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Chronic kidney disease represents a complex and multifaceted pathology characterized by the presence of structural or functional renal anomalies associated with a persistent reduction in renal function. As the disease progresses, complications arise due to the chronic inflammatory syndrome, hydro-electrolytic disorders, and toxicity secondary to the uremic environment. Cardiovascular complications are the leading cause of death for these patients. Ischemic cardiac pathology can be both a consequence and complication of chronic kidney disease, highlighting the need to identify specific cardiorenal dysfunction biomarkers targeting pathophysiological mechanisms common to both conditions. This identification is crucial for establishing accurate diagnoses, prognoses, and risk stratifications for patients. This work is intended to elucidate the intricate relationship between chronic kidney disease and ischemic heart disease and to investigate the roles of cardiorenal biomarkers, including cardiac troponin, natriuretic peptides, galectin-3, copeptin, fibroblast growth factor 23 and its co-receptor Klotho, soluble suppression of tumorigenicity 2, and plasma growth differentiation factor 15.

The overweight status or obesity can be confirmed through classical methods such as the body mass index (BMI) and the waist-to-hip ratio (WHR). Apart from metabolic issues such as atherosclerosis, liver steatosis, or diabetes mellitus, long-term obesity or overweight status can pose a risk for cardiovascular and neurovascular complications. While some acute adverse events like coronary syndromes of strokes are well-documented to be linked to an increased body mass, there are also chronic processes that, due to their silent onset and evolution, are underdiagnosed and not as thoroughly studied. Through this review, we aimed to collect all relevant data with regard to the long-term impact of obesity on cognitive function in all ages and its correlation with an earlier onset of dementia such as Alzheimer's disease (AD). The exact mechanisms through which a decline in cognitive functions occurs in overweight or obese persons are still being discussed. A combination of factors has been acknowledged as potential triggers, such as a sedentary lifestyle and stress, as well as a genetic predisposition, for example, the apolipoprotein E (ApoE) alleles in AD. Most research highlights the impact of vascular dysfunction and systemic inflammation on the nervous system in patients with obesity and the subsequent neurological changes. Obesity during the early to mid-ages leads to an earlier onset of cognitive dysfunction in various forms. Also, lifestyle intervention can reverse cognitive dysfunction, especially dieting, to encourage weight loss.

Advances in the treatment of hemophilia have increased the life expectancy of this population and we are currently facing diseases associated with aging, including cardiovascular ones. Coronary atherosclerosis, with acute myocardial infarction as the most severe form of manifestation, has been recognized as part of the comorbidities of hemophiliacs. However, little is known about peripheral artery disease. Available data show that hemophiliacs have cardiovascular risk factors and atherosclerosis similar to the general population. Impaired thrombus formation and phenotype of atheroma plaque rather than the burden of atherosclerosis explains their lower cardiovascular mortality. Since the effect of traditional cardiovascular risk factors overpowers that of decreased coagulability and promotes the onset and progression of atherosclerotic lesions, screening for traditional cardiovascular risk factors and peripheral artery disease should be integrated into standard hemophilia care. There is evidence that invasive treatments and long-term antithrombotic therapy are generally safe, provided that coagulation factor levels are taken into account and replacement therapy is given when necessary.

Background and Objectives : Cortisol is a valuable marker for assessing the body's response to any form of stress. We conducted this study in order to evaluate the variations of salivary and serum cortisol levels in professional football players in relation to cardiopulmonary exercise testing (CPET) and their significance in potentially evaluating overtraining in athletes. Also, the question of whether salivary cortisol determination could fully substitute serum sampling was addressed. Materials and Methods : A total of 19 male professional football players were evaluated by measuring serum cortisol levels at rest (T0) and immediately after a CPET (T1) and salivary cortisol levels at rest (T0), 10 min after a CPET (T2), and 30 min after a CPET (T3). Results : T0 serum cortisol showed a statistically significant correlation with the oxygen uptake at the anaerobic threshold divided by the body weight (VO 2 -AT/weight), as did the T2 salivary cortisol with the maximum oxygen uptake at the anaerobic threshold (VO 2 -AT) and VO 2 -AT/weight. T0 salivary cortisol was significantly correlated with the subjects' height and the predicted O 2 pulse. Conclusions : While some correlations were discovered, they are insufficient to recommend cortisol as a routine biomarker in athletes' evaluation. However, significant correlations were established between salivary and serum determinations, meaning that the non-invasive procedure could substitute venous blood sampling.

Atherosclerosis is a significant health concern with a growing incidence worldwide. It is directly linked to an increased cardiovascular risk and to major adverse cardiovascular events, such as acute coronary syndromes. In this review, we try to assess the potential diagnostic role of biomarkers in the early identification of patients susceptible to the development of atherosclerosis and other adverse cardiovascular events. We have collected publications concerning already established parameters, such as low-density lipoprotein cholesterol (LDL-C), as well as newer markers, e.g., apolipoprotein B (apoB) and the ratio between apoB and apoA. Additionally, given the inflammatory nature of the development of atherosclerosis, high-sensitivity c-reactive protein (hs-CRP) or interleukin-6 (IL-6) are also discussed. Additionally, newer publications on other emerging components linked to atherosclerosis were considered in the context of patient evaluation. Apart from the already in-use markers (e.g., LDL-C), emerging research highlights the potential of newer molecules in optimizing the diagnosis of atherosclerotic disease in earlier stages. After further studies, they might be fully implemented in the screening protocols.

Acute heart failure (AHF) is a life-threatening condition with high morbidity and mortality. Even though this pathology has been extensively researched, there are still challenges in establishing an accurate and early diagnosis, determining the long- and short-term prognosis and choosing a targeted therapeutic strategy. The use of reliable biomarkers to support clinical judgment has been shown to improve the management of AHF patients. Despite a large pool of interesting candidate biomarkers, endothelin-1 (ET-1) appears to be involved in multiple aspects of AHF pathogenesis that include neurohormonal activation, cardiac remodeling, endothelial dysfunction, inflammation, atherosclerosis and alteration of the renal function. Since its discovery, numerous studies have shown that the level of ET-1 is associated with the severity of symptoms and cardiac dysfunction in this pathology. The purpose of this paper is to review the existing information on ET-1 and answer the question of whether this neurohormone could be a promising biomarker in AHF.

Factor V (FV) Leiden and prothrombin G20210A are the most common hereditary thrombophilias. While their role in venous thromboembolism is well known, there are still uncertainties regarding their relationship with arterial thrombotic events, especially coronary ones. Our research, based on an in-depth analysis of the available literature, provides up-to-date information on the relationship between FV Leiden and prothrombin G20210A and acute myocardial infarction. FV Leiden and prothrombin G20210A screening should be implemented only in select cases, such as acute coronary syndrome in young individuals and/or in the absence of traditional cardiovascular risk factors and/or in the absence of significant coronary artery stenosis at angiography. Their identification should be followed by the implementation of optimal control of modifiable traditional cardiovascular risk factors to reduce the risk of recurrent events and genotyping and genetic counseling of all family members of affected cases for proper prophylaxis. An extended dual antiplatelet therapy (DAPT) may be considered, given the lower risk of bleeding under DAPT conferred by FV Leiden.

