Search Results (8,886)

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: Pericardial effusion (PEf) is a frequent finding after cardiac surgery. Progression to cardiac tamponade (CT) is a rare but life-threatening complication. Current evidence remains limited due to insufficient data on prevalence, progression predictors and management strategies. Methods: We retrospectively analyzed anamnestic, clinical, laboratory, echocardiographic and therapeutic data from 2662 patients (74 ± 11 years) admitted to the Cardiac Rehabilitation ward between 2022 and 2024. Results: Among 2152 (81%) cardiac surgery patients, 382 (18%) developed PEf: 58% mild, 38% moderate, and 4% severe. Patients developing PEf tended to be younger and more frequently male. In addition, PEf development was seen more commonly after aortic and combined surgeries. All patients with severe PEf or CT had undergone surgery via sternotomy, whereas minithoracotomy was inversely associated with PEf severity. Postoperative complications occurred in 92% of PEf patients, mainly due to arrhythmia, hemodynamic deterioration, or heart failure. Overall outcome was favourable in 98% of patients. CT occurred in eight patients (2%). Anticoagulation therapy was more frequent among patients who developed PEf or CT. Preventive colchicine was prescribed in only 16% of cases. No PEf-specific therapy was administered in 56% of PEf patients, while corticosteroids and nonsteroidal anti-inflammatory drugs were used in 28% and 8% of cases, respectively, without surgical wound complications. No PEf recurrences were observed during follow up (517 ± 424 days). Conclusions: PEf is a common complication after cardiac surgery, more frequently in young males, usually of mild or moderate severity. The majority of these cases resolve using either a conservative or pharmacological approach, predominantly via corticosteroids. Patients undergoing aortic surgery, experiencing postoperative complications (especially arrhythmias), and receiving anticoagulation therapy were associated with severe PEf or CT. Despite guideline recommendations, colchicine remains markedly underutilized. Full article

Over the past years, burn care has evolved from a discipline focused on survival to one centered on restoring long-term health, function, and quality of life. Significant advances in critical care, early excision and grafting, infection control, and metabolic support have transformed survival outcomes for even the most severe injuries. As a result, the field now faces a new frontier: understanding and managing the long-term physical, psychological, and systemic sequelae of survival. This review traces the evolution of burn care over the last century and outlines the challenges and priorities for the next 25 years. The first era of progress, defined by innovations in resuscitation, surgery, and critical care, has given rise to a growing cohort of long-term survivors. Research over the past decade has revealed that major burns induce chronic multisystem alterations, including metabolic, cardiovascular, neurocognitive, and immunological dysfunctions. Emerging concepts such as burn-associated heart failure exemplify this shift from acute to chronic disease understanding. Looking ahead, the future of burn medicine lies in personalized and lifelong care, supported by translational research, digital health, regenerative therapies, and interdisciplinary collaboration. Overall, burn care stands at a pivotal crossroads. By integrating precision medicine, rehabilitation science, and psychosocial care, we aim to move the field from survival toward sustained, holistic recovery over the next 25 years. Full article

Non-infectious cardiac failure in feedyard cattle has become more frequently diagnosed. There is limited research assessing gross and histologic lesions in grossly abnormal hearts of harvested cattle. Cases were stratified by heart score (HS) using a scale of 1–5, with 1 representing a normal heart and 5 representing severely remodeled ventricles. Cattle were evaluated for gross lesions of the heart, lung, and liver. Samples collected from each animal for histology included cardiac (n = 4), pulmonary (n = 4), and hepatic (n = 1) tissues. Histologic evaluation scored cardiac and hepatic fibrosis and necrosis, embedded myocardial protozoal cysts (EMPCs) were quantified, and pulmonary lesions were categorized based on histologic patterns. Of 103 cases, 40 had normal HSs (NHSs) (1 or 2), and 63 had abnormal HSs (AHSs) (3, 4, or 5). There were 64 cases with normal lung deflation scores, and 39 cases with abnormal lung deflation scores. At least one cardiac section contained EMPCs in 67 cases. Cattle with abnormal lung deflation scores were more likely to have an AHS (0.76 ± 0.07, p ≤ 0.01) compared with cattle with normal deflation scores (0.52 ± 0.06). Cattle with EMPCs present in at least one cardiac section were more likely to also have an AHS (0.73 ± 0.05, p ≤ 0.1) compared with cattle without EMPCs (0.39 ± 0.08). No histological findings for the lungs or liver were associated with abnormal heart score; however, lung deflation and EMPCs were associated with abnormal heart score. Full article

