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Hypoglycemic medications are widely used in managing diabetes mellitus, with emerging evidence suggesting their role in cardiac reverse remodeling. This systematic review aims to quantitatively synthesize data regarding the impact of these medications on left ventricular end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD), and to evaluate the clinical relevance of these changes in promoting favorable cardiac outcomes. We conducted a comprehensive search across PubMed, Scopus, and the Web of Science up to 22 April 2024, selecting studies based on inclusion criteria that focused on the impact of hypoglycemic medications on LVEDD and LVESD in patients with diabetes. Studies were selected through a rigorous process, adhering to PRISMA guidelines, and involving various designs including randomized controlled trials and observational studies. The main outcomes were changes in LVEDD and LVESD measured by validated cardiac imaging techniques. A total of ten studies met the inclusion criteria, involving a total of 1180 patients. Treatment durations ranged from 3 to 24 months. Significant improvements in cardiac dimensions were noted with some medications. For instance, Liraglutide treatment over three months significantly improved LVEF from 47.2% to 57.2% and reduced LVEDD and LVESD from 46.5 mm to 45.2 mm and 35.2 mm to 32.7 mm, respectively. In contrast, other medications like Sitagliptin showed minimal impact over 24 months. On average, hypoglycemic medications reduced LVEDD from 58.2 mm to 55.0 mm and LVESD from 48.3 mm to 44.3 mm, with a mean improvement in LVEF from 38.9% to 43.8%. Hypoglycemic medications contribute variably to cardiac reverse remodeling. Medications such as Liraglutide and Dapagliflozin demonstrate significant potential in improving cardiac dimensions and function, indicating their utility beyond glycemic control. This review highlights the need for tailored treatment approaches to maximize cardiac outcomes in patients with diabetes, suggesting a broader therapeutic role for these agents.

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.

This review aims to explore the intricate relationship among epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorder occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes, such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay among genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

Purpose: The objective of this research was to determine if there is any correlation between the severity of neurocognitive disorder and hearing impairment in the elderly., Patients and Methods: This is a population-based observational study that included subjects aged ≥ 65 years. They were evaluated for the existence of cardiovascular risk factors, diabetes, stroke, alcohol abuse, and smoking. Hearing impairment was diagnosed by an audiologist, using behavioral audiometric examination. These evaluations might have been performed in response to concerns about hearing loss, or they could have been a routine component of yearly comprehensive health screenings that included a Mini-Mental State Examination 2nd Edition (MMSE-2) test. According to the results of the MMSE-2 scale, we divided the individuals into two groups, Group I for those who had cognitive impairment and severe neurocognitive disorder, and Group II for those who did not have cognitive impairment., Results: The study enrolled 203 patients with a mean age of 77 ± 7.5 years (range 65-98), 99 (48%) were males. When comparing the two groups, group I patients presented more often cardiovascular risk factors, stroke, diabetes, and impaired hearing. The univariable logistic regression found that cognitive impairment was significantly more frequent in the elderly with cardiovascular disease, diabetes, and stroke (p<0.0001). The multivariate regression analysis found that stroke (p<0.0001) diabetes (p=0.0008), cardiovascular disease (p=0.0004), and impaired hearing (p=0.0011) were significantly linked to cognitive impairment. The occurrence of hearing impairment in the elderly was related to having an MMSE-2 score of 14 or below., Conclusion: According to the findings of this research, the elderly who have trouble hearing in addition to other conditions might have an increased risk for severe neurocognitive disorder., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Arnautu et al.)

The goal of this study was to assess whether subtle changes in myocardial work indices may predict left ventricular (LV) remodeling and major cardiac events (MACEs) in patients with a first ST-elevation acute myocardial infarction (STEMI) and preserved LVEF after successful myocardial revascularization with PCI. Methods. Consecutive STEMI patients in sinus rhythm and with an LV ejection fraction ≥ 50% following a successful PCI were recruited. Conventional and two-dimensional speckle tracking echocardiography (2D-STE) was conducted within 36 h of the PCI and 3 months later. Patients having an increase of more than 20% in LV diastolic volume were included in the LV remodeling group. MACEs were noted throughout a four-year period of follow-up. Results: The study comprised 246 STEMI patients with a mean age of 66; 72% of whom were men. In 24% (58) of the patients, LV remodeling developed. These patients were older, more frequently hypertensive, and had a smoking history. They also exhibited significantly lower baseline and 3-month values for the myocardial global index (GWI), global constructive work (GCW), and global myocardial efficiency (GWE). The cut-off values of 1670 mmHg% for GWI and 83% for GWE were predictive of LV remodeling ( p < 0.0001). During the four-year follow-up period, 19% of STEMI patients experienced a MACE, involving 15% from non-LV remodelers and 34% from LV remodelers ( p = 0.01). The cut-off values for baseline GWI of 1680 mmHg% and baseline GWE of 84% had the best accuracy in predicting MACEs. In conclusion, non-invasive myocardial work indices offered a reproducible and accurate method to predict post-MI LV remodeling and MACEs.

Purpose: Atrial fibrillation (AF) and diabetes mellitus (DM) are common pathogenic diseases. Diabetes is an independent risk factor for AF, and coexisting AF is a risk factor for the diabetic pa-tient's progression. The purpose of this study was to see if two-dimensional-speckle tracking echocardiography (2D-STE) might provide valuable criteria for determining the risk of AF in diabetic patients., Patients and Methods: This retrospective study compared 30 adult diabetic patients with documented paroxysmal atrial fibrillation (PAF) with 30 age- and sex-matched diabetic patients without PAF. Inclusion criteria were: age ≥18 years, sinus rhythm, diabetes mellitus type 2, and the ability to sign the informed consent. Exclusion criteria included: moderate or severe valvular disease, previous myocardial infarction, left ventricular ejection fraction (LVEF) <50%, congenital heart disease, a history of cardiac surgery, paced atrial or ventricular rhythm, inadequate echocardiography imaging. The medical history, clinical, biochemical data and the results of the transthoracic cardiac ultrasound examination were registered during their evaluation at the outpatients cardiology clinics., Results: The mean age of the patients was 62.5±1.7 years, 60% were men. Diabetic patients who experienced PAF episodes demonstrated significantly impaired left atrial (LA) deformation patterns, with decreased LA strains and increased LA stiffness (p < 0.05)., Conclusion: The present study demonstrates that LA strains and LA stiffness are significantly associated with the occurrence of PAF in diabetic patients. As 2D-STE of the LA is more sensitive than routine echocardiographic examination, it should be performed in patients suspected of being suffering from PAF., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Arnautu et al.)