Atrial fibrillation, the most frequent arrhythmia in clinical practice and chronic coronary syndrome, is one of the forms of coronary ischemia to have a strong dual relationship. Atrial fibrillation may accelerate atherosclerosis and may increase oxygen consumption in the myocardium, creating a mismatch between supply and demand, thus promoting the development or worsening of coronary ischemia. Chronic coronary syndrome alters the structure and function of gap junction proteins, affecting the conduction of action potential and leading to ischemic necrosis of cardiomyocytes and their replacement with fibrous tissue, in this way sustaining the focal ectopic activity in atrial myocardium. They have many risk factors in common, such as hypertension, obesity, type 2 diabetes mellitus, and dyslipidemia. It is vital for the prognosis of patients to break this vicious circle by controlling risk factors, drug therapies, of which antithrombotic therapy may sometimes be challenging in terms of prothrombotic and bleeding risk, and interventional therapies (revascularization and catheter ablation).

Myocardial ischemia is a pathophysiological state characterized by inadequate perfusion of the myocardium, resulting in an imbalance between myocardial oxygen demand and supply. It is most commonly caused by coronary artery disease, in which atherosclerotic plaques lead to luminal narrowing and reduced blood flow to the heart. Myocardial ischemia can manifest as angina pectoris or silent myocardial ischemia and can progress to myocardial infarction or heart failure if left untreated. Diagnosis of myocardial ischemia typically involves a combination of clinical evaluation, electrocardiography and imaging studies. Electrocardiographic parameters, as assessed by 24 h Holter ECG monitoring, can predict the occurrence of major adverse cardiovascular events in patients with myocardial ischemia, independent of other risk factors. The T-waves in patients with myocardial ischemia have prognostic value for predicting major adverse cardiovascular events, and their electrophysiological heterogeneity can be visualized using various techniques. Combining the electrocardiographic findings with the assessment of myocardial substrate may offer a better picture of the factors that can contribute to cardiovascular death.

Despite the improvements in the treatment of coronary artery disease (CAD) and acute myocardial infarction (MI) over the past 20 years, ischemic heart disease (IHD) continues to be the most common cause of heart failure (HF). In clinical trials, over 70% of patients diagnosed with HF had IHD as the underlying cause. Furthermore, IHD predicts a worse outcome for patients with HF, leading to a substantial increase in late morbidity, mortality, and healthcare costs. In recent years, new pharmacological therapies have emerged for the treatment of HF, such as sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, selective cardiac myosin activators, and oral soluble guanylate cyclase stimulators, demonstrating clear or potential benefits in patients with HF with reduced ejection fraction. Interventional strategies such as cardiac resynchronization therapy, cardiac contractility modulation, or baroreflex activation therapy might provide additional therapeutic benefits by improving symptoms and promoting reverse remodeling. Furthermore, cardiac regenerative therapies such as stem cell transplantation could become a new therapeutic resource in the management of HF. By analyzing the existing data from the literature, this review aims to evaluate the impact of new HF therapies in patients with IHD in order to gain further insight into the best form of therapeutic management for this large proportion of HF patients.

(1) Background: Acute heart failure (HF) represents a complex clinical syndrome burdened by increased mortality and a high rate of systemic complications. Although natriuretic peptides (e.g., NT-proBNP) currently represent the diagnostic and prognostic gold standard in acute HF, those molecules do not accurately reflect all the pathophysiological mechanisms involved in the progression of this pathology when determined independently. Therefore, the current paradigm tends to focus on a multi-marker approach for the risk stratification of patients with acute HF. Syndecan-1 is a less studied biomarker in cardiovascular diseases; its assessment in patients with acute HF being potentially able to reflect the myocardial pathological changes, such as fibrosis, inflammation, endothelial dysfunction or global wall stress. (2) Methods: We conducted a single center prospective study that enrolled 173 patients (120 patients admitted for acute HF, compared to 53 controls with stable chronic HF). A complete standardized clinical, echocardiography and laboratory evaluation was performed at admission, including serum samples for the determination of syndecan-1 by the enzyme-linked immunosorbent assay (ELISA) method. (3) Results: The serum concentration of syndecan-1 was significantly higher in patients with acute HF, compared to controls [121.4 (69.3-257.9) vs. 72.1 (41.4-135.8) ng/mL, p = 0.015]. Syndecan-1 was a significant predictor for the diagnosis of acute HF, expressed by an area under the curve (AUC) of 0.898, similar to NT-proBNP (AUC: 0.976) or cardiac troponin (AUC: 0.839). Moreover, syndecan-1 was independently associated with impaired kidney and liver function at admission, being also a predictor for early, subclinical organ dysfunction in patients with normal biological parameters at admission. When included in the multi-marker model, syndecan-1 levels influenced mortality more significantly than NT-proBNP or troponin. A multivariable regression including syndecan-1, NT-proBNP and troponin provided additional prognostic value compared to each independent biomarker. (4) Conclusions: Syndecan-1 can be considered a promising novel biomarker in acute HF, exhibiting adequate diagnostic and prognostic value. Additionally, syndecan-1 can be used as a surrogate biomarker for non-cardiac organ dysfunction, as its highs levels can accurately reflect early acute kidney and liver injury.

Over the past 100 years, cardiovascular disease (CVD) has become a leading cause of mortality and morbidity in developed countries, and similar trends have occurred for chronic liver disease. Subsequent research also indicated that people with non-alcoholic fatty liver disease (NAFLD) had a twofold increased risk of CV events and that this risk was doubled in those with liver fibrosis. However, no validated CVD risk score specific for NAFLD patients has yet been validated, as traditional risk scores tend to underestimate the CV risk in NAFLD patients. From a practical perspective, identifying NAFLD patients and assessing severity of liver fibrosis when concurrent atherosclerotic risk factors are already established may serve as an important criterion in new CV risk scores. The current review aims to assess current risk scores and their utility for the prediction of CV events among patients with NAFLD.

Atrial fibrillation is frequently diagnosed in patients with liver cirrhosis, especially in those with non-alcoholic steatohepatitis or alcoholic etiology. Anticoagulant treatment is recommended for thromboembolic protection in patients with atrial fibrillation. Considering the impaired coagulation balance in liver cirrhosis, predisposing patients to bleed or thrombotic events, the anticoagulant treatment is still a matter of debate. Although patients with liver cirrhosis were excluded from the pivotal studies that confirmed the efficacy and safety of the anticoagulant treatment in patients with atrial fibrillation, data from real-life cohorts demonstrated that the anticoagulant treatment in patients with liver cirrhosis could be safe. This review aimed to evaluate the recent data regarding the safety and efficacy of anticoagulant treatment in patients with decompensated liver cirrhosis. Direct oral anticoagulants are safer than warfarin in patients with compensated liver cirrhosis. In Child-Pugh class C liver cirrhosis, direct oral anticoagulants are contraindicated. New bleeding and ischemic risk scores should be developed especially for patients with liver cirrhosis, and biomarkers for bleeding complications should be implemented in clinical practice to personalize this treatment in a very difficult population represented by decompensated liver cirrhosis patients.

Ischemia with nonobstructive coronary artery disease (INOCA) is increasingly recognized as a significant cause of angina, myocardial remodeling, and eventually heart failure (HF). Coronary microvascular dysfunction (CMD) is a major endotype of INOCA, and it is caused by structural and functional alterations of the coronary microcirculation. At the same time, atrial cardiomyopathy (ACM) defined by structural, functional, and electrical atrial remodeling has a major clinical impact due to its manifestations: atrial fibrillation (AF), atrial thrombosis, stroke, and HF symptoms. Both these pathologies share similar risk factors and have a high comorbidity burden. CMD causing INOCA and ACM frequently coexist. Thus, questions arise whether there is a potential link between these pathologies. Does CMD promote AF or the reverse? Which are the mechanisms that ultimately lead to CMD and ACM? Are both part of a systemic disease characterized by endothelial dysfunction? Lastly, which are the therapeutic strategies that can target endothelial dysfunction and improve the prognosis of patients with CMD and ACM? This review aims to address these questions by analyzing the existing body of evidence, offering further insight into the mechanisms of CMD and ACM, and discussing potential therapeutic strategies.

