Impact of ellagic acid application on doxorubicin-induced cardiovascular toxicity model.

Doxorubicin is an anticancer agent that is commonly used to treat a number of tumors and is associated with acute and chronic changes of the cardiovascular system. Ellagic acid has strong free radical scavenging capacity, neuroprotective and hepatoprotective effects, and is known to protect against changes occurring due to diabetes, cardiovascular diseases, and cancer. Twenty-four Wistar rats were divided in four groups: control group received saline, doxorubicin group received doxorubicin in a single dose of 20 mg/kg, ellagic acid group received ellagic acid in a dose of 4 mg/kg, and doxorubicin + ellagic acid group received doxorubicin and ellagic acid in same doses as in previous groups. The effect of ellagic acid treatment, alone or in combination with doxorubicin, was studied on isolated heart frequency and strength of the contraction, and on thoracic aorta contractile responses. Application of ellagic acid to rats pre-treated with doxorubicin significantly prevented functional changes occurring in the heart, but not in the thoracic aorta tissue. Ellagic acid statistically significantly (p < 0.001) prevented doxorubicin-induced increase in heart rate, while at the same time increased single contraction force (p < 0.001) and attenuated morphological changes on heart tissue induced by doxorubicin. We can conclude that ellagic acid has potential to prevent doxorubicin-induced changes of the cardiovascular system.

Effects of oleuropein on rat's atria and thoracic aorta: a study of antihypertensive mechanisms.

Oleuropein (OLE) is the main bioactive ingredient in the leaves of the olive plant Olea europaea L. (Oleaceae), which has proven beneficial due to the antiinflammatory, antiatherogenic, anticancer, antimicrobial, and antiviral effects. This study aimed to investigate the antihypertensive and vasodilator potential of OLE by analyzing its acute effects on spontaneous atrial contractions and vasomotor responses of the isolated thoracic aorta in rats. We showed that the application of OLE induces negative chronotropic and inotropic effects on the heart. OLE also causes mild aortic vasodilation given that the maximal reduction in tension of intact aortic rings precontracted with phenylephrine was approximately 30%. This vasodilation is likely dependent on the nitric oxide released from the endothelium based on the effect obtained on denuded and phenylephrine precontracted aortic rings and responses reordered following vasoconstriction induced by high concentrations of K+ and heparin. Our findings provide a basis for further testing of OLE cardiovascular effects, which may lead to subsequent clinical research for its application in the treatment of hypertension and heart disease.

Prognostic Value and Immunohistochemical Analysis of Mismatch Repair Deficiency in Patients with Stage II and III Colorectal Carcinoma-A Single-Center Study.

Background and objectives: Deficient mismatch repair (MMR) status is associated with good prognosis but poor therapeutic response to adjuvant chemotherapy in patients with colorectal cancer. However, there are some opposed arguments considering therapeutic outcomes in patients with evidenced MMR deficiency in colorectal cancer. The aim of the study was the investigation of prognostic value and immunohistochemical analysis of the MMR-deficiency tumors. Materials and Methods: The study enrolled 104 patients with resected stage II and III colorectal cancer samples from the period 2018-2019. Results: The tumors with deficient MMR status were significantly associated with age up to 50 years and right-sided localization (p < 0.001). During the follow-up period of 22.43 ± 6.66 months, 21 patients (20.2%) died, whereas 14 patients (13.5%) had relapses. The loss of mutL homologue 1/postmeiotic segregation increased 2 (MLH1/PMS2) expression, compared to proficient MMR tumors, was associated with shorter disease-free survival in patients with lymphovascular invasion (p < 0.05), perineural invasion (p < 0.01), stage III (p < 0.05) and high-grade tumor (p < 0.05). Conclusions: This retrospective pilot study of a single-center cohort of patients with stage II and III colorectal cancer highlights the clinical importance of using immunohistochemistry (IHC) analysis as a guide for diagnostic algorithm in a country with limited resources, but with a high prevalence of colorectal carcinoma in the young patients. MMR-deficiency tumors compared with proficient MMR colorectal cancer was not shown to be a significant predictor of disease-free and overall survival.

Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome.

To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed ß1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.

Elevated Serum Ferritin Levels Are Predictive of Renal Function Recovery among Patients with Acute Kidney Injury.

Oxidative stress (OS) frequently contributes to the development of acute kidney injury (AKI). Iron can promote oxidative stress and tissue injury by catalyzing free reactive oxygen species (ROS) generation and increasing the steady-state concentration of these potent oxidants. The anticipated role of ferritin is to protect from OS by sequestering iron and limiting its involvement in reactions that generate ROS. In this prospective study, we aimed to investigate the association between serum ferritin levels and kidney function recovery among patients with AKI. Renal recovery was determined as a return of serum creatinine to less than 1.25 times the baseline value after 90 days of follow-up. One hundred twelve patients (72 males and 40 females, 63.68 ± 10.6 years old) were included in the final analysis. They were divided into AKI recovery (n = 76) and non-recovery groups (n = 36). Ferritin levels on admission were higher in AKI recovery group [284 (IQR 153-525) ng/mL] compared with the non-recovery group [127.4 (IQR 30-243) ng/mL], p < 0.001. Serum ferritin levels and the renal recovery significantly positively correlated (r = 0.72, p < 0.001). In multiple linear regression analysis, higher serum ferritin was associated with renal function recovery (OR 3.68, CI 2.02-3.97, p < 0.001). The optimal cut-off point of 240.5 ng/mL was determined for serum ferritin, which showed a sensitivity of 75.8% and a positive predictive value of 90%. In conclusion, serum ferritin levels on admission may be used as a prognostic marker for predicting renal recovery in AKI patients.

Galectin-3 in Acute Myocardial Infarction Patients with Atrial Fibrillation.

OBJECTIVE: Atrial fibrillation (AF) is common in acute myocardial infarction (AMI), and galectin-3 is possibly involved in its occurrence. Galectin-3 has been shown to play a central role in fibrosis and tissue remodeling and has a role in inflammatory and proliferative responses. The aim of our study was to measure galectin-3 levels in patients with myocardial infarction and to compare its levels in patients with or without AF, in order to investigate the potential predictive role of galectin-3 in this setting. SUBJECTS AND METHODS: The study included 51 consecutive AMI patients with AF; 27 AMI patients (52.9%) had permanent/persistent AF, and 24 patients (47.1%) had paroxysmal AF. Thirty-eight consecutive AMI patients without AF were used as a control group. Blood samples were obtained from venous blood on the third day after reperfusion. RESULTS: Patients with AF had higher levels of C-reactive protein (p < 0.01) and galectin-3 (p < 0.05) than those without AF. Patients with high galectin-3 had 4.4 times greater odds of having AF. Galectin-3 levels were lower in patients without AF (p < 0.01) than in those with permanent/persistent AF. CONCLUSION: AMI patients with AF had higher levels of galectin-3 than those without this arrhythmia. This biomarker of inflammation and fibrosis could be a potential target for treating AMI patients at high risk.

Pulmonary embolism bleeding score index (PEBSI): A new tool for the detection of patients with low risk for major bleeding on thrombolytic therapy.

BACKGROUND: Estimation of bleeding risk is an unmet need for individualized therapy in acute pulmonary embolism (PE) patients with increased mortality risk. METHODS: We analyzed the association between various patients' characteristics and occurrence of major bleeding (MB) according to the modified International Society of Thrombosis and Hemostasis (ISTH) criteria ("overt" bleeding is the only modification from the original criteria) at 7 days from admission to the hospital and thrombolytic therapy with a tissue-plasminogen activator (tPA). Pulmonary embolism bleeding score index (PEBSI) was created using multivariate regression analyses, and finely, dichotomous index was used for the discrimination of patients with low risk for MB from those with high risk. RESULTS: During the 6-year period (2015-2021) 367 PE patients were treated with tPA and included in the Regional PE registry. Among them, 29 (7.9%) fulfilled the criteria for MB. Five factors were identified as significantly associated with MB and were used to build the PEBSI score: previous bleeding, recent surgery, diabetes, the use of drugs that could be associated with bleeding, and anemia. PEBSI score showed c-index for 7-day MB 0.794 (95CI% 0.698-0.889). Patients with PEBSI scores of 0 or 1 had a low risk for MB (2.8%) and those with scores>1 had a high risk for MB (18.6%) (p < 0.001). Internal validation of PEBSI score using a randomly, equally split method confirmed the discriminative value of the PEBSI score. CONCLUSION: Novel PEBSI score has significant power to discriminate patients with low risk for MB on thrombolytic therapy from those with high risk.

