Search Results (816)

Background: Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD), driven by mechanisms distinct from the general population. Fibroblast Growth Factor 23 (FGF-23), a phosphaturic hormone elevated early in CKD, has been mechanistically linked to left ventricular hypertrophy, vascular dysfunction, and disordered mineral metabolism. This study examines the associations between FGF-23 and key renal, mineral, and cardiovascular parameters and its utility in risk stratification. Methods: We conducted a cross-sectional study of 60 adults with CKD stages 1–5. Serum FGF-23 was quantified using ELISA, alongside measures of iPTH, phosphorus, calcium, and eGFR (Estimated Glomerular Filtration Rate). Cardiovascular evaluation included transthoracic echocardiography and carotid intima-media thickness (CIMT). Associations were analyzed using Spearman correlations, ROC analysis, and multivariable logistic regression. Results: FGF-23 levels were significantly associated with declining eGFR (r = –0.288; p < 0.05), elevated iPTH (Intact Parathyroid Hormone) (r = 0.361; p < 0.05), and serum phosphorus (r = 0.335; p < 0.05). Patients with structural cardiac abnormalities (left atrial enlargement or left ventricular hypertrophy) exhibited higher FGF-23 concentrations (154 vs. 128 pg/mL; p = 0.027). FGF-23 alone predicted high cardiovascular risk with moderate accuracy (AUC 0.70; sensitivity 76%; specificity 67%). A composite model including iPTH and eGFR improved discriminatory power (AUC 0.76). Conclusions: FGF-23 correlates with subclinical cardiovascular remodeling and key mineral abnormalities in CKD. Its integration with iPTH and eGFR enhances cardiovascular risk stratification, supporting its potential as a multidimensional biomarker in early CKD. However, the cross-sectional design and modest correlation strengths limit causal inference and generalizability of the findings. Full article

The nitric oxide (NO) pathway is a fundamental regulator of vascular tone, myocardial function, and inflammation. In heart failure (HF), especially in advanced stages, dysregulation of NO–soluble guanylate cyclase (sGC)–cyclic guanosine monophosphate (cGMP) signaling contributes to endothelial dysfunction, increased vascular resistance, myocardial fibrosis, and impaired cardiac performance. Chronic inflammation further reduces NO bioavailability, exacerbating HF progression This review synthesizes current knowledge on the role of the NO pathway in HF pathophysiology, with a focus on stable and advanced HF. Special attention is given to patient subgroups with comorbidities such as chronic kidney disease, where modulation of NO signaling may be particularly beneficial. We also evaluate therapeutic strategies targeting NO bioavailability and sGC stimulation. Evidence shows that impaired NO signaling promotes systemic and pulmonary vasoconstriction, elevates ventricular afterload, and worsens cardiac remodeling. Pharmacological agents that restore NO levels or activate downstream effectors such as sGC improve vasodilation, reduce fibrosis, and enhance myocardial relaxation. These effects are especially relevant in advanced HF patients and those with renal impairment, who often exhibit limited responses to conventional therapies. The NO pathway represents a promising therapeutic target in both stable and advanced HF. Modulating this pathway could improve outcomes, particularly in complex populations with multiple comorbidities, highlighting the need for further clinical research and tailored treatments. Full article

Hypertension is a major risk factor for heart failure. Acetylation of p53 is known to regulate its activities. We have previously identified that p53 acetylation is required for cardiac remodeling in a mouse model of pressure overload-induced heart failure. Acetylation mutant p53 (p53aceKO) mice have been shown to have the ability to regulate SIRT3 KO-induced cardiac fibrosis. In the present study, we hypothesized that p53aceKO mice would exhibit cardiac protection and blunt cardiac fibrosis when subjected to Ang-II-induced hypertension. Control and p53aceKO mice received either a micro-osmotic pump implant administering Ang-II for 28 days or a sham procedure. Blood pressure was measured weekly, and echocardiography was performed every two weeks. Mice were euthanized and hearts were processed for histological analysis. While both control and p53aceKO mice receiving Ang-II exhibit increased systolic and diastolic blood pressures, control mice also demonstrate increases in ejection fraction and fractional shortening compared to the sham, while p53aceKO mice do not. Furthermore, control mice receiving Ang-II exhibit decreased left ventricular diameter and volume at end-systole and end-diastole, as well as thickening of both the anterior and posterior walls, while p53aceKO mice exhibit no significant changes in any of these parameters. Additionally, p53aceKO mice do not exhibit the Ang-II infusion-induced cardiac fibrosis seen in control mice treated with Ang-II. Mutation of p53 acetylation is protective against Ang-II infusion-induced cardiac fibrosis and dysfunction in mice. Acetylated p53 may, therefore, be a novel therapeutic target to address complications in the heart associated with hypertension. Full article

