Search Results (1,086)

Background/objectives: Anderson-Fabry disease (FD) is a rare hereditary disorder caused by deficient alpha-galactosidase A activity, which leads to multisystemic complications, including significant cardiac involvement. In this case report, we describe two siblings with distinct cardiac manifestations of FD. Methods: The medical data of two siblings who were managed and treated at a tertiary hospital center in Croatia were obtained by detailed analysis of electronic medical records. All available data were structured in chronological order. Results: A 42-year-old male with chronic renal failure and severe left ventricular hypertrophy (LVH) was diagnosed with FD during testing for inclusion on the kidney transplant waiting list. The diagnosis was confirmed by cardiac magnetic resonance imaging (CMR), which revealed non-ischemic fibrosis typical of FD. Following enzyme replacement therapy (ERT), he underwent a successful kidney transplantation. The second case describes the 36-year-old brother, who was diagnosed through family screening and, despite normal initial cardiac ultrasound findings, exhibited early cardiac involvement through reduced T1-mapping values. Immediate initiation of ERT led to normalization of T1 values and successful renal transplantation. Conclusions: This report underscores the importance of family screening and early diagnosis in FD and highlights the role of CMR in detecting preclinical cardiac involvement. Full article

Background: In the era of personalized medicine, tools for risk stratification after cardiovascular interventions are crucial to reduce mortality and morbidity, especially in the aging population. Biomarker-based approaches, in particular, have gained significant importance. Mid-regional pro-adrenomedullin (MR-proADM) represents an easily assessable biomarker that mirrors cardiac function and fibrosis. Therefore, we aimed to investigate the prognostic potential of MR-proADM in patients undergoing elective cardiac surgery. Methods: Patients undergoing elective cardiac bypass and/or valve surgery were prospectively enrolled between May 2013 and August 2018. The primary endpoint was the composite of hospitalization for heart failure (HHF) or cardiovascular (CV) mortality. Results: In total, 500 patients (146 female [29.2%]; median age 69.8 years (IQR 60.6–75.5 years) were included. Individuals were stratified into risk categories based on their MR-proADM values (Low Risk ≤ 0.63 nmol/L, Intermediate Risk > 0.63 and ≤0.84, High Risk > 0.84). A significant increase in 5-year event rates for HHF/CV mortality in patients in the high-risk category (Low Risk 8.6% vs. High Risk 37.7%, p < 0.001) was observed. MR-pro ADM showed an independent association with HHF/ CV mortality (adjusted HR of 3.43, 95% CI 1.83–6.42; p < 0.001 comparing the High-Risk group to the Low-Risk group). Conclusions: MR-pro ADM was found to be a strong and independent predictor for HHF/CV mortality in patients undergoing elective cardiac surgery. Considering a personalized diagnostic and prognostic work-up, a standardized preoperative evaluation of MR-proADM levels might help to identify patients at risk for major adverse events and early re-hospitalization. Full article

CAR-T cell therapy has shown promising results in treating malignant hematologic diseases. The principle of this therapy is based on the use of genetically modified T lymphocytes to express a Chimeric Antigen Receptor (CAR) on their membrane that specifically recognizes an antigen predominantly expressed on target cells. The molecular design of the CAR, along with advancements in molecular techniques and the development of “omics”, has opened the possibility of discovering new therapeutic targets and thereby expanding the range of diseases treated with CAR-T cells beyond the use of anti-CD19 and anti-BCMA for hematologic cancer. This review summarizes the novel therapeutic targets that are currently used in clinical trials with CAR-T cell therapy on autoimmune diseases and other challenging conditions, such as cardiac fibrosis, and different infections. Additionally, challenges and novel opportunities are discussed for expanding clinical access to this innovative therapy. Full article