Less Known but Clinically Relevant Comorbidities of Atrial Fibrillation: A Narrative Review.

BACKGROUND: The important risk factors for atrial fibrillation (AF) in the general population are not always equally important in specific and relatively prevalent diseases. OBJECTIVE: The main goal of this narrative review is to focus attention on the presence and the relationship of AF with several important diseases, such as cancer or sepsis, in order to: 1) stimulate further research in the field, and 2) draw attention to this relationship and search for AF in clinical practice. METHODS: We searched PubMed, SCOPUS, Elsevier, Wiley, Springer, Oxford Journals, Cambridge, SAGE, and Google Scholar for less-known comorbidities of AF. The search was limited to publications in English. No time limits were applied. RESULTS: AF is widely represented in cardiovascular and other important diseases, even in those in which AF is rarely mentioned. In some specific clinical subsets of AF patients (e.g., patients with sepsis or cancer), the general risk factors for AF may not be so important. Patients with new-onset AF have a several-fold increase in relative risk of cancer, deep vein thrombosis, and pulmonary thromboembolism (PTE) during the follow-up. CONCLUSION: AF presence, prognosis, and optimal therapeutic approach are insufficiently recognised in several prevalent diseases, including life-threatening ones. There is a need for a better search for AF in PTE, pulmonary oedema, aortic dissection, sepsis, cancer and several gastrointestinal diseases. Improved AF detection would influence treatment and improve outcomes.

Prognostic significance of symptomatic deep vein thrombosis in patients with acute symptomatic pulmonary embolism regarding the European Society of Cardiology mortality risk model.

BACKGROUND: Deep vein thrombosis (DVT) can be symptomatic or asymptomatic in patients with acute pulmonary embolism (PE). The prognostic value of the symptomatic DVT at the presentation regarding the prognosis of PE is unknown. METHODS: Data were extracted from the REgional Pulmonary Embolism Registry (REPER) which enrolled 1604 hospitalized patients after multidetector computed tomography (MDCT) diagnosed symptomatic acute PE. According to the ESC risk model, patients were classified into four subgroups. Patients who had leg edema with or without pain, and patients with leg pain and DVT confirmed by compression ultrasound were considered to have symptomatic DVT. This study aimed to compare all-cause hospital mortality between patients with symptomatic DVT and patients without symptoms or signs of DVT across the PE risk stratums. RESULTS: All-cause mortality in patients with symptomatic DVT compared to those who had no symptoms or signs of DVT were 2/196 (1.0%) vs. 11/316 (3.5%), P=0.145, 4/129 (3.1%) vs. 17/228 (7.5%), P=0.106, 14/196 (7.1%) vs. 54/290 (18.6%), P<0.001 and 16/55 (29.1%) vs. 51/139 (36.7%), P=0.402 in patients with low, intermediate-low, intermediate-high and high-risk PE, respectively. In multivariate analysis symptomatic DVT was associated with decreased in-hospital mortality only in patients with intermediate-high PE (OR 0.320, 95%CI 0.164-0.627; P=0.001). Intermediate-high risk PE patients with symptomatic DVT who were treated with thrombolysis had significantly lower hospital mortality than patients without symptoms or signs of DVT (2.2% vs. 11.4%, P=0.003). CONCLUSIONS: Intermediate-high risk PE patients with symptomatic DVT at presentation may benefit from thrombolysis and have lower hospital all-cause mortality in such circumstances.