In recent years, direct oral anticoagulants (DOAC) have accumulated evidence of efficacy and safety in various clinical scenarios and are approved for a wide spectrum of indications. Still, they are currently used off-label for left ventricular thrombus owing to a paucity of evidence. For the same reason, there is a lack of guideline indication as well. Our work is based on an exhaustive analysis of the available literature and provides a structured and detailed update on the use of DOACs in patients with left ventricle thrombus. The safety and efficacy of DOACs were analyzed in particular clinical scenarios. As far as we know, this is the first paper that analyzes DOACs in this approach.

1., Background: Literature data on bacterial infections and their impact on the mortality rates of COVID-19 patients from Romania are scarce, while worldwide reports are contrasting. 2., Materials and Methods: We conducted a unicentric retrospective observational study that included 280 patients with SARS-CoV-2 infection, on whom we performed various microbiological determinations. Based on the administration or not of the antibiotic treatment, we divided the patients into two groups. First, we sought to investigate the rates and predictors of bacterial infections, the causative microbial strains, and the prescribed antibiotic treatment. Secondly, the study aimed to identify the risk factors associated with in-hospital death and evaluate the biomarkers' performance for predicting short-term mortality. 3., Results: Bacterial co-infections or secondary infections were confirmed in 23 (8.2%) patients. Acinetobacter baumannii was the pathogen responsible for most of the confirmed bacterial infections. Almost three quarters of the patients (72.8%) received empiric antibiotic therapy. Multivariate logistic regression has shown leukocytosis and intensive care unit admission as risk factors for bacterial infections and C-reactive protein, together with the length of hospital stay, as mortality predictors. The ROC curves revealed an acceptable performance for the erythrocyte sedimentation rate (AUC: 0.781), and C-reactive protein (AUC: 0.797), but a poor performance for fibrinogen (AUC: 0.664) in predicting fatal events. 4., Conclusions: This study highlighted the somewhat paradoxical association of a low rate of confirmed infections with a high rate of empiric antibiotic therapy. A thorough assessment of the risk factors for bacterial infections, in addition to the acknowledgment of various mortality predictors, is crucial for identifying high-risk patients, thus allowing a timely therapeutic intervention, with a direct impact on improving patients' prognosis.

(1) Background: Pulmonary embolism (PE) represents the third most important cardiovascular cause of death after myocardial infarction and stroke. The proper management of this condition is dependent on adequate risk stratification, due to the life-threatening complications of more aggressive therapies such as thrombolysis. Copeptin is a surrogate marker of vasopressin which is found increased in several cardiovascular conditions. The Mastora score is an imagistic evaluation of the degree of pulmonary arteries thrombotic burden based on computed tomography angiography. In this study, we aimed to evaluate the diagnostic and prognostic role of copeptin in patients with acute PE. Furthermore, we analyzed the relationship between copeptin and Mastora score and their role in PE risk profiling. (2) Methods: We conducted a single center prospective study that included 112 patients with PE and 53 healthy volunteers. Clinical and paraclinical parameters, together with plasma levels of copeptin and the Mastora score, were evaluated in all patients after admission. (3) Results: Copeptin levels were significantly increased in PE patients compared with the general population (26.05 vs. 9.5 pmol/L, p < 0.001), while receiver operating characteristic (ROC) analysis revealed an AUC of 0.800 (95% CI 0.728−0.873, p < 0.001). Copeptin directly correlated with the Mastora score (r = 0.535, p = 0.011) and both parameters were strong predictors for adverse clinical events and death. Receiver operating characteristic (ROC) analysis for death within 30 days revealed a copeptin cut-off of 38.36 pmol/L, which presented a specificity of 79.6% and a sensitivity of 88.9%, and a Mastora score cut-off of 82 points, which presented a specificity of 74.8% and a sensitivity of 77.8%. (4) Conclusions: Our results showed that copeptin and the Mastora score are both correlated with adverse cardiovascular events and mortality in PE patients, and this may pave the way for their use in clinical practice, helping physicians to select the best therapeutical management.

Sustained physical activity induces morphological and functional changes in the cardiovascular system. While mostly physiological, they can also become a trigger for major adverse cardiovascular events, the most severe of which are sudden cardiac arrest and sudden cardiac death. Therefore, any novel method which can help more accurately estimate the cardiovascular risk should be considered for further studying and future implementation in the standard protocols. The study of biomarkers is gaining more and more ground as they have already established their utility in diagnosing ischemic cardiac disease or in evaluating cardiac dysfunction in patients with heart failure. Nowadays, they are being implemented in the screening of apparently healthy individuals for the assessment of the cardiovascular risk. The aim of this paper is to gather published data regarding the measurements of cardiac biomarkers in athletes, i.e., troponins, myoglobin, CK-MB, NT-proBNP, and D-Dimers, and their potential use in the field of sports cardiology.

This research focused on establishing a hierarchy concerning the influence of various biological markers and body composition parameters on preventing, diagnosing and managing Metabolic Syndrome (MetS). Our cross-sectional cohort study included 104 subjects without any atherosclerotic antecedent pathology, organized in two groups (with and without MetS). All participants underwent clinical and anthropometric measurements, DEXA investigation and blood tests for all MetS criteria, together with adiponectin, leptin, insulin, uric acid and CRP. Based on mathematical logic, we calculated a normalized sensitivity score to compare the predictive power of biomarkers and parameters associated with MetS, upon the prevalence of MetS. Patients with MetS report higher levels of uric acid ( p = 0.02), CRP ( p = 0.012) and lower levels of adiponectin ( p = 0.025) than patients without MetS. The top three biological markers with the highest predictive power of the prevalence of the disease are HDL, insulin, and adiponectin:leptin ratio, and the top three body composition parameters are trunk fat-free percentage, waist-height ratio and trunk fat percentage. Their high sensitivity scores differentiate them from all the other markers analysed in the study. Our findings report relevant scores for estimating the importance of cardiometabolic risks in the prevalence of MetS. The high rank of protective markers, HDL and trunk fat-free percentage, suggest that positive effects have a stronger association with the prevalence of MetS, than negative ones do. Therefore, this risk stratification study provides important support for prevention and management programs regarding MetS.

Background: Biomarkers, electrocardiogram (ECG) and Holter ECG are basic, accessible and feasible cardiac investigations. The combination of their results may lead to a more complex predictive model that may improve the clinical approach in acute heart failure (AHF). The main objective was to investigate which ECG parameters are correlated with the usual cardiac biomarkers (prohormone N-terminal proBNP, high-sensitive cardiac troponin I) in patients with acute heart failure, in a population from Romania. The relationship between certain ECG parameters and cardiac biomarkers may support future research on their combined prognostic value. Methods: In this prospective case-control study were included 49 patients with acute heart failure and 31 participants in the control group. For all patients we measured levels of prohormone N-terminal proBNP (NT-proBNP), high-sensitive cardiac troponin I (hs-cTnI) and MB isoenzyme of creatine phosphokinase (CK-MB) and evaluated the 12-lead ECG and 24 h Holter monitoring. Complete clinical and paraclinical evaluation was performed. Results: NT-proBNP level was significantly higher in patients with AHF (p < 0.001). In patients with AHF, NT-proBNP correlated with cQTi (p = 0.027), pathological Q wave (p = 0.029), complex premature ventricular contractions (PVCs) (p = 0.034) and ventricular tachycardia (p = 0.048). Hs-cTnI and CK-MB were correlated with ST-segment modification (p = 0.038; p = 0.018) and hs-cTnI alone with complex PVCs (p = 0.031). Conclusions: The statistical relationships found between cardiac biomarkers and ECG patterns support the added value of ECG in the diagnosis of AHF. We emphasize the importance of proper ECG analysis of more subtle parameters that can easily be missed. As a non-invasive technique, ECG can be used in the outpatient setting as a warning signal, announcing the acute decompensation of HF. In addition, the information provided by the ECG complements the biomarker results, supporting the diagnosis of AHF in cases of dyspnea of uncertain etiology. Further studies are needed to confirm long-term prognosis in a multi-marker approach.