Atrial fibrillation is a prevalent cardiac arrhythmia influenced by multifactorial mechanisms, including the emerging role of epicardial adipose tissue. Left atrial epicardial adipose tissue, through its endocrine and paracrine activities, contributes to atrial remodeling by fostering inflammation, fibrosis, and electrical remodeling. Objectives: This review aims to explore the interaction between left atrial epicardial adipose tissue and atrial dysfunction, highlighting the utility of strain imaging as a diagnostic and prognostic tool in atrial fibrillation management. Additionally, it examines emerging therapeutic strategies targeting epicardial adipose tissue to improve outcomes. Methods: We analyzed recent advances in imaging techniques, with a specific focus on speckle-tracking echocardiography for non-invasive strain assessment. Strain imaging parameters, including atrial reservoir, conduit, and contractile strain, were evaluated alongside volumetric measures of epicardial adipose tissue. Emerging therapies, such as weight management and GLP-1 receptor agonists, were reviewed for their impact on left atrial epicardial adipose tissue and atrial remodeling. Results: Strain imaging demonstrates a significant association between reduced strain parameters and atrial remodeling induced by left atrial epicardial adipose tissue. Combining strain assessment with volumetric measures enhances diagnostic accuracy and stratification of patients at risk for recurrent or progressive atrial fibrillation. Emerging therapies, particularly GLP-1 receptor agonists, show promise in reducing epicardial adipose tissue volume and mitigating atrial remodeling, thereby improving catheter ablation outcomes. Conclusions: Strain imaging is a valuable tool for the early detection of atrial dysfunction and personalized treatment planning in atrial fibrillation. Integrating these imaging approaches into routine clinical practice can optimize atrial fibrillation management and improve patient outcomes. Full article

Background/Objectives: ST-segment elevation acute coronary syndrome (STE-ACS) represents a significant global health challenge, with cardiac remodeling and fibrosis critically affecting recovery after percutaneous coronary intervention (PCI). Colchicine, known for its anti-inflammatory effects, may regulate key fibrotic markers such as Procollagen III N-terminal Propeptide (PIIINP) and Galectin-3. This study assesses colchicine’s effect on these biomarkers in STE-ACS patients undergoing delayed PCI. Methods: In this multicenter, randomized, double-blind trial, we examined colchicine’s impact on Galectin-3 and PIIINP in 164 STE-ACS patients undergoing early or delayed PCI. Patients received colchicine shortly after hospital admission. Biomarker changes were evaluated at 24 h and five days post-treatment using two-way ANOVA. Results: Clinical trials in the early PCI group revealed that Galectin-3 levels decreased significantly on day one (p < 0.01) and further on day five (p < 0.0001), indicating Primary PCI has benefits to inhibition of fibrosis beyond colchicine add-on treatment. But, in the delayed PCI group, Galectin-3 levels significantly increased on day one (p < 0.01), but the decrease observed by day five was not statistically significant. It is related that the benefits of colchicine treatment may exceed PCI implantation in preventing cardiac remodeling. In the delayed PCI group, PIIINP levels showed a significant reduction on day five (p < 0.0001). Conclusions: This Colchicine demonstrates novel efficacy in delayed PCI, with a significant increase in Galectin-3 and a sharp reduction in PIIINP, indicating its ability to control fibrosis. This positions colchicine as a breakthrough therapy for improving outcomes in STE-ACS patients with delayed intervention. Full article

Background/Objectives: Diffuse myocardial fibrosis and altered deformation are relevant prognostic factors in aortic stenosis (AS) patients. The aim of this exploratory study was to investigate the relationship between myocardial strain, and myocardial extracellular volume (ECV) in patients with severe AS with a photon-counting detector (PCD)-CT. Methods: We retrospectively included 77 patients with severe AS undergoing PCD-CT imaging for transcatheter aortic valve replacement (TAVR) planning between January 2022 and May 2024 with a protocol including a non-contrast cardiac scan, an ECG-gated helical coronary CT angiography (CCTA), and a cardiac late enhancement scan. Myocardial strain was assessed with feature tracking from CCTA and ECV was calculated from spectral cardiac late enhancement scans. Results: Patients with cardiac amyloidosis (n = 4) exhibited significantly higher median mid-myocardial ECV (48.2% versus 25.5%, p = 0.048) but no significant differences in strain values (p > 0.05). Patients with prior myocardial infarction (n = 6) had reduced median global longitudinal strain values (−9.1% versus −21.7%, p < 0.001) but no significant differences in global mid-myocardial ECV (p > 0.05). Significant correlations were identified between the global longitudinal, circumferential, and radial strains and the CT-derived left ventricular ejection fraction (EF) (all, p < 0.001). Patients with low-flow, low-gradient AS and reduced EF exhibited lower median global longitudinal strain values compared with those with high-gradient AS (−15.2% versus −25.8%, p < 0.001). In these patients, the baso-apical mid-myocardial ECV gradient correlated with GLS values (R = 0.28, p = 0.02). Conclusions: In patients undergoing PCD-CT for TAVR planning, ECV and GLS may enable us to detect patients with cardiac amyloidosis and reduced myocardial contractility Full article

