Search Results (299)

Background/Objective: Sacubitril/Valsartan are a combination drug approved for heart failure treatment, known to enhance natriuretic peptide activity and inhibit the renin–angiotensin–aldosterone system (RAAS). While its clinical efficacy is well-established, its broader impact on human metabolism remains insufficiently characterized. This study aimed to explore the time-resolved metabolic changes induced by Sacubitril/Valsartan in healthy individuals using an untargeted metabolomics approach. Methods: Fourteen healthy male volunteers received a single oral dose of Sacubitril/Valsartan (200 mg; 97.2 mg Sacubitril and 102.8 mg Valsartan) across two phases separated by a two-week washout period. Plasma samples were collected at eight individualized time points based on pharmacokinetic profiles. Metabolites were extracted and analyzed using high-resolution liquid chromatography–mass spectrometry (LC-QToF HRMS). Data processing included peak alignment, annotation via HMDB and METLIN, and statistical modeling through multivariate (PLS-DA, OPLS-DA) and univariate (ANOVA with FDR correction) analyses. Results: Out of 20,472 detected features, 13,840 were retained after quality filtering. A total of 315 metabolites were significantly dysregulated (FDR p < 0.05), of which 31 were confidently annotated as endogenous human metabolites. Among these, key changes were observed in the pyrimidine metabolism pathway, particularly elevated levels of uridine triphosphate (UTP) associated with cellular proliferation and metabolic remodeling. OPLS-DA models demonstrated clear separation between pre-dose and Cmax samples (R²Y = 0.993, Q² = 0.768), supporting the robustness of the time-dependent effects. Conclusions: This is the first study to characterize the dynamic metabolomic signature of Sacubitril/Valsartan in healthy humans. The findings reveal a distinctive perturbation in pyrimidine metabolism, suggesting possible links to drug mechanisms relevant to cardiac cell cycle regulation. These results underscore the utility of untargeted pharmacometabolomics in uncovering systemic drug effects and highlight potential biomarkers for monitoring therapeutic response or guiding precision treatment strategies in heart failure. Full article

Background/Objectives: Cardiac sarcoidosis (CS) is an inflammatory cardiomyopathy with a strong clinical impact on patients affected by the disease and a challenging diagnosis. Methods: This comprehensive narrative review evaluates the role of [18F]fluorodesoxyglucose ([18F]FDG) positron emission tomography (PET)-based radiomics and machine learning (ML) analyses in the assessment of CS. Results: The value of [18F]FDG PET-based radiomics and ML has been investigated for the clinical settings of diagnosis and prognosis of patients affected by CS. Even though different radiomics features and ML models have proved their clinical role in these settings in different cohorts, the clear superiority and added value of one of them across different studies has not been demonstrated. In particular, textural analysis and ML showed high diagnostic value for the diagnosis of CS in some papers, but had controversial results in other works, and may potentially provide prognostic information and predict adverse clinical events. When comparing these analyses with the classic semiquantitative evaluation, a conclusion about which method best suits the final objective cannot be drawn with the available references. Different methodological issues are present when comparing different papers, such as image segmentation and feature extraction differences that are more evident. Furthermore, the intrinsic limitations of radiomics analysis and ML need to be overcome with future research developed in multicentric settings with protocol harmonization. Conclusions: [18F]FDG PET-based radiomics and ML show preliminary promising results for CS evaluation, but remain investigational tools since the current evidence is insufficient for clinical adoption due to methodological heterogeneity, small sample sizes, and lack of standardization. Full article

Background: The guidelines recommend mitral valve repair whenever possible in patients undergoing surgical treatment for active infective endocarditis of the native mitral valve. However, the impact of causative microorganisms in relation to treatment strategies, especially Staphylococcus aureus, has not been studied. In this study, we aimed to compare the outcomes of mitral valve repair versus replacement in patients with native mitral valve infective endocarditis caused by methicillin-susceptible Staphylococcus aureus. Methods: Consecutive patients with definitive active infective endocarditis of the native mitral valve caused by methicillin-susceptible Staphylococcus aureus undergoing cardiac surgery between 2012 and 2022 were selected. Patients were classified according to the treatment received in two groups: repair and replacement. Inverse propensity treatment weighting was employed to correct for confounders. The endpoints were all-cause mortality, incidence of recurrent endocarditis, reoperation rate, and event-free survival at two-year follow-up. Results: Among 170 operated-upon patients with active infective endocarditis of the native mitral valve, 44 cases were caused by methicillin-susceptible Staphylococcus aureus. A total of 23 patients underwent mitral valve repair and 21 patients received mitral valve replacement. Weighted 30-day mortality in the repair group was 43%, versus 27% in the replacement group (p = 0.15). Two-year mortality increased to 57% in the repair group and 32% in the replacement group (p = 0.02). Three patients developed recurrent endocarditis in the repair group, while no recurrent endocarditis occurred in the replacement group. Three patients in the repair group required reoperation due to recurrence and one patient in the replacement group underwent re-operation due to paravalvular leakage. Weighted two-year event-free survival was 29% in the repair group and 59% in the replacement group (p < 0.01). Conclusions: Mortality in patients with mitral valve infective endocarditis caused by Staphylococcus aureus is extremely high, especially in patients undergoing mitral valve repair. The risk of recurrent endocarditis and mid-term mortality seems to be higher in mitral valve repair, resulting in poor event-free survival during two-year follow-up. However, the sample size was likely insufficient for drawing definitive conclusions. Full article