(1) Background: Acute heart failure (HF) represents one of the most common yet extremely severe presentations in emergency services worldwide, requiring prompt diagnosis, followed by an adequate therapeutic approach, and a thorough risk stratification. Natriuretic peptides (NPs) are currently the most widely implemented biomarkers in acute HF, but due to their lack of specificity, they are mainly used as ruling-out criteria. Growth differentiation factor-15 (GDF-15) is a novel molecule expressing different pathophysiological pathways in HF, such as fibrosis, remodeling, and oxidative stress. It is also considered a very promising predictor of mortality and poor outcome. In this study, we aimed to investigate the GDF-15’s expression and particularities in patients with acute HF, focusing mainly on its role as a prognosis biomarker, either per se or as part of a multimarker panel. (2) Methods: This unicentric prospective study included a total of 173 subjects, divided into 2 subgroups: 120 patients presented in emergency with acute HF, while 53 were ambulatory-evaluated controls with chronic HF. At admission, all patients were evaluated according to standard clinical echocardiography and laboratory panel, including the assessment of GDF-15. (3) Results: The levels of GDF-15 were significantly higher in patients with acute HF, compared to controls [596 (305−904) vs. 216 (139−305) ng/L, p < 0.01]. GDF-15 also exhibited an adequate diagnostic performance in acute HF, expressed as an area under the curve (AUC) of 0.883 [confidence interval (CI) 95%: 0.828−0.938], similar to that of NT-proBNP (AUC: 0.976, CI 95%: 0.952−1.000), or troponin (AUC: 0.839, CI 95%: 0.733−0.944). High concentrations of GDF-15 were significantly correlated with mortality risk. In a multivariate regression model, GDF-15 was the most important predictor of a poor outcome, superior to NT-proBNP or troponin. (4) Conclusions: GDF-15 proved to be a reliable tool in the multimarker assessment of patients with acute HF. Compared to the gold standard NT-proBNP, GDF-15 presented a similar diagnostic performance, doubled by a significantly superior prognostic value, making it worth being included in a standardized multimarker panel.

Persistent left superior vena cava (PLSVC) is the most common congenital malformation of the thoracic venous system, being present in 0.3% to 0.5% of the general population. In the majority of the cases, PLSVC is asymptomatic, but in certain patients, it can manifest through several symptoms, such as arrhythmias and cyanosis, especially when it is associated with complex cardiac pathologies. The clinical significance of this venous anomaly depends on the anatomical variant of the drainage site. In this article, we will present the experience of our clinic, with patients with PLSVC that were diagnosed intraprocedurally, during cardiac pacemaker (CP) or cardioverter defibrillator (ICD) implantation, highlighting the technical difficulties that this anomaly poses for cardiac device implantation. Out of 4000 patients who were admitted to our clinic for CP or ICD implantation, we encountered six cases of PLSVC (four reported in this article and two previously published) corresponding to different anatomical types of this congenital anomaly. In all of these situations, we had to adapt our technique to the patient's anatomy in order to avoid certain complications, the most serious being the improper placement of the right ventricle lead at the level of the coronary sinus.

Background: Data regarding the combined prognostic role of biomarkers and risk scores in relation with the history of atherosclerotic cardiovascular disease (ASCVD) in COVID-19 patients are lacking., Methods: The aim of this observational cohort study was to evaluate the combined prognostic value of N-terminal pro B-type natriuretic peptide (NT-pro BNP), troponin and risk scores in relation with ASCVD history in hospitalized COVID-19 patients. The primary composite endpoint was Intensive Care Unit (ICU) admission and death., Results: From April 2020 to June 2022, 1066 consecutive COVID-19 patients with available biomarkers upon admission were included. During a median follow-up period of 12 days, 176 patients (16.5%) died. Independent predictors of ICU admission and death in patients with ASCVD were NT-pro BNP (HR 2.63; 95% CI, 1.65-4.18) and troponin (HR 1.51; 95% CI, 1.13-2.03). In patients without ASCVD, only NT-pro BNP was predictive for the primary endpoint (HR 1.66; 95% CI, 1.10-2.53). This remained significant after adjustment for other relevant covariates (HR 3.54; 95% CI, 1.98-6.33) in patients with ASCVD and in patients without ASCVD (HR 1.82; 95% CI, 1.02-3.26)., Conclusions: These data showed the combined prognostic accuracy of NT-pro BNP and troponin in relation with ASCVD history for ICU admission and death in COVID-19 patients.

(1) Background: Pulmonary embolism (PE) is a severe condition, representing the third most important cardiovascular cause of death after myocardial infarction and stroke. Despite the use of clinical pre-test probability scores, D-dimer measuring, and computer tomography pulmonary angiography (CTPA), PE diagnosis remains a challenge. Brain-derived neurotrophic factor (BDNF) is the most important member of the neurotrophin family, which has also been shown to be involved in the physiopathology of cardiovascular conditions such as heart failure and myocardial infarction. In this study, we aimed to assess the BDNF expression in patients with acute PE compared to the general population, and to also investigate its diagnostic and prognostic role. (2) Methods: We conducted a single center prospective study, which included 90 patients with PE and 55 healthy volunteers. Clinical and paraclinical parameters, together with plasma levels of BDNF, were evaluated in all patients after admission. (3) Results: The plasma levels of BDNF were significantly lower in the PE patients compared with the control group (403 vs. 644 pg/mL, p < 0.001). ROC analysis revealed an AUC of 0.806 (95% CI 0.738−0.876, p < 0.001) and a cut-off value of 564 pg/mL, which associated a sensitivity of 74.4% and a specificity of 78.2% for PE. Low BDNF levels also correlated with prognostic markers of PE, such as PESI score (p = 0.023), NT-proBNP (p < 0.01), right ventricular diameter (p = 0.029), and tricuspid annular plane systolic elevation (p = 0.016). Moreover, we identified a decreased BDNF expression in patients with high-risk PE (p < 0.01), thrombolytic treatment (p = 0.01), and patients who died within 30 days (p = 0.05). (4) Conclusions: Our study revealed that plasma BNDF is significantly lower in patients with PE when compared with the general population, and may be considered as a promising biomarker in complementing the current diagnostic tools for PE. Furthermore, low levels of BDNF might also be used to predict a poor outcome of this condition.

In cancer survivors, cardiac dysfunction is the main cause of mortality. Cardiotoxicity represents a decline in cardiac function associated with cancer therapy, and the risk factors include smoking, dyslipidemia, an age of over 60 years, obesity, and a history of coronary artery disease, diabetes, atrial fibrillation, or heart failure. Troponin is a biomarker that is widely used in the detection of acute coronary syndromes. It has a high specificity, although it is not exclusively associated with myocardial ischemia. The aim of this paper is to summarize published studies and to establish the role of troponin assays in the diagnosis of cardiotoxicity associated with various chemotherapeutic agents. Troponin has been shown to be a significant biomarker in the diagnosis of the cardiac dysfunction associated with several types of chemotherapeutic drugs: anthracyclines, anti-human epidermal growth factor receptor 2 treatment, and anti-vascular endothelial growth factor therapy. Based on the data available at this moment, troponin is useful for baseline risk assessment, the diagnosis of cardiotoxicity, and as a guide for the initiation of cardioprotective treatment. There are currently clear regulations regarding the timing of troponin surveillance depending on the patient's risk of cardiotoxicity and the type of medication administered, but data on the cut-off values of this biomarker are still under investigation.