Background: Epidemiological and toxicological studies have shown that inhalation of particulate matter (PM), a major component of air pollution, is associated with the development of cardiovascular diseases (CVDs). Cellular senescence and other aging mechanisms are also key factors in the development and progression of CVD. This study aims to investigate age-related susceptibility to cardiac remodeling and senescence due to PM exposure. Methods: Young and old male C57BL/6 mice were exposed to filtered or polluted air for six months using an ambient particle concentrator. Cardiac hypertrophy, fibrosis, and markers of cellular senescence (p53, p21, p-H2AX, and lipofuscin) in the myocardium were evaluated in the experimental groups. Results: PM exposure induces signs of cardiac remodeling, including cardiomyocyte enlargement and increased fibrosis, in young mice, along with elevated p53 expression. However, no significant alterations in cardiac structure or senescence markers were observed between aged mice exposed or not to PM. Conclusions: Our study indicates that younger individuals may be more vulnerable to the cardiovascular effects of chronic PM than older individuals exposed later. Further studies are needed to explore detailed mechanisms of this age-dependent response. Full article

Background: Heart failure (HF) is a serious public health concern. Baicalin is one of the major active ingredients of a traditional Chinese herbal medicine, Huang Qin, which is used to treat patients with chest pain or cardiac discomfort. However, the underlying mechanism(s) of the cardioprotective effect of baicalin are still not fully understood. Methods: Isoprenaline injection or transverse aortic constriction-induced animal models and isoprenaline or angiotensin 2 administration-induced cell models of heart failure were established. Baicalin (15 mg/kg/day or 25 mg/kg/day) was administered in vivo, and 10 μM baicalin was administered in vitro. Potential pharmacological targets of baicalin and genes related to heart failure were identified via different databases, which suggested that PI3K–Akt may be involved in the effects of baicalin. Molecular docking was carried out to reveal the effect of baicalin on p85a. Results: We observed significant antihypertrophic and antifibrotic effects of baicalin both in vivo and in vitro. The mean cross-sectional area of cardiomyocytes recovered from 390 μm² in the HF group to 195 μm² in the baicalin-treated group. The area of fibrosis was reduced from 2.8-fold in the HF group to 1.62-fold in the baicalin-treated group. Baicalin displayed a significant cardioprotective effect via the inhibition of the PI3K signaling pathway by binding with five amino acid residues of the p85a regulatory subunit of PI3K. The combination treatment of baicalin and an inhibitor of PI3K p110 demonstrated a stronger cardioprotective effect. The mean ejection fraction increased from 54% in the baicalin-treated group to 67% in the combination treatment group. Conclusions: Our work identified baicalin as a new active herbal ingredient that is able to treat isoprenaline-induced heart dysfunction and suggests that p85a is a pharmacological target. These findings reveal the significant potential of baicalin combined with an inhibitor of PI3K p110 for the treatment of heart failure and support more clinical trials in the future. Full article

Background/Objectives: Aging is associated with structural and functional changes in the heart, including hypertrophy, fibrosis, and impaired contractility. Cellular mechanisms such as senescence, telomere shortening, and DNA damage contribute to these processes. Nuclear factor kappa B (NF-κB) has been implicated in mediating cellular responses in aging tissues, and increased NF-κB expression has been observed in the hearts of aging rodents. Therefore, NF-κB is suspected to play an important regulatory role in the cellular and molecular processes occurring in the heart during aging. This study investigates the in vivo role of NF-κB in aging-related cardiac alterations, focusing on senescence and associated cellular events. Methods: Young and old wild-type (WT) and transgenic male mice with cardiomyocyte-specific NF-κB suppression (3M) were used to assess cardiac function, morphology, senescence markers, lipofuscin deposition, DNA damage, and apoptosis. Results: Kaplan–Meier analysis revealed reduced survival in 3M mice compared to WT. Echocardiography showed evidence of eccentric hypertrophy, and both diastolic and systolic dysfunction in 3M mice. Both aged WT and 3M mice exhibited cardiac hypertrophy, with more pronounced hypertrophic changes in cardiomyocytes from 3M mice. Additionally, cardiac fibrosis, senescence-associated β-galactosidase activity, p21 protein expression, and DNA damage (marked by phosphorylated H2A.X) were elevated in aged WT and both young and aged 3M mice. Conclusions: The suppression of NF-κB in cardiomyocytes leads to pronounced cardiac remodeling, dysfunction, and cellular damage associated with the aging process. These findings suggest that NF-κB plays a critical regulatory role in cardiac aging, influencing both cellular senescence and molecular damage pathways. This has important implications for the development of therapeutic strategies aimed at mitigating age-related cardiovascular diseases. Full article

