Myosin VI in the nucleolus of neurosecretory PC12 cells: its involvement in the maintenance of nucleolar structure and ribosome organization.

We have previously shown that unconventional myosin VI (MVI), a unique actin-based motor protein, shuttles between the cytoplasm and nucleus in neurosecretory PC12 cells in a stimulation-dependent manner and interacts with numerous proteins involved in nuclear processes. Among the identified potential MVI partners was nucleolin, a major nucleolar protein implicated in rRNA processing and ribosome assembly. Several other nucleolar proteins such as fibrillarin, UBF (upstream binding factor), and B23 (also termed nucleophosmin) have been shown to interact with MVI. A bioinformatics tool predicted the presence of the nucleolar localization signal (NoLS) within the MVI globular tail domain, and immunostaining confirmed the presence of MVI within the nucleolus. Depletion of MVI, previously shown to impair PC12 cell proliferation and motility, caused disorganization of the nucleolus and rough endoplasmic reticulum (rER). However, lack of MVI does not affect nucleolar transcription. In light of these data, we propose that MVI is important for nucleolar and ribosome maintenance but not for RNA polymerase 1-related transcription.

Characteristics and outcomes for patients with heart failure diagnosed according to the universal definition and classification of heart failure. Data from a single-center registry.

BACKGROUND: There are no data on the characteristics and outcomes for patients with heart failure (HF) with reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF) ejection fraction diagnosed according to the universal definition and classification of HF. AIMS: We used the universal HF definition to compare baseline characteristics, hospital readmission and mortality rates in individuals with HFrEF, HFmrEF, and HFpEF diagnosed retrospectively. RESULTS: The study was designed as a single-center retrospective analysis of all consecutive 40732 hospital admissions between 2013 and 2021 in a tertiary department of cardiology. All patients with HF, defined according to the universal definition and classification of HF, were identified. The study included 8471 patients with a mean age of 65.1 (12.8) years, of whom 2823 (33.3%) were females. Most individuals had a prior diagnosis of HF (76.3%) and elevated N-terminal pro-B-type natriuretic peptide levels (99.0%) with a median of 1548 (629-3786) pg/ml. Mean ejection fraction (EF) was 36.2 (14.9)%. The median follow-up was 39.1 (18.1-70.5) months. The most frequent type of HF was HFrEF (n = 4947; 58.4%), followed by HFpEF (n = 1138; 28.2%) and HFmrEF (n = 2386; 13.4%). Urgent HF readmissions and all-cause deaths were highest in HFrEF (40.8% and 42.7%), followed by HFmrEF (25.4% and 31.5%) and HFpEF (15.2% and 23.8%, respectively). CONCLUSIONS: The highest rates of urgent HF readmissions and all-cause mortality were observed in patients with HFrEF, followed by HFmrEF and HFpEF. In all HF groups, the all-cause mortality rate was higher than the rates of urgent HF readmission.

Spot Urinary Creatinine Concentration in Patients with Chronic Heart Failure Identifies a Distinct Muscle-Wasting Phenotype with a Strikingly Different Risk of Mortality.