Sex-related difference in the prognostic value of syncope for 30-day mortality among hospitalized pulmonary embolism patients.

INTRODUCTION: Recent studies report that syncope is not a significant predictor of 30-day mortality in pulmonary embolism (PE) patients, yet some data suggest sex-related differences may be relevant. OBJECTIVES: To evaluate sex-specific prediction significance of syncope for 30-day mortality in PE patients. METHODS: A multicentric, retrospective, observational, registry-based study on consecutive PE patients was undertaken. Patients were allocated into either a men or a women group before comparisons were made between patients with syncope and those without syncope. A sex-related prediction of the significance of syncope for 30-day mortality was evaluated. RESULTS: Overall 588 patients [294 (50%) men and 294 (50%) women] were included within the study. Among men, patients with syncope were older and had significantly higher parameters of increased 30-day mortality then patients without syncope. Within the same group, however, difference in the 30-day mortality rate was not significant (log rank P = .942). In contrast to the men, fewer differences in admission characteristics were noticed among women, but those with syncope had significantly increased signs of the right ventricular dysfunction and increased 30-day mortality rate, as compared with those without syncope (log rank P = .025). After adjustment for age in a Cox regression analysis, syncope was a significant predictor of 30-day mortality in women (HR = 2.01, 95%CI 1.02-3.95). CONCLUSION: Although syncope is associated with other predictors of higher early mortality in both male and female PE patients, only in women it is a significant predictor of 30-day mortality.

Renal dysfunction as intrahospital prognostic indicator in acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE), due to hemodynamic disturbances, may lead to multi-organ damage, including acute renal dysfunction. The aim of our study was to investigate the predictive role of renal dysfunction at admission regarding the short-term mortality and bleeding risk in hospitalized PE patients. METHODS: The retrospective cohort study included 1330 consecutive patients with PE. The glomerular filtration rate (GFR) was calculated using the serum creatinine value and Cocroft-Gault formula, at hospital admission. Primary outcomes were all-cause mortality and PE-related mortality in the 30 days following admission, as well as major bleeding events. RESULTS: Based on the estimated GFR, patients were divided into three groups: the first with GFR < 30 mL/min, the second with GFR 30-60 mL/min, and the third group with GFR > 60 mL/min. A multivariable analysis showed that GFR at admission was strongly associated with all-cause death, as well as with death due to PE. Patients in the first and second group had a significantly higher risk of 30-day all-cause mortality (HR 7.109, 95% CI 4.243-11.911, p < 0.001; HR 2.554, 95% CI 1.598-4.081, p < 0.001). Fatal bleeding was recorded in 1.6%, 0.5% and 0.8% of patients in the first, second and in the third group (p < 0.05). There were no significant differences regarding major bleeding rates among the groups. CONCLUSION: Renal dysfunction at admission in patients with acute pulmonary embolism is strongly associated with overall PE mortality.

Predictive value of heart failure with reduced versus preserved ejection fraction for outcome in pulmonary embolism.

AIMS: This study aimed to investigate whether the risk of short-term mortality is different in pulmonary embolism (PE) patients who have heart failure with reduced ejection fraction (HFrEF) as compared with those with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Predictive value of HFrEF or HFpEF for 7-day (intrahospital) and 30-day all-cause mortality was determined in the cohort of 1055 out of 1201 consecutive acute PE patients from the Serbian multicentre PE registry. Patients were classified into either HFrEF or HFpEF group, according to guideline-proposed criteria. A 7-day (intrahospital) and 30-day all-cause mortality was 18.5% vs. 7.3% vs. 4.5% (P < 0.001) and 22.2% vs. 16.3% vs. 7.9% (P < 0.001) for patients with the history of HFrEF, HFpEF, and without HF, respectively. Multivariable analysis adjusted to age, gender, history of chronic obstructive pulmonary disease, diabetes mellitus, arterial hypertension, presence of atrial fibrillation, and mortality risk assessment at admission has shown that only HFrEF, but not HFpEF, was an independent predictor for 7-day mortality (hazard ratio 2.22, 95% confidence interval 1.25-4,38.41, P = 0.021) and neither HFrEF or HFpEF was an independent predictor for 30-day mortality. Among various admission parameters associated to PE outcome, only systolic pressure in HFrEF patients (P < 0.001), heart rate (P = 0.01), and right ventricle systolic pressure (P = 0.039) in HFpEF patients were significantly different in patients who died compared with those who survived at 7 days. CONCLUSIONS: Our study has shown that the presence of previous history of HFrEF, but not HFpEF, in acute PE is an independent risk factor for mortality at 7 days.