Hemodialysis-associated pericarditis is a significant but insufficiently acknowledged complication in patients with end-stage renal disease (ESRD). It can manifest as either uremic pericarditis, typically occurring before or shortly after the initiation of dialysis, or dialysis-associated pericarditis, which results from prolonged dialysis treatment. The condition is associated with substantial morbidity and potential mortality due to risks, such as cardiac tamponade and constrictive pericarditis. Pericardial involvement in ESRD most frequently presents as acute uremic or dialysis-associated pericarditis, whereas chronic constrictive pericarditis represents a less common manifestation. The aim of the article is to review the current understanding of the epidemiology, pathophysiology, clinical presentation, diagnostic criteria and therapy strategies of this pathology based on a case of hemodialysis-associated pericarditis in a patient diagnosed with sudden shortness of breath during a hemodialysis session. When assessing pericarditis in this group of population, it is recommended to distinguish between uremic and dialysis-associated forms, to recognize clinical warning signs, and to customize the treatment. Probably the therapy should include anti-inflammatory drugs, colchicine, intensified dialysis, and in severe cases, even pericardiocentesis or surgical intervention. Rising awareness and timely intervention are critical to improve outcomes in this vulnerable population. Full article

Background: The NeoChord procedure is a trans-ventricular, echo-guided, beating-heart mitral valve (MV) repair technique used to treat degenerative mitral regurgitation (MR) caused by leaflet prolapse and/or flail. Objectives: This study aimed to develop a machine learning (ML) scoring system using pre-procedural clinical and echocardiographic variables to predict the success of the NeoChord procedure—defined as less than moderate MR at follow-up. Methods: A total of 80 patients were included. Preoperative MV anatomical parameters were assessed using three-dimensional (3D) transesophageal echocardiography and analyzed with dedicated post-processing software (QLAB software, version 15.0, Philips Healthcare, Amstelveen, NL, The Netherlands). Two supervised ML models (random forest and decision tree) were trained on the dataset, with hyperparameters optimized via 10-fold cross-validation. The random forest model also provided a variable importance ranking using a filter-based method. Key predictors identified by the models included age, flail gap, early systolic mitral valve area, and indexed left atrial volume. Results: The mean and median cross-validated area under the curve of the ML models were 0.79 and 0.83 for the random forest model and 0.72 and 0.77 for the decision tree model, respectively. Conclusions: A machine learning approach integrating clinical and 3D echocardiographic parameters can effectively predict mid-term procedural success of the NeoChord technique. This method may support future preoperative patient selection, pending validation in larger cohorts. Full article

Non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) often coexists with multivessel coronary artery disease (MVD), complicating treatment decisions. Current guidelines suggest complete revascularization (CR), yet robust evidence in hemodynamically stable patients remains insufficient. However, the comparative benefit of CR over incomplete revascularization (IR) in reducing ischemic events and improving cardiac function in this population is not well established. The aim of this study was to evaluate the impact of CR on all-cause mortality, cardiac death, and ischemic readmissions at 6 and 12 months, as the composite primary outcome, and to assess left ventricular ejection fraction (LVEF) improvement at discharge and hospital length of stay, as secondary outcomes. A total of 282 hemodynamically stable NSTE-ACS patients with MVD were included, of whom 218 (77.3%) underwent CR and 64 (22.7%) IR. The primary composite outcome occurred in 40.6% of IR patients versus 11.0% in the CR group at 6 months (p < 0.001), and 68.8% vs. 22.0% at 12 months (p < 0.001). CR was associated with significantly lower rates of all-cause and cardiac death, myocardial infarction, and unstable angina. Stroke incidence was similar. Event-free survival favored CR. Multivariable analysis identified CR and baseline LVEF as independent predictors of 12-month outcomes (HR for CR: 7.797; 95% CI: 3.961–15.348; p < 0.001; HR for LVEF: 0.959; CI: 0.926–0.994; p = 0.021). These findings strongly support CR as the preferred therapeutic strategy. Future prospective randomized studies are warranted to confirm the results. Full article