BACKGROUND: There is a raising awareness that heart failure (HF) is a highly heterogeneous, multiorgan syndrome with an increasing global prevalence and still poor prognosis. The comorbidities of HF are one of the key reasons for presence of various phenotypes with different clinical profile and outcome. Heterogeneity of skeletal muscles (SMs) quantity and function may have an impact on patient's phenotype. AIM: We intended to compare clinical characteristics of phenotypes defined by a combination of various SM mass taken as a fat-free compartment from DEXA scans and different levels of SUCR (Spot Urinary Creatinine). All-cause mortality with mortality predicted by MAGGIC in such phenotypes were compared. METHODS: In 720 HF patients with reduced ejection fraction (age: 52.3 ± 10 years, female: 14%, NYHA: 2.7 ± 0.7, LVEF: 24.3 ± 7.3%), admitted to the hospital for heart transplantation candidacy assessment, morning SUCR along with body composition scanning (DEXA) was performed. All study participants were dichotomized twice, first by low or normal appendicular muscle mass index (ASMI) and second by SUCR (Spot Urinary Creatinine) < and ≥of 1.34 g/L. Four study groups (phenotypes) were created as combinations of lower or higher SUCR and low or normal ASMI. RESULTS: Low ASMI was found in 242 (33.6%) patients, while the remaining 478 had normal muscle mass. In 446 patients (61.9%), SUCR was <1.34 g/L. During 3 years of follow-up, 223 (31.0%) patients died (all-cause). The phenotype of lower both ASMI and SUCR was associated with the highest mortality. The death rate in phenotype with both low ASMI and SUCR exceeded by 70% the risk estimated by MAGGIC. This difference was significant as judged by the 95% confidence interval for MAGGIC estimation. In Cox regression analysis adjusted for MAGGIC and parameters known to increase risk, the relative risk of patients with phenotype of low both ASMI and SUCR was elevated by 45-55% as compared to patients with all other phenotypes. The protective role of higher SUCR in patients with muscle wasting was, therefore, confirmed in Cox analysis. CONCLUSIONS: Measurement of SUCR in HF patients can identify clinical phenotypes with skeletal muscle wasting but strikingly different risk of death that is actually not captured by MAGGIC score. The higher level of SUCR was associated with similar risk independently of presence of muscle wasting. As the analysis of SUCR is cheap and easy to perform, it should be further tested as a potentially useful biomarker, which may precisely phenotype HF patients independently of their skeletal muscle status.

Sacubitril/valsartan for cardioprotection in breast cancer (MAINSTREAM): design and rationale of the randomized trial.

AIMS: In recent years, survival in patients with breast cancer has increased. Despite the improvement in outcomes of those patients, the risk of treatment-related cardiotoxicity remains high, and its presence has been associated with a higher risk of treatment termination and thus lower therapeutic efficacy. Prior trials demonstrated that a preventive initiation of heart failure drugs, including the renin-angiotensin-aldosterone inhibitors, might reduce the risk of treatment-related cardiotoxicity. However, to date, no study investigated the efficacy of sacubitril/valsartan, a novel antineurohormonal drug shown to be superior to the previous therapies, in the prevention of cardiotoxicity in patients with early-stage breast cancer, which is the aim of the trial. METHODS AND RESULTS: MAINSTREAM is a randomized, placebo-controlled, double-blind, multicentre, clinical trial. After the run-in period, a total of 480 patients with early breast cancer undergoing treatment with anthracyclines and/or anti-human epidermal growth factor receptor 2 drugs will be randomized to the highest tolerated dose of sacubitril/valsartan, being preferably 97/103 mg twice daily or placebo in 1:1 ratio. The patients will be monitored, including routine transthoracic echocardiography (TTE) and laboratory biomarker monitoring, for 24 months. The primary endpoint of the trial will be the occurrence of a decrease in left ventricular ejection fraction by ≥5% in TTE within 24 months. The key secondary endpoints will be the composite endpoint of death from any cause or hospitalization for heart failure, as well as other imaging, laboratory, and clinical outcomes, including the occurrence of the cancer therapy-related cardiac dysfunction resulting in the necessity to initiate treatment. The first patients are expected to be recruited in the coming months, and the estimated completion of the study and publication of the results are expected in December 2027, pending recruitment. CONCLUSIONS: The MAINSTREAM trial will determine the efficacy and safety of treatment with sacubitril/valsartan as a prevention of cardiotoxicity in patients with early breast cancer (ClinicalTrials.gov number: NCT05465031).

Long-term prognostic scores may underestimate the risk of death in patients with heart failure with reduced ejection fraction in whom red cell distribution width is elevated.