Heart failure management has been repeatedly reviewed over time. This strategy has resulted in improved quality of life, especially in patients with heart failure with reduced ejection fraction (HFrEF). It is for this reason that new mechanisms involved in the development and progression of heart failure, along with specific therapies, have been identified. This review focuses on the most recent guidelines of therapeutic interventions, trials that explore novel therapies, and also new molecules that could improve prognosis of different HFrEF phenotypes.

Myocardial infarction (MI) is the leading cause of death and morbidity worldwide, with an incidence relatively high in developed countries and rapidly growing in developing countries. The most common cause of MI is the rupture of an atherosclerotic plaque with subsequent thrombotic occlusion in the coronary circulation. This causes cardiomyocyte death and myocardial necrosis, with subsequent inflammation and fibrosis. Current therapies aim to restore coronary flow by thrombus dissolution with pharmaceutical treatment and/or intravascular stent implantation and to counteract neurohormonal activation. Despite these therapies, the injury caused by myocardial ischemia leads to left ventricular remodeling; this process involves changes in cardiac geometry, dimension and function and eventually progression to heart failure (HF). This review describes the pathophysiological mechanism that leads to cardiac remodeling and the therapeutic strategies with a role in slowing the progression of remodeling and improving cardiac structure and function.

The intricate relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the cardiovascular system is an extensively studied pandemic topic, as there is an ever-increasing amount of evidence that reports a high prevalence of acute cardiac injury in the context of viral infection. In patients with Coronavirus disease 2019, COVID-19, a significant increase in serum levels of cardiac troponin or other various biomarkers was observed, suggesting acute cardiac injury, thus predicting both a severe course of the disease and a poor outcome. Pathogenesis of acute cardiac injury is not yet completely elucidated, though several mechanisms are allegedly involved, such as a direct cardiomyocyte injury, oxygen supply-demand inequity caused by hypoxia, several active myocardial depressant factors during sepsis, and endothelial dysfunction due to the hyperinflammatory status. Moreover, the increased levels of plasma cytokines and catecholamines and a significantly enhanced prothrombotic environment may lead to the destabilization and rupture of atheroma plaques, subsequently triggering an acute coronary syndrome. In the present review, we focus on describing the epidemiology, pathogenesis, and role of biomarkers in the diagnosis and prognosis of patients with acute cardiac injury in the setting of the COVID-19 pandemic. We also explore some novel therapeutic strategies involving immunomodulatory therapy, as well as their role in preventing a severe form of the disease, with both the short-term outcome and the long-term cardiovascular sequelae being equally important in patients with SARS-CoV-2 induced acute cardiac injury.

The link between heart and liver cirrhosis was recognized decades ago, although much data regarding atherosclerosis and ischemic heart disease are still missing. Ischemic heart disease or coronary artery disease (CAD) and liver cirrhosis could be associated with characteristic epidemiological and pathophysiological features. This connection determines increased rates of morbidity and all-cause mortality in patients with liver cirrhosis. In the era of a metabolic syndrome and non-alcoholic fatty liver disease pandemic, primary prevention and early diagnosis of coronary artery disease could improve the prognosis of liver cirrhosis patients. This review outlines a summary of the literature regarding prevalence, risk assessment and medical and interventional treatment options in this particular population. A collaborative heart-liver team-based approach is imperative for critical management decisions for patients with CAD and liver cirrhosis.

Modern antineoplastic therapy improves survival and quality of life in cancer patients, but its indisputable benefits are accompanied by multiple and major side effects, such as cardiovascular ones. Endothelial dysfunction, arterial spasm, intravascular thrombosis, and accelerated atherosclerosis affect the coronary arteries, leading to acute and chronic coronary syndromes that negatively interfere with the oncologic treatment. The cardiac toxicity of antineoplastic agents may be mitigated by using adequate prophylactic measures. In the absence of dedicated guidelines, our work provides the most comprehensive, systematized, structured, and up-to-date analyses of the available literature focusing on measures aiming to protect the coronary arteries from the toxicity of cancer therapy. Our work facilitates the implementation of these measures in daily practice. The ultimate goal is to offer clinicians the necessary data for a personalized therapeutic approach for cancer patients receiving evidence-based oncology treatments with potential cardiovascular toxicity.

Given the possible pathophysiological links between myocardial ischemia and SARS-CoV-2 infection, several studies have focused attention on acute coronary syndromes in order to improve patients' morbidity and mortality. Understanding the pathophysiological aspects of myocardial ischemia in patients infected with SARS-CoV-2 can open a broad perspective on the proper management for each patient. The electrocardiogram (ECG) remains the easiest assessment of cardiac involvement in COVID-19 patients, due to its non-invasive profile, accessibility, low cost, and lack of radiation. The ECG changes provide insight into the patient's prognosis, indicating either the worsening of an underlying cardiac illnesses or the acute direct injury by the virus. This indicates that the ECG is an important prognostic tool that can affect the outcome of COVID-19 patients, which important to correlate its aspects with the clinical characteristics and patient's medical history. The ECG changes in myocardial ischemia include a broad spectrum in patients with COVID-19 with different cases reported of ST-segment elevation, ST-segment depression, and T wave inversion, which are associated with severe COVID-19 disease.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health concern and is characterized by an exaggerated inflammatory response that can lead to a large variety of clinical manifestations such as respiratory distress, sepsis, coagulopathy, and death. While it was initially considered primarily a respiratory illness, different data suggests that COVID-19 can lead to a pro-inflammatory milieu and a hypercoagulable state. Several mechanisms attempt to explain the pro-coagulant state seen in COVID-19 patients, including increased fibrinogen concentration, different receptor binding, exhausted fibrinolysis, cytokine storm, and endothelial dysfunction. Some hematological parameters, such as elevated D-dimers and other fibrinolytic products, indicate that the essence of coagulopathy is massive fibrin formation. Moreover, elevated D-dimer levels have emerged as an independent risk factor for a worse outcome, including death, indicating a potential risk for deep vein thrombosis and pulmonary thromboembolism. Prophylactic anticoagulation is recommended in all in-patients with COVID-19 to reduce the incidence of thrombosis. Those with elevated D-dimer values or with a higher risk of developing thromboembolic events should be treated with higher doses of anticoagulant. Anticoagulation may not be enough in some circumstances, highlighting the need for alternative therapies. An understanding of the complex cross-talk between inflammation and coagulopathy is necessary for developing direct appropriate interventional strategies.

In the modern era, coronary artery disease (CAD) has become the most common form of heart disease and, due to the severity of its clinical manifestations and its acute complications, is a major cause of morbidity and mortality worldwide. The phenotypic variability of CAD is correlated with the complex etiology, multifactorial (caused by the interaction of genetic and environmental factors) but also monogenic. The purpose of this review is to present the genetic factors involved in the etiology of CAD and their relationship to the pathogenic mechanisms of the disease. Method: we analyzed data from the literature, starting with candidate gene-based association studies, then continuing with extensive association studies such as Genome-Wide Association Studies (GWAS) and Whole Exome Sequencing (WES). The results of these studies revealed that the number of genetic factors involved in CAD etiology is impressive. The identification of new genetic factors through GWASs offers new perspectives on understanding the complex pathophysiological mechanisms that determine CAD. In conclusion, deciphering the genetic architecture of CAD by extended genomic analysis (GWAS/WES) will establish new therapeutic targets and lead to the development of new treatments. The identification of individuals at high risk for CAD using polygenic risk scores (PRS) will allow early prophylactic measures and personalized therapy to improve their prognosis.