Cardiac magnetic resonance (CMR) allows for analysis of cardiac function and myocardial tissue characterization. Increased left ventricular mass (LVM) is an independent predictor of cardiovascular events; however, the diagnosis of left ventricular hypertrophy and its prognostic value strongly depend on the LVM indexation method. Evaluation of the quantity and distribution of late gadolinium enhancement assists in clinical decisions on diagnosis, cardiovascular assessment, and interventions, including the placement of cardiac implantable electronic devices and the choice of an optimal procedural approach. Novel CMR techniques, such as T1 and T2 mapping, may be used for the longitudinal follow-up of myocardial fibrosis and myocardial edema or inflammation in different groups of patients, including patients with systemic sclerosis, myocarditis, cardiac sarcoidosis, amyloidosis, and both ischemic and non-ischemic cardiomyopathy, among others. Moreover, CMR tagging and feature tracking techniques might improve cardiovascular risk stratification in patients with different etiologies of left ventricular dysfunction. This review summarizes the knowledge about the current role of CMR in diagnostics and cardiovascular risk assessment to enable more personalized approach in clinical decision making. Full article

Hypertrophic cardiomyopathy (HCM) is a heterogeneous cardiac disease and one of its major challenges is the limited accuracy in stratifying the risk of sudden cardiac death (SCD). Positron emission tomography (PET), through the evaluation of myocardial blood flow (MBF) and metabolism using fluorodeoxyglucose (FDG) uptake, can reveal microvascular dysfunction, ischemia, and increased metabolic demands in the hypertrophied myocardium. These abnormalities are linked to several factors influencing disease progression, including arrhythmia development, ventricular dilation, and myocardial fibrosis. Fibroblast activation can also be evaluated using PET imaging, providing further insights into early-stage myocardial fibrosis. Conflicting findings underscore the need for further research into PET’s role in risk stratification for HCM. If PET can establish a connection between parameters such as abnormal MBF or increased FDG uptake and SCD risk, it could enhance predictive accuracy. Additionally, PET holds significant potential for monitoring therapeutic outcomes. The aim of this review is to provide a comprehensive overview of the most significant data on disease progression, risk stratification, and prognosis in patients with HCM using cardiac PET-CT imaging. Full article

Chemotherapy-induced cardiotoxicity is a critical issue in cardio-oncology, as cancer treatments often lead to severe cardiovascular complications. Approximately 10% of cancer patients succumb to cardiovascular problems, with lung cancer patients frequently experiencing arrhythmias, cardiac failure, tamponade, and cardiac metastasis. The cardiotoxic effects of anti-cancer treatments manifest at both cellular and tissue levels, causing deformation of cardiomyocytes, leading to contractility issues and fibrosis. Repeated irradiation and chemotherapy increase the risk of valvular, pericardial, or myocardial diseases. Multi-OMICs analyses reveal that targeting specific pathways as well as specific protein modifications, such as ubiquitination and phosphorylation, could offer potential therapeutic alternatives to current treatments, including Angiotensin converting enzymes (ACE) inhibitors and beta-blockers that mitigate symptoms but do not prevent cardiomyocyte death, highlighting the need for more effective therapies to manage cardiovascular defects in cancer survivors. This review explores the xenobiotic nature of chemotherapy agents and their impact on cardiovascular health, aiming to identify novel biomarkers and therapeutic targets to mitigate cardiotoxicity. Full article