INTRODUCTION: Risk prediction in patients with heart failure with reduced ejection fraction (HFrEF) is one of the key challenges for clinicians. Novel biomarkers aggregating several important pathophysiological pathways may modify the diagnostic discrimination of validated scores. The red cell distribution width (RDW) is a cheap and easily available measure of anisocytosis, and was shown to have a strong independent prognostic power in short- and medium­term prognosis in HFrEF. OBJECTIVES: Our aim was to assess the prognostic power of RDW in optimally treated chronic HFrEF, and to investigate whether different RDW may impact the prognostic accuracy of validated long­term scores in HFrEF. PATIENTS AND METHODS: The study included 551 patients at a median (interquartile range [IQR]) age of 54 (47-59) years, of whom 86.6% were men. The patients represented the median New York Heart Association class III (IQR, II-III), and ischemic etiology occurred in 56.6% of the cases. In all patients, RDW as a coefficient of variation was calculated, along with Meta­Analysis Global Group in Chronic Heart Failure Score (MAGGIC­HF) and Seattle Heart Failure Survival Model (SHFSM). RESULTS: The patients were followed for 5 years and all­cause mortality was assessed. We recorded 166 (30.1%) and 225 (40.8%) deaths at 3 and 5 years, respectively. Scores based on MAGGIC­HF and SHFSM algorithms for the respective prediction of 3- and 5­year mortality were calculated for each patient and compared with the observed mortality. There was a significant underestimation of mortality in the patients with RDW above 15.4% (reference values, 11.5%-14.5%), while in those with lower RDW SHFSM overestimated the actual risk. The excess mortality in the higher RDW group was confirmed by the Hosmer-Lemeshow statistic. CONCLUSIONS: The RDW has a strong prognostic value in chronic HFrEF, independently of the risk assessed by the MAGGIC­HF or the SHFSM score.

Prognostic Value of Spot Urinary Creatinine Concentration and Its Relationship with Body Composition Parameters in HF Patients.

BACKGROUND: Low 24-h urinary excretion of creatinine in patients with heart failure (HF) is believed to reflect muscle wasting and is associated with a poor prognosis. Recently, spot urinary creatinine concentration (SUCR) has been suggested as a useful prognostic factor in selected HF cohorts. This more practical and cheaper approach has never been tested in an unselected HF population. Moreover, neither the relation between SUCR and body composition markers nor the association of SUCR with the markers of volume overload, which are known to worsen clinical outcome, has been studied so far. The aim of the study was to check the prognostic value of SUCR in HF patients after adjusting for body composition and indirect markers of volume overload. METHODS: In 911 HF patients, morning SUCR was determined and body composition scanning using dual X-ray absorptiometry (DEXA) was performed. Univariable and multivariable predictors of log SUCR were analyzed. All participants were divided into quartiles of SUCR. RESULTS: In univariable analysis, SUCR weakly correlated with fat-free mass (R = 0.09, p = 0.01). Stronger correlations were shown between SUCR and loop diuretic dose (R = 0.16, p < 0.0001), NTproBNP (R = -0.15, p < 0.0001) and serum sodium (R = 0.16, p < 0.0001). During 3 years of follow-up, 353 (38.7%) patients died. Patients with lower SUCR were more frequently female, and their functional status was worse. The lowest mortality was observed in the top quartile of SUCR. In the unadjusted Cox regression analysis, the relative risk of death in all three lower quartiles of SUCR was higher by roughly 80% compared to the top SUCR quartile. Apart from lower SUCR, the significant predictors of death were age and malnutrition but not body composition. After adjustment for loop diuretic dose and percent of recommended dose of mineralocorticoid receptor antagonists, the difference in mortality vanished completely. CONCLUSIONS: Lower SUCR levels in HF patients are associated with a worse outcome, but this effect is not correlated with fat-free mass. Fluid overload-driven effects may link lower SUCR with higher mortality in HF.

