Search Results (1,063)

Patient health knowledge graphs provide a means for high-quality and interoperable clinical data representation, while graph neural networks are a key enabler in order to learn their underlying relationships for downstream prediction tasks. In this work, we propose a sequential graph neural network (SeqGNN) framework that models patient visit trajectories for multiple binary clinical tasks, namely diagnosis, readmission, and mortality prediction. The proposed architecture integrates temporal dynamics with graph-based representations that enhances patient-level embeddings. Focusing on patients at the risk of Heart Failure (HF), our methodology achieves comparatively high accuracy and precision-versus-recall tradeoffs on highly heterogeneous graphs and imbalanced labeled data. We additionally quantify the uncertainty concerning each clinical decision making task and, compared with the state-of-the-art, show that AUROC and AUPRC scores reliably improve for onset diagnosis in particular, as high as 93.1 and 79.1 respectively. Our experiments conducted on real-world data from an intensive care unit demonstrate the potential for sequential representation learning over patient health knowledge graphs that can be provided for high-precision decision-making in clinical settings. Full article

Background: Pulmonary arterial hypertension is a rare but life-threatening condition in children, with hereditary forms often being linked to mutations in genes such as bone morphogenetic protein receptor type 2 (BMPR2), caveolin 1 (CAV1), and potassium channel subfamily K member 3 (KCNK3). Among these, CAV1 mutations are associated with severe disease phenotypes, though cases resulting from de novo heterozygous CAV1 mutations with multi-system involvement remain rarely reported. The CAV1 mutation (c.424C > T, p.Q142X) disrupts caveolin-1 function, leading to dysregulated pulmonary vascular remodeling and multi-system abnormalities. Methods: This was a retrospective case study of a pediatric patient with hereditary PAH. The patient was followed at our hospital from initial presentation until death. Clinical data were collected from medical records, including physical examinations, laboratory tests, echocardiography, chest X-ray, computed tomography pulmonary angiography (CTPA), and genetic analysis. The patient was treated sequentially with various PAH-targeted medications. This report also includes a review of the relevant literature on CAV1-associated PAH. Results: A female aged 3 years and 11 months was diagnosed with hereditary PAH associated with a de novo heterozygous CAV1 mutation (c.424C > T, p.Q142X). Both parents underwent genetic testing and were negative for the mutation, confirming its de novo origin. Clinical manifestations included special facial features, congenital telangiectasia, cutis marmorata (marbled skin), congenital cataract, hereditary lipodystrophy, and severe PAH. The patient presented with progressive exercise intolerance, syncope, and worsening dyspnea over nine years. Echocardiography revealed pulmonary hypertension with an estimated pulmonary artery systolic pressure of 69–105 mmHg, right heart enlargement, right ventricular hypertrophy, and moderate tricuspid regurgitation. Blood and urine metabolic screenings were normal. A chest X-ray showed progressive enlargement of the cardiac silhouette and bulging of the pulmonary artery segment. CTPA demonstrated pulmonary hypertension, secondary right heart dysfunction, decompensated right ventricular function, and mosaic perfusion in both lungs, suggestive of small arterial branch occlusion. Right heart catheterization was declined by the parents. Thus, the diagnosis of PAH was established based on clinical, echocardiographic, CTPA, and genetic findings. The patient was hospitalized four times and lost to follow-up from 2017 to 2023. She received sequential treatment with digoxin, hydrochlorothiazide, tadalafil, ambrisentan, selexipag, and treprostinil. Despite these therapies, pulmonary artery pressure continued to rise with progressive clinical deterioration. The patient ultimately died at 13 years of age due to a pulmonary hypertensive crisis and multiple organ failure following a severe episode of gastroenteritis. Conclusions: Despite aggressive treatment with multiple targeted reduced pulmonary artery pressure drug therapies, managing hereditary PAH caused by CAV1 mutations in children remains a significant challenge, with a high mortality rate. Early genetic diagnosis, regular follow-up, and individualized treatment are crucial. It requires the joint efforts of patients, parents, and healthcare providers. Full article

