Search Results (5,974)

A relevant role of osteopontin (OPN) and gremlin 1 (Grem1) in regulating cardiac tissue remodeling and formation of heart failure (HF) are documented, with the changes of OPN and Grem1 levels in blood plasma due to acute ischemia, ischemic heart disease-induced advanced HF or dilatative cardiomyopathy being the primary focus in most of these studies. However, knowledge on the early OPN and Grem1 proteins expression changes within cardiomyocytes during remodeling due to chronic ischemia remains insufficient. The aim of this study was to determine the OPN and Grem1 proteins expression changes in human cardiomyocytes at different stages of ischemic HF. A semi-quantitative immunohistochemical analysis was performed in 105 myocardial tissue samples obtained from the left cardiac ventricles. Increased OPN immunostaining intensity was already detected in the stage A HF group, compared to the control group (p < 0.001), and continued to increase in the stage B HF (p < 0.001), achieving the peak of immunostaining in the stages C/D HF group (p < 0.001). Similar data of Grem1 immunostaining intensity changes in cardiomyocytes were documented. Significantly positive correlations were detected between OPN, Grem1 expression in cardiomyocytes and their diameter as well as the length, in addition to positive correlation between OPN and Grem1 expression changes within cardiomyocytes. These novel findings suggest that OPN and Grem1 contribute significantly to reorganization of cellular geometry from the earliest stage of cardiomyocyte remodeling, providing new insights into the ischemic HF pathogenesis. Full article

Background: Patients with cardiogenic shock (CS) and mitral regurgitation (MI) have a prohibitive risk that contraindicates surgical treatment. Although the feasibility of transcatheter edge-to-edge therapy (TEER) has been demonstrated in this setting, the benefit of the combined use of TEER with mechanical circulatory support devices (MCS) has not been studied. The aim of this study was to evaluate the clinical outcomes of TEER in patients with MCS. Methods: The MITRA-ASSIST study is a retrospective multicentre Spanish registry that included patients with MR and CS who underwent TEER in combination with MCS. The primary endpoint was death from any cause at 12 months. The secondary endpoint was a composite of death from any cause or hospitalisation for heart failure at 12 months. Results: A total of twenty-four patients in nine high-volume Spanish centres (66.2 (51–82) years, 70.8% female, EuroSCORE II 20.4 ± 17.8) were included. Acute ST-elevation myocardial infarction was the main CS aetiology (56%), and the most implanted MCS was the intra-aortic balloon pump (82.6%), followed by ECMO (8.7%), IMPELLACP^® (4.3%), or a combination of both (4.3%). Procedural success was 95.8%, with 87.5% in-hospital survival. At 12-month follow-up, 25.0% of patients died, and 33.3% had a composite event of death from any cause or hospitalisation for heart failure. Conclusions: TEER in patients with concomitant CS and MR who require MCS appears to be a promising therapeutic alternative with a high device procedural success rate and acceptable mortality and heart failure readmission rates at follow-up. Full article

Heart failure persists as a critical public health challenge, with heart transplantation esteemed as the optimal treatment for patients with end-stage heart failure. However, the limited availability of donor hearts presents a major obstacle to meeting patient needs. In recent years, the most groundbreaking progress in heart transplantation has been in donor heart procurement, significantly expanding the donor pool and enhancing clinical outcomes. This review comprehensively examines these advancements, including the resurgence of heart donation after circulatory death and innovative recovery and evaluation technologies such as normothermic machine perfusion and thoraco-abdominal normothermic regional perfusion. Additionally, novel preservation methods, including controlled hypothermic preservation and hypothermic oxygenated perfusion, are evaluated. The review also explores the use of extended-criteria donors, post-cardiopulmonary resuscitation donors, and high-risk donors, all contributing to increased donor availability without compromising outcomes. Future directions, such as xenotransplantation, biomarkers, and artificial intelligence in donor heart evaluation and procurement, are discussed. These innovations promise to address current limitations and optimize donor heart utilization, ultimately enhancing transplantation success. By identifying recent advancements and proposing future research directions, this review aims to provide insights into advancing heart transplantation and improving patient outcomes. Full article