Sodium-Glucose Cotransporter-2 Inhibitors-from the Treatment of Diabetes to Therapy of Chronic Heart Failure.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are currently the second-line pharmacotherapy in type 2 diabetes, particularly through their effectiveness in reducing glycemia, but also due to their cardioprotective and nephroprotective effects. In light of surprisingly satisfactory results from large, randomized trials on gliflozins, SGLT2 received the highest recommendation (Class IA) with the highest level of evidence (A) in the treatment algorithm for HF with reduced LVEF in recent ESC HF guidelines. This great breakthrough in the treatment of HF is due to different mechanisms of action of gliflozins that are reported to be able to change the natural course of HF by reducing the risk of both hospitalization and death. They are recommended regardless of the patient's diabetes status. This review summarizes the up-to-date literature on their beneficial and pleiotropic impact on the cardiovascular system.

Long-term outcomes in patients after left atrial appendage occlusion: The results from the LAAO SILESIA registry.

BACKGROUND: The benefits of oral anticoagulation (OAC) therapy are undeniable. However, such treatment is contraindicated in 2%-10% of patients. According to the latest guidelines, percutaneous left atrial appendage occlusion (LAAO) may be considered in stroke prevention. AIMS: We analyzed the data of patients from the Polish population, who had undergone LAAO procedures in the Silesian Province based on limited reports. METHODS: The data from the SILCARD database of all patients who underwent LAAO between 2006 and 2019, and the data from the databases of the centers performing the procedures in the Silesian Province were included in the LAAO SILESIA registry. We analyzed the efficacy and safety of the procedure and its relationship with the occurrence of stroke and bleeding in the post-hospital follow-up. RESULTS: We analyzed 649 patients with the mean values of CHA2DS2-VASc and HAS-BLED scores of 4.1 and 3.2, respectively. The predominant indication for LAAO was a history of bleeding during OAC. The most frequent in-hospital major adverse cardiac events were anemia, which required blood transfusion (5.5%), and pericardial effusion, which was treated either conservatively (0.9%) or interventionally (1.2%). During hospitalization, stroke was detected in 4 patients and three patients died of any cause. LAAO reduced the annual risk of stroke by 84% and the annual risk of bleeding by 27%. CONCLUSIONS: Based on a "real-life" cohort of patients from the Silesian Province, we concluded that LAAO is related to low in-hospital major cardiovascular adverse events. In the long-term follow-up, LAAO reduced the rates of stroke and bleeding.

Impact of cellular myocardial infiltration on clinical outcome in non-ischaemic heart failure.

AIMS: So far, little has been known on whether myocardial inflammatory infiltration influences heart failure (HF) progression. Thus, the aim of this study was to test the impact of intramyocardial infiltration on clinical outcomes. METHODS: Biopsy samples from 358 patients with stable HF secondary to dilated cardiomyopathy were studied. Immunohistochemistry for lymphocyte (CD3) and macrophage (CD68) markers was performed and counted. After a 1-year follow-up, patients were classified as improved based on the predefined definition of improvement. The clinical data were collected from 324 patients (90.5%). RESULTS: According to the predefined definition of improvement, 133 patients improved (41.0%) but 191 remained unchanged or deteriorated (58.9%). After a 12-month follow-up, the OR with 95% CI of counts of myocardial inflammatory CD68-positive ≥4 cell/high power field (HPF) compared with CD68-positive <4 cell/HPF for lack of improvement was 1.91 (1.65-2.54). However, the number of CD3 positive cell infiltration had no impact on clinical outcome after a 1-year follow-up. In the baseline study, a reasonably negative correlation was found between the number of CD68 positive cells and troponin T (r=-0.39; p<0.001 by Spearman's r). This was corroborated with a low negative correlation between these cells and myocardial form of creatine kinase (CK-MB) fraction (r=-0.27; p=0.006). There was no correlation between CD3 and CD68 positive cells (Spearman's r; r=-0.17, p=0.16). CONCLUSIONS: The current results provide evidence that high macrophage counts may be a predisposing factor for HF progression.

Nutritional and Non-Nutritional Predictors of Low Spot Urinary Creatinine Concentration in Patients with Heart Failure.