Background/Objectives: Aortic stenosis (AS) leads to progressive left ventricular (LV) pressure overload, adverse myocardial remodeling, and eventual functional decline. While traditional parameters such as left ventricular ejection fraction (LVEF) may remain preserved until advanced stages, they are insufficiently sensitive to early dysfunction. Global longitudinal strain (GLS) offers improved detection but remains load-dependent. In contrast, non-invasive myocardial work (MW)—derived from pressure-strain loops—offers a more load-independent assessment of myocardial function. This systematic review and meta-analysis aimed to evaluate the effects of transcatheter aortic valve implantation (TAVI) on MW indices in patients with severe AS. Methods: We performed a systematic review and meta-analysis of studies reporting non-invasive myocardial work parameters before and after TAVI (PROSPERO ID: CRD420250517138). Databases were searched through 31 March 2025. Pooled mean differences in global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were calculated using random-effects models. Sensitivity analyses and meta-regression were conducted to explore heterogeneity and the influence of baseline characteristics. Results: Eleven studies encompassing 1493 patients were included. TAVI was associated with a significant reduction in GWI (−236.67 mmHg% [95% CI: −373.82 to −99.52]; I² = 97.0%; p = 0.002) and GCW (−243.71 mmHg% [95% CI: −407.38 to −80.03]; I² = 97.4%; p = 0.006). No significant changes were observed in GWW or GWE. Meta-regression showed age and baseline LVEF significantly influenced GWE changes, but not other parameters. Conclusions: TAVI leads to a significant reduction in GWI and GCW, reflecting decreased myocardial workload and afterload relief. These findings support the utility of MW indices as valuable tools for assessing myocardial adaptation post-TAVI and potentially guiding clinical decision-making. Full article

Left ventricular (LV) hypertrabeculation is increasingly recognized as a phenotype that may reflect physiological adaptation, particularly in athletes exposed to chronic overload, although its functional relevance remains uncertain. This study evaluated the prevalence of excessive trabeculation and its physiological correlation with LV remodeling. We conducted a single-center, cross-sectional study involving 320 Olympic-level athletes without cardiovascular disease. All underwent cardiac magnetic resonance (CMR). Hypertrabeculation was defined by the Petersen criteria. Athletes meeting these criteria were classified as hypertrabeculated and compared with non-hypertrabeculated matched for age, sex, and sport category. LV morphology, function, strain parameters, and hemodynamic forces (HDFs) were analyzed. Hypertrabeculation was identified in 9% of the cohort. No significant differences were observed between groups for training exposure (p = 0.262), body surface area (p = 0.762), LV volumes (end-diastolic volume indexed p = 0.397 end-systolic volume indexed p = 0.118), ejection fraction (p = 0.101), mass (p = 0.919), sphericity index (p = 0.419), myocardial wall thickness (p = 0.394), tissue characterization (T1 mapping p = 0.366, T2 mapping p = 0.833), global longitudinal strain (GLS p = 0.898), global circumferential strain (GCS p = 0.219), or HDFs. All values were within the normal range. In our cohort, LV hypertrabeculation, evaluated by CMR, was relatively common but not associated with structural or functional abnormalities, supporting its interpretation as a benign variant in asymptomatic athletes with normal cardiac function. Full article