Design and development of novel therapeutics for coronary heart disease treatment based on cholesteryl ester transfer protein inhibition - in silico approach.

Cholesteryl ester transfer protein (CETP) belongs to the group of enzymes which inhibition have the application in the treatment of cardiovascular diseases. This study presents QSAR modeling for a set of compounds acting as CETP inhibitors based on the Monte Carlo optimization with SMILES notation and molecular graph-based descriptors, and field-based 3D modeling. A 3D QSAR model was developed for one random split into the training and test sets, whereas conformation independent QSAR models were developed for three random splits, with the results suggesting there is an excellent correlation between them. Various statistical approaches were used to assess the statistical quality of the developed models, including robustness and predictability, and the obtained results were very good. This study used a novel statistical metric known as the index of ideality of correlation for the final assessment of the model, and the results that were obtained suggested that the model was good. Also, molecular fragments which account for the increases and/or decreases of a studied activity were defined and then used for the computer-aided design of new compounds as potential CETP inhibitors. The final assessment of the developed QSAR model and designed inhibitors was done using molecular docking, which revealed an excellent correlation with the results from QSAR modeling.Communicated by Ramaswamy H. Sarma.

Protein Carbonyl Content Is a Predictive Biomarker of Eccentric Left Ventricular Hypertrophy in Hemodialysis Patients.

High prevalence of left ventricular hypertrophy (LVH) and elevated oxidative stress are associated with poor outcomes in chronic hemodialysis patients. Abnormal left ventriculаr geomеtry and different geometric patterns play an important role as well. Our study analyzed the role of oxidative stress on myocardial remodeling in these patients. Plasma malondialdehyde (MDA), protein carbonyl (PC) content, and total antioxidative capacity (TAC) were investigated in 104 hemodialysis patients together with transthoracic echocardiography. Compared to patients with normal ventricular geometry, patients with LVH had increased MDA and PC plasma concentration. Multivariate analysis demonstrated that protein carbonyls, as biomarkers of oxidative protein modification, were an independent predictor of eccentric hypertrophy (eLVH), including higher LV end-diastolic diameter and LV end-diastolic volume, (ß = 0.32 and ß = 0.28, p < 0.001 for both). The incidence of eLVH increased progressively from the lowest to the highest baseline PC tertile (p < 0.001 for the trend) and the subjects in the former group showed a 76% greater risk of developing eLVH compared to their counterparts. After further adjustment for the potential mediators, PCs carried eLVH odds (95% confidence interval (CI)) of 1.256 (0.998-1.514), per standard deviation increase. High plasma protein carbonyls levels are a significant independent predictor of eccentric LVH in chronic hemodialysis patients.

Development and design of novel cardiovascular therapeutics based on Rho kinase inhibition-In silico approach.