Low spot urinary creatinine concentration (SUCR) is a marker of muscle wasting and clinical outcome. The risk factors for low SUCR in heart failure (HF) remain poorly understood. We explored the risk factors for low SUCR related to poor outcomes. In 721 HF patients (age: 52.3 ± 11 years, female: 14%, NYHA: 2.7 ± 0.7) SUCR and Dexa body composition scans were performed. BMI prior HF-onset, weight loss, and appendicular muscle mass were obtained. Each patient was classified as malnutrition or normal by GLIM criteria and three other biochemical indices (CONUT, PNI, and GRNI). Sarcopenia index (SI) as creatinine to cystatin C ratio was also calculated. Within 1 year, 80 (11.1%) patients died. In ROC curve we identified a SUCR value of 0.628 g/L as optimally discriminating surviving from dead. In low SUCR group more advanced HF, higher weight loss and catabolic components of weight trajectory (CCWT), more frequent under-nutrition by GLIM, and lower SI were observed. In multivariate analysis the independent predictors of low SUCR were SI, CCWT, and GNRI score. In conclusion: the risk of low SUCR was associated with a worse outcome. Low SUCR was associated with greater catabolism and sarcopenia but not with biochemical indices of malnutrition.

Risk-factors associated with extremely high cardiovascular risk of mid- and long-term mortality following myocardial infarction: Analysis of the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) registry.

BACKGROUND AND AIMS: Risk-factor identification and risk stratification are prerequisites to the effective primary and secondary prevention of cardiovascular disease (CVD). Patients at the highest risk benefit the most from the intensive risk-factor reduction. However, the high-risk patients' group is heterogeneous, and it is increasingly recognised that there is an 'extreme-risk' category of patients who may require particularly close attention and intensive therapeutic approach. The aim of this study was to identify subgroups of patients at the highest risk of death following myocardial infarction (MI) that might be considered as those at extremely high CVD risk. METHODS: We used data from 19,582 participants of the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) Registry (NCT03065543) of patients with ischaemic heart disease in Poland from 2006 to present. Characteristics of 13,052 patients with chronic coronary syndromes (CCS) were compared with those of 4295 patients with myocardial infarction (STEMI and NSTEMI). Multivariable logistic regression with stepwise backward elimination was used to identify risk factors associated with mortality in the 12-36 months following the index hospitalisation. RESULTS: The mortality rates were significantly higher in patients after MI than in patients with CCS. In the multivariable analysis, the risk factors most strongly associated with 12-month mortality in patients after MI were left ventricular ejection fraction (LVEF) lower than 35% (hazard ratio [HR] 3.83, 95% confidence interval [CI] 3.14-4.67), age >75 years (HR 1.91, 95%CI 1.55-2.35), multivessel coronary artery disease (HR 1.61, 95%CI 1.30-1.99), atrial fibrillation (HR 1.53, 95%CI 1.21-1.94) diabetes mellitus (HR 1.35, 95%CI 1.11-1.64) and increased LDL-C (HR per 1 mmol/l 1.09, 95%CI 1.01-1.19) or creatinine levels (HR per 10 µmol/L 1.04, 95% CI 1.04-1.05). The risk factors that influenced mortality after 24-36 months were consistent with those after 12 months, with additional low haemoglobin (20-25% risk increase per 1 mmol reduction) and chronic obstructive pulmonary disease (65% risk increase after 36 months). CONCLUSIONS: In our large, single-center real-world analysis, we identified the patients with the highest risk of death who could probably benefit the most from the most intensive therapy, and hence should be considered to be an 'extreme risk' population.

Iron deficiency contributes to resistance to endogenous erythropoietin in anaemic heart failure patients.