Background: Uraemic cardiomyopathy (UCM), the cardiac manifestation of chronic kidney disease, represents a significant clinical challenge that is often underdiagnosed despite being one of the strongest predictors of mortality in the chronic kidney disease (CKD) population. It develops through pathophysiological mechanisms unique to the uraemic state—left ventricular hypertrophy, myocardial fibrosis, and diastolic dysfunction—that often progress silently, sometimes even without traditional cardiovascular risk factors. Purpose: This review synthesises nephrology-centric mechanisms with clinical phenotypes and contemporary imaging (including CMR T1/T2 mapping and ECV), and proposes a CKD-stage–tailored diagnostic–therapeutic framework. It offers a distinct perspective by integrating the complex pathophysiology of UCM with practical diagnostic approaches and evolving management strategies, differentiating it from prior cardiology-focused overviews. Methods: A comprehensive literature search was conducted across Ovid MEDLINE, Embase, PubMed, Google Scholar, BMJ Best Practice, and UpToDate for studies published up to March 2025. Key findings were extracted from the final evidence set and manually verified for relevance. This review introduces a patho-mechanical cascade model of uraemic cardiomyopathy, integrating toxin-driven, metabolic, and haemodynamic axes. Nephrology-led screening protocols are proposed, leveraging proteomics and strain echo, and advocate mineralocorticoid receptor antagonists with sodium–glucose co-transporter-2 (SGLT2) inhibitor initiation at CKD Stage 3a. Cardiorenal clinics are essential for improved outcomes. Key Insights: UCM develops from a multifactorial process. This involves neurohormonal activation, oxidative stress, chronic inflammation, and exposure to toxins such as indoxyl sulfate and p-cresyl sulfate, arising from uraemia. Diagnosis is challenging, masked by overlapping features of fluid overload and anaemia. SGLT2 inhibitors, non-steroidal mineralocorticoid antagonists, and renin–angiotensin–aldosterone system modulation offer promising interventions. The effect of the dialysis modality, its timing, and renal transplantation on cardiac remodelling also emerging from recent studies. Conclusions: UCM sits at the intersection of two failing organ systems. Managing it effectively requires a paradigm shift to incorporate pharmacological and early diagnostic interventions and the integration of cardiology and nephrology care, and the timely implementation of interventions. Full article

Myocardial hypoxia is a major cause of cardiac dysfunction, triggering cellular injury and apoptosis. This study aims to investigate the effects of subacute hypoxia on cardiac remodeling and mitochondrial oxygen consumption. This study is based on a rabbit experimental model. Hypoxia was induced using a rabbit tracheal stenosis model. Endotracheal intubation with a 1.5 cm segmented tube wrapped with an absorbable hemostat was used to generate tracheal stenosis in six rabbits. Sham controls (n = 3) underwent tracheotomy, with the tracheal exposure site being sutured immediately. After 1 week, the tube was removed. Echocardiography and mitochondrial function from both groups were morphologically and functionally analyzed at 2 weeks after endoscopic confirmation of tracheal stenosis. Compared to sham group, tracheal stenosis group showed significantly reduced interventricular septal wall thickness (2.3 ± 0.1 mm vs. 2.7 ± 0.2 mm, p = 0.08) and enlarged left ventricular end-diastolic volume (5.86 ± 0.58 mL vs. 5.39 ± 0.18 mL, p = 0.46) with reduced left ventricular ejection fraction (54.5 ± 5.3% vs. 66.9 ± 4.0%, p = 0.005). The tracheal stenosis group showed significantly reduced mitochondrial oxygen consumption at state 3 with reduced respiratory control ratio. Caspase activities (caspase-9 and caspase-3) were increased in the tracheal stenosis group than in the sham group. Subacute hypoxia induced by the tracheal stenosis model causes cardiac remodeling and mitochondrial dysfunction through apoptotic pathways. This study suggests that management of hypoxia could prevent cellular apoptosis and cardiac dysfunction. Full article