Rho kinases, one of the best-known members of the serine/threonine (Ser/Thr) protein kinase family, can be used as target enzymes for the treatment of many diseases such as cancer or multiple sclerosis, and especially for the treatment of cardiovascular diseases. This study presents QSAR modeling for a series of 41 chemical compounds as Rho kinase inhibitors based on the Monte Carlo method. QSAR models were developed for three random splits into the training and test set. Molecular descriptors used for QSAR modeling were based on the SMILES notation and local invariants of the molecular graph. The statistical quality of the developed model, including robustness and predictability, was tested with different statistical approaches and satisfying results were obtained. The best calculated QSAR model had the following statistical parameters: r2 = 0.8825 and q2 = 0.8626 for the training set and r2 = 0.9377 and q2 = 0.9124 for the test set. Novel statistical metric entitled as the index of ideality of correlation was used for the final model assessment, and the obtained results were 0.6631 for the training and 0.9683 for the test set. Molecular fragments responsible for the increases and decreases of the studied activity were defined and they were further used for the computer-aided design of new compounds as potential Rho kinase inhibitors. The final assessment of the developed QSAR model and designed inhibitors was achieved with the application of molecular docking. An excellent correlation between the results from QSAR and molecular docking studies was obtained.

Erectile dysfunction as a predictor of two-year prognosis in acute myocardial infarction.

BACKGROUND: Erectile dysfunction (ED) is a predictor or marker of coronary artery disease in patients at high risk of cardiovascular diseases. The aim of this study was to investigate the prevalence of ED in patients with acute myocardial infarction (AMI) and after 2 years of follow-up, and to determine the association between ED and the concentrations of the markers of inflammation, endothelial dysfunction and oxidative stress which were measured on the third day after hospital admission. METHODS: The study included 80 patients aged 62.25 ± 10.47 years. The primary endpoints of interest were re-hospitalization due to cardiovascular causes and death during the 2 year period after hospital-ization. The Sexual Health Inventory for Men (SHIM) was assessed at the point of hospital discharge and 24 months thereafter. RESULTS: 40.1% of patients had some degree of ED. The percentage of patients without ED increased (13.2%), while the percentage of patients with severe ED significantly decreased (14.7%) after 2 years. Patients with ED had significantly higher B-type natriuretic peptide (BNP) levels and decreased levels of nitric-oxide. During the 2 years of follow-up, 9 patients died (6.5% without ED, 68.6% with ED) (c2 = 7.19, p = 0.015). During the same time period, 22 (27.5%) patients were re-hospitalized due to cardiovascular causes, of whom 59.1% had ED at hospital admission (p < 0.05). CONCLUSIONS: Low levels of nitric-oxide were the best predictors of ED during AMI and after 2 years. ED predicted the worst outcomes of AMI: death and re-hospitalization. Lifestyle changes and nitric- -oxide donors could assist in the treatment of ED and in the improvement of long-term prognosis for AMI. (Cardiol J 2017; 24, 4: 393-402).

Manifestations of Lyme carditis.

The first data of Lyme carditis, a relatively rare manifestation of Lyme disease, were published in eighties of the last century. Clinical manifestations include syncope, light-headedness, fainting, shortness of breath, palpitations, and/or chest pain. Atrioventricular (AV) electrical block of varying severity presents the most common conduction disorder in Lyme carditis. Although is usually mild, AV block can fluctuates rapidly and progress from a prolonged P-R interval to a His-Purkinje block within minutes to hours and days. Rarely, Lyme disease may be the cause of endocarditis, while some studies and reports, based on serological and/or molecular investigations, have suggested possible influence of Borrelia burgdorferi on degenerative cardiac valvular disease. Myocarditis, pericarditis, pancarditis, dilated cardiomyopathy, and heart failure have also been described as possible manifestations of Lyme carditis. The clinical course of Lyme carditis is generally mild, short term, and in most cases, completely reversible after adequate antibiotic treatment.

A first-in-man clinical evaluation of Ultimaster, a new drug-eluting coronary stent system: CENTURY study.