AIMS: Abnormal endogenous erythropoietin (EPO) constitutes an important cause of anaemia in chronic diseases. We analysed the relationships between iron deficiency (ID) and the adequacy of endogenous EPO in anaemic heart failure (HF) patients, and the impact of abnormal EPO on 12-month mortality. METHODS AND RESULTS: We investigated 435 anaemic HF patients (age: 74 ± 10 years; males: 60%; New York Heart Association class I or II: 39%; left ventricular ejection fraction: 43 ± 17%). Patients with EPO higher than expected for a given haemoglobin were considered EPO-resistant whereas those with EPO lower than expected - EPO-deficient. ID was defined as serum ferritin <100 µg/L or 100-299 µg/L with transferrin saturation <20%. EPO-resistant patients (22%) had more advanced HF whereas those with EPO deficiency (57%) were more frequently females and had worse renal function. Lower serum ferritin (indicating depleted body iron stores) was related to higher EPO observed/predicted ratio when adjusted for significant clinical confounders, including C-reactive protein. One year all-cause mortality was 28% in patients with EPO resistance compared to 17% in patients with EPO deficiency and 10% in patients with adequate EPO (log-rank test for the comparison EPO resistance vs. adequate EPO: P = 0.02). When adjusted for other prognosticators, there was still a trend towards increased 12-month mortality in patients with higher EPO level. CONCLUSION: Anaemic HF patients with endogenous EPO deficiency vs. resistance have different clinical and laboratory characteristics. In such patients, ID contributes to EPO resistance independently of inflammation.

High soluble transferrin receptor in patients with heart failure: a measure of iron deficiency and a strong predictor of mortality.

AIMS: Iron deficiency (ID) is frequent in heart failure (HF), linked with exercise intolerance and poor prognosis. Intravenous iron repletion improves clinical status in HF patients with left ventricular ejection fraction (LVEF) ≤45%. However, uncertainty exists about the accuracy of serum biomarkers in diagnosing ID. The aims of this study were (i) to identify the iron biomarker with the greatest accuracy for the diagnosis of ID in bone marrow in patients with ischaemic HF, and (ii) to establish the prevalence of ID using this biomarker and its prognostic value in HF patients. METHODS AND RESULTS: Bone marrow was stained for iron in 30 patients with ischaemic HF with LVEF ≤45% and 10 healthy controls, and ID was diagnosed for 0-1 grades (Gale scale). A total of 791 patients with HF with LVEF ≤45% were prospectively followed up for 3 years. Serum ferritin, transferrin saturation, soluble transferrin receptor (sTfR) were assessed as iron biomarkers. Most patients with HF (n = 25, 83%) had ID in bone marrow, but none of the controls (P < 0.001). Serum sTfR had the best accuracy in predicting ID in bone marrow (area under the curve 0.920, 95% confidence interval 0.761-0.987, for cut-off 1.25 mg/L sensitivity 84%, specificity 100%). Serum sTfR was ≥1.25 mg/L in 47% of HF patients, in 56% and 46% of anaemics and non-anaemics, respectively (P < 0.05). The reclassification methods revealed that serum sTfR significantly added the prognostic value to the baseline prognostic model, and to the greater extent than plasma N-terminal pro B-type natriuretic peptide. Based on internal derivation and validation procedures, serum sTfR ≥1.41 mg/L was the optimal threshold for predicting 3-year mortality, independent of other established variables. CONCLUSIONS: High serum sTfR accurately reflects depleted iron stores in bone marrow in patients with HF, and identifies those with a high 3-year mortality.

The Association between Serum Levels of 25[OH]D, Body Weight Changes and Body Composition Indices in Patients with Heart Failure.