Background: While lifestyle changes, management of coronary artery disease (CAD) risk factors, myocardial revascularization procedures, and medication can improve a patient's prognosis, de novo native coronary lesions and in-stent restenosis (ISR) remain significant clinical concerns. ISR is more frequent with a bare-metal stent than with a drug-eluting stent and has been documented in around 12% of DES patients. Acute coronary syndrome (ACS) manifests as unstable angina in about 30% to 60% of ISR patients. Myocardial work imaging is a modern, non-invasive technique able to identify individuals with critical coronary artery lesions with high sensitivity and specificity., Case Report: We present the case of a 72-year-old Caucasian gentleman with multiple cardiovascular risk factors, admitted to the Cardiology Clinic of Timișoara Municipal Hospital with unstable angina. From 1999 to 2021, the patient experienced two myocardial infarctions, a double aortocoronary bypass graft, and multiple percutaneous coronary interventions with 11 stent implantations, including 6 for ISR. Using two-dimensional speckle-tracking echocardiography and myocardial work assessment, we detected that the lateral wall of the left ventricle had a severely impaired deformation pattern. Angio-coronarography was performed, and sub-occlusion of the posterolateral branch of the right coronary artery was found. Angioplasty was performed and a DES was inserted, with a good final angiographic result and complete release of symptoms., Conclusion: In patients with a history of multiple myocardial revascularization interventions and ISR, it is challenging to identify the critical ischemia region by non-invasive methods. Myocardial work imaging was beneficial in the detection of the altered deformation patterns indicating significant ischemia, its accuracy being superior to that of LV strain, as proven by coronary angiography. Urgent coronary angiography followed by angioplasty and stent implantation resolved the issue.

Background and Objectives : Falls are frequent among the elderly, imply large social and economic costs, and have serious outcomes. The purpose of this study was to investigate the links between insomnia, comorbidities, multisite pain, physical activity, and fall risk in the elderly. Materials and Methods : This retrospective cross-sectional study included persons recruited from nursing homes for the elderly in Timisoara. We separated the participants into two groups by the absence (group I) or presence of fractures (group II) starting with the age of 65 years. Participants were asked how they feel about their sleep using one item on a 4-point scale from the Assessment of Quality of Life questionnaire. The risk of fall was evaluated using the Falls Risk Assessment Tool. Results : The study enrolled 140 patients with a mean age of 78.4 ± 2.4 years (range 65-98 years), 55 of them being males (39%). By comparing the two groups, we found that the elderly with a history of fractures had a greater number of comorbidities, a higher risk of fall, and more severe sleep disturbances. When using univariate logistic regression, the occurrence of fractures in the elderly was significantly associated with the number of comorbidities, the risk of fall, and the presence of sleep disturbances ( p < 0.0001). The multivariate regression analysis selected four independent parameters significantly linked to fractures, and these were the number of comorbidities ( p < 0.03), the risk of fall score ( p < 0.006), and the sleep disturbances of type 3 ( p < 0.003) and 4 ( p = 0.001). Conclusions : A fall-risk score over 14 and a number of comorbidities over 2 were notably associated with the occurrence of fractures. We also found strong positive correlations between the type of sleep disturbance and the risk of fall score, the number of comorbidities, and the number of fractures in the elderly.

Background and Objectives: Diabetes mellitus (DM) is connected to both cardiovascular disease and non-alcoholic fatty liver disease (NAFLD), and is an important component of metabolic syndrome (MetS). NAFLD can be detected and quantified using the vibration controlled transient elastography (VCTE) and the controlled attenuation parameter (CAP), whereas traditional and two-dimensional speckle tracking echocardiography (2D-STE) can reveal subclinical abnormalities in heart function. We sought to see if there was a link between left cardiac dysfunction and different levels of hepatic fibrosis in MetS patients with DM and NAFLD. Patients and Methods: We recruited successive adult subjects with MetS and a normal left ventricular ejection fraction, who were divided into two groups according to the presence or absence of DM. The presence of NAFLD was established by CAP and VCTE, while conventional and 2D-STE were used to assess left heart's systolic and diastolic function. The mean age of the MetS subjects was 62 ± 10 years, 82 (55%) were men. The distribution of liver steatosis severity was similar among diabetics and non-diabetics, while liver fibrosis grade 2 and 3 was significantly more frequent in diabetics ( p = 0.02, respectively p = 0.001). LV diastolic dysfunction was found in 52% of diabetic and in 36% of non-diabetic MetS patients ( p = 0.04). 2D-STE identified in the diabetic subjects increased LA stiffness (40% versus 24%, p = 0.03) and reduced global left ventricular longitudinal strain (47% versus 16%, p < 0.0001). Liver fibrosis grade ≥ 2 was identified as an independent predictor of both subclinical LV systolic dysfunction and of LA dysfunction in MetS patients with DM ( p < 0.0001). Conclusions: The current investigation confirms the link between liver stiffness and subclinical cardiac dysfunction as detected by 2D-STE in MetS patients with DM. The novel parameters derived from LA and LV 2D-STE have demonstrated greater sensitivity compared to the older measurements, and a substantial connection with hepatic fibrosis., Competing Interests: The authors declare no conflict of interest.

Betulinic acid, a small molecule from pentacyclic triterpenes class, has been widely studied for its antitumor activity, revealing that it induces the apoptosis of tumor cells in a selective manner. In recent years, digoxin, a cardiac glycoside found particularly in the plant species Digitalis lanata , has drawn interest for its potential antitumor properties. The present study was designed to evaluate the antimelanoma potential of betulinic acid (BA), digoxin (DG), and their association (DG + BA). In vitro assessments were performed 24 h post-treatment on two human melanoma cell lines (SK-Mel-28 and RPMI-7951). In addition, the potential irritant effects of the test samples were evaluated using the chorioallantoic membrane of hen's eggs. BA and DG exhibit a concentration-dependent cytotoxic activity, with the combination of the two having a more marked effect on the decrease in cell viability (~17% for SK-Mel-28 cells and ~23% for RPMI-7951 cells). Further, morphological changes (rounding of the cells and their separation from the plaque) and alterations in the nucleus and actin fibers (condensation of chromatin and actin fibers, formation of apoptotic bodies) were observed, indicating an apoptotic-like process. Moreover, no irritating effects were observed in ovo. As a result, DG + BA acid may have synergistic potential in the antitumor treatment of melanoma, but future studies are needed in order to clarify the biological mechanisms involved.

(1) Acute myocardial infarction (AMI) patients are at risk of left ventricular (LV) remodeling and heart failure (HF), even after successful revascularization by percutaneous coronary intervention (PCI). We wanted to assess the independent predictors of these outcomes in AMI patients. (2) Methods: The study enrolled patients with a LVEF ≥50% after a successful PCI for their first AMI. After 24 months, patients were separated into two groups based on whether their LVEF remained ≥50% (group I), or decreased to <50% (group II). (3) Outcomes: 26% of the patients experienced a decrease in LVEF below 50%, 41% showed LV remodeling, and 8% had experienced HF hospitalizations. HF hospitalizations were significantly more frequent in group II patients (p < 0.0001). The Killip class at admission >2, infarct-related longitudinal strain ≤−12.5%, and the presence of LV remodeling were identified as independent predictors of HF hospitalizations. (4) Conclusions: About 26% of AMI patients with normal LV function after a successful PCI developed HF. More sensitive techniques are required that allow for a more efficient risk-stratification and preventive therapy to reduce LV remodeling and HF in AMI patients with LVEF ≥50% after a successful PCI. The detection of abnormal ventricular deformation patterns after PCI by speckle-tracking echocardiography might be a valuable method in this approach.