Cardiomyopathy is the predominant defect in Barth syndrome (BTHS) and is caused by a mutation of the X-linked Tafazzin (TAZ) gene, which encodes an enzyme responsible for remodeling mitochondrial cardiolipin. Despite the known importance of mitochondrial dysfunction in BTHS, how specific TAZ mutations cause diverse BTHS heart phenotypes remains poorly understood. We generated a patient-tailored CRISPR/Cas9 knock-in mouse allele (Taz^PM) that phenocopies BTHS clinical traits. As Taz^PM males express a stable mutant protein, we assessed cardiac metabolic dysfunction and mitochondrial changes and identified temporally altered cardioprotective signaling effectors. Specifically, juvenile Taz^PM males exhibit mild left ventricular dilation in systole but have unaltered fatty acid/amino acid metabolism and normal adenosine triphosphate (ATP). This occurs in concert with a hyperactive p53 pathway, elevation of cardioprotective antioxidant pathways, and induced autophagy-mediated early senescence in juvenile Taz^PM hearts. However, adult Taz^PM males exhibit chronic heart failure with reduced growth and ejection fraction, cardiac fibrosis, reduced ATP, and suppressed fatty acid/amino acid metabolism. This biphasic changeover from a mild-to-severe heart phenotype coincides with p53 suppression, downregulation of cardioprotective antioxidant pathways, and the onset of terminal senescence in adult Taz^PM hearts. Herein, we report a BTHS genotype/phenotype correlation and reveal that absent Taz acyltransferase function is sufficient to drive progressive cardiomyopathy. Full article

Objectives: To evaluate the quality of life (QoL) in a group of patients with type 2 diabetes (T2DM) and to identify predictive factors to apply the necessary measures to improve it. Methods: For this, 299 patients with T2DM were enrolled in a cross-sectional study, and their QoL was assessed using the EQ-5D-3L questionnaire. All patients underwent clinical exams, routine laboratory tests, and nerve conduction velocity (NCV) at the common peroneal nerve. Results: Patients had a median age of 66 (57; 70) years, median duration of T2DM of 10 (6; 15) years, median HbA1c of 8 (7; 9.3)%, and mean EQ-5D-3L score of 55%. In addition, 9.7% presented extreme difficulty in mobility, 18.5% severe difficulty in self-care, and 16.4% in usual activities. One-third presented with severe pain or discomfort, anxiety, or depression (level 3 EQ-5D-3L). DPN, heart failure (HF), cerebral stroke, and insulin therapy increased the likelihood of a reduced QoL (EQ-5D-3L < 50). The EQ-5D-3L score inversely correlated with serum creatinine, glycemic control, lipid profile, diabetes duration, age, mobility, self-care, pain/discomfort, usual activities, and anxiety/depression and positively correlated with NCV, HDLc, and eGFR. Conclusions: Preventing neuropathic complications, chronic kidney disease, stroke, and HF and obtaining the glycemic and lipid targets could improve the QoL in patients with T2DM. Full article

Background/Objectives: Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. Methods and Results: This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m² or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, p = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Conclusions: Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events. Full article

Although the postmortem interval estimation still represents one of the main goals of forensic medicine, there are still several limitations that weigh on the methods most used for its determination: for this reason, even today, precisely estimating the postmortem interval remains one of the most important challenges in the forensic pathology field. To try to overcome these limitations, in recent years, numerous studies have been conducted on the potential use of the mRNA degradation time for reaching a more precise post mortem interval (PMI) estimation. An evidence-based systematic review of the literature has been conducted to evaluate the state of the art of the knowledge focusing on the potential correlation between mRNA degradation and PMI estimation. The research has been performed using the electronic databases PubMed and Scopus. The analysis conducted made it possible to confirm the potential applicability of mRNA for reaching a more precise PMI estimation. The analysis of the results highlighted the usefulness of some mRNAs, such as β-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, especially in short time frames, within a few hours or days of death. The matrices on which these analyses were conducted were also analyzed, resulting in less exposure to the external environment, including the heart, brain, and dental pulp. The major limitations were also reported, including the short time intervals analyzed in most of the articles, the lack of mathematical models, and the failure to report the error rate between the mRNA degradation time and PMI. Given the still small number of published articles, the lack of globally recognized standardized methods, and the numerous techniques used to evaluate the mRNA degradation times, numerous and larger studies are still necessary to reach more solid and shared evidence. Full article