Background: Clinical outcomes among older adults hospitalized with heart failure with preserved ejection fraction (HFpEF) in the setting of metabolically healthy obesity (MHO) remain insufficiently explored. This study aimed to evaluate whether MHO status is associated with different rates of major adverse cardiac and cerebrovascular events (MACCEs) during HFpEF-related hospitalizations compared to patients without MHO. Methods: Data from the 2019 National Inpatient Sample (NIS) database was analyzed using relevant ICD-10 codes to identify HFpEF admissions in older adults. Propensity score matching (1:1) was applied to generate balanced cohorts of patients with and without MHO. Multivariable adjustments were performed to assess primary outcomes, including MACCEs, all-cause mortality (ACM), acute myocardial infarction (AMI), dysrhythmia, cardiac arrest (CA), and stroke. Statistical significance was set at p < 0.05. Results: Each MHO cohort included 22,405 patients with a median age of 75 years. The MHO+ group demonstrated a significantly higher risk of dysrhythmia (OR 1.32, 95% CI 1.21–1.43, p < 0.001). Interestingly, an “obesity paradox” was observed, as the MHO+ cohort had lower odds of MACCEs (OR 0.70, 95% CI 0.61–0.81, p < 0.001), ACM (OR 0.66, 95% CI 0.54–0.82, p < 0.001), and AMI (OR 0.71, 95% CI 0.59–0.86, p = 0.001) compared to MHO−. No significant differences were found for CA or stroke between the groups. Conclusions: Although the MHO+ group had an elevated risk of dysrhythmia, they exhibited more favorable outcomes in terms of MACCEs, ACM, and AMI—supporting the concept of an “obesity paradox.” Further research is needed to better understand the role of MHO as a comorbid condition in patients with HFpEF. Full article

The image represents the post-mortem heart of a 28-year-old female patient, diagnosed in childhood with complete common atrioventricular canal defect. At time of diagnosis, the family refused surgery, as did the patient during her adulthood. Despite being advised against pregnancy, she became pregnant. On presentation to hospital, she was cyanotic, with clubbed fingers, and hemodynamically unstable, in sinus rhythm, with Eisenmenger syndrome and respiratory failure partially responsive to oxygen. During pregnancy, owing to systemic vasodilatation, the right-to-left shunt is increased, with more severe cyanosis and low cardiac output. Echocardiography revealed the complete common atrioventricular canal defect, with a single atrioventricular valve with severe regurgitation, right ventricular hypertrophy, pulmonary artery dilatation, severe pulmonary hypertension and a hypoplastic left ventricle. The gestational age at delivery was 38 weeks. She gave birth to a healthy boy, with an Apgar score of 10. The vaginal delivery was chosen by an interdisciplinary team. The cesarean delivery and the anesthesia were considered too risky compared to vaginal delivery. Three days later, the patient died. The autopsy revealed hepatomegaly, a greatly hypertrophied right ventricle with a purplish clot ascending the dilated pulmonary arteries and a hypoplastic left ventricle with a narrowed chamber. A single valve was observed between the atria and ventricles, making all four heart chambers communicate, also insufficiently developed interventricular septum and its congenital absence in the cranial third. These morphological changes indicate the complete common atrioventricular canal defect, with right ventricular dominance, which is a rare and impressive malformation that requires mandatory treatment in early childhood in order for the condition to be solved. Full article