Objective: We aimed to conduct a review of the literature relevant to cardiac imaging techniques and summarize the use of different non-invasive imaging modalities in the assessment of ventricular size, function, and mechanics. The current review emphasizes the benefits of speckle tracking imaging (STI), highlighting its use in demonstrating myocardial strain. This robust technique is a recent addition to the existing imaging techniques that are used to assess the myocardium. In terms of effectively determining the left ventricle ejection fraction, it is a comparable technique to cardiac magnetic resonance. The use of STI method for image acquisition relies on semiautomatic identification of the border and deformation of the region of interest, and is also independent of the angle of insonation, thus it increases the inter-and intra-observer reproducibility in contrast to the conventional tissue doppler imaging., Materials and Methods: The databases of PubMed, Scopus, and Embase were thoroughly searched for the following keywords: 2- dimensional/ two-dimensional/ 2-D, speckle/strain tracking, systolic dysfunction, and heart failure. The studies selected described image acquisition techniques and the application of this imaging modality in various clinical settings. The selected journal articles were perused to provide the best possible analysis of STI., Results: Our comparative analysis demonstrated that the STI, when compared with the conventional echocardiography, is a more sensitive image acquiring technique for detecting subclinical myocardial dysfunction. Based on the analysis it can be stated that the STI can provide valuable information on both regional and global myocardial function, and it can also quantify cardiac synchronicity and rotation. Additionally, it serves as a better prognostic indicator., Conclusions: The change in longitudinal strain can serve as an early marker of the left ventricular systolic dysfunction, and therefore, monitoring via STI has both diagnostic and prognostic value in heart failure, ischemic heart disease, valvulopathies, chemotherapy-induced cardiotoxicity, and cardiac resynchronization therapy. Despite the lack of standardization, the method is also effective in assessing the right ventricle and left atrial function and arterial rigidity.

Purpose: The goal of this study is to see if carotid strain and strain rate can predict major cardio-vascular events (MACE) in people who have metabolic syndrome (MS) over a 3-year period of time., Methods: In this prospective observational research, we enrolled 220 adult MS patients (60.7 ± 7.5 years old, 53% male). Two-dimensional common carotid carotid artery (CCA) speckle-tracking ultrasound was used to determine the peak circumferential strain (CS) and the peak circumferential strain rate (CSR). Clinical outcomes were assessed throughout a three-year follow-up period., Results: After a 3-year follow-up period follow-up, 14 (7%) experienced MACE: Eight (4%) suffered an atherothrombotic ischemic stroke, four (2%) had acute coronary syndrome, and two (1%) were hospitalized for heart failure. Univariate regression analysis of the clinical and echocardiographic features of the MS patients found that age, systemic hypertension, diabetes mellitus, and the CCA circumferential strain and strain rate were significantly associated with the risk of MACE. Multivariate logistic regression identified two independent predictors of MACE in patients with MS, namely the CCA-related CS (%) and CSR (1/s), p < 0.01. The Receiver operating characteristic (ROC) curve analyses of these independent predictors of MACE indicated appropriate sensitivities and specificities. CS (AUC = 0.806, sensitivity = 82.6%, specificity = 79.2%, p < 0.0001) and CSR (AUC = 0.779, sensitivity = 82.6%, specificity = 72.4%, p < 0.0001) with cut-off values of ≤ 2.9% for carotid CS and ≤ 0.35 s - 1 for carotid CSR. Using these cut-off values, we obtained Kaplan-Meier survival curves, and these showed that MACE, ischemic stroke, and ACS-free survival was significantly lower among the MS patients with lower carotid CS and CSR ( p < 0.0001)., Conclusions: Carotid CS and CSR were independent predictors of major cardio- and cerebro-vascular events in prospectively monitored MS patients without established cardiovascular disease. Carotid deformation could be valuable as an early prognostic indicator for the cardiovascular risk in this population group., Competing Interests: The author reports no conflicts of interest in this work., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Purpose: Patients with transient ischemic attacks often present asymptomatic and paroxysmal atrial fibrillation. Since atrial fibrillation initiates in the atria, we aimed to identify whether the abnormalities in left atrial structure and function could identify the cardioembolic etiology of the transient ischemic attacks in patients at sinus rhythm., Patients and Methods: A total of 190 patients over 50 years old with sinus rhythm discharged after a transient ischemic attack were included in the study and divided into two groups according to the presence (group I) or absence (group II) of documented paroxysmal atrial fibrillation. The documentation of paroxysmal atrial fibrillation was based on the examination of medical registers. Cardiac ultrasound assessment was performed at a minimum of 14 days after the onset of the transient ischemic attack, to avoid assessment of atrial stunning., Results: The group I patients were older, more frequent women, with a history of stroke or transient ischemic attack and a higher CHA2DS2-VASc score. They also presented larger left atrial volumes, lower left atrial emptying fraction, and significantly impaired left atrial deformation patterns. Multivariate logistic regression identified three variables that were independently associated with paroxysmal atrial fibrillation: age, left atrial reservoir strain, and left atrial emptying fraction (P < 0.0001). The cut-off levels for the variables were age > 55 years, reservoir strain < -17%, and emptying fraction < 51%., Conclusion: The present study demonstrates that the LA strain is independently associated with paroxysmal atrial fibrillation in transient ischemic attack patients and might be of great help in identifying their cardioembolic etiology and preventing subsequent strokes by the initiation of anticoagulant therapy., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Arnăutu et al.)

Older age is known as a negative prognostic parameter in patients with acute myocardial infarction (AMI). In this study, we aimed to investigate age-related differences in treatment protocols, in-hospital and 1-year mortality. This retrospective observational single-center study enrolled consecutive AMI patients with an urgent percutaneous coronary intervention (PCI) as the main method of myocardial revascularization. The patients divided were divided by age into group I (≥65 years) and group II (<65 years). The primary endpoint was in-hospital mortality, the secondary endpoints were 1-year mortality and rehospitalization rates. Of the 522 admitted with AMI, 476 were enrolled in the study. The mean age was 67 ± 13 years; 62% were men. Group I patients had a significantly lower rate of performed PCI (65% vs. 79%, P < 0.001). 53 patients (12.3%) died during hospitalization, and this proportion was notably higher in the older population (20% vs. 6%, P < 0.0001). The cardiac causes of death were more frequent in group I patients (12% vs. 5.6%, P = 0.016). The multivariate logistic regression selected two variables as independent predictors for the risk of in-hospital death: age ≥65 years ( P = 0.0170), and Killip class at admission ( P < 0.0001). The 1-year mortality was 3.3%, slightly higher in group I patients (4.8% vs. 1.5%, P = 0.05). In conclusion, patients aged ≥65 years have three times higher in-hospital mortality, but similar 1-year mortality and readmission rates when compared with the younger patients. It is obvious that there is a large potential for improvement of the AMI care in this age group of patients., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