Metabolic reprogramming plays a critical role in the pathogenesis of cardiovascular diseases. Historically regarded as a metabolic waste product, lactate has recently emerged as a critical regulator of vascular biology, exerting both metabolic and signaling functions. Moreover, the discovery of protein lactylation, a novel post-translational modification derived from lactate, has revealed a direct link between metabolic flux and gene regulation. This review provides a comprehensive overview of the evolving roles of lactate and lactylation in cardiovascular physiology and disease, offering insights into potential therapeutic interventions. It first provides a historical perspective of lactate and lactylation, followed by an overview of lactate metabolism, lactate shuttle theory and signaling pathways. It then discusses the mechanism and regulation of lactylation, focusing on its writers, erasers, and readers. Finally, this review summarizes clinical implications of lactate and lactylation in various cardiovascular diseases, including atherosclerosis, pulmonary hypertension, myocardial infarction, heart failure, and diabetic vascular complications. A deeper understanding of the mechanisms underlying the lactate–lactylation axis may facilitate the development of new therapeutic strategies to prevent or treat cardiovascular diseases. 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

Background and Clinical Significance: Mechanical complications and intracavitary thrombus are both recognized causes of clinical deterioration following acute myocardial infarction, yet they require fundamentally different therapeutic approaches. Distinguishing between these entities is critical, as misdiagnosis may lead to unnecessary surgical intervention or delayed anticoagulation with serious consequences. Left ventricular (LV) thrombus typically appears as a well-defined mass; however, atypical and highly mobile morphologies may closely mimic catastrophic post-infarction mechanical complications, creating significant diagnostic uncertainty. This case highlights the pivotal role of contrast-enhanced echocardiography in resolving such ambiguity and guiding appropriate management in a high-stakes clinical setting. Case Presentation: A 60-year-old man presented with acute dyspnea and pulmonary edema ten days after an anterior myocardial infarction treated with percutaneous coronary intervention, complicated by ischemic stroke. Transthoracic echocardiography demonstrated severe LV systolic dysfunction with moderate-to-severe mitral regurgitation and an unexpected, highly mobile, irregular mass protruding into the LV apex. The mass exhibited a shredded, tissue-like appearance, raising urgent concern for post-infarction mechanical complications, including papillary muscle rupture or apical myocardial disruption, and prompting immediate consideration of surgical intervention. Contrast-enhanced echocardiography was performed and revealed a mobile LV apical thrombus. Surgical management was avoided, and systemic anticoagulation was initiated, followed by transition to rivaroxaban in combination with ongoing dual antiplatelet therapy. The patient demonstrated rapid clinical improvement with optimized heart failure treatment and was discharged after four days, with planned follow-up imaging to assess thrombus resolution. Conclusions: Left ventricular thrombus may present with atypical, misleading morphologies that closely resemble life-threatening mechanical complications after myocardial infarction. Full article