Heart failure (HF) is one of the largest contributors to disease burden and healthcare expenditure worldwide. Countless studies have shown that microRNAs (miRNAs) are pivotal regulators of heart homeostasis and promising biomarkers for the diagnosis and management of HF. Among the reported miRNAs, miR-106b-5p and miR-185-5p have been implicated in various cardiovascular diseases through involvement in cardiac injury, fibrosis, and cell survival pathways. Although cellular functions of miR-106b-5p and miR-185-5p have been investigated intensively, their circulating levels remain largely elusive in patients with HF. This study examined expression levels of plasma miR-106b-5p and miR-185-5p by quantitative reverse transcription PCR (RT-qPCR) in a study cohort comprising 41 chronic HF patients and 41 matched, non-HF subjects. Bioinformatic analysis was conducted for miR-106b-5p and miR-185-5p to discover their potential target genes, biological functions, and association with cardiovascular-related clinical phenotypes. Chronic HF patients presented a significant increase in plasma miR-106b-5p and miR-185-5p levels. Diverse expressive patterns of miR-106b-5p and miR-185-5p were observed in different types and functional classes of HF. A positive correlation between plasma miR-106b-5p and miR-185-5p was also identified. In silico analysis suggested that many genes related to cell proliferation and metabolic pathways were shared targets of miR-106b-5p and miR-185-5p. Our study reveals dysregulation of plasma miR-106b-5p and miR-185-5p in patients with chronic HF that may contribute to the pathological course of this disease. Full article

Heart failure (HF) is a multifactorial and heterogeneous syndrome with substantial epidemiological burden, high mortality, and impact on quality of life. In the context of heart failure, left ventricular ejection fraction (LVEF) has been regarded as the most important marker of systolic function and is fundamental in medical research and clinical practice. In research, LVEF has been a major inclusion criterion in most clinical trials over the past few decades. Furthermore, international heart failure guidelines rely on LVEF for the diagnosis of HF and to guide effective treatment. Additionally, our understanding of HF phenotypes and prognosis is mostly grounded in a classification based on LVEF. Nevertheless, there has been a growing debate regarding the role of LVEF in heart failure. In this context, the purpose of this review is to discuss both the advantages and contemporary relevance of LVEF in heart failure, as well as its limitations and controversies. In addition, this review aims to discuss potential alternatives and future directions in heart failure classification, such as new classification methods, alternative measurements of systolic function and imaging techniques, the HLM score, and the use of artificial intelligence and machine learning. Full article

Background: Heart failure (HF) is a complex clinical syndrome that presents significant challenges in diagnosis and treatment. Exploring innovative pathways to better understand the physiopathological mechanisms has led to the concept of cardiac remodeling (CR), which helps elucidate the diversity in clinical manifestations and treatment responses. However, the extent to which CR influences autonomic cardiac dynamics across the circadian cycle remains unclear. Methods: Recordings of 24 h ECG recordings from 86 Control subjects and 86 patients meeting the criteria for cardiac remodeling were analyzed. Heart rate variability (HRV) parameters were estimated using 5 min Blackman–Harris windows per hour. Autonomic influences on cardiac electrical activity were assessed using time-domain, frequency-domain, and nonlinear methods. Circadian parameters (MESOR, amplitude, and acrophase) were derived via Cosinor modeling, and group differences were evaluated while controlling for age, sex, and medication effects. Results: Patients with CR exhibited reduced oscillatory activity in HRV measures compared with Control. MESOR and amplitude were significantly lower in CR patients, who also displayed an advanced-phase phenotype across multiple HRV domains over 24 h. Additionally, CR patients showed decreased complexity and entropy in nonlinear dynamics. Conclusions: Altered circadian rhythmicity of cardiac electrical activity is evidenced in cardiac remodeling by changes in circadian HRV parameters and nonlinear dynamics. Full article