Older age is known as a negative prognostic parameter in acute myocardial infarction (AMI) patients. In this study, we aimed to explore age-associated differences in treatment protocols, in-hospital and 1-year mortality. This cohort observational study included 277 consecutive AMI patients, separated into 2 groups according to whether their age was ≥80 years or not. We found that group I patients (aged ≥80 years) had a notably lower rate of percutaneous coronary intervention (PCI) performed ( P < 0.0001) and a notably higher in-hospital death rate ( P < 0.003). The multivariate logistic regression analysis found that three variables were independent predictors of in-hospital mortality: age ≥80 years ( P < 0.0001), LVEF <40% ( P < 0.0001), and Killip class ≥3 ( P < 0.0001). The 1-year death rate was again significantly higher in group I patients ( P < 0.001) and was independently predicted by the triple-vessel coronary artery disease ( P = 0.004) and an LVEF <40% at admission ( P = 0.001). The 1-year readmission rate was superior in group I ( P < 0.01) and independently predicted by an age ≥80 years ( P < 0.001), and an history of congestive heart failure ( P < 0.0001) or permanent atrial fibrillation ( P < 0.001). We concluded that patients aged ≥80 benefit less often from a PCI and have higher rates of in-hospital mortality, as well as of 1-year readmission and mortality rates., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

Purpose: The constitutive elements of the metabolic syndrome (MetS) are linked with both non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. Controlled attenuation parameter (CAP), and vibration controlled transient elastography (VCTE), are able to detect and quantify NAFLD, while conventional and two-dimensional speckle tracking echocardiography (2D-STE) is capable to identify subclinical changes in cardiac function. We wanted to evaluate whether there is any correspondence between left ventricular (LV) diastolic dysfunction and different degrees of liver steatosis and fibrosis in MetS subjects with NAFLD., Patients and Methods: A total of 150 adult subjects having MetS and a normal left ventricular (LV) systolic function were recorded in the study, while 150 age- and sex- matched adults without MetS were enrolled as controls. NAFLD was established by VCTE and CAP. The left heart systolic and diastolic function was evaluated by conventional and 2D-ST echocardiography. Left atrial (LA) stiffness was calculated as the ratio between the E/A ratio and the LA reservoir-strain., Results: In univariate regression analysis, the variables associated with LV diastolic dysfunction in MetS patients were: liver steatosis grade ≥2, liver fibrosis grade ≥2, the longitudinal LA peak strain during the reservoir phase, the LA strain rate during ventricular contraction and the LA stiffness. In multivariate logistic regression, two variables were selected as independent predictors of LV diastolic dysfunction, namely the liver stiffness (P=0.0003) and the LA stiffness (P<0.0001). LA stiffness predicted subclinical LV diastolic dysfunction in MetS patients with a sensitivity of 45% and a specificity of 96% when using a cut-off value >0.38, and was significantly correlated with liver steatosis stage ≥2 and liver fibrosis stage ≥2., Conclusion: The present study confirms the association between liver stiffness, LA stiffness and LV diastolic dysfunction in MetS patients. Our study suggests that liver elastography and 2D-STE should become habitual assessments in MetS patients., Competing Interests: Prof. Dr. Ioan Sporea reports personal fees from General Electric, Philips, Siemens, Toshiba/Canon, outside the submitted work. The authors report no other conflicts of interest in this study., (© 2021 Parvanescu et al.)

Background: Patients with acute myocardial infarction (AMI) are at high risk for left ventricular (LV) remodeling and heart failure. We aimed to study whether LV strains (S) and strain rates (SR) could predict cardiac remodeling in patients with AMI having a midrange or preserved LV ejection fraction (EF) following a percutaneous coronary intervention (PCI) within the first 12 hours from the onset of symptoms., Patients and Methods: This is a case-control observational study including patients admitted for their first AMI, either with ST-segment elevation (STEMI) or without ST elevation (NSTEMI), with an LVEF > 40% after a successful PCI. Echocardiography was repeated after 6 months, and the patients were divided into two groups, according to whether LV remodeling was determined on echocardiography., Results: Of the 253 AMI patients (mean 66 aged ± 13 years), including 185 males (73%), 61 (24%) presented signs of LV remodeling. In univariate logistic regression analysis, age, male sex, smoking history, hypertension, hypercholesterolemia, Killip class, renal function, peak creatine phosphokinase - MB level, 2- and 3-vessel coronary artery disease (CAD), and several echocardiographic parameters were significantly associated with LV remodeling ( P <0.05). In multivariate logistic regression analysis harmed (H) LS and SR, Killip class, 3-vessel CAD, and LV end-diastolic volume were outlined as independent predictors for LV remodeling. Receiver operating characteristic curve analyses showed that HLS and HLSR were the most powerful independent predictors for LV remodeling ( P <0.001), with an area under the curve (AUC) of 0.85 (sensitivity 83%; specificity 84%; p <0.001) and 0.77 (sensitivity 93; specificity 61%; p <0.001), respectively. The identified cut-off values for predictor variables were HLS< -11%, and HLSR< -0.65s -1 ., Conclusion: We concluded that 2D-STE was the best method to evaluate LV remodeling in patients with AMI and midrange or preserved LVEF following myocardial revascularization by a PCI., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Bordejevic et al.)

Purpose: The components of metabolic syndrome (MS) are risk factors for developing both cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Strain (SI) and strain‑rate imaging (SRI) are able to recognize early changes in cardiac function. Vibration-controlled transient elastography (VCTE) and controlled attenuation parameter (CAP) detect and quantify liver fibrosis and steatosis. We aimed to assess whether there is any correlation between liver fibrosis and steatosis and left ventricular (LV) dysfunction in MS patients., Patients and Methods: A total of 150 adults with MS were registered in the study. They were compared with a control group of 150 age- and sex-matched adults without MS. After the classic echocardiographic assessment of LV function, two-dimensional speckle echocardiography (2D-STE) was used to evaluate LV peak systolic strain (S) and peak systolic strain rate (SR), while liver steatosis and fibrosis were evaluated by VCTE and CAP., Results: LV diastolic dysfunction was significantly more frequent among the patients with MS. We found significant differences between the two groups regarding the presence of subtle LV systolic dysfunction, detected by reduced values of S and SR. The risk for LV diastolic dysfunction was 3.6 times higher in MS with severe steatosis and 8 times higher in patients with severe fibrosis, P<0.0001. The risk for LV systolic dysfunction was double in MS with severe steatosis and 1.7 times higher in MS with severe fibrosis, P<0.0001., Conclusion: In MS patients with normal LV ejection fraction, conventional echocardiography parameters identified diastolic LV dysfunction, while SI and SRI identified subtle impairment of systolic LV dysfunction. The presence of hepatic steatosis and fibrosis increases significantly the risk for cardiac dysfunction in MS patients (P<0.0001)., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Vitel et al.)

