Data on its natural history, genotype–phenotype correlations, and risk stratification remain limited. We aimed to evaluate all families with a confirmed diagnosis of SQTS identified at our National Referral Center through a descriptive case series, thereby contributing additional real-world data on this rare condition. Methods: A retrospective review was conducted of all families evaluated for suspected SQTS between 2011 and 2025 at the Inherited Cardiac Diseases Unit. Diagnosis was based on 2022 ESC guidelines (QTc ≤320 ms or ≤360 ms plus supportive features), clinical evaluation, and genetic testing. Families meeting diagnostic criteria were included for detailed phenotypic and genotypic characterization and longitudinal follow-up. Results: Among all patients assessed, two families met the criteria for SQTS. One family with three phenotype-positive individuals was gene-elusive. This family had a history of SCD and the proband presented atrial fibrillation. The second family carried a pathogenic KCNJ2 variant (p.Asp172Asn). However, only the proband fulfilled ECG criteria for SQTS (phenotype-positive) and there was no family history of SCD. No patients were treated with pharmacological therapy for QT prolongation. All affected individuals showed stable QT intervals (none <320 ms) and there were no malignant arrhythmic events during follow-up. Conclusions: These two families illustrate the wide phenotypic spectrum of SQTS and underscore the difficulty of risk stratification in asymptomatic individuals. The rarity of the disease, variable penetrance, and absence of robust prospective data hinder evidence-based management. Systematic registry participation and longitudinal studies are essential to refine risk prediction and therapeutic strategies. Full article

HIV-associated cardiomyopathy is a significant cause of morbidity and mortality among people living with HIV, contributing to heart failure, arrhythmia, and sudden cardiac death. Despite its clinical importance, its individual-patient clinical spectrum has not been systematically synthesized. We conducted a systematic review of published English-language case reports and small case series describing cardiomyopathy in HIV-infected individuals. Etiologies were classified using a framework distinguishing cardiomyopathy arising from uncontrolled HIV from that occurring despite virologic control. Stratified analyses examined temporal trends and geographic differences. We identified 99 patients (75 male, 20 female, 4 unspecified) from 27 countries (80% high-income). Median age was 35 years (IQR 28–45). Among 52 patients with CD4 data, median was 154 cells/µL (IQR 84–391); 52% had CD4 < 200. Systolic dysfunction was present in 94% with echocardiographic data. Uncontrolled HIV phenotypes predominated (64%), but controlled phenotypes (21%)—including drug-induced cardiomyopathy (n = 19, predominantly zidovudine-associated) and autoimmune or inflammatory mechanisms (n = 13)—were substantial. Mortality declined across eras: 65% pre-ART, 32% early ART, 21% modern ART. Recovery occurred in 58%. HIV-associated cardiomyopathy is heterogeneous with improving outcomes across treatment eras. Systematic etiologic evaluation is warranted in all affected patients. The near absence of data from sub-Saharan Africa represents a critical gap. Full article

Ventricular repolarization abnormalities are among the most frequent electrocardiographic findings in pediatric athletes undergoing cardiovascular screening, yet their clinical significance remains a major source of diagnostic uncertainty. While most of them represent benign expressions of training-induced cardiac remodeling and developmental maturation, selected patterns may constitute the earliest phenotypic manifestation of cardiomyopathies or primary electrical disease. Distinguishing physiological adaptation from early pathology is therefore essential to prevent both sudden cardiac events and unnecessary restrictions on sports participation. This review integrates contemporary international electrocardiographic interpretation criteria with emerging pediatric evidence to provide a clinically oriented framework for evaluation and risk stratification of ventricular repolarization abnormalities in pediatric athletes. Early repolarization and anterior T-wave inversion are commonly benign when occurring within recognized age- and ethnicity-specific patterns and in the absence of symptoms, concerning family history, or structural abnormalities. Conversely, lateral or inferolateral T-wave inversion, atypical ST-segment morphology, complex ventricular arrhythmias, and abnormal imaging findings represent red flags requiring comprehensive investigation, including multimodality imaging when indicated. Due to the dynamic electrophysiological evolution during adolescence, longitudinal reassessment is crucial. A structured, risk-based approach integrating electrocardiographic features, demographic/familial context, clinical evaluation, imaging findings, and follow-up provides a pragmatic strategy to optimize risk detection while safeguarding appropriate athletic participation in young athletes. Full article