We try to determine the association between weight changes (WC), both loss or gain, body composition indices (BCI) and serum levels of 25[OH]D during heart failure (HF). WC was determined in 412 patients (14.3% female, aged: 53.6 ± 10.0 years, NYHA class: 2.5 ± 0.8). Body fat, fat percentage and fat-free mass determined by dual energy X-rays absorptiometry (DEXA) and serum levels of 25[OH]D were analyzed. Logistic regression was used to calculate odds ratios for 25[OH]D insufficiency (<30 ng/mL) or deficiency (<20 ng/mL) by quintiles of WC, in comparison to weight-stable subgroup. The serum 25[OH]D was lower in weight loosing than weight stable subgroup. In fully adjusted models the risk of either insufficient or deficient 25[OH]D levels was independent of BCI and HF severity markers. The risk was elevated in higher weight loss subgroups but also in weight gain subgroup. In full adjustment, the odds for 25[OH]D deficiency in the top weight loss and weight gain subgroups were 3.30; 95%CI: 1.37-7.93, p = 0.008 and 2.41; 95%CI: 0.91-6.38, p = 0.08, respectively. The risk of 25[OH]D deficiency/insufficiency was also independently associated with potential UVB exposure, but not with nutritional status and BCI. Metabolic instability in HF was reflected by edema-free WC, but not nutritional status. BCI is independently associated with deficiency/insufficiency of serum 25[OH]D.

Comparison of Oxidative Stress Parameters in Heart Failure Patients Depending on Ischaemic or Nonischaemic Aetiology.

BACKGROUND: Abnormalities in the oxidative and antioxidant states causing oxidative stress were both found in heart failure (HF) of various aetiologies and atherosclerosis. AIM OF STUDY: The goals of the study were as follows: comparison of oxidative stress parameters (OSP) in ischaemic cardiomyopathy (ICM) (n = 479) and nonischaemic cardiomyopathy (nICM) (n = 295) patients; assessment of the relationships of OSP with functional capacity (NYHA class), maximal oxygen consumption (max.O2), left ventricle ejection fraction (LVEF), and NT-proBNP concentration; and determination of the mutual relations of OSP in subgroups of patients with ICM and n-ICM. METHODS: Serum concentrations of total antioxidant capacity (TAC), total oxidant status (TOS), uric acid (UA), bilirubin, albumin, protein sulfhydryl groups (PSH), and malondialdehyde (MDA) were measured. The oxidative stress index (OSI) and MDA/PSH ratio were calculated. RESULTS: Higher concentrations of TAC (1.14 vs 1.11 mmol/l; p < 0.001) and MDA (1.80 vs 1.70 µmol/l; p < 0.05) and higher MDA/PSH ratios (0.435 vs 0.358; p < 0,001) were observed in ICM than in nICM patients. Simultaneously, lower values of the OSI index (4.27 vs 4.6; p < 0, 05), PSH (4.10 vs 4.75 µmol/g of protein; p < 0,001), and bilirubin (12.70 vs 15.40 µmol/l; p < 0,001) concentrations were indicated in ICM patients. There were no differences in TOS, UA, and albumin between the examined groups. The NYHA class and VO2max correlate with MDA, bilirubin, and albumin in both groups, while with UA only in the ICM group. Correlations between the NYHA class, VO2max, and PSH were indicated in nICM. The association of LVEF with UA, bilirubin, and albumin has been demonstrated in the ICM group. The study showed negative correlations between TAC, MDA, and PSH and positive between TAC and MDA in both groups. In ICM patients, MDA positively correlated with UA. A negative correlation between PSH and concentrations of UA and bilirubin was expressed only in the nICM group. CONCLUSION: The obtained results confirm the relationship between the severity of HF and oxidative stress. The mechanisms of oxidative stress and antioxidant defence are partially different in the ICM and the nICM patients.

The prevalence and management of familial hypercholesterolemia in patients with acute coronary syndrome in the Polish tertiary centre: Results from the TERCET registry with 19,781 individuals.