Although doxorubicin (Dox) is an effective antitumor antibiotic in the anthracycline class, it often induces the undesirable side effect of cardiomyopathy leading to congestive heart failure, which limits its clinical use. The primary goal of this study is to evaluate a reliable translational method for Dox-induced cardiotoxicity (CTX) screening, aiming to identify a high-risk population and to discover new strategies to predict and investigate this phenomenon. Early identification of the presence of iron deposits and genetic and environmental triggers that predispose individuals to increased risk of Dox-induced CTX (e.g., overexpression of Toll-like receptor 4 (TLR4)) will enable the early implementation of countermeasure therapy, which will improve the patient's chance of survival. Our cohort consisted of 25 consecutive patients with pathologically confirmed cancer undergoing Dox chemotherapy and 12 control patients. The following parameters were measured: serum TLR4 (baseline), serum transferrin (baseline and 6-week follow-up) and iron deposition (baseline and 6-week follow-up). The average number of gene expression units was 0.121 for TLR4 (range 0.051-0.801). We subsequently correlated serum TLR4 levels in our cohort with myocardial iron overload using the cardiac magnetic resonance (CMR) T2* technique, the ventricular function (% ejection fraction, %EF) and serum transferrin levels. There is a strong negative linear relationship between serum TLR4 and CMR T2* values (r =  - 0.9106, ****P < 0.0001). There is also a linear correlation (either positive or negative) with EF and transferrin; no established relationship related to the sex of the patients was found. Patients with elevated serum TLR4 at baseline also exhibited an increase in serum transferrin levels and Dox-induced left ventricular dysfunction with a decreased EF (< 50%); this phenomenon was observed in 7 of 25 patients (28%) at the 6-week follow-up. There were no significant differences or correlations based on sex. We concluded that there is a direct relationship between Dox-induced CTX (indicated by elevated serum TLR4) and the times (ms) for T2* (decreases in which correspond to immediate and rapid iron overload).

Due to their effect of vasodilatation, isosorbide nitrates represent one of the most important and most used solutions for angina pectoris. Unfortunately, these compounds have multiple dose-related adverse drug reactions such as headache, weakness, mild dizziness, and occasionally heart rate changes, nausea, vomiting, and sweating. The main aims of this research were to obtain and to evaluate new polyurethane (PU) structures that can be used as a proper transmembrane carrier with an improved release kinetic. Chitosan-based PU structures were obtained by a polyaddition process between hexamethylene diisocyanate and a mixture of chitosan, butanediol, and polyethylene glycol in the presence of caffeine as a synthesis catalyst. The obtained samples (with and without isosorbide nitrates) were characterized regarding the encapsulation and release rate (UV-Vis spectra), chemical composition (FTIR), thermal stability (thermal analysis), morphology changes (SEM and SANS), and in vivo irritation tests. These methods revealed no significant differences between the two sample structures. Multipopulational structures with sizes between 73 and 310 nm, with an increased tendency to form clusters and a high resistance to heat (up to 280°C), were obtained. This study presents an alternative administration of isosorbide derivatives based on a PU carrier with a high biocompatibility and a prolonged release., (Copyright © 2020 Borcan, Len, Bordejevic, Dudás, Tomescu and Valeanu.)

Purpose: This study aimed to assess the serum levels of intracellular adhesion molecule (sICAM-1), and vascular cell adhesion molecule (sVCAM-1), in the first psychotic episode schizophrenia (SZ) patients, before and after six months of antipsychotic treatment., Patients and Methods: The study included 50 patients with a first hospitalization for SZ and 50 healthy control subjects that were patient-matched regarding age, gender, body mass index and smoking status. The evaluation included the presence of cardiovascular risk factors, measurements of systolic and diastolic blood pressure, body mass index, smoking status, ankle-brachial index, carotid intima-media thickness, and echocardiography. The Brief Psychiatric Rating Scale (BPRS) score was calculated for the patients. The plasma levels of fasting glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, sICAM-1 and sVCAM-1 were determined at baseline in all subjects and after six months of antipsychotic treatment. Thirty patients (60%) were treated with olanzapine and 20 (40%) with risperidone., Results: The average age of patients experiencing their first episode of SZ was 29.7±6.6 years, and 23 (46%) were men. The initial sICAM-1 levels of the patients were lower than those of the control group ( P <0.0001), and increased after treatment ( P =0.02), but remained lower than in the healthy controls ( P =0.026). The initial levels of sVCAM-1 levels were higher in the patients ( P <0.0001) and decreased after treatment ( P <0.0001) to values that were similar to those of the control group ( P =0.39). The only independent predictor of a baseline BPRS over 120 was the baseline sVCAM-1 level ( P <0.0001). Antipsychotic treatment induced significant decreases in BPRS score ( P <0.0001), in systolic ( P =0.005) and diastolic ( P <0.0001) blood pressure, in HDL-c ( P =0.02), as well as significant increases in blood glucose ( P <0.01) and LDL-c ( P <0.001), with no differences between olanzapine and risperidone., Conclusion: In the patients experiencing an FEP of SZ, the levels of sICAM-1 were lower, while the levels of sVCAM-1 were higher than in the healthy control subjects. The antipsychotics used in the treatment of schizophrenia increased sICAM-1 and decreased sVCAM. The baseline level of sVCAM-1 was an independent predictor of a BPRS score >120 at baseline., Competing Interests: Liana Dehelean reports personal fees from Angelini, Johnson & Johnson, Lundbek, Eli Lilly, and Gedeon Richter outside the submitted work. The authors report no other conflicts of interest in this work., (© 2020 Radu et al.)

Background: Thrombospondin-1 (TSP-1) is a matricellular functional protein of the extracellular matrix. As it is not constitutively present extracellularly, its secretion is enhanced in several situations, namely injury, chronic pathology, tissue remodeling, angiogenesis, and aging. Over the last decade, TSP-1 has been reported to be involved in complex and opposing biological effects on vasculature in the context of NO signaling. Several studies have reported high patient TSP-1 plasma levels, indicating that the protein can potentially serve as a prognostic marker for pulmonary arterial hypertension., Materials and Methods: Here, we aimed to quantify TSP-1 serum levels in hypertensive patients with endothelial dysfunction before and after one year of treatment with Perindopril (an antihypertensive drug with vasoprotective properties)., Results: After one year of treatment, TSP-1 levels increased in hypertensive patients compared to baseline (T0: 8061.9 ± 3684.80 vs T1: 15380±5887 ng/mL, p<0.001) and compared to non-hypertensive controls (9221.03 ± 6510.21 ng/mL). In contrast, pentraxin-3 plasma levels were decreased after one year of Perindopril treatment in both hypertensive (T0: 0.91 ± 0.51 vs T1: 0.50 ± 0.24 ng/mL, p<0.001) and control group (1.36 ±1.5 ng/mL) patients, although flow-mediated vasodilation and intima-media thickness assessment parameters were not significantly changed. Systolic and diastolic blood pressure values as well as levels of fibrinogen, high-sensitivity C-reactive protein, triglycerides, and alanine aminotransferase were found to be significantly lower after one year of treatment with Perindopril. High levels of TSP-1 strongly correlated with platelet count (positive), lymphocytes (positive), red cell distribution width-CV (positive), systolic blood pressure (negative), and mean corpuscular hemoglobin (negative) after one year of treatment. Blood urea nitrogen was found to be a protective factor for TSP-1, while glucose and heart rate were found to be risk factors prior to and after treatment., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Buda et al.)

