Cardiac and Renal Fibrosis, the Silent Killer in the Cardiovascular Continuum: An Up-to-Date.

Cardiovascular disease (CVD) and chronic kidney disease (CKD) often coexist and have a major impact on patient prognosis. Organ fibrosis plays a significant role in the pathogenesis of cardio-renal syndrome (CRS), explaining the high incidence of heart failure and sudden cardiac death in these patients. Various mediators and mechanisms have been proposed as contributors to the alteration of fibroblasts and collagen turnover, varying from hemodynamic changes to the activation of the renin-angiotensin system, involvement of FGF 23, and Klotho protein or collagen deposition. A better understanding of all the mechanisms involved has prompted the search for alternative therapeutic targets, such as novel inhibitors of the renin-angiotensin-aldosterone system (RAAS), serelaxin, and neutralizing interleukin-11 (IL-11) antibodies. This review focuses on the molecular mechanisms of cardiac and renal fibrosis in the CKD and heart failure (HF) population and highlights the therapeutic alternatives designed to target the responsible pathways.

Patient-Related Factors Predicting Stent Thrombosis in Percutaneous Coronary Interventions.

Over the past four decades, percutaneous coronary intervention (PCI) safety and efficacy have significantly improved, particularly with the advent of the drug-eluting stent (DES). First-generation DESs reduced in-stent restenosis rates and targeted lesion revascularization; however, safety issues emerged, due to high incidences of stent thrombosis (ST) linked to death, myocardial infarction, and repeat revascularization. Second-generation DESs were developed to overcome these issues, reducing late-thrombotic-event risk while maintaining anti-restenosis efficacy. Nevertheless, ST still occurs with second-generation DES use. Stent thrombosis etiology is multifaceted, encompassing lesion-, patient-, procedural-, and stent-related factors. Overall, most early-stent-thrombosis cases are linked to procedural and patient-related aspects. Factors like premature discontinuation of dual antiplatelet therapy, resistance to clopidogrel, smoking, diabetes mellitus, malignancy, reduced ejection fraction or undertaking coronary angioplasty for an acute coronary syndrome can increase the risk of stent thrombosis. The aim of this study is to assess patient-related factors that potentially heighten the risk of stent thrombosis, with the objective of pinpointing and addressing modifiable contributors to this risk. By focusing on both patient- and procedure-related factors, a multifaceted approach to coronary revascularization can help minimize complications and maximize long-term benefits in managing ST.

Assessment of Inflammatory Hematological Ratios (NLR, PLR, MLR, LMR and Monocyte/HDL-Cholesterol Ratio) in Acute Myocardial Infarction and Particularities in Young Patients.

Cardiovascular disease, particularly coronary artery disease (CAD), remains a predominant cause of mortality globally. Factors such as atherosclerosis and inflammation play significant roles in the pathogenesis of CAD. The nexus between inflammation and CAD is underscored by the role of immune cells, such as neutrophils, lymphocytes, monocytes, and macrophages. These cells orchestrate the inflammatory process, a core component in the initiation and progression of atherosclerosis. The activation of these pathways and the subsequent lipid, fibrous element, and calcification accumulation can result in vessel narrowing. Hematological parameters derived from routine blood tests offer insights into the underlying inflammatory state. Recent studies have highlighted the potential of inflammatory hematological ratios, such as the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio and lymphocyte/monocyte ratio. These parameters are not only accessible and cost-effective but also mirror the degree of systemic inflammation. Several studies have indicated a correlation between these markers and the severity, prognosis, and presence of CAD. Despite the burgeoning interest in the relationship between inflammatory markers and CAD, there remains a paucity of data exploring these parameters in young patients with acute myocardial infarction. Such data could offer valuable insights into the unique pathophysiology of early-onset CAD and improve risk assessment and predictive strategies.

An Update on MYBPC3 Gene Mutation in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetically inherited cardiomyopathy that follows an autosomal dominant inheritance pattern. The majority of HCM cases can be attributed to mutation of the MYBPC3 gene, which encodes cMyBP-C, a crucial structural protein of the cardiac muscle. The manifestation of HCM's morphological, histological, and clinical symptoms is subject to the complex interplay of various determinants, including genetic mutation and environmental factors. Approximately half of MYBPC3 mutations give rise to truncated protein products, while the remaining mutations cause insertion/deletion, frameshift, or missense mutations of single amino acids. In addition, the onset of HCM may be attributed to disturbances in the protein and transcript quality control systems, namely, the ubiquitin-proteasome system and nonsense-mediated RNA dysfunctions. The aforementioned genetic modifications, which appear to be associated with unfavorable lifelong outcomes and are largely influenced by the type of mutation, exhibit a unique array of clinical manifestations ranging from asymptomatic to arrhythmic syncope and even sudden cardiac death. Although the current understanding of the MYBPC3 mutation does not comprehensively explain the varied phenotypic manifestations witnessed in patients with HCM, patients with pathogenic MYBPC3 mutations can exhibit an array of clinical manifestations ranging from asymptomatic to advanced heart failure and sudden cardiac death, leading to a higher rate of adverse clinical outcomes. This review focuses on MYBPC3 mutation and its characteristics as a prognostic determinant for disease onset and related clinical consequences in HCM.