Background: This study examined the relationship between behavioural thresholds as measured by pure tone audiometry and electrophysiological thresholds measured by the Auditory Steady-State Response (ASSR) in children with normal hearing and sensorineural hearing loss. Materials and Methods: After being assessed, 45 children of both sexes, ranging in age from 5 to 15, were split into four groups: 10 with moderate to moderately severe sensorineural hearing loss (G2M); 10 with steeply sloping sensorineural hearing loss (G2D); 10 with profound and severe sensorineural hearing loss (G2S); and 15 with normal hearing (G1). ASSR, tympanometry, acoustic reflex testing, pure tone audiometry, and speech audiometry (SRT and SDT) were performed. Results: The electrophysiological maximum in the group with normal hearing thresholds varied from 19 to 27 dB NA. The correlation in the group with moderate to moderately severe hearing loss was 0.42–0.74. The correlation in the steeply sloping hearing loss group was 0.68–0.94. The correlation in the group of people with profound and severe hearing loss was 0.59–0.86. The normal hearing group’s mean differences in ASSR threshold and audiometric threshold ranged from −0.3 to 12 dB, in the moderate and moderately severe hearing loss group from −9 to 2 dB, in the steeply sloping hearing loss group from 1.4 to 7.5 dB, and in the severe and profound hearing loss group from −0.40 to 8.5 dB. Conclusion: As expected, there was no strong relationship between behavioural and electrophysiological thresholds in the group with normal hearing. But in children with hearing loss, there was a strong correlation between electrophysiological and behavioural thresholds; this relationship was especially evident in children with severe and profound hearing loss and those with steeply sloping hearing loss. Full article

Heart failure (HF) remains a significant burden on global healthcare systems, necessitating innovative approaches for its management. This manuscript critically evaluates the role of remote monitoring and telemedicine in revolutionizing HF care delivery. Drawing upon a synthesis of current literature and clinical practices, it delineates the pivotal benefits, challenges, and personalized strategies associated with these technologies in HF management. The analysis highlights the potential of remote monitoring and telemedicine in facilitating timely interventions, enhancing patient engagement, and optimizing treatment adherence, thereby ameliorating clinical outcomes. However, technical intricacies, regulatory frameworks, and socioeconomic factors pose formidable hurdles to widespread adoption. The manuscript emphasizes the imperative of tailored interventions, leveraging advancements in artificial intelligence and machine learning, to address individual patient needs effectively. Looking forward, sustained innovation, interdisciplinary collaboration, and strategic investment are advocated to realize the transformative potential of remote monitoring and telemedicine in HF management, thereby advancing patient-centric care paradigms and optimizing healthcare resource allocation. Full article

Myocarditis (MC) is defined as an immunological inflammatory reaction with various etiologies, clinical presentations and prognoses within the myocardium. Currently, parvovirus B19 (PVB19) has become the main factor leading to this disease, replacing the previously dominant viruses A and B. In the case of chronic heart failure with subsequent dilated cardiomyopathy, approximately 67% have a viral etiology, and most of them are the result of PVB19 infection. However, the analysis showed a correlation between PVB19 infection and the risk of developing inflammatory dilated cardiomyopathy (DCMi). PVB19 is detected in 23% of patients with DCMi. Chronic infection may also contribute to progressive left ventricular failure in patients with a history of MC. The above effect suggests the active replication of PVB19 only in heart biopsies with inflammation due to MC or DCMi. Moreover, the supply of IFN-β to suppress the active transcription of PVB19 accompanied by DCMi over a period of 6 months results in the normalization of NT-proBNP and an improvement in LVEF along with NYHA performance. The small number of reports on this topic and inaccuracies resulting from constantly conducted research and ongoing changes make it impossible to clearly answer the question of whether PVB19 is a factor inducing de novo MC and DCM or only accompanies the above conditions. However, large clinical cohort studies lead to the perception of PVB19 as a viral etiological agent capable of causing de novo MC together with DCMi. Full article