Purpose: Endoglin is a transmembrane glycoprotein which plays an important role in maintaining cardiovascular homeostasis. One of its forms, soluble endoglin (sEng), a molecule with antiangiogenic properties, has been found overexpressed in patients suffering from hypercholesterolemia, diabetes mellitus and hypertension, and is proposed as a marker of endothelial damage. Accordingly, we aimed to quantify the efficacy of various antihypertensive regimens on sEng levels, in hypertensive patients with endothelial dysfunction. Patients and methods: 323 patients were enrolled, and there were 99 patients with normal blood pressure values, 106 hypertensive patients under chronic treatment with different types of antihypertensive molecules (beta blockers, calcium channel blockers, and diuretics) in monotherapy, and 118 hypertensive patients under chronic treatment with perindopril. sEng plasma levels were quantified and were correlated with classical methods of assessing the endothelial damage. Results: Patients under chronic treatment with perindopril had lower sEng plasma levels compared with the other group of hypertensive patients under different regimens of antihypertensive treatment (sEng: 4.73±1.39 versus 5.63±2.33, p <0.01). Conclusion: Decreased sEng plasma levels were found in patients under chronic treatment with perindopril, when compared with other antihypertensive regimens of treatment (beta blockers, calcium channel blockers, and/or diuretics)., Competing Interests: The authors report no conflicts of interest in this work.

Background and aim: The extract of ginger, obtained from the rhizome of Zingiber officinale , contains 6-gingerol, 6-shogaol, 8-gingerol, and 10-gingerol. It has many therapeutic effects such as being chemopreventive against stroke and heart diseases, malabsorption, bacterial infections, indigestion, and nausea, which have been observed since ancient times. The main aim of this study is to evaluate the polyurethane (PU) as a proper material for the hollow nanoparticles' preparation. Methods: The PU nanoparticles were obtained by a spontaneous emulsification, in the presence of a nonionic surfactant, combined with an interfacial polyaddition process between an aliphatic diisocyanate and different mixtures of etheric and esteric polyols. The synthesis was done without any PU additives, such as catalysts, blowing agents, chains promoters, cross-linking agents, and stabilizers. Results: The particles present almost neutral pH values and low water solubility. They are heat resistant up to 280°C. Decreased irritation level was found in the assay of PU nanoparticles loaded with pure ginger extract (GE) on the murine skin tests than the irritation level recorded for pure GE. Conclusion: This research shows the reduced noxiousness of these PU nanoparticles and consequently the possibility of their use as a possible cardiovascular protector., Competing Interests: The authors report no conflicts of interest in this work.

Purpose: Red chili peppers have been highly valued in gastronomy and traditional medicine since ancient times; it seems that it is not just an ingredient for food but also a good remedy for various medical conditions such as increased blood pressure and high levels of serum triglycerides and cholesterol, myocardial infarction, arthritis, and migraines. The objective of this study is the characterization of a new carrier used for encapsulated extract., Methods: Chili pepper extract was obtained and was physically entrapped inside polyurethane microparticles in order to diminish the irritative potential of this extract. The particles were evaluated by Zetasizer measurements, small-angle neutron scattering and thermal analysis, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy; the encapsulation efficacy and the drug release profile were assessed by UV-Vis spectroscopy. Bioevaluations on mice skin were performed to predict the irritative potential of the samples., Results: Two different types of samples were compared: hollow polyurethane microparticles vs polyurethane particles containing the natural extract. The sizes of the particles were very similar, but the sample containing the extract presents three particle populations (the polydispersity index increases from 0.3 to 0.6 from one sample to another). The zeta-potential measurements and SEM images indicate a medium tendency to form clusters, while the UV-Vis study revealed an almost 70% encapsulation efficacy., Conclusion: The results suggest that encapsulation of a chili pepper extract inside polyurethane microparticles leads to a non-irritative product with a prolonged release: ~30% of encapsulated extract is released within the first 8 days and a maximum 45% is reached in 2 weeks., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: The aim of this study was to assess whether nebivolol treatment could have beneficial effects in the prevention of anthracyclines-induced cardiotoxicity., Patients and Methods: Our prospective study included 60 women, mean age 52.6±13 years, with HER2 negative breast cancer, scheduled to undergo treatment with doxorubicin. The patients were randomly divided into two groups: the treatment group (n=30) which received nebivolol 5 mg once daily for the duration of chemotherapy and the control group (n=30) without treatment with nebivolol. Cytostatic treatment was performed with doxorubicin 70 mg/m 2 administered intravenously every 21 days for six cycles. The average cumulative dose of doxorubicin was 520±8 mg/m 2 . Echocardiography was performed immediately before and after six cycles of doxorubicin therapy., Results: We found no significant differences between the two groups regarding baseline clinical and echocardiographic parameters. The two groups reached a similar cumulative dose of doxorubicin. No patient died during the study. None of the patients withdrew from chemotherapy. After six cycles of doxorubicin therapy, the left ventricular (LV) ejection fraction, shortening fraction, and LV diameters changed, but not significantly. Tissue Doppler imaging (TDI) detected in the control group a significant decrease of myocardial velocities, indicating a LV diastolic dysfunction. In the same group, speckle tracking imaging (STI) revealed a statistically significant alteration of the ventricular deformation, which means a decrease in LV systolic function. In the nebivolol treatment group, no significant alterations in the LV systolic and diastolic function were observed., Conclusion: The results of this study show the benefit of new echocardiographic imaging methods such as TDI and STI in the screening of early cardiac dysfunction induced by cytostatic treatment. Nebivolol treatment prevented the occurrence of anthracyclines-induced cardiomyopathy in the short term. In order to confirm these preliminary results, larger studies with a longer follow-up period are required., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: The purpose of this retrospective study was to evaluate the prognostic impact of systolic blood pressure (SBP) and heart rate (HR) on in-hospital mortality in ST-segment elevation acute myocardial infarction (STEMI) patients, after primary percutaneous intervention (PCI)., Patients and Methods: The study included 294 patients admitted for STEMI. They were divided into five groups according to the SBP at admission: group I, <105 mmHg; group II, 105-125 mmHg; group III, 126-140 mmHg; group IV, 141-158 mmHg; and group V, ≥159 mmHg. Increased HR was defined as ≥80 beats per minute (bpm). In-hospital death was defined as all-cause death during admission and classified into cardiac and noncardiac death., Results: Among the 294 patients admitted for STEMI, 218 (74%) were men. The mean age was 62±17 years. In-hospital mortality rate was 6% (n=18), with 11 (3.7%) deaths having cardiac causes. The highest mortality was registered in group I (n=9, 16%, P =0.018). Compared to the other groups, group I patients were older ( P =0.033), more often smokers ( P =0.026), and had a history of myocardial infarction ( P =0.003), systemic hypertension ( P =0.023), diabetes ( P =0.041), or chronic kidney disease ( P =0.0200). They more often had a HR ≥80 bpm ( P =0.028) and a Killip class 3 or 4 at admission ( P =0.020). The peak creatine phosphokinase-MB level was significantly higher in this group ( P =0.005), while the angiographic findings more often identified as culprit lesions were the right coronary artery ( P =0.005), the left main trunk ( P =0.040), or a multivessel coronary artery disease ( P =0.044). Multivariate analysis showed that group I patients had a significantly higher risk for both all-cause death ( P =0.006) and cardiac death ( P =0.003). Patients with HR ≥80 bpm also had higher mortality rates ( P =0.0272 for general mortality and P =0.0280 for cardiac mortality)., Conclusion: The present study suggests that SBP <105 mmHg and HR ≥80 bpm at admission of STEMI patients are associated with a higher risk of in-hospital death, even after primary PCI., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: In the last decades, the studies performed on the field of endothelial dysfunction confirmed the fact that the starting point of this pathology is the inflammation. Several inflammatory biomarkers had been discovered and studied, ones showing systemic inflammation, and others being more specific biomarkers and showing the local inflammation. Pentraxin-3 (PTX3) is a new inflammatory biomarker, from the same family as high-selectivity C-reactive protein (hs-CRP), but it is a more specific biomarker, due to its local production: the endothelial cells and not the liver like in the case of hs-CRP., Aims: Several antihypertensive classes of drugs seem to have a positive impact on reducing the local endothelial inflammation, beyond their effect of lowering the blood pressure, so this study aims to analyze the effect of candesartan on the two inflammatory biomarkers: PTX3 and CRP, compared with other antihypertensive drugs, in hypertensive patients with endothelial dysfunction., Methods: A total of 365 patients were included in the study: 127 hypertensive patients were under treatment with candesartan, 134 patients were under treatment with other hypotensive medication (beta blockers, calcium channel blockers, and diuretics), both groups with controlled values of blood pressure, and 104 were normotensive persons. Classical methods of assessing the endothelial function were correlated with these biochemical markers., Results: The patients treated with candesartan had a significant lower value of PTX3 and hs-CRP, compared with those under treatment with other antihypertensive medication as follows: PTX3: 0.61 ± 0.49 vs 0.95 ± 1.04 ng/ml, P = 0.006 and hs-CRP: 0.19 ± 0.20 vs 0.20 ± 0.22 mg/dl, P = 0.54., Conclusions: Candesartan decreases PTX3 and hs-CRP plasma levels more powerful than other classes of antihypertensive drugs (beta blockers, calcium channel blockers, and diuretics), so we may assume that candesartan has a more potent action in reversing endothelial dysfunction and that it offers a higher vascular protection than other classes of antihypertensive drugs. We are suggesting that this new biochemical marker, PTX3, might be better and more specific marker for endothelial dysfunction, than hs-CRP.

Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment. As a conclusion, patients under treatment with Perindopril had increased plasma levels of TSP-1 compared with other hypertensive patients and with the control group. The results of this study confirms the pleiotropic properties of Perindopril: anti-proliferative, anti-inflammatory, with effects showed by quantifying a single biomarker: TSP-1.

This paper presents the results obtained after studying the thermal stability and decomposition kinetics of perindopril erbumine as a pure active pharmaceutical ingredient as well as a solid pharmaceutical formulation containing the same active pharmaceutical ingredient (API). Since no data were found in the literature regarding the spectroscopic description, thermal behavior, or decomposition kinetics of perindopril, our goal was the evaluation of the compatibility of this antihypertensive agent with the excipients in the tablet under ambient conditions and to study the effect of thermal treatment on the stability of perindopril erbumine. ATR-FTIR (Attenuated Total Reflectance Fourier Transform Infrared) spectroscopy, thermal analysis (thermogravimetric mass curve (TG-thermogravimetry), derivative thermogravimetric mass curve (DTG), and heat flow (HF)) and model-free kinetics were chosen as investigational tools. Since thermal behavior is a simplistic approach in evaluating the thermal stability of pharmaceuticals, in-depth kinetic studies were carried out by classical kinetic methods (Kissinger and ASTM E698) and later with the isoconversional methods of Friedman, Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa. It was shown that the main thermal degradation step of perindopril erbumine is characterized by activation energy between 59 and 69 kJ/mol (depending on the method used), while for the tablet, the values were around 170 kJ/mol. The used excipients (anhydrous colloidal silica, microcrystalline cellulose, lactose, and magnesium stearate) should be used in newly-developed generic solid pharmaceutical formulations, since they contribute to an increased thermal stability of perindopril erbumine., Competing Interests: The authors declare no conflict of interest.

Background: Essential hypertension is a chronic pathology that causes long-term complications due to late diagnosis of patients, the inability to control the disease through medication, or due to the complexity of associated risk factors., Aims: Our study sets out to identify specific patterns of response to arterial hypertension treatment, by taking into consideration the multiple connections between risk factors in a relevant population of hypertensive patients., Methods: Network science is an emerging paradigm, branching over multiple aspects of physical, biological and social phenomena. One such branch, which has brought significant contributions to medical science, is the field of network medicine. To apply this methodology, we create a complex network of hypertensive patients based on their common medical conditions. Consequently, we obtain a community-based representation which pinpoints specific-and previously uncharted-patterns of hypertension development. This approach creates incentives for evaluating patient's treatment efficacy, by considering its network topological position., Results: Distinct clusters of patients with common properties have emerged for each study group (group A-treated with nebivolol, group B-treated with perindopril and group C-treated with candesartan cilexetil). Therefore, our network-based clustering allows for a better treatment assessment.

Background: Several risk scores were developed for acute coronary syndrome (ACS) patients, but their use is limited by their complexity., Purpose: The purpose of this study was to identify predictors at admission for in-hospital mortality in ACS patients in western Romania, using a simple risk-assessment tool - the new Canada acute coronary syndrome (C-ACS) risk score., Patients and Methods: The baseline risk of patients admitted with ACS was retrospectively assessed using the C-ACS risk score. The score ranged from 0 to 4; 1 point was assigned for the presence of each of the following parameters: age ≥75 years, Killip class >1, systolic blood pressure <100 mmHg, and heart rate >100 bpm., Results: A total of 960 patients with ACS were included, 409 (43%) with ST-segment elevation myocardial infarction (STEMI) and 551 (57%) with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). The C-ACS score predicted in-hospital mortality in all ACS patients with a C-statistic of 0.95 (95% CI: 0.93-0.96), in STEMI patients with a C-statistic of 0.92 (95% confidence interval [CI]: 0.89-0.94), and in NSTE-ACS patients with a C-statistic of 0.97 (95% CI: 0.95-0.98). Of the 960 patients, 218 (22.7%) were aged ≥75 years. The proportion of patients aged ≥75 years was 21.7% in the STEMI subgroup and 23.4% in the NSTE-ACS subgroup (P>0.05). Age ≥75 years was significantly associated with in-hospital mortality in ACS patients (odds ratio [OR]: 3.25, 95% CI: 1.24-8.25) and in the STEMI subgroup (OR >3.99, 95% CI: 1.28-12.44). Female sex was strongly associated with mortality in the NSTE-ACS subgroup (OR: 27.72, 95% CI: 1.83-39.99)., Conclusion: We conclude that C-ACS score was the strongest predictor of in-hospital mortality in all ACS patients while age ≥75 years predicted the mortality well in the STEMI subgroup.