A Systematic Review on the Risk Modulators of Myocardial Infarction in the "Young"-Implications of Lipoprotein (a).

The presence of a myocardial infarction at a younger age is of special interest, considering the psychological and socioeconomic impact, as well as long-term morbidity and mortality. However, this group has a unique risk profile, with less traditional cardiovascular risk factors that are not well studied. This systematic review aims to evaluate traditional risk factors of myocardial infarction in the "young", highlighting the clinical implications of lipoprotein (a). We performed a comprehensive search using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards; we systematically searched the PubMed, EMBASE, and Science Direct Scopus databases, using the terms: "myocardial infarction", "young", "lipoprotein (a)", "low-density lipoprotein", "risk factors". The search identified 334 articles which were screened, and, at the end, 9 original research articles regarding the implications of lipoprotein (a) in myocardial infarction in the "young" were included in the qualitative synthesis. Elevated lipoprotein (a) levels were independently associated with an increased risk of coronary artery disease, especially in young patients, where this risk increased by threefold. Thus, it is recommended to measure the lipoprotein (a) levels in individuals with suspected familial hypercholesterolaemia or with premature atherosclerotic cardiovascular disease and no other identifiable risk factors, in order to identify patients who might benefit from a more intensive therapeutic approach and follow-up.

The Challenge of High Coronary Thrombotic Events in Patients with ST-Segment Elevation Myocardial Infarction and COVID-19.

The aim of this observational study was to describe the characteristics and outcomes of coronavirus disease 2019 (COVID-19)-positive patients with ST-segment elevation myocardial infarction (STEMI), with a special focus on factors associated with a high risk of coronary thrombosis and in-hospital mortality. Comparing the two groups of patients with STEMI separated according to the presence of SARS-CoV-2 infections, it was observed that COVID-19 patients were more likely to present with dyspnea (82.43% vs. 61.41%, p = 0.048) and cardiogenic shock (10.52% vs. 5.40%, p = 0.012). A longer total ischemia time was observed in COVID-19 patients, and they were twice as likely to undergo coronary angiography more than 12 hours after the onset of symptoms (19.29% vs. 10.13%, p = 0.024). In 10 of 57 COVID-19-positive patients, a primary PCI was not necessary, and only thromboaspiration was performed (17.54% vs. 2.70%, p < 0.001). Platelet level was inversely correlated (r = −0.512, p = 0.025) with a higher risk of coronary thrombosis without an atherosclerotic lesion. Using a cut-off value of 740 ng/ml, D-dimers predicted a higher risk of coronary thrombosis, with a sensitivity of 80% and a specificity of 66% (ROC area under the curve: 0.826, 95% CI: 0.716−0.935, p = 0.001). These are novel findings that raise the question of whether more aggressive antithrombotic therapy is necessary for selected COVID-19 and STEMI patients.

From Classic to Modern Prognostic Biomarkers in Patients with Acute Myocardial Infarction.

Despite all the important advances in its diagnosis and treatment, acute myocardial infarction (AMI) is still one of the most prominent causes of morbidity and mortality worldwide. Early identification of patients at high risk of poor outcomes through the measurement of various biomarker concentrations might contribute to more accurate risk stratification and help to guide more individualized therapeutic strategies, thus improving prognoses. The aim of this article is to provide an overview of the role and applications of cardiac biomarkers in risk stratification and prognostic assessment for patients with myocardial infarction. Although there is no ideal biomarker that can provide prognostic information for risk assessment in patients with AMI, the results obtained in recent years are promising. Several novel biomarkers related to the pathophysiological processes found in patients with myocardial infarction, such as inflammation, neurohormonal activation, myocardial stress, myocardial necrosis, cardiac remodeling and vasoactive processes, have been identified; they may bring additional value for AMI prognosis when included in multi-biomarker strategies. Furthermore, the use of artificial intelligence algorithms for risk stratification and prognostic assessment in these patients may have an extremely important role in improving outcomes.