Although hypergravity may influence cardiac mechanosensitivity, the effects on specific ion channels remain inadequately understood. This research examined the effects of long-term hypergravity on the functional activity and transcriptional expression of mechanosensitive channels (MSCs) in rat ventricular cardiomyocytes. After 14 days of exposure to 4g, rats were subjected to molecular and electrophysiological analyses. Significant remodeling of MSC-encoding genes was revealed by RNA-seq. Trpm7 (+41.23%, p = 0.0073) and Trpc1 (+68.23%, p = 0.0026) were significantly upregulated among non-selective cation channels, while Trpv2 (−62.19%, p = 0.0044) and Piezo2 (−57.58%, p = 0.0079) were significantly downregulated. Kcnmb1 (−47.84%, p = 0.0203) was suppressed, whereas Traak/K2P4.1 showed a strong increase (+239.48%, p = 0.0092), among K⁺-selective MSCs. Furthermore, Kir6.1 was significantly downregulated (−75.8%, p = 0.0085), whereas Kir6.2 was significantly upregulated (+38.58%, p = 0.0317). These results suggest targeted transcriptional reprogramming that suppresses pathways associated with maladaptive Ca²⁺ influx while enhancing Ca²⁺-permeable mechanosensitive channels alongside stabilized K⁺ conductance. At the structural level, cardiomyocytes from hypergravity exposure showed a 44% increase in membrane capacitance, consistent with hypertrophic remodeling, and sarcomere elongation (p < 0.001). Functionally, stretch-activated current (I_SAC) was markedly hypersensitive in patch-clamp analysis: currents were induced at very small displacements (1–2 µm) and were significantly larger under 4–10 µm stretch (222–107% of control values). These findings indicate that chronic hypergravity induces coordinated molecular, structural, and functional remodeling of cardiomyocytes, characterized by increased membrane excitability, compensatory stabilizing mechanisms, and enhanced Ca²⁺ signaling. This demonstrates the flexibility of cardiac mechanotransduction under prolonged gravitational stress, with potential implications for understanding cardiovascular risks, arrhythmias, and hypertrophy associated with altered gravity environments. Full article

Introduction: The increasingly active role of nurses in the management of heart failure (HF) has become important in HF units (HCUs). This study aims to determine the effect of opening a specialised HF nursing (NSHF) consultation in a tertiary hospital on drug titration, and its subsequent impact on cardiac remodelling and prognosis. Methods: A retrospective cohort study was conducted on patients with HF with reduced ejection fraction (HFrEF) who were treated between 2017 and 2020. Patients who were followed by the NSHF were compared with those who underwent conventional clinical follow-up (non-NSHF), focusing on drug optimisation, echocardiographic parameters, biomarkers, and clinical outcomes in terms of mortality and hospital readmissions for HF. Results: A total of 411 patients were analysed, 85 of whom (20.7%) were treated with NSHF. There were hardly any differences in baseline characteristics. At the end of follow-up, the NSHF group had a higher prescription rate of angiotensin receptor–neprilysin inhibitor (+31.7% vs. +23.3%; p < 0.001), beta-blockers (+2.4% vs. −5.8%; p < 0.001), and sodium glucose co-transporter type 2 inhibitors (+24.7% vs. +17.8%; p < 0.001). There was also a higher rate of loop diuretic withdrawal (−16.7% vs. −6.7%; p < 0.001). However, no improvement in reverse remodelling or neurohormonal response was observed. Patients treated with NSHF had a lower probability of dying from HF (88.6% vs. 63.3%; p = 0.006), but this did not reduce hospital admissions for HF. Conclusions: Patients with HFrEF who are cared for through NSHF are more likely to be prescribed drugs that modify the prognosis of the disease. This has an impact on their mortality. Full article

Anthracyclines are widely used chemotherapeutic agents with proven efficacy against a broad range of malignancies, but their clinical utility is limited by a well-documented, dose-dependent cardiotoxicity. While this toxicity has traditionally been attributed to direct cardiomyocyte injury, emerging evidence highlights the pivotal role of cardiac fibroblasts (CFs) in the development and progression of anthracycline-induced cardiotoxicity. This review examines the diverse effects of anthracycline focusing on doxorubicin (DOX) and CFs across the temporal phases of cardiac injury. DOX activates fibroblast-driven extracellular matrix remodeling and promotes fibrosis through enhanced collagen production and the induction of cellular senescence, thereby exacerbating early myocardial inflammation and dysfunction. Clinically, anthracycline cardiotoxicity may present as acute (within days), subacute (within weeks), or chronic progressive forms manifesting either early (within one year) or late (up to decades post-treatment). While early manifestations may be reversible with timely detection and management, late-phase cardiotoxicity is often irreversible, characterized by declining left ventricular ejection fraction and heart failure. A deeper understanding of the molecular and cellular contributions of CFs may uncover novel therapeutic targets to prevent or attenuate anthracycline-related cardiac damage. Full article