Background/Objectives: Sudden cardiac death (SCD) constitutes approximately 50% of cardiovascular mortality. Numerous studies have established an interrelation and a strong association between SCD and pulmonary diseases, such as chronic obstructive pulmonary disease (COPD). The aim of this study is to examine the presence of more pronounced cardiopulmonary histopathological changes in individuals who died from SCD compared to the histopathological changes in those who died from violent deaths, in two groups with comparable demographic characteristics, age and sex. Methods: This retrospective case–control study investigated the histopathological changes in cardiac and pulmonary tissues in two cohorts, each comprising 40 cases of SCD and 40 cases of violent death (self-inflicted hanging). Forensic autopsies were conducted at the Maramureș County Forensic Medicine Service, Romania, between 2019 and 2020. Results: The mean ages recorded were 43.88 years (SD 5.49) for the SCD cohort and 41.98 years (SD 8.55) for the control cohort. In the SCD cases, pulmonary parenchyma exhibited inflammatory infiltrate in 57.5% (23), fibrosis in 62.5% (25), blood extravasation in 45% (18), and vascular media thickening in 37.5% (15), compared to the control cohort, where these parameters were extremely low. In myocardial tissue, fibrosis was identified in 47.5% (19) and subendocardial adipose tissue in 22.5% (9) of the control cohort. Conclusions: A close association exists between SCD and the histopathological alterations observed in the pulmonary parenchyma, including inflammation, fibrosis, emphysema, blood extravasation, stasis, intimal lesions, and vascular media thickening in intraparenchymal vessels. Both the histopathological modifications in the pulmonary parenchyma and vessels, as well as those in myocardial tissue, were associated with an increased risk of SCD, ranging from 2.17 times (presence of intimal lesions) to 58.50 times (presence of interstitial and perivascular inflammatory infiltrate in myocardial tissue). Full article

Immuno-fibrotic networks and their protein mediators, such as cytokines and chemokines, have increasingly been appreciated for their critical role in cardiac healing and fibrosis during cardiomyopathy. Immune activation, trafficking, and extravasation are tightly regulated to ensure a targeted and effective response against non-self antigens/pathogens while preserving tolerance towards self-antigens and coordinate fibrotic responses for efficient scar formation, a distinction that is severely compromised during chronic diseases. It is clear that immune cells are not only the critical regulators of post-infarct healing and scarring but are also the key players in regulating fibroblast activation during left-ventricular (LV) remodeling. Incomplete resolution coupled with sustained low-grade inflammation during dilated cardiomyopathy precipitates a “frustrated” immune cell response resulting in unconstrained pro-fibrotic and pro-hypertrophic signaling to induce maladaptive structural and functional changes in the myocardium. The aims of this review are to (i) briefly summarize the role of key immune cells that regulate wound healing during MI and fibrosis during LV remodeling; (ii) underscore phenotypic diversities in immune cells and their subsets to underscore their role in regulating fibrotic responses, and, last but not the least, (iii) highlight gaps in our understanding that restrict the translation of immuno-modulatory therapies from the preclinical models to heart failure patients. Full article

Cirrhotic cardiomyopathy (CCM) is a diagnostic entity defined as cardiac dysfunction (diastolic and/or systolic) in patients with liver cirrhosis, in the absence of overt cardiac disorder. Pathogenically, CCM stems from a combination of systemic and local hepatic factors that, through hemodynamic and neurohormonal changes, affect the balance of cardiac function and lead to its remodeling. Vascular changes in cirrhosis, mostly driven by portal hypertension, splanchnic vasodilatation, and increased cardiac output alongside maladaptively upregulated feedback systems, lead to fluid accumulation, venostasis, and cardiac dysfunction. Autocrine and endocrine proinflammatory cytokines (TNF-alpha, IL-6), as well as systemic endotoxemia stemming from impaired intestinal permeability, contribute to myocardial remodeling and fibrosis, which further compromise the contractility and relaxation of the heart. Additionally, relative adrenal insufficiency is often present in cirrhosis, further potentiating cardiac dysfunction, ultimately leading to the development of CCM. Considering its subclinical course, CCM diagnosis remains challenging. It relies mostly on stress echocardiography or advanced imaging techniques such as speckle-tracking echocardiography. Currently, there is no specific treatment for CCM, as it vastly overlaps with the treatment of heart failure. Diuretics play a central role. The role of non-selective beta-blockers in treating portal hypertension is established; however, their role in CCM remains somewhat controversial as their effect on prognosis is unclear. However, our group still advocates them as essential tools in optimizing the neurohumoral pathologic axis that perpetuates CCM. Other targeted therapies with direct anti-inflammatory and antioxidative effects still lack sufficient evidence for wide approval. This is not only a review but also a comprehensive distillation of the insights from practicing clinical hepatologists and other specialties engaged in advanced approaches to treating liver disease and its sequelae. Full article