Constant and intense physical activity causes physiological adaptive changes in the human body, but it can also become a trigger for adverse events, such as sudden cardiac arrest or sudden cardiac death. Our main objective was to assess the use of combined cardiopulmonary exercise testing (CPET) and cardiac biomarker determinants in young professional athletes. We conducted a study which involved the full examination of 19 football players, all male, aged between 18 and 20 years old. They underwent standard clinical and paraclinical evaluation, a 12-lead electrocardiogram (ECG), and transthoracic echocardiography (TTE). Afterwards, a tailored CPET was performed and peripheral venous blood samples were taken before and 3 h after the test in order to determine five biomarker levels at rest and post-effort. The measured biomarkers were cardiac troponin I (cTnI), myoglobin (Myo), the MB isoenzyme of creatine-kinase (CK-MB), the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and D-dimers. While cTnI and NT-proBNP levels were undetectable both at rest and post-effort in all subjects, the variations in Myo, CK-MB and D-dimers showed significant correlations with CPET parameters. This highlights the potential use of combined CPET and biomarker determinants to evaluate professional athletes, and encourages further research on larger study groups.

Implantable cardioverter defibrillators (ICDs) are the cornerstone of primary and secondary prevention of sudden cardiac death (SCD) all around the globe. In almost 40 years of technological advances and multiple clinical trials, there has been a continuous increase in the implantation rate. The purpose of this review is to highlight the grey areas related to actual ICD recommendations, focusing specifically on the primary prevention of SCD. We will discuss the still-existing controversies strongly reflected in the differences between the international guidelines regarding ICD indication class in non-ischemic cardiomyopathy, and also address the question of early implantation after myocardial infarction in the absence of clear protocols for patients at high risk of life-threatening arrhythmias. Correlating the insufficient data in the literature for 40-day waiting times with the increased risk of SCD in the first month after myocardial infarction, we review the pros and cons of early ICD implantation.

Background: Prevention of sudden cardiac death (SCD) early after acute myocardial infarction (AMI) is still a challenge, without clear recommendations in spite of the high incidence of life-threatening ventricular arrhythmias, as implantable cardiac defibrillator (ICD) placement is not indicated in the first 40 days after an AMI; this timing is aleatory and it is owed to fact that the two pivotal studies for evaluation of ICDs in primary prevention, MADIT and MADIT II, excluded the patients within three, respectively four weeks after AMI., Methods: We conducted a retrospective, single-center study that included 77 patients with AMI. All patients were monitored by continuous ECG in the first week after the event. Transthoracic echocardiography was performed at discharge and 40 days after the event. Patients with ejection fraction of 35% or less as assessed by 2D echocardiography 40 days after the MI, which received an ICD for the primary prevention of SCD, were included in the study. The subjects were followed for a median of 38 months, by means of device interrogation and echocardiography., Results: We divided our patients into two groups: in the first group, with left ventricular ejection fraction (LVEF) under 30% after MI, all patients remained in the reduced ejection fraction heart failure category, with an increase from an initial mean of 18.93 ± 4.99% to a mean of 22.18 ± 4.53% after a period of 40 days; we obtained a positive and statistically significant correlation ( p < 0.001 and r - 0.547), and all patients presented indication of ICD implant 40 day after MI. In the second group with LVEF between 30% and 35% after MI, the mean LVEF increased from an initial mean of 31.73 ± 1.33% to a mean of 32.33 ± 1.49% after a period of 40 days. A statistically significant correlation ( p - 0.02 and r - 0.78) was obtained, although 3 patients presented a LVEF over 35% at 40 days post-MI. Most of the ICD therapies (14.54%) appeared in patients with LVEF < 30% and these patients also presented a higher percentage of NSVT at initial ECG monitoring (54% vs. 50%) and NSVT at ICD interrogation (80% vs. 66.7%); statistical significance was not reached - p > 0.05. The majority of the ICD therapies (11.9% from 13.4%) appeared in patients with NSVT at initial ECG monitoring; also, these presented an increased number of NSVT at ICD interrogation (77.6% vs. 6%) when compared to patients without VT detection at the initial ECG monitoring. Still, statistical significance was not reached - p > 0.15., Conclusions: The patients could benefit from ICD implant earlier than stated in the actual guidelines, since there are insufficient data in the literature for the waiting time of 40 days. Correlated with the increased risk of SCD in the first months post myocardial infarction, the present study proves the benefit of early ICD implantation considering that all our patients with a low ejection fraction immediately after infarction remained in the same category and the great majority (96.1%) required the implantation of an ICD after 40 days. Thus, we could avoid exposing our patients at risk of SCD for an unnecessary prolonged period, and choose early ICD implantation., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Despite progress in understanding the pathogenesis of atherosclerosis, the development of effective therapeutic strategies is a challenging task that requires more research to attain its full potential. This review discusses current pharmacotherapy in atherosclerosis and explores the potential of some important emerging therapies (antibody-based therapeutics, cytokine-targeting therapy, antisense oligonucleotides, photodynamic therapy and theranostics) in terms of clinical translation. A chemopreventive approach based on modern research of plant-derived products is also presented. Future perspectives on preventive and therapeutic management of atherosclerosis and the design of tailored treatments are outlined.

Background: The present study aimed to investigate the association of obesity phenotypes and quality of life (QoL) scales and their relationship with fat mass (FM) parameters., Methods: This study categorized 104 subjects into 4 obesity phenotypes based on BMI and metabolic syndrome status: metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), metabolically healthy non-obese (MHNO), and metabolically unhealthy non-obese (MUNO). Body composition was measured by dual-energy X-ray absorptiometry (DEXA) and metabolic profile was characterized by blood samples. All subjects completed the SF-36 item Short Form Health Survey Questionnaire., Results: Comparing the four obesity phenotypes, significant results were reported for Bodily Pain between MHNO/MUNO ( p = 0.034), for Vitality between MHO/MUO ( p = 0.024), and for Mental Component Score between MHO/MUO ( p = 0.026) and MUO/MUNO ( p = 0.003). A more thorough inside-groups analysis yielded a positive and moderate to high correlation between FM parameters and QoL scales in MHO and MHNO, while a negative and weak to moderate correlation was observed in MUO and MUNO., Conclusion: This study reported an inverse U-shaped relationship between FM and QoL in obesity phenotypes, suggesting that metabolic status is a key factor involved in modulating QoL and therefore challenging the idea of obesity as a main driver of low QoL. We recommend the inclusion of FM percentage in the definition of obesity phenotypes in future research, to better evaluate QoL of obesity phenotypes.

Cardiovascular disease in hemophiliacs has an increasing prevalence due to the aging of this population. Hemophiliacs are perceived as having a high bleeding risk due to the coagulation factor VIII/IX deficiency, but it is currently acknowledged that they also have an important ischemic risk. The treatment of atrial fibrillation (AF) is particularly challenging since it usually requires anticoagulant treatment. The CHA 2 DS 2 -VASc score is used to estimate the risk of stroke and peripheral embolism, and along with the severity of hemophilia, guide the therapeutic strategy. Our work provides the most complete, structured, and updated analysis of the current therapeutic approach of AF in hemophiliacs, emphasizing that there is a growing interest in therapeutic strategies that allow for short-term anticoagulant therapy. Catheter ablation and left atrial appendage occlusion have proven to be efficient and safe procedures in hemophiliacs, if appropriate replacement therapy can be provided.