Background/Objectives: Pulmonary vein isolation (PVI) via cryoballoon ablation (CBA) is a recommended therapeutic strategy for patients with symptomatic paroxysmal and persistent atrial fibrillation (AF) who are refractory to antiarrhythmic drugs. Although PVI has demonstrated efficacy in reducing AF recurrence and improving patients’ quality of life, its impact on respiratory function is not well understood, particularly in patients with comorbid conditions. The aim of the study was to search for functional predictors of the respiratory system in the process of evaluating the efficiency of clinical assessment of CBA in patients with AF. Methods: We conducted a prospective study on 42 patients with symptomatic AF who underwent CBA, assessing their respiratory function through spirometry before and 30 days after the procedure. Exclusion criteria included pre-existing lung disease and cardiac insufficiency. The impact of variables such as body mass index (BMI), coronary artery disease (CAD) and heart failure (HF) on spirometry parameters was analyzed using statistical tests. Results: No significant changes were observed in overall post-PVI spirometry parameters for the full cohort. However, post hoc analyses revealed a significant decline in ΔMEF₇₅ in patients with CAD and BMI ≥ 30 kg/m², whereas ΔFEV₁/FVCex was significantly increased in patients with HF, as well as in patients with ejection fraction (EF) < 50%. Conclusions: CBA for AF does not universally affect respiratory function in the short term, but specific subgroups, including patients with CAD and a higher BMI, may require post-procedure respiratory monitoring. In addition, PVI may improve lung function in patients with HF and reduced EF. Full article

Background and Objectives: Implantation of cardiac implantable electronic devices (CIEDs) is increasingly performed in elderly and comorbid patients, for whom minimizing perioperative complications—including pain and systemic drug use—is critical. Traditional local infiltration often provides insufficient analgesia. The ultrasound-guided PECS II block, an interfascial regional technique, offers promising analgesic benefits in thoracic wall procedures but remains underutilized in cardiac electrophysiology. Materials and Methods: We conducted a prospective, controlled, non-randomized clinical study including 106 patients undergoing de novo CIED implantation. Patients were assigned to receive either a PECS II block (n = 53) or standard lidocaine-based local anesthesia (n = 53). Pain intensity was assessed using the numeric rating scale (NRS) intraoperatively and at 1, 6, and 12 h postoperatively. Secondary outcomes included the need for rescue analgesia, procedural duration, length of hospitalization, and patient satisfaction. Results: Patients in the PECS II group reported significantly lower NRS scores at all time points (mean intraoperative score: 2.1 ± 1.2 vs. 5.7 ± 1.6, p < 0.001; at 1 h: 2.5 ± 1.5 vs. 6.1 ± 1.7, p < 0.001). Rescue analgesia (metamizole sodium) was required in only four PECS II patients (7.5%) vs. 100% in the control group within 1 h. Hospital stay and procedural time were also modestly reduced in the PECS II group. Patient satisfaction scores were significantly higher in the intervention group. Conclusions: The ultrasound-guided PECS II block significantly reduces perioperative pain and the need for additional analgesia during CIED implantation, offering an effective, safe, and opioid-sparing alternative to conventional local infiltration. Its integration into clinical protocols for device implantation may enhance procedural comfort and recovery. Full article

Background/Objectives: Sudden cardiac arrest (SCA) is a major global health concern with high mortality despite advances in resuscitation techniques. Achieving return of spontaneous circulation (ROSC) represents merely the initial step in the extensive rehabilitation journey. This review highlights the critical role of structured, multidisciplinary rehabilitation following ROSC, emphasizing the necessity of integrated physiotherapy, neurocognitive therapy, and psychosocial support to enhance quality of life and societal reintegration in survivors. Methods: This narrative review analyzed peer-reviewed literature from 2020–2025, sourced from databases such as PubMed, Scopus, Web of Science, and Google Scholar. Emphasis was on clinical trials, expert guidelines (e.g., European Resuscitation Council 2021, American Heart Association 2020), and high-impact journals, with systematic thematic analysis across rehabilitation phases. Results: The review confirms rehabilitation as essential in addressing Intensive Care Unit–acquired weakness, cognitive impairment, and post-intensive care syndrome. Early rehabilitation (0–7 days post-ROSC), focusing on parameter-guided mobilization and cognitive stimulation, significantly improves functional outcomes. Structured interdisciplinary interventions encompassing cardiopulmonary, neuromuscular, and cognitive domains effectively mitigate long-term disability, facilitating return to daily activities and employment. However, access disparities and insufficient randomized controlled trials limit evidence-based standardization. Discussion: Optimal recovery after SCA necessitates early and continuous interdisciplinary engagement, tailored to individual physiological and cognitive profiles. Persistent cognitive fatigue, executive dysfunction, and emotional instability remain significant barriers, underscoring the need for holistic and sustained rehabilitative approaches. Conclusions: Comprehensive, individualized rehabilitation following cardiac arrest is not supplementary but fundamental to meaningful recovery. Emphasizing early mobilization, neurocognitive therapy, family involvement, and structured social reintegration pathways is crucial. Addressing healthcare disparities and investing in rigorous randomized trials are imperative to achieving standardized, equitable, and outcome-oriented rehabilitation services globally. Full article