Background: Heart failure with preserved ejection fraction (HFpEF) is more frequent in the elderly and is associated with important economic implications because of repetitive and prolonged hospitalizations, due to both cardiovascular and noncardiovascular causes., Purpose: To identify the causes, as well as the clinical and biological markers, that could be used as predictors of hospital readmissions in HFpEF patients aged ≥65 years., Patients and Methods: Consecutive eligible patients hospitalized for a first heart failure (HF) episode were prospectively included and divided into one of two age groups (elderly: ≥65 years; and nonelderly: <65 years). The clinical features, therapeutic approaches, and clinical outcomes during the 1-year follow-up period were analyzed., Results: A total of 178 patients were included, with a mean age of 64.6±8.6 years; 80 (45%) were women. A total of 98 patients (55%) were aged ≥65 years, and 80 (45%) were aged <65 years. In the group aged ≥65 years, 58 patients (59%) were women, while in the group aged <65 years, 22 patients (28%) were women (P=0.0001). During the 1-year follow-up, no patients died or were lost to follow-up. Moreover, 116 (65%) of the HFpEF patients experienced hospital readmissions. The elderly patients had a significantly higher readmission rate (73% vs 55%, respectively; P<0.02); readmissions due to aggravated HF were significantly more frequent in this age group (41% vs 18%, respectively; P<0.002). Multivariate logistic regression analysis indicated that the independent predictors of readmission due to HF aggravation included plasma levels of brain natriuretic peptide >450 pg/mL (P<0.01) and N-terminal-pro-brain natriuretic peptide >477 pg/mL (P<0.02) in the elderly group, while in the nonelderly group, the independent predictors of this outcome were a New York Heart Association functional class of IV at initial hospitalization (P<0.04), as well as plasma levels of brain natriuretic peptide >390 pg/mL (P=0.03) and tumor necrosis factor (TNF)-α >7.1 pg/mL (P<0.001). Readmissions due to noncardiovascular causes were independently predicted by plasma levels of TNF-α >10 pg/mL in the elderly (P=0.003) and of interleukin (IL)-6 >1.9 pg/mL in the nonelderly (P<0.04)., Conclusion: We conclude that in HFpEF patients aged ≥65 years, the main cause of rehospitalization during the 1-year follow-up was HF aggravation. The risk of this outcome was independently predicted by increased levels of cardiac peptides, while the risk of noncardiovascular readmissions was predicted by increased levels of inflammatory biomarkers. Increased TNF-α levels predicted both cardiovascular and noncardiovascular readmissions, while increased levels of high-sensitivity C-reactive protein did not predict any of these outcomes in our study.

Purpose: Bronchial asthma (BA) is a chronic inflammatory disorder of the airways, featuring variable and often reversible airflow limitations. An accurate assessment of BA control is difficult in practice, especially in the elderly, requiring the assessment of several clinical and paraclinical parameters that are influenced not only by asthma, but also by comorbidities. The purpose of this study was to evaluate the predictors of uncontrolled BA in a group of elderly patients from western Romania., Patients and Methods: We retrospectively evaluated 126 elderly patients (aged $ 65 years), who were consecutively evaluated in the Pulmonology Department of Victor Babes Hospital, Timisoara, Romania, between March 2009 and July 2012. We collected demographic data, performed pulmonary function testing and an asthma control test (ACT), and evaluated the level of BA control based on the 2012 Global Initiative for Asthma guidelines. Statistical processing of the data was done using the Epi Info and STATA programs., Results: In our study group, 36 (29%) patients were men and 90 (71%) were women; their mean age was 74.42±8.32 years (range: 65-85 years). A total of 14.28% of patients were smokers. About 30.15% of patients had an ACT score <19, 54.76% had an ACT score 20-24, and 15.09% had an ACT of 25. Moreover, 59.52% had normal spirometry results. Infectious exacerbations were found in 58.73% of patients. A history of allergies was demonstrated in 48.41% of patients, 34.12% had occupational exposure, and 82.53% of patients were treated with inhaled corticosteroids. Our results showed that 30.15% of patients had uncontrolled BA. We found six predictive factors for uncontrolled BA: infectious exacerbation, occupational exposure, mixed (obstructive and restrictive) ventilatory dysfunction, persistent airway obstruction on spirometry, duration of disease in months, and current smoking status. Infectious exacerbations, persistent airway obstructions, and occupational exposure were the most powerful predictors., Conclusion: Elderly patients represent an important group that is at risk for developing uncontrolled BA. Predictors may identify those elderly patients with uncontrolled BA and facilitate early medical interventions.

Purpose: The purpose of this prospective study was to identify factors associated with prolonged hospitalization, readmission, and death in elderly patients presenting heart failure with reduced ejection fraction., Patients and Methods: All consecutive patients aged ≥65 years discharged with a diagnosis of acute new-onset heart failure and a left ventricular ejection fraction (LVEF) ≤45% were included and followed up for 1 year. The variables associated with outcomes were analyzed in univariate and multivariate logistic regression. For the independent predictors identified by multivariate analysis, receiver operating characteristic (ROC) analysis was performed., Results: A total of 71 patients were included in the study. The patient mean age was 72.5 years, 50% were female, and the mean LVEF was 31.25%±5.76%. In all, 34 (48%) patients experienced prolonged hospitalization, and this was independently associated with patients who were living in a rural area (P=0.005), those with a New York Heart Association functional class of 4 (P<0.001), the presence of comorbidities (P=0.023), chronic obstructive pulmonary disease (COPD) infectious exacerbation (P<0.001), and chronic kidney disease (P=0.025). In the multivariate analysis, only COPD infectious exacerbation was independently associated with prolonged hospitalization (P=0.003). A total 19 patients (27%) experienced readmissions during the 1-year follow up, of which 12 (17%) had cardiovascular causes and seven (10%) had noncardiovascular causes. The following independent variables associated with rehospitalizations were outlined in the univariate analysis: infections (P<0.020); COPD infectious exacerbation (P=0.015); one or more comorbidity (P<0.0001); and prolonged baseline hospitalization (P<0.0001). During the multivariate analysis, it was found that the independent predictors of readmissions were the presence of comorbidities (P<0.001) and prolonged baseline hospitalization (P<0.01). The 1-year mortality rate was 9.8%, with no significant difference between cardiovascular (5.6%) and noncardiovascular (4.2%) deaths. The only independent predictive variable for mortality was a New York Heart Association NYHA functional class 4 at baseline hospitalization (P=0.001)., Conclusion: Elderly patients are at high risk for prolonged hospitalization, readmission, and death following a first hospitalization for heart failure with reduced ejection fraction. The most powerful predictors for outcomes are the severity of heart failure, the presence of comorbidities, and prolonged hospitalization at baseline.

Aim: To analyze the expression and distribution of annexins V and VI in intact human hearts and in dilated cardiomyopathy (DCM) in patients with irreducible heart failure., Material and Methods: The study included nine patients with DCM and irreducible heart failure. By immunoblotting and indirect immunofluorescence, the amount and location of annexins was determined using samples of left ventricular (LV) myocardium collected during orthotopic heart allotransplantation. Samples of LV myocardium from 9 individuals who died of craniocerebral trauma served as controls., Results: Quantitative analysis showed an increased level of both annexins in the myocardium of DCM patients compared with normal myocardium: 122 +/- 5% (p < 0.05) and 119 +/- 5% (p < 0.05) for annexins V and VI, respectively. In the intact heart annexin V was located at the sarcolemma and intercalated discs, while in the myocardium with heart failure mainly in the interstitium. In normal hearts, annexin VI was located at the sarcolema, including T-tubules, Z-lines and intercalated discs. In heart failure, annexin V1 was also located in the interstitium., Conclusions: Redistribution of annexins V and VI in the cardiomyocytes in the interstitial space may have important functional consequences and indicates the role of myocardial protein expression disturbances in the etiology and/or pathogenesis of heart failure in pa-