(1) Background: There are limited clinical data in patients from the Eastern European regions hospitalized for a severe form of Coronavirus disease 2019 (COVID-19). This study aims to identify risk factors associated with intra-hospital mortality in patients with COVID-19 severe pneumonia admitted to a tertiary center in Iasi, Romania. (2) Methods: The study is of a unicentric retrospective observational type and includes 150 patients with severe COVID-19 pneumonia divided into two subgroups, survivors and non-survivors. Demographic and clinical parameters, as well as comorbidities, laboratory and imaging investigations upon admission, treatments, and evolution during hospitalization were recorded. First, we sought to identify the risk factors associated with intra-hospital mortality using logistic regression. Secondly, we assessed the correlations between D-Dimer and C-reactive protein and predictors of poor prognosis. (3) Results: The predictors of in-hospital mortality identified in the study are D-dimers >0.5 mg/L ( p = 0.002), C-reactive protein >5 mg/L ( p = 0.001), and heart rate above 100 beats per minute ( p = 0.001). The biomarkers were also significantly correlated the need for mechanical ventilation, admission to intensive care unit, or multiple organ dysfunction syndrome. By area under the curve (AUC) analysis, we noticed that both D-Dimer (AUC 0.741) and C-reactive protein (AUC 0.707) exhibit adequate performance in predicting a poor prognosis in patients with severe viral infection. (4) Conclusions: COVID-19's outcome is significantly influenced by several laboratory and clinical factors. As mortality induced by severe COVID-19 pneumonia is considerable, the identification of risk factors associated with negative outcome coupled with an early therapeutic approach are of paramount importance, as they may significantly improve the outcome and survival rates.

Background : Heart failure (HF) is a complex clinical syndrome that represents a great burden on public health systems due to its increased prevalence, disability and mortality rates. There are multiple triggers that can induce or aggravate a preexisting HF, socioeconomic status (SES) emerging as one of the most common modifiable risk factors. Our study aimed to analyze the influence of certain SES indicators on the outcome, clinical aspects and laboratory parameters of patients with HF in North-Eastern Romania, as well as their relationship with other traditional cardiovascular risk factors. Methods : We conducted a prospective, single-center study comprising 120 consecutively enrolled patients admitted for acute HF. The evaluation of individual SES was based upon a standard questionnaire and evidence from official documents. Results : the patients' age ranged between 18 and 94 years; Out of 120 patients, 49 (40.8%) were women and 71 (59.2%) were men, residing in rural 59 (49.2%) or urban 61 (50.8%) areas. 14.2% were university graduates, while 15.8% had only attended primary school. The majority of the patients are or were employed in the service sector (54.5%), followed by industry (29.2%) and agriculture (20%). The mean monthly income was 306.1 ± 177.4 euro, while the mean hospitalization cost was 2471.8 ± 2073.8 euro per patient. The individual income level was positively correlated with urban area of residence, adequate household sanitation facilities and healthcare access, and negatively associated with advanced age and previous hospitalizations due to HF. However, the individual financial situation was also positively correlated with the increased prevalence of certain cardiovascular risk factors, such as arterial hypertension, anemia or obesity, but not with total cholesterol or male gender. Concerning the direct impact of a poor economic status upon prognosis in the setting of acute HF, our results showed no statistically significant differences concerning the in-hospital or at 1-month follow-up mortality rates. Rather than inducing a direct impact on the short-term outcome, these findings concerning SES indicators are meant to enhance the implementation of policies aimed to provide adequate healthcare for people from all social layers, with a primary focus on modifiable cardiovascular risk factors.

(1) Background: In patients suffering from heart failure, the main causes of death are either hemodynamic failure, or ventricular arrhythmias. The only tool to significantly reduce arrhythmic sudden death is the implantable cardioverter defibrillator (ICD), but not all patients benefit to the same extent from these devices. (2) Methods: The primary outcome of this single-center study was defined as cardiovascular death in patients with ischemic and non-ischemic heart failure who have benefited from ICD therapy. The secondary outcomes were death from any cause, sudden cardiac death, ICD-related therapies (appropriate antitachycardia pacing or shock therapy for ventricular tachycardia or fibrillation) and recurrences of ventricular tachyarrhythmias. (3) Results: A total of 403 consecutive ICD recipients-symptomatic heart failure patients with ICD for the primary prevention of sudden cardiac death-were included retrospectively: 59% ischemic cardiomyopathy (ICMP) and 41% non-ischemic cardiomyopathy (NICMP) patients. Within a median follow-up period of 36 months, the incidence of cardiovascular mortality was not significantly different in patients with NICMP and ICMP: the primary outcome had occurred in 9 patients (5.4%) in the NICMP group and in 14 patients (5.9%) in the ICMP group (hazard ratio 1; 95% confidence interval (CI) 0.45 to 2.28; p = 0.97). All-cause mortality occurred in 14 of 166 patients (8.4%) in the NICMP group and 18 of 237 patients (7.6%) in the ICMP group. Sudden cardiac death occurred in two patients (1.2%) in the NICMP group and in four patients (1.7%) in the ICMP group (hazard ratio 0.71; 95% CI, 0.13 to 3.88; p = 0.69). The rate of appropriate device therapies was comparable in both groups. (4) Conclusions: In this study, ICD implantation for primary prevention of sudden cardiac death in patients with symptomatic systolic heart failure was associated with similar rates of cardiovascular and all-cause mortality in patients with ischemic heart disease, and in patients with heart failure from other causes. NICMP and ICMP showed comparable rates of recurrent ventricular tachyarrhythmias and appropriate ICD therapies.

The research of biomarkers continues to emerge as a developing academic field which is attracting substantial interest. The study of biomarkers proves to be useful in developing and implementing new screening methods for a wide variety of diseases including in the sports area, whether for leisure activities or professional sports. Novel research has brought into question the immune system and the limitations it may impose on sports practicing. As the well-being of athletes is a priority, the state of their immune function offers valuable information regarding their health status and their ability to continue training. The assessment of various biomarkers may contribute to a more accurate risk stratification and subsequent prevention of some invalidating or even fatal pathologies such as the sudden cardiac death. Therefore, we have reviewed several studies that included sports-related pathology or specific morphofunctional alterations for which some immune biomarkers may represent an expression of the underlying mechanism. These include the defensins, immunoglobulin A (IgA), interleukin-6 (IL-6), the tumoral necrosis factor α (TNF-α), and the white blood cells (WBC) count. Similarly, also of significant interest are various endocrine biomarkers, such as cortisol and testosterone, as well as anabolic or catabolic markers, respectively. Literature data highlight that these values are greatly influenced not only by the duration, but also by the intensity of the physical exercise; moderate training sessions actually enhance the immune function of the body, while a significant increase in both duration and intensity of sports activity acts as a deleterious factor. Therefore, in this paper we aim to highlight the importance of biomarkers' evaluation in connection with sports activities and a subsequent more adequate approach towards personalized training regimens.