Brugada syndrome (BrS) is a rare but potentially life-threatening condition that may lead to sudden cardiac death. Among the causes, dysfunctions of ion channels involved in the cardiac action potential (specifically in SCN5A and SCN10A genes) are particularly significant. Among diagnosed Brugada patients, fever-induced episodes occur in 20–30% of cases. Fever worsens sodium channel dysfunction, as elevated temperature further reduces their conductance. First clinical manifestation of BrS occurs usually during a febrile episode, especially in young people. We performed a multiparametric examination in addition to genetic analysis. We treated a 19-year-old man presenting with subfebrility. During the patient’s subfebrile episodes, 12-lead ECG recordings revealed ST-segment elevations in leads V1–V3. Notably, the patient remained asymptomatic. Targeted genetic testing of SCN5A did not reveal any disease-causing variants as an underlying cause of the syndrome, but the temperature-inducing effect was demonstrated. The occurrence of the Brugada type 1 pattern has also been observed at subfebrile episodes, although significantly rarely. This case demonstrates that in susceptible patients, even a relatively mild elevation in body temperature can trigger ion channel dysfunctions. Timely diagnosis and follow-up are important in preserving quality of life and preventing fatal outcomes. Full article

Emery–Dreifuss muscular dystrophy (EDMD) is a rare inherited neuromuscular disorder within the spectrum of nuclear envelope diseases, classically characterized by early musculo-tendinous contractures, slowly progressive myopathy, and cardiac involvement dominated by conduction disease and arrhythmias, with variable evolution toward cardiomyopathy and heart failure. This narrative review provides a comprehensive and clinically actionable synthesis of cardiovascular manifestations across EDMD genotypes and phenotypes, outlining pragmatic diagnostic and therapeutic pathways for real-world care. A targeted literature search was performed in PubMed, Embase, and Web of Science, focusing on studies addressing cardiovascular involvement in EDMD. Relevant original studies, case series, registries, guideline documents, and high-quality reviews were selected and synthesized narratively, with particular emphasis on diagnostic strategies, risk stratification, and management approaches. Cardiac involvement in EDMD encompasses a broad and heterogeneous spectrum, including atrial disease and conduction disturbances, ventricular arrhythmias, dilated cardiomyopathy, thromboembolic complications, and sudden cardiac death. Phenotypic expression varies according to the underlying genetic substrate, with distinct atrial- and ventricular-dominant trajectories. Early recognition and structured cardiovascular surveillance are essential to guide timely intervention, including anticoagulation, device therapy, and heart failure management. Despite growing awareness, significant gaps remain in risk prediction and standardized management strategies. EDMD represents a paradigmatic model of cardiomyopathy characterized by prominent electrical instability and systemic involvement. A structured, genotype- and phenotype-informed approach centered on early surveillance, proactive arrhythmia and thromboembolic risk management and timely device therapy may improve clinical decision-making in real-world settings. Future perspectives include the integration of precision medicine and the development of gene- and pathway-targeted therapies, with the potential to shift from symptomatic management toward disease-modifying strategies. Full article

Avian infective endocarditis is an uncommon but severe disease that is typically diagnosed postmortem because of nonspecific clinical signs and rapid progression. In the present study, five broiler chickens (n = 5) from a commercial flock were examined with septicemia and lesions suggestive of endocarditis. This study reports the first molecularly confirmed and characterized case of valvular endocarditis associated with multidrug-resistant Vagococcus fluvialis in poultry and provides a comprehensive review of bacterial endocarditis in avian species. The case involved a broiler chicken that presented with sudden death and septicemic lesions, including vegetative valvular endocarditis, pericarditis, and multiorgan involvement. Bacterial isolates recovered from cardiac lesions were identified as V. fluvialis using MALDI-TOF mass spectrometry and confirmed by 16S rRNA gene sequencing. Antimicrobial susceptibility testing revealed a multidrug resistance profile, with resistance to several antimicrobial classes commonly used in poultry production. The literature review identified published studies describing avian infective endocarditis, which predominantly affects poultry and is caused mainly by Gram-positive bacteria, with clinical signs and necropsy findings largely overlapping across etiologies. These findings highlight the novelty of V. fluvialis as a potential etiological agent of avian infective endocarditis and underscores the diagnostic challenges associated with avian endocarditis, particularly when uncommon pathogens are involved, and underscore the importance of advanced identification methods for an accurate etiological determination. Collectively, the results of this study expand the spectrum of bacterial species associated with avian infective endocarditis and emphasize the relevance of antimicrobial resistance and improved diagnostic strategies in poultry health and disease surveillance. Full article