Background: Rheumatic diseases (RDs) are associated with increased cardiovascular morbidity, including a 40% higher risk of atrial fibrillation (AF). While ablation has become the cornerstone of rhythm control, its safety in patients with rheumatic diseases remains poorly defined. Methods: Adults with a primary admission diagnosis of AF catheter ablation from 2016 to 2022 were identified using the National Inpatient Sample. We excluded patients with other forms of supraventricular tachycardia, pacemaker/defibrillator procedures, and atrioventricular junction ablations. Sociodemographic, clinical characteristics, and outcomes were compared between groups. Multivariate logistic regression adjusted for age, race, sex, and potential comorbid confounders was used to assess for independent associations. Results: A weighted total of 48,855 patients were included, 2.5% of which had RD. These patients were predominantly female, older, and had higher rates of renal dysfunction, hypertension, heart failure, history of stroke, ischemic heart disease, heart failure, and obstructive sleep apnea (all p < 0.001). Patients with RD had higher complication rates (12.9% vs. 8.8%, p < 0.001); specifically, bleeding (p < 0.001), infection (p = 0.008), pericardial (p = 0.003), and respiratory complications (p < 0.001). RDs were not found to be an independent predictor of complications, though there was a trend towards more complications (odds ratio 1.43, 95% confidence interval 0.97–2.11, p = 0.070). Conclusions: Patients with RD undergoing AF ablation were older, female, and had higher rates of comorbidities. This translated to higher unadjusted periprocedural complications in patients with rheumatic diseases. While RDs were not independently associated with adverse outcomes, a trend towards increased complications was observed. 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: Recent studies have shown that catheter ablation of atrial fibrillation leads to an improvement in mortality and a reduction in hospitalization in patients with end-stage heart failure. It is therefore hypothesized that in an end-stage heart failure population, atrial fibrillation is of great relevance and that interventional therapy is crucial to preventing further progression, especially with the aim of avoiding a heart transplant. In this paper, we describe the clinical presentation of atrial fibrillation and its management in a real end-stage heart failure cohort of patients actively waiting on a heart transplant through EUROTRANSPLANT. Methods: A total of 577 patients have been actively listed for heart transplant in our clinic. Of these, we examined all patients who were actively listed by the key date of 31 December 2024. Patients already treated by assist devices such as the left-ventricular assist device and high-urgency listed patients were excluded, as were minors and patients in need of simultaneous transplantation of other organs in addition to the heart. Results: Thirty-one patients were included in our analysis. In this cohort, 18 patients (58%) had no diagnosis of atrial fibrillation or atrial flutter. A total of 13 patients (42%) presented with atrial fibrillation or flutter: 3/13 (23%) paroxysmal, 8/13 (62%) persistent, 1/13 (8%) permanent atrial fibrillation, and 1/13 (8%) atrial flutter. Moreover, 9/13 (69%) patients with atrial fibrillation had been diagnosed during evaluation and before the active listing period for heart transplant. Only three patients developed atrial fibrillation during the active listing period (two with atypical atrial flutter, one with atrial fibrillation). In those three patients, rhythm control could be achieved: the patient with new-onset atrial fibrillation was treated by pulmonary vein ablation, and in the two patients with newly diagnosed atypical atrial flutter, electrical cardioversion was performed. Conclusions: In our real end-stage heart failure cohort, more than half of the patients do not have atrial fibrillation. Patients diagnosed with atrial fibrillation often receive their diagnosis before they are listed for heart transplant. However, atrial fibrillation is not a common cause of clinical worsening while actively waiting on a heart transplant. Full article