Biomarkers are important diagnostic and prognostic tools as they provide results in a short time while still being an inexpensive, reproducible and accessible method. Their well-known benefits have placed them at the forefront of research in recent years, with new and innovative discoveries being implemented. Cardiovascular and neurological diseases often share common risk factors and pathological pathways which may play an important role in the use and interpretation of biomarkers' values. Among the biomarkers used extensively in clinical practice in cardiology, hs-TroponinT, CK-MB and NTproBNP have been shown to be strongly influenced by multiple neurological conditions. Newer ones such as galectin-3, lysophosphatidylcholine, copeptin, sST2, S100B, myeloperoxidase and GDF-15 have been extensively studied in recent years as alternatives with an increased sensitivity for cardiovascular diseases, but also with significant results in the field of neurology. Thus, given their low specificity, the values interpretation must be correlated with the clinical judgment and other available investigations.

Background: Acute heart failure (HF) represents an increasingly common and challenging presentation in the emergency room, also inducing a great socio-economic burden. Extensive research was conducted toward finding an ideal biomarker of acute HF, both in terms of sensitivity and specificity, but today practicians' interest has shifted towards a more realistic multimarker approach. Natriuretic peptides (NPs) currently represent the gold standard for diagnosing HF in routine clinical practice, but novel molecules, such as sST2, emerge as potentially useful biomarkers, providing additional diagnostic and prognostic value., Methods: We conducted a prospective, single-center study that included 120 patients with acute HF and 53 controls with chronic HF. Of these, 13 patients (eight with acute HF, five from the control group) associated the coronavirus-19 disease (COVID-19). The diagnosis of HF was confirmed by a complete clinical, biological and echocardiographic approach., Results: The serum levels of all studied biomarkers (sST2, NT-proBNP, cardiac troponin) were significantly higher in the group with acute HF. By area under the curve (AUC) analysis, we noticed that NT-proBNP (AUC: 0.976) still had the best diagnostic performance, closely followed by sST2 (AUC: 0.889). However, sST2 was a significantly better predictor of fatal events, showing positive correlations for both in-hospital and at 1-month mortality rates. Moreover, sST2 was also associated with other markers of poor prognosis, such as the use of inotropes or high lactate levels, but not with left ventricle ejection fraction, age, body mass index or mean arterial pressure. sST2 levels were higher in patients with a positive history of COVID-19 as compared with non-COVID-19 patients, but the differences were statistically significant only within the control group. Bivariate regression showed a positive and linear relationship between NT-proBNP and sST2 ( r (120) = 0.20, p < 0.002)., Conclusions: we consider that sST2 has certain qualities worth integrating in a future multimarker test kit alongside traditional biomarkers, as it provides similar diagnostic value as NT-proBNP, but is emerging as a more valuable prognostic factor, with a better predictive value of fatal events in patients with acute HF.

The incidence of urinary tract infections (UTIs) caused by Klebsiella pneumoniae has exhibited an increasing trend and has become a high burden for many public health systems, especially in hospital settings. Multidrug resistance associated with the production of extended-spectrum β-lactamases (ESBL) among K. pneumoniae isolates is endemic in Southeastern Europe. We retrospectively analyzed 75 cases admitted to 'St. Parascheva' Clinical Hospital of Infectious Diseases in Iasi, Romania, during the first 6 months of 2019 (January 1 to June 30), who had a confirmed diagnosis of K. pneumoniae UTI at discharge. From a total of 75 patients, 34 (45.3%) presented ESBL + K. pneumoniae. The mean age was 66 years (70.1 for the ESBL + patients vs. 62.6 for the ESBL - patients, P=0.0365). There was a symmetrical sex distribution (37 men vs . 38 women). Of these, 22 men had ESBL + K. pneumoniae UTIs, compared to only 15 with an ESBL - strain, P=0.0087. Another risk factor for ESBL + K. pneumoniae UTIs was the presence of hospitalization in the past 6 months; 20 (58.82%) patients with ESBL + infections were previously hospitalized, compared to only 5 (12.19%) patients with ESBL - strains, P<0.0001. The urinary catheter carriers presented an increased prevalence of ESBL + infections (15/34 vs. 5/41, P=0.0012). Regarding mortality, ESBL + infections caused 6 fatalities, compared to only 1 death in the ESBL - group, P=0.0166. ESBL + K. pneumoniae strains represent an important cause of healthcare-related UTIs, with a significantly higher mortality rate compared to ESBL - strains. Early identification and adequate management of the risk factors incriminated in ESBL + UTIs should be a priority for physicians in order to limit the dissemination of the ESBL-producing strains and thus to improve the outcome of these patients., Competing Interests: There are no competing interests regarding the authors of this research., (Copyright: © Miftode et al.)

The present study aimed to explore the correlations between clinical, biological, imagistic and procedural factors with the risk of intra-stent restenosis (ISR) in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI). An observational cross-sectional study was conducted in a high-volume PCI center over a period of 2 years. A total of 235 consecutive patients diagnosed with angina or acute coronary syndrome treated by PCI were included in the study. Diagnosis of ISR was documented by coronary angiography in patients with suggestive coronary symptoms and ischemic changes in non-invasive or invasive paraclinical investigations. Thus, they were assigned to two groups: With or without ISR. All patients underwent clinical and laboratory examination, providing clinical and paraclinical variables that could be considered risk factors for ISR. Current smokers [risk ratio (RR)=1.63; 95% confidence interval (95% CI): 1.25-2.13], arterial hypertension (RR=1.86; 95% CI: 1.41-2.45), diabetes (RR=1.83; 95% CI: 1.42-2.36), high C-reactive protein (CRP) levels (RR=1.44; 95% CI: 0.93-2.24), chronic kidney disease (CKD) (RR=1.90; 95% CI: 1.53-2.36) and thrombolysis in myocardial infarction (TIMI) score were found to have a significant role in estimating the risk for ISR. Moreover, the ISR group (119 patients) presented with a lower stent inflation pressure when compared to the control group (116 patients) (14.47 vs. 16.14 mmHg, P=0.004). An increased mean stent diameter used for PCI was not associated with a high ISR incidence (P=0.810) as well as complex coronary treated lesions with longer stents (mean length of 24.98 mm in patients without ISR vs. 25.22 mm in patients with ISR; P=0.311). There was an estimated two times higher risk (RR=2.13; 95% CI: 1.17-3.88) concerning multi-stenting and restenosis degree >70%. To conclude, smoking, hypertension, diabetes mellitus, high CRP levels, CKD, TIMI score, stent type, low pressure for stent implantation and multi-stenting were found to be associated with ISR in patients following PCI. Therefore, a close follow-up should be targeted in such patients., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Alexandrescu et al.)

Objective: This study aimed to identify possible differences between blood culture-negative and blood culture-positive groups of infective endocarditis (IE), and explore the associations between biological parameters and in-hospital mortality., Methods: This was a retrospective study of patients hospitalized for IE between 2007 and 2017. Epidemiological, clinical and paraclinical characteristics, by blood culture-negative and positive groups, were collected. The best predictors of in-hospital mortality based on the receiver-operating characteristic (ROC) analysis and AUC (area under the curve) results were identified., Results: A total of 126 IE patients were included, 54% with negative blood cultures at admission. Overall, the in-hospital mortality was 28.6%, higher in the blood culture-negative than positive group (17.5% vs. 11.1%, p = 0.207). A significant increase in the Model for End-Stage Liver Disease Excluding International Normalized Ratio (MELD-XI) score was observed in the blood culture-negative group ( p = 0.004), but no baseline characteristics differed between the groups. The best laboratory predictors of in-hospital death in the total study group were the neutrophil count (AUC = 0.824), white blood cell count (AUC = 0.724) and MELD-XI score (AUC = 0.700)., Conclusion: Classic laboratory parameters, such as the white blood cell count and neutrophil count, were associated with in-hospital mortality in infective endocarditis. In addition, MELD-XI was a good predictor of in-hospital death.