Introduction: Hypertrophic cardiomyopathy (HCM) is a common myocardial disease worldwide and is associated with heart failure symptoms and sudden cardiac death. In a subset of patients, it may produce dynamic left ventricular outflow tract obstruction (LVOTO) and systolic anterior motion (SAM)-related mitral valve dysfunction through drag forces and altered mitral–septal geometry. In contrast, subaortic stenosis caused by a subaortic membrane is an uncommon congenital lesion that may lead to fixed subvalvular LVOTO in adulthood. The coexistence of these entities is rare and can substantially complicate diagnosis and management. Case presentation: A 51-year-old woman with HCM, paroxysmal atrial fibrillation, and heart failure presented with acute decompensation and cardiogenic shock. After initial hemodynamic stabilization and cardioversion for atrial fibrillation with rapid ventricular response, multimodality imaging with transthoracic and transesophageal echocardiography, coronary computed tomography angiography, and cardiac magnetic resonance demonstrated dual LVOTO, with a dynamic component related to HCM/SAM physiology and a fixed component caused by an elongated subaortic membrane, accompanied by severe SAM-related mitral regurgitation. Echocardiography showed a resting peak LVOT gradient of 49 mmHg, increasing to 85 mmHg with the Valsalva maneuver. After exclusion of obstructive coronary artery disease and evaluation for selected phenocopies, the patient underwent septal myectomy, subaortic membrane resection, and adjunctive mitral valve plication. Early postoperative echocardiography showed reduction in the maximum provoked LVOT gradient to 38 mmHg and improvement of mitral regurgitation from severe to mild. At 3-month follow-up, she remained in sinus rhythm, improved to New York Heart Association functional class II, and had no documented readmissions for heart failure. Conclusions: Combined fixed and dynamic LVOTO due to concomitant subaortic membrane and HCM is exceedingly rare. Accurate diagnosis requires a high index of suspicion and a multimodality imaging strategy to define the obstructive mechanisms and support mechanism-based surgical management and avoid incomplete treatment when a coexisting fixed lesion is present. Full article

Background/Objectives: Determining the cardiovascular cause of death, particularly distinguishing ischemic from congestive mechanisms, remains challenging in forensic practice, especially in early ischemia without definitive histological findings. Proteomic techniques and molecular profiling may provide complementary diagnostic information beyond conventional autopsy. Methods: We applied an untargeted high-resolution proteomic approach to postmortem cardiac tissue samples from cardiovascular (ischemic and congestive) and non-cardiovascular deaths. Identified proteins were analyzed using bioinformatic and differential expression workflows. Selected candidates were evaluated in peripheral blood samples for translational validation using statistical modeling, including regression analyses and receiver operating characteristic (ROC) curve assessment. Results: A total of 572 proteins were identified. Although no proteins fulfilled strict exclusivity criteria for a single cause-of-death group, differential expression analysis revealed distinct molecular patterns distinguishing ischemic, congestive, and non-cardiovascular deaths. Thirty-one proteins were differentially expressed between ischemic and congestive cases, including α-1 antitrypsin (AAT), plasma levels did not demonstrate statistically significant discrimination. In contrast, plasma Apolipoprotein A-IV (ApoA-IV) levels were significantly associated with ischemic death in regression models, and ROC analysis yielded a cutoff point with complete separation between ischemic and selected non-cardiovascular cases. However, the limited sample size warrants cautious interpretation due to potential overfitting. Conclusions: Postmortem cardiac proteomic profiling reveals biologically coherent molecular signatures associated with different cardiovascular causes of death. Although further validation in larger independent cohorts is required, ApoA-IV emerges as a promising candidate biomarker for ischemic cardiac death. Multimarker proteomic strategies may complement traditional autopsy to enhance diagnostic accuracy in forensic investigations, particularly in cases with equivocal morphological findings. Full article