Activating PIK3CA mutations occur in approximately 40% of hormone receptor-positive (HR+)/HER2-negative breast cancers and represent a major driver of endocrine resistance. The PI3Kα-selective inhibitor alpelisib, in combination with fulvestrant, significantly improves progression-free survival in patients with PIK3CA-mutant disease, as demonstrated in the SOLAR-1 trial. However, this therapeutic strategy is frequently complicated by treatment-induced hyperglycemia, a metabolic disturbance that promotes oxidative stress, mitochondrial dysfunction, and inflammatory signaling, thereby increasing cardiovascular vulnerability. Sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as cardiometabolic modulators with benefits extending beyond glucose lowering. In this study, we used a human cardiomyocyte in vitro model designed to recapitulate the hyperglycemic metabolic milieu observed in breast cancer patients receiving PI3Kα-targeted therapy, to investigate whether the SGLT2 inhibitor dapagliflozin directly protects cardiomyocytes from alpelisib- and fulvestrant-induced injury. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured under hyperglycemic conditions (25 mM glucose) to mimic the metabolic environment associated with PI3Kα inhibitor-induced dysglycemia. Cells were exposed to alpelisib (100 nM) and fulvestrant (100 nM), alone or in combination, in the absence or presence of dapagliflozin (1 μM). Cardiomyocyte viability was assessed using the MTS assay, mitochondrial function by TMRM-based mitochondrial membrane potential (ΔΨm) measurements, and apoptosis by caspase-3 quantification. Cardiomyocyte injury was evaluated by release of cardiac troponin I and heart-type fatty acid binding protein (H-FABP). Lipid peroxidation markers (MDA and 4-HNE) were measured to assess oxidative membrane damage. Intracellular inflammasome-related signaling (NLRP3 and MyD88) and secreted inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2) were quantified by ELISA. Exposure to alpelisib, particularly in combination with fulvestrant, significantly reduced cardiomyocyte viability, induced mitochondrial depolarization, and increased caspase-3-mediated apoptotic signaling. These alterations were accompanied by elevated lipid peroxidation (MDA and 4-HNE) and increased release of cardiac injury biomarkers (troponin I and H-FABP). Alpelisib-based treatments also activated inflammasome-related signaling, as indicated by increased intracellular NLRP3 and MyD88 levels and enhanced secretion of pro-inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2). Co-treatment with dapagliflozin significantly attenuated these alterations, preserving mitochondrial membrane potential, reducing apoptotic signaling, limiting oxidative membrane damage, and suppressing inflammatory cytokine release. This study provides evidence that alpelisib-based therapy under hyperglycemic conditions is associated with oxidative, mitochondrial, and inflammatory stress responses in human cardiomyocytes, recapitulating key features of cardiometabolic stress relevant to PI3Kα-targeted therapy. Importantly, dapagliflozin markedly attenuated these alterations, supporting a potential cardioprotective role that may extend beyond glycemic control. These findings provide a mechanistic rationale for further investigation of SGLT2 inhibition as a cardiometabolic protective strategy in patients receiving PI3Kα inhibitor-based cancer therapy. Full article

Objectives: We aimed to evaluate the reliability and validity of the Arabic version of the Chronic Heart Failure Health-Related Quality of Life Questionnaire (CHFQOLQ-20) among patients with heart failure in Jordan. Methods: A cross-sectional study was conducted among 399 adults with heart failure recruited from a tertiary hospital in Jordan (median age 68 years; 55.9% male). The CHFQOLQ-20 was translated using forward–backward procedures. Construct validity was examined using confirmatory factor analysis (CFA) and a multidimensional Partial Credit Model. Differential item functioning by sex and internal consistency were assessed. Results: CFA supported the original four-domain structure (physical, cognitive, mental, and general health), with all items showing significant factor loadings. Item-level analyses demonstrated acceptable model fit, ordered response thresholds, and minimal sex-related bias. Physical health scores were lower than other domains. Conclusions: The Arabic CHFQOLQ-20 is a valid, reliable, and multidimensional measure of HRQoL in patients with heart failure, supporting its use in clinical practice and research. Full article