Ventricular arrhythmias (VAs) are common and clinically important complications in patients supported by left ventricular assist devices (LVADs), occurring in up to 50% of cases within the first year after implantation. Despite the hemodynamic support provided by LVADs, VAs are linked to increased morbidity and mortality, primarily through recurrent implantable cardioverter defibrillator (ICD) shocks and right ventricular failure. The underlying mechanisms of VAs in this population are multifactorial, involving structural myocardial remodeling, device-related factors, and pre-existing arrhythmic substrates. Catheter ablation has become a valuable treatment option when antiarrhythmic drug therapy and device reprogramming are inadequate, though procedural timing (pre-, intra-, or post-implantation) and approaches remain under discussion. Epicardial access during LVAD surgery may provide advantages for selected patients, while ablation after implantation poses technical challenges due to altered anatomy and electromagnetic interference. This review offers a comprehensive overview of the epidemiology, pathophysiology, risk stratification, and management of VAs in LVAD recipients, emphasizing technical considerations, procedural safety, and clinical outcomes of catheter ablation. A multidisciplinary approach remains essential in guiding personalized treatment and optimizing outcomes for this complex population. Undergoing studies will provide more insight into optimal management of arrhythmias, particularly regarding the optimal timing of catheter ablation. The impact of new technologies such as non-invasive mapping alongside pre-procedural imaging needs also to be further evaluated. Full article

Pulmonary arterial hypertension (PAH) is a progressive, currently incurable disease characterized by elevated pulmonary arterial pressure, vascular remodeling, and right ventricular hypertrophy, eventually leading to heart failure and death. Sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase, regulates endothelial and vascular smooth muscle function, and its activation by compounds such as resveratrol or SRT1720 shows therapeutic potential by reducing pulmonary and right ventricular pressures and limiting vascular remodeling in both preventive and therapeutic experimental models, highlighting their potential translational relevance. To date, no comprehensive review has focused on the role of SIRT1 in PAH. This review summarizes the molecular mechanisms of SIRT1 action in the cardiopulmonary system and discusses its therapeutic potential in PAH treatment. Full article

Background and Objectives: Cardiovascular disease remains the leading cause of mortality in end-stage renal disease, with systemic inflammation implicated in myocardial remodeling. We aimed to assess the associations between IL-6, TNF-α, and IL-1β and echocardiographic parameters of cardiac remodeling, including left ventricular mass (LVM), global longitudinal strain (GLS), interventricular septum (IVS), left ventricular end-diastolic diameter (LVEDD), and right ventricular diameter (RVD), in patients undergoing maintenance hemodialysis. This was a single-center retrospective observational study. Materials and Methods: In 58 maintenance hemodialysis patients (mean age 60.4 ± 11.7 years; 55% male), pre-dialysis serum cytokines (IL-6, TNF-α, IL-1β) and standard laboratory markers (C-reactive protein [CRP], albumin, hemoglobin) were measured. Echocardiography was performed under clinically stable conditions. Spearman correlations assessed relationships between cytokines and imaging parameters; multivariate linear regression identified independent predictors. Results: Median IL-6 was 7.36 pg/mL (interquartile range [IQR] 4.52–11.03), and median TNF-α was 9.35 pg/mL (IQR 7.9–12.57). IL-6 correlated positively with LVM (ρ = 0.63, p < 0.001), RVD (ρ = 0.53, p < 0.001), and CRP (ρ = 0.52, p < 0.001). In contrast, TNF-α inversely correlated with LVM (ρ = −0.36, p = 0.006). Multivariate regression showed IL-6 was independently predicted by LVM (p = 0.019) and RVD (p = 0.042), while TNF-α was predicted by age (p < 0.001), CRP (p = 0.038), and albumin (p = 0.012). Conclusions: In hemodialysis patients, IL-6 showed stronger associations with echocardiographic hypertrophy and dilation than TNF-α, supporting its role as a potential biomarker of subclinical cardiac remodeling.IL-6 showed stronger correlations with echocardiographic remodeling markers compared with TNF-α and may warrant further investigation as a potential biomarker in this setting. Full article