The current gold standard in device therapy for advanced heart failure (HF), which has been firmly established in HF management for more than 25 years, is classical biventricular pacing (BiV-CRT). In the last decade, a new pacing modality called conduction system pacing (CSP) has emerged as a variant for advanced cardiac device therapy. It provides pacing with preserved intrinsic cardiac activation by direct stimulation of the specific cardiac conduction system. The term CSP integrates the modalities of HIS bundle pacing (HBP) and left bundle branch area pacing (LBBAP), both of which have provided convincing data in smaller randomized and big non-randomized studies for the prevention of pacemaker-induced cardiomyopathy and for providing effective cardiac resynchronization therapy in patients with classical CRT-indication (primary approach or after failed CRT). Recent American guidelines proposed the term “cardiac physiological pacing” (CPP), which summarizes CSP including left ventricular septal pacing (LVSP), a technical variant of LBBAP together with classical BiV-CRT. The terms HOT-CRT (HIS-optimized CRT) and LOT-CRT (LBBP-optimized CRT) describe hybrid technologies that combine CSP with an additional coronary-sinus electrode, which is sometimes useful in patients with advanced HF and diffuse interventricular conduction delay. If CSP continues providing promising data that can be confirmed in big, randomized trials, it is likely to become the new gold standard for patients with an expected high percentage of pacing (>20%), possibly also for cardiac resynchronization therapy. CSP is a sophisticated new treatment option that has the potential to raise the term “cardiac resynchronization therapy” to a new level. The aim of this review is to provide basic technical, anatomical, and functional knowledge of these new pacemaker techniques in order to facilitate the understanding of the different modalities, as well as to provide an up-to-date overview of the existing randomized and non-randomized evidence, particularly in direct comparison to right ventricular and classical biventricular pacing. Full article

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterised by multiple risk factors touching various organs outside the heart. Using a murine HFpEF model, we studied cardiac reverse remodelling (RR) after stopping the causing metabolic-hypertensive stress (MHS; Angiotensin II [AngII] and a high-fat diet [HFD]) after 28 days and introducing voluntary exercise (VE) for four more weeks. We measured the effects of MHS and RR on the plasma and myocardial microRNA (miR) profile (miRNome) to characterise better cardiac and non-cardiac responses to HFpEF-inducing risk factors and their reversibility. AngII alone, the HFD or the MHS caused cardiac hypertrophy (CH), left ventricular (LV) concentric remodelling and left atrial enlargement in females. Only AngII and the MHS, but not HFD, did in males. After RR, CH, LV concentric remodelling and atrial enlargement were normalised. Among the 25 most abundant circulating miRs, 10 were modulated by MHS. Plasma miRNomes from AngII, HFD or MHS mice shared 31 common significantly modulated miRs (24 upregulated and 7 downregulated), suggesting that the response of organs producing the bulk of those circulating miRs was similar even for seemingly different stress. In the LV, 19 out of 25 most expressed miRs were modulated. RR restored normality for the plasma miRNome but not for the LV miRNome, which remained mostly unchanged. Our results suggest that abnormalities persist in the myocardium of the HFpEF mice and that the normalisation of circulatory markers may be falsely reassuring after recovery. Full article