Background: Trace elements function as essential micronutrients involved in oxidative balance, mitochondrial activity, and cardiovascular metabolism. Cigarette smoking represents a significant source of toxic metals and may disrupt systemic trace element homeostasis. Alterations in micronutrient and metal balance may contribute to oxidative stress, endothelial dysfunction, and myocardial remodeling, which are central mechanisms in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). This study aimed to investigate whether smokers with HFpEF exhibit distinct hair trace element profiles compared with smokers without HFpEF. Methods: In this prospective pilot study, scalp hair samples were collected from adults undergoing clinical evaluation for suspected cardiovascular disease. Trace element concentrations were determined using inductively coupled plasma mass spectrometry (ICP-MS). Participants were first stratified according to smoking status and subsequently, within the smoker subgroup, according to HFpEF diagnosis based on the Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide score (HFA-PEFF) algorithm. Differences in trace element concentrations were analyzed using appropriate statistical tests, with multiple-comparison correction using the Benjamini–Hochberg false discovery rate (FDR). Active smoking was defined as ≥10 cigarettes per day for at least 1 year, and cumulative exposure was quantified in pack-years. Results: Fifty-eight participants were included, including 27 active smokers. In unadjusted analyses, several trace elements differed between smokers with HFpEF and those without HFpEF, including vanadium, lithium, aluminum, and copper. However, after FDR correction, only copper remained significantly elevated in smokers with HFpEF (q = 0.004). Hair copper concentrations were markedly higher in the HFpEF group compared with smokers without HFpEF. These differences were observed alongside echocardiographic features consistent with diastolic dysfunction and structural cardiac remodeling. Conclusions: In this hypothesis-generating pilot study, smokers with HFpEF demonstrated elevated hair copper concentrations, suggesting disturbances in trace element and micronutrient homeostasis. Altered copper metabolism may reflect oxidative stress-related cardiometabolic remodeling associated with HFpEF. These findings raise the hypothesis that cardiometabolic phenotype, rather than smoking exposure alone, may modulate trace element homeostasis in HFpEF; however, causal relationships cannot be established. 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: Cardiac involvement represents a major determinant of morbidity and mortality in patients with muscular dystrophies (MDs). Evidence supporting guideline-directed heart failure (HF) therapy in this population remains limited. We aimed to retrospectively assess the effectiveness and tolerability of sodium–glucose co-transporter 2 inhibitors (SGLT2i) in patients with MDs and a previous history of HFrEF, HFpEF and HFmrEF and/or echocardiographic evidence of an LVEF < 50% Methods: In this retrospective, single-center study, we enrolled consecutive patients with MD treated with empagliflozin or dapagliflozin between October 2021 and October 2024. Comprehensive clinical, laboratory, echocardiographic, and functional data were collected at a baseline (V1) and at follow-up (V3) visit to evaluate longitudinal changes. Results: Twenty-four patients (mean age 42 ± 16 years; 92% male) were included, with a median follow-up of 418 ± 104 days. SGLT2i therapy was well tolerated; one patient discontinued treatment due to a urinary tract infection. LVEF significantly improved from 41 ± 5% to 44 ± 6% (p = 0.005). FSS decreased from 36 to 30 (p < 0.001), indicating improved functional capacity. Background HF therapy was intensified over time, with increased prescription of mineralocorticoid receptor antagonists (21% vs. 52%; p = 0.039) and β-blockers (67% vs. 91%). The interval between MD diagnosis and cardiomyopathy onset independently predicted LVEF improvement (β = 0.17; p = 0.012). Conclusions: In patients with MDs and HF, SGLT2i therapy was safe and associated with a modest but significant improvement in LVEF, reduced fatigue, and enhanced prescription of guideline-directed HF therapy. These findings support the potential role of SGLT2i in this high-risk population and warrant confirmation in larger prospective studies. Full article

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, underscoring the need to better define the molecular mechanisms that govern cardiovascular homeostasis and disease progression. Among post-transcriptional regulators, microRNAs have emerged as important modulators of endothelial function, vascular smooth muscle cell plasticity, cardiomyocyte integrity, and cardiac fibroblast activity. This narrative review examines how microRNAs orchestrate molecular networks linking cellular homeostasis to inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, fibrosis, angiogenesis, and pathological remodeling across major cardiovascular cell types. It further discusses how these regulatory programs are reflected in specific cardiovascular diseases, including atherosclerosis, hypertension, acute myocardial infarction, heart failure, and arrhythmias. In addition, the review addresses the growing relevance of circulating and extracellular vesicle-associated microRNAs as candidate biomarkers for diagnosis, prognosis, and disease monitoring, as well as their therapeutic potential through mimics, inhibitors, antagomirs, and emerging delivery systems. Finally, current translation barriers are considered, including methodological heterogeneity, limited tissue specificity, delivery challenges, safety concerns, and the need for large-scale clinical validation. Overall, microRNAs are presented as integrative regulators connecting cardiovascular cell biology with disease mechanisms and clinical applications. Full article

Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by microvascular dysfunction, immune activation, and progressive fibrosis affecting multiple organs, including the heart. Myocardial involvement represents an important but frequently underrecognized manifestation of SSc and may develop even in the absence of overt clinical symptoms. Cardiac manifestations include ventricular dysfunction, arrhythmias, conduction abnormalities, and heart failure, contributing substantially to morbidity and mortality. The underlying pathophysiology involves coronary microvascular dysfunction, immune-mediated myocardial inflammation, and progressive myocardial fibrosis, which often precede clinically apparent cardiac disease. This review aims to summarize the current understanding of myocardial involvement in SSc and to provide a comprehensive overview of contemporary multimodality cardiovascular imaging techniques for its detection, characterization, and risk stratification. A comprehensive overview of the current literature was conducted focusing on established and emerging cardiovascular imaging modalities for the evaluation of myocardial involvement in SSc. Particular attention was given to echocardiography, cardiac magnetic resonance (CMR), nuclear imaging techniques including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), and cardiac computed tomography (CT). Recent advances in imaging biomarkers, parametric mapping, myocardial strain analysis, and emerging technologies such as artificial intelligence (AI), radiomics, and molecular imaging were also considered. Multimodality cardiovascular imaging plays a central role in the early detection and comprehensive assessment of myocardial involvement in SSc. Advanced imaging techniques enable improved identification of subclinical myocardial dysfunction, microvascular impairment, inflammation, and fibrosis. An integrated imaging approach combining echocardiography, CMR, nuclear imaging, and CT may facilitate earlier diagnosis, enhance risk stratification, and ultimately improve cardiovascular outcomes in patients with SSc. Full article

Early identification of ischemic heart failure (IHF) is critical for improving patient prognosis and clinical outcomes. However, effective diagnostic biomarkers and targeted therapeutic strategies for IHF remain limited. Total flavonoids from Dracocephalum moldavica L. (TFDM) exert potential cardioprotective effects; however, the molecular mechanisms by which TFDM acts against IHF have not been fully elucidated. Therefore, this study aims to identify diagnostic biomarkers for IHF and explore the potential therapeutic mechanism of TFDM targeting these key genes. Given the small sample size (n = 17) of the clinical dataset, LASSO regression and Random Forest were employed due to their superior performance in feature selection, noise reduction, and stability in small-sample scenarios. In this study, we screened key characteristic genes of IHF through bioinformatics analysis and further investigated the binding potential between these key genes and active components of TFDM using molecular docking, thus providing new targets for the early diagnosis of IHF and new evidence for the intervention mechanism of TFDM in IHF. Full article

In patients with co-morbid CHF and COPD, the diagnosis of CHF can be delayed. It is also well known that left ventricular dysfunction can arise from progressive disease-related hyperinflation. Apart from the longitudinal risk of developing CHF in some patients, a short-term or subclinical risk of cardiac events has been reported after hospitalization for COPD exacerbation. Currently there are no data or strategies to support screening for the early diagnosis of CHF in patients with COPD. Similarly, pulmonary function testing results can also be confounding and inaccurate in establishing the severity of COPD during an active exacerbation of CHF. The hyperinflation of the lungs, which can alter LV geometry and mechanics, is at the root of many of the causes of LV underfilling, which eventually contributes to CHF. Conventional echocardiography can often miss subclinical myocardial dysfunction and hence make early diagnosis even more challenging. Advanced cardiac imaging modalities and revised echocardiographic parameters can help detect subclinical LV dysfunction and PH earlier, but there are no clinical outcome data to validate their routine use in day-to-day clinical practice. Beta-blockers are generally regarded as safe to be used for appropriate cardiovascular indications in patients with COPD, and recent trials have also established the safety of long-acting beta agonists for treating COPD in patients with elevated cardiac risk. Full article