Cardiac arrhythmias remain a major source of morbidity and mortality, often stemming from molecular and structural abnormalities that are insufficiently addressed by current pharmacologic and interventional therapies. Gene therapy has emerged as a transformative approach, offering precise and durable interventions that directly target the arrhythmogenic substrate. Across the spectrum of inherited and acquired arrhythmias—including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, atrial fibrillation, and post-infarction ventricular tachycardia—gene-based strategies such as allele-specific silencing, gene replacement, CRISPR-mediated editing, and suppression-and-replacement constructs are showing growing translational potential. Advances in delivery platforms, including cardiotropic viral vectors, lipid nanoparticle-encapsulated mRNA, and non-viral reprogramming tools, have further enhanced the specificity and safety of these approaches. Additionally, innovative applications such as biological pacemaker development and mutation-agnostic therapies underscore the versatility of genetic modulation. Nonetheless, significant challenges remain, including vector tropism, immune responses, payload limitations, and the translational gap between preclinical models and human electrophysiology. Integration of patient-derived cardiomyocytes, computational simulations, and large-animal studies is expected to accelerate clinical translation. This review provides a comprehensive synthesis of the mechanistic rationale, therapeutic strategies, delivery platforms, and translational frontiers of gene therapy for cardiac arrhythmias. Full article

Cardiac amyloidosis (CA) results from the deposition of either immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid fibrils in the myocardium, causing restrictive cardiomyopathy and, if left untreated, can lead to early death. Advancements in non-invasive diagnostic modalities have led to an increased recognition of the disease. Monoclonal gammopathy plays a pivotal role in the diagnostic algorithm for CA, particularly in differentiating AL from ATTR. This review highlights the importance of monoclonal protein detection through serum protein electrophoresis, immunofixation electrophoresis, and serum free light chain assays as initial screening tools. However, these tests alone are insufficient for a definitive diagnosis due to the complexities associated with coexisting monoclonal gammopathies and the potential for false negative and positive results. Advanced imaging modalities, such as echocardiography, cardiac magnetic resonance, and nuclear scintigraphy, along with tissue biopsy, are crucial for confirming CA and accurately determining the CA subtype. Full article

Protein S-nitrosylation is a selective post-translational modification in which a nitrosyl group is covalently attached to the reactive thiol group of cysteine, forming S-nitrosothiol. This modification plays a pivotal role in modulating physiological and pathological cardiovascular processes by altering protein conformation, activity, stability, and other post-translational modifications. It is instrumental in regulating vascular and myocardial systolic and diastolic functions, vascular endothelial cell and cardiomyocyte apoptosis, and cardiac action potential and repolarization. Aberrant S-nitrosylation levels are implicated in the pathogenesis of various cardiovascular diseases, including systemic hypertension, pulmonary arterial hypertension, atherosclerosis, heart failure, myocardial infarction, arrhythmia, and diabetic cardiomyopathy. Insufficient S-nitrosylation leads to impaired vasodilation and increased vascular resistance, while excessive S-nitrosylation contributes to cardiac hypertrophy and myocardial fibrosis, thereby accelerating ventricular remodeling. This paper reviews the S-nitrosylated proteins in the above-mentioned diseases and their impact on these conditions through various signaling pathways, with the aim of providing a theoretical foundation for the development of novel therapeutic strategies or drugs targeting S-nitrosylated proteins. Full article

Fever is a frequent complication in children receiving chemotherapy, primarily caused by bloodstream infections and non-infectious inflammation. Yet, the pathophysiological mechanisms remain unclear, and diagnostics are insufficient, which often results in continued antibiotic treatment despite negative blood cultures. In a nationwide study, we collected whole blood in PAXgene tubes from 168 febrile episodes in children with hematological malignancies, including 37 episodes with bacteremia, and performed single-cell RNA sequencing. We compared transcriptomic profiles between febrile children with and without bacteremia. In children with bacteremia, differentially expressed genes were related to immunoregulation and cardiac and vascular function. Children without bacteremia had distinct gene expression patterns, suggesting a viral or other inflammatory cause of fever. Several differentially expressed genes overlapped with previously published transcriptomics-based diagnostic signatures developed in immunocompetent children. In conclusion, blood transcriptomics provided novel insights into the pathophysiological mechanisms of febrile children with hematological malignancies. We found differentially expressed genes suggesting viral infections or non-bacterial inflammation as causes of fever in children with negative blood cultures, supporting early antibiotic discontinuation in children with cancer. Full article