The autonomic nervous system plays a key role in maintaining body hemostasis through both the sympathetic and parasympathetic nervous systems. Sympathetic overstimulation as a reflex to multiple pathologies, such as septic shock, brain injury, cardiogenic shock, and cardiac arrest, could be harmful and lead to autonomic and immunologic dysfunction. The continuous stimulation of the beta receptors on immune cells has an inhibitory effect on these cells and may lead to immunologic dysfunction through enhancing the production of anti-inflammatory cytokines, such as interleukin-10 (IL-10), and inhibiting the production of pro-inflammatory factors, such as interleukin-1B IL-1B and tissue necrotizing factor-alpha (TNF-alpha). Sympathetic overstimulation-induced autonomic dysfunction may also happen due to adrenergic receptor insensitivity or downregulation. Administering anti-adrenergic medication, such as beta-blockers, is a promising treatment to compensate against the undesired effects of adrenergic surge. Despite many misconceptions about beta-blockers, beta-blockers have shown a promising effect in decreasing mortality in patients with critical illness. In this review, we summarize the recently published articles that have discussed using beta-blockers as a promising treatment to decrease mortality in critically ill patients, such as patients with septic shock, traumatic brain injury, cardiogenic shock, acute decompensated heart failure, and electrical storm. We also discuss the potential pathophysiology of beta-blockers in various types of critical illness. More clinical trials are encouraged to evaluate the safety and effectiveness of beta-blockers in improving mortality among critically ill patients. Full article

Cardiovascular diseases (CVDs) remain a leading global cause of morbidity and mortality. These diseases have a multifaceted nature being influenced by a multitude of biochemical, genetic, environmental, and behavioral factors. Epigenetic modifications have a crucial role in the onset and progression of CVD. Epigenetics, which regulates gene activity without altering the DNA’s primary structure, can modulate cardiovascular homeostasis through DNA methylation, histone modification, and non-coding RNA regulation. The effects of environmental stimuli on CVD are mediated by epigenetic changes, which can be reversible and, hence, are susceptible to pharmacological interventions. This represents an opportunity to prevent diseases by targeting harmful epigenetic modifications. Factors such as high-fat diets or nutrient deficiencies can influence epigenetic enzymes, affecting fetal growth, metabolism, oxidative stress, inflammation, and atherosclerosis. Recent studies have shown that plant-derived bioactive compounds can modulate epigenetic regulators and inflammatory responses, contributing to the cardioprotective effects of diets. Understanding these nutriepigenetic effects and their reversibility is crucial for developing effective interventions to combat CVD. This review delves into the general mechanisms of epigenetics, its regulatory roles in CVD, and the potential of epigenetics as a CVD therapeutic strategy. It also examines the role of epigenetic natural compounds (ENCs) in CVD and their potential as intervention tools for prevention and therapy. Full article

Considering the worldwide impact of heart failure, it is crucial to develop approaches that can help us comprehend its root cause and make accurate predictions about its outcome. This is essential for lowering the suffering and death rates connected with this widespread illness. Cardiomyopathies frequently result from genetic factors, and the study of heart failure genetics is advancing quickly. Dilated cardiomyopathy (DCM) is the most prevalent kind of cardiomyopathy, encompassing both genetic and nongenetic abnormalities. It is distinguished by the enlargement of the left ventricle or both ventricles, accompanied by reduced contractility. The discovery of the molecular origins and subsequent awareness of the molecular mechanism is broadening our knowledge of DCM development. Additionally, it emphasizes the complicated nature of DCM and the necessity to formulate several different strategies to address the diverse underlying factors contributing to this disease. Genetic variants that can be transmitted from one generation to another can be a significant contributor to causing family or sporadic hereditary DCM. Genetic variants also play a significant role in determining susceptibility for acquired triggers for DCM. The genetic causes of DCM can have a large range of phenotypic expressions. It is crucial to select patients who are most probable to gain advantages from genetic testing. The purpose of this research is to emphasize the significance of identifying genetic DCM, the relationships between genotype and phenotype, risk assessment, and personalized therapy for both those affected and their relatives. This approach is expected to gain importance once treatment is guided by genotype-specific advice and disease-modifying medications. Full article