Background: The mitral valve apparatus is a complex system that requires sufficient function of all involved structures. Previous studies have demonstrated that ventricular remodeling can cause displacement of subannular structures, including the papillary muscles, which in turn promotes the development of mitral regurgitation. Furthermore, in such cases, annuloplasty alone is often insufficient to restore optimal valve function. Instead, additional reconstruction of the subannular apparatus is associated with improved clinical outcomes. Our study aimed to analyze the topography of the papillary muscles in the mitral valve complex and their relevance for mitral valve function. Methods: In 148 patients who underwent both cardiac computed tomography (CT) and echocardiography, the position of the papillary muscles within the left ventricle was assessed. CT scans were evaluated in end-diastolic four-chamber view, two-chamber view, and short-axis view. CT analysis involved determining the position of the papillary muscles based on a modified left ventricular segmentation scheme, which subdivided the original segments into “a” and “b” subsegments in a counterclockwise manner. Furthermore, the midventricular diameter, ventricular length, as well as the angle between the papillary muscle (PM) and the left ventricular wall, were measured. Comorbidities were assessed. The presence of mitral regurgitation (MR) and ejection fraction was determined based on echocardiographic data. Echocardiography was conducted either as part of initial cardiological assessments or during follow-up examinations. For detailed statistical analysis, the patients were divided into the following groups: control group, MR-only group, coronary heart disease (CHD)-only group, and combined CHD and MR subgroup. Results: Mitral regurgitation was significantly correlated with age (p < 0.001) and hypertension (r = 0.1900, p = 0.0208), and in the MR-only subgroup, additionally with atrial fibrillation (r = 0.2426, p = 0.0462). The length (p < 0.001) and internal diameter (p < 0.001) of the left ventricle were significantly larger in men than in women. Different positions of the papillary muscles were identified. Segment 7a was significantly correlated with MR in the combined CHD and MR subgroup. In normal-sized ventricles, patients with MR and papillary muscle in 12a (p = 0.0095) or 10a (p = 0.0460) showed a significantly larger angle than patients without MR (overall dataset). Conclusions: Assessment of papillary muscle position is essential in diagnosing mitral regurgitation and should guide the consideration of subannular repair during surgical treatment. Full article

Background: Mitral valve prolapse is a common valvular heart disorder, usually associated with a benign prognosis in the absence of significant mitral regurgitation. However, a subset of patients is at increased risk for complex ventricular arrhythmias and sudden cardiac death. Identifying these high-risk individuals remains a major clinical challenge. Case Summary: We present the case of a 71-year-old female patient with recurrent syncopal episodes, a strong family history of sudden cardiac death, and complex ventricular ectopy. Multimodality imaging revealed bileaflet mitral valve prolapse, severe mitral regurgitation, mitral annular disjunction, and the Pickelhaube sign, with no evidence of myocardial fibrosis on cardiac magnetic resonance imaging. The patient underwent minimally invasive mitral valve repair and received an implantable cardioverter-defibrillator for primary prevention of sudden cardiac death. Follow-up revealed significant reverse cardiac remodeling, marked reduction in arrhythmic burden, and restoration of mitral valve function. Family screening identified mitral annular disjunction in both of her daughters, who were asymptomatic and without arrhythmias. Discussion: Mitral annular disjunction has emerged as a potentially arrhythmogenic substrate, especially in patients with familial clustering, raising the possibility of a genetic predisposition. Risk stratification remains difficult, as no individual clinical, electrocardiographic, or imaging marker has demonstrated consistent predictive value. Surgical correction of mitral valve prolapse with associated mitral annular disjunction may lead to a reduction in arrhythmic risk and promote favorable structural remodeling. Conclusions: This case-based review emphasizes the importance of advanced imaging techniques in the identification and management of high-risk mitral valve prolapse phenotypes. Early surgical intervention and close arrhythmic surveillance may improve outcomes, although further research is necessary to define risk assessment tools and explore the genetic background of arrhythmogenic mitral valve disease. Full article