Introduction: Major Depressive Disorder (MDD) has been increasingly associated with inflammatory dysregulation, particularly involving tumor necrosis factor-alpha (TNF-α). Genetic polymorphisms within the TNFA promoter region have been investigated as potential modulators of depressive susceptibility, symptom expression, treatment response, and inflammatory comorbidity. However, findings remain inconsistent across populations and clinical contexts. Methods: This systematic review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251242724). Observational and interventional studies evaluating associations between TNFA polymorphisms—specifically rs1800629 (−308 G/A), rs1799724 (−857 C/T), and rs1799964 (−1031 T/C)—and MDD-related outcomes in adults were included. Data extraction and methodological quality assessment were performed independently using an adapted GRIPS framework. Results: Eleven studies met the inclusion criteria, with eight investigating MDD without cardiovascular comorbidity and three assessing cardiovascular populations. Across diverse cohorts, rs1800629 and rs1799724 did not demonstrate consistent associations with MDD susceptibility. Although isolated population-specific findings were reported, genotype and allele distributions were generally comparable between cases and controls. Rs1799724 was associated with symptom dimensions and altered TNF-α expression in two cohorts. Rs1799964 was not linked to disease occurrence but showed potential association with antidepressant response and adverse cardiovascular outcomes in patients with chronic heart failure and comorbid depression. Overall, findings were heterogeneous and influenced by population characteristics, sample size, and clinical context. Conclusions: Current evidence does not support a robust etiological role for TNFA promoter polymorphisms in major depressive disorder. These variants may exert context-dependent modulatory effects on symptom expression, treatment response, or inflammatory-cardiovascular interactions rather than serving as primary susceptibility determinants. Larger, ethnically diverse studies integrating genetic, inflammatory, and clinical data are required to clarify the contribution of inflammatory genetic variability in depressive disorders. Full article

Background and Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular (CV) death and heart failure hospitalizations (HFH) in patients with heart failure with reduced ejection fraction (HFrEF). However, data regarding their use in combination with different doses of guideline-directed medical therapy (GDMT) remain limited. This study aimed to evaluate whether SGLT2i combined with low-dose conventional triple therapy is non-inferior to high-dose conventional triple therapy in preventing adverse cardiovascular outcomes. Materials and Methods: This retrospective observational study included 334 patients with HFrEF treated between 31 March 2018 and 31 March 2024. Of these, 110 received SGLT2i plus low-dose conventional triple therapy, and 224 received high-dose conventional triple therapy. A non-inferiority framework was applied to compare outcomes between groups. The primary endpoint was a composite of CV death and HFH, while secondary endpoints included the individual components. Results: The composite endpoint occurred more frequently in the SGLT2i plus low-dose group. After inverse probability of treatment weighting and multivariable Cox analysis, this group demonstrated a significantly higher risk of the composite outcome (adjusted HR 4.10, 95% CI 2.07–8.13; p < 0.001). CV death was similar between groups; however, HFH was significantly more frequent in the SGLT2i plus low-dose group. Conclusions: In patients with HFrEF, SGLT2i combined with low-dose conventional triple therapy did not demonstrate comparable clinical outcomes to high-dose conventional triple therapy in reducing CV death and HFH, particularly in patients with a higher baseline burden of disease severity. These findings underscore the importance of optimizing background GDMT dosing alongside the incorporation of SGLT2i into clinical practice. Full article

Background/Objectives: Patient-derived mesenchymal stem cells (MSCs) represent a promising avenue for myocardial regeneration, yet therapeutic application remains limited by inconsistent differentiation capacity and the absence of standardized cardiogenic induction protocols. This study demonstrates a proof-of-concept for guiding patient-specific bone marrow MSCs toward a functional cardiomyocyte phenotype using paracrine signals from differentiating iPSC-derived cardiomyocytes (iPSC-CMs). Materials and Methods: MSCs were maintained in conditioned medium from a concurrent, validated iPSC-CM differentiation protocol, with evaluation via immunocytochemistry, optical mapping, and whole-cell patch-clamp recordings. Results: Differentiated MSCs acquired organized sarcomeric architecture with cross-striations and displayed spontaneous calcium oscillations with decay kinetics matching source iPSC-CMs (CaT50 ≈ 283 ms vs. 301 ms). In co-culture, MSC-derived cells exhibited synchronized calcium dynamics with iPSC-CMs, confirming functional coupling, while patch-clamp detected hallmark cardiac ion currents (INa, ICa,L, and IKv). Morphologically, MSC-CMs displayed more mature, elongated rod-like shapes. Conclusions: Although current densities indicate partial immaturity, their reproducible detection validates successful cardiomyogenic commitment. This “parallel differentiation” platform eliminates donor-specific protocol tuning, providing a streamlined, paracrine-mediated approach to generate autologous cardiomyocyte-like cells for disease modeling, pharmacological testing, and future regenerative applications. 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