AIMS: To report the six-month angiographic and two-year clinical outcome data from the first-in-man study with the Ultimaster DES, a thin-strut cobalt-chromium sirolimus-eluting stent (SES) with an innovative abluminal-gradient-coated bioresorbable polymer. METHODS AND RESULTS: CENTURY is a multicentre, single-arm, prospective study that enrolled 105 patients (113 lesions) with coronary artery disease. All patients were scheduled to have an angiographic follow-up at six months, while 45 and 20 patients respectively had IVUS and OCT assessments. The primary endpoint was six-month in-stent late lumen loss. Secondary endpoints included clinical, IVUS and OCT outcomes. Clinical follow-up is available up to two years and will continue up to five years. Procedural success was 97.1% and device success was 100%. Angiographic late loss at six months was 0.04±0.35 mm, also reflected in a low binary restenosis rate of 0.9% and confirmed by IVUS-assessed neointimal volume obstruction of 1.02±1.62%. The mean strut coverage assessed by OCT was 96.2% with 1.66±4.02 malapposed stent struts. There were no deaths in the study, three (2.9%) periprocedural and one (0.9%) spontaneous myocardial infarction, not related to the target vessel. At one and two years, the target lesion failure rate was 3.8% and 5.7%, while the TLR rate was 1.9% and 2.8%, respectively. There was one acute definite stent thrombosis. CONCLUSIONS: The Ultimaster™ novel bioresorbable polymer sirolimus-eluting stent demonstrated good performance, including high procedural success and strong suppression of neointimal proliferation at six months. Good safety and effectiveness were shown up to two years in the studied population.

A successful retrieval of stripped outer coating of J-tip diagnostic guidewire from the left popliteal artery during elective coronary angiography.

INTRODUCTION: Entrapment and fracture of diagnostic or therapeutic devices within the coronary circulatory system are a rare, but increasing problem. CASE REPORT: A 70-year-old man was admitted in our clinic for coronary angiography before the planned aortic valve replacement. An arterial sheath was inserted in the right common femoral artery. After introducing a J-tip diagnostic coronary guidewire into the aorta and advancing a left Judkins diagnostic catheter over it, suddenly occured peeling off of the wire's hydrophilic coating at the aortic arch level. Very soon, this outer coating of guidewire carried by the blood stream was entered into the left femoral artery, then into the left popliteal artery. This stripped part of guidewire was successfully caught and extracted out by using a goose-neck snare catheter. CONCLUSION: A sudden stripping of outer coating of a J-tip diagnostic hydrophilic coronary guidewire during coronary angiography is possible to manage quickly and successfully by the use of a simple cathether.

Regional differences among female patients with heart failure from the Cardiac Insufficiency BIsoprolol Study in ELDerly (CIBIS-ELD).

BACKGROUND: The aim of our study was to examine regional differences in the demographics, etiology, risk factors, comorbidities and treatment of female patients with heart failure (HF) in the Cardiac Insufficiency BIsoprolol Study in ELDerly (CIBIS-ELD) clinical trial. METHODS AND RESULTS: One hundred and fifty-nine female patients from Germany and 169 from Southeastern (SE) Europe (Serbia, Slovenia and Montenegro) were included in this subanalysis of the CIBIS-ELD trial. Women comprised 54% of the study population in Germany and 29% in SE Europe. German patients were significantly older. The leading cause of HF was arterial hypertension in German patients, 71.7% of whom had a preserved ejection fraction. The leading etiology in SE Europe was the coronary artery disease; 67.6% of these patients had a reduced left ventricular ejection fraction (34.64 ± 7.75%). No significant differences were found in the prevalence of traditional cardiovascular risk factors between the two regions (hypertension, diabetes, hypercholesterolemia, smoking and family history of myocardial infarction). Depression, chronic obstructive pulmonary disease and malignancies were the comorbidities that were noted more frequently in the German patients, while the patients from SE Europe had a lower glomerular filtration rate. Compared with the German HF patients, the females in SE Europe received significantly more angiotensin converting enzyme inhibitors, loop diuretics and less frequently angiotensin receptor blockers and mineralocorticoid receptor antagonists. CONCLUSIONS: Significant regional differences were noted in the etiology, comorbidities and treatment of female patients with HF despite similar risk factors. Such differences should be considered in the design and implementation of future clinical trials, especially as women remain underrepresented in large trial populations.