Background: Cardiac resynchronization therapy (CRT) improves outcomes in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) and a wide QRS complex. However, up to 30–50% of patients fail to respond. The QRS Index, which quantifies QRS shortening after CRT, has emerged as a potential predictor of response. We aimed to perform a systematic review and meta-analysis to evaluate the association between QRS Index and CRT response. Methods: We searched PubMed, Scopus and Cochrane for studies reporting QRS Index values in CRT responders and non-responders. Studies defining response based on clinical, echocardiographic, or combined criteria were included. Heterogeneity was assessed using the I² statistic, and a random-effects model was applied. A meta-regression analysis explored the relationship between baseline echocardiographic parameters and QRS Index. Results: Nine studies with 1274 patients met the inclusion criteria, with 760 (59%) classified as responders and 514 (41%) as non-responders. The weighted mean ± standard deviation was 16.14 ± 13.19 in responders and 7.22 ± 14.96 in non-responders. The QRS Index was significantly higher in the responder group compared to non-responders (mean difference: 8.76; 95% CI: 6.45–11.06; I² = 45%; p < 0.00001). Meta-regression revealed that lower left ventricular end-systolic volume (LVESV) values were associated with even higher QRS Index in responders compared to non-responders (β = −0.0483; 95% CI: −0.0938; −0.0029, p = 0.0372). Conclusions: QRS Index is significantly higher in CRT responders, supporting its role as a predictor of response. Further studies are needed to standardize its clinical use and assess its prognostic impact. Full article

Background: Heart failure (HF) is a chronic condition associated with frequent hospitalizations and impaired quality of life. Malnutrition is common in HF and is linked to adverse clinical outcomes, while self-care is an important component of HF management. This study aimed to examine the associations between nutritional status, self-care behaviors, and clinical characteristics in patients with chronic HF. Methods: A cross-sectional study was conducted among 100 hospitalized HF patients (mean age 75.9 ± 9.8 years; 63% men). Nutritional status was assessed using the Mini Nutritional Assessment (MNA), and self-care using the nine-item European Heart Failure Self-care Behaviour Scale (9-EHFScBS). Clinical variables included NYHA class, LVEF, comorbidities, BMI, and laboratory parameters. Comparative analyses and multivariate linear regression were performed. Results: Patients who were malnourished or at risk of malnutrition had significantly higher NT-proBNP levels (p = 0.004) and higher NYHA class (p = 0.002), whereas well-nourished individuals had significantly higher triglyceride levels (p = 0.032). Nutritional status was negatively associated with NYHA class and NT-proBNP, and positively associated with BMI. Among laboratory parameters, significant positive correlations were observed with hemoglobin, hematocrit, albumin, and triglyceride levels. In multivariate analysis, the following variables were independently associated with MNA score: self-care score (B = 0.083 per point), BMI (B = 0.368 per kg/m²), comorbidity burden (B = −0.401 per comorbidity), and NYHA class (NYHA III: B = −2.425; NYHA IV: B = −5.966, vs. NYHA II). Conclusions: In patients with chronic heart failure, nutritional status is associated with disease severity, metabolic parameters, comorbidity burden, BMI, and self-care behaviors. These findings support the importance of routine nutritional screening as part of comprehensive HF management. Full article