BACKGROUND AND AIMS: The prevalence of familial hypercholesterolemia (FH) is high among patients with stable coronary artery disease (CAD). However, data on FH on admission among patients with acute coronary syndrome (ACS) are still relatively scarce. Therefore, we aimed to assess the prevalence, lipid-lowering therapy and short- and long-term outcomes in patients with FH among ACS patients. METHODS AND RESULTS: The investigation was performed in a cohort of 19,781 consecutive patients from the TERCET Registry. There were 7319 patients admitted with ACS: 3085 due to STEMI, 2256 due to NSTEMI, and 1978 due to UA. The stable CAD group (n = 12,462) was considered the reference group. Based on the personal and familial history of premature cardiovascular disease and LDL cholesterol concentration, the Dutch Lipid Clinic Network (DLCN) algorithm was used for FH diagnosis. The overall occurrence of probable/definite FH and possible FH was 1.2% and 13.5% respectively. Among patients with ACS, 1.6% had probable/definite FH and 17.0% possible FH. The highest occurrence of FH was observed in the STEMI subgroup (20.6%). Patients with definite and probable FH had higher 30-day mortality than patients without FH (8.2% and 3.8% vs. 2.0%, respectively; p = 0.0052). No significant differences were observed between the FH groups in the 12-, 36- and 60-month follow-up. Propensity-score matching analysis showed that definite/probable FH patients had significantly higher all-cause mortality at 36- and 60-month follow-up in comparison to non-FH subjects (11.4% vs. 4.8% and 19.2% vs. 7.2%, respectively; p ≤ 0.021 for both). CONCLUSIONS: The prevalence of FH according to the DLCN criteria in the Polish very high-risk population is significantly higher in patients with ACS than in patients with sCAD. FH is a cause of increased all-cause mortality in the long-term follow-up.

The role of echocardiographic parameters in predicting survival of patients with lung diseases referred for lung transplantation.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) show poor prognosis. The importance of left (LV) and right (RV) ventricular morphology and function in patients with end-stage lung diseases referred for lung transplantation (LT) is not well established. OBJECTIVES: To assess whether LV and RV echocardiographic parameters influence survival of patients with IPF, COPD and other interstitial lung diseases (ILD) awaiting LT. METHODS: In 65 patients (20 patients with COPD, 37 with IPF and 8 with other ILD), we performed transthoracic echocardiography and right heart catheterization. Echocardiographic parameters were assessed with regard to 1-year all-cause mortality. RESULTS: The mortality rate was higher in patients with smaller dimensions of LV end-systolic (LVESD) and end-diastolic (LVEDD) diameter (HR 3.03, 95% CI 1.16-7.69, P = .023; and HR 2.9, 95% CI 1.16-7.14, P = .022; respectively), higher RV-to-LV (RV/LV-4CH) ratio (HR 7.6, 95% CI 1.6-29.5, P = .009) and RV proximal outflow tract (RVOT-PLAX) dilatation (HR 2.69, 95% CI 1.22-5.96, P = .015). These associations were independent of age, gender, body mass index, VC, FEV1% and pulmonary diagnosis. The subanalysis of IPF patients demonstrated that the smaller LVESD and LVEDD increased mortality rate (HR 15.0, 95% CI 2.87-89.72, P = .003; HR 4.95, 95% CI 1.5-15.5, P = .006; respectively). No such associations were found in the COPD patients. CONCLUSION: LV echocardiographic parameters (LVESD or LVEDD) are useful in predicting survival in patients with end-stage lung diseases, mainly in IPF patients awaiting LT. Other parameters (RV/LV-4CH and RVOT-PLAX dilatation) may also influence survival.

Characteristics of lipid profile and effectiveness of management of dyslipidaemia in patients with acute coronary syndromes - Data from the TERCET registry with 19,287 patients.

Despite well-defined therapeutic low-density lipoprotein cholesterol (LDL-C) target in the highest-risk population, low percentage of patients is administered with intensive lipid-lowering therapy and achieves recommended levels. Therefore, based on the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) Registry data we investigated the characteristics of lipid profile and management of dyslipidemia in acute coronary syndrome (ACS) patients. 19,287 consecutive patients hospitalized between 2006 and 2016 have been included in the study. The lipid profile on admission and long-term laboratory effects (namely the efficacy of achievement of the therapeutic target of LDL-C <70 mg/dl [1.8 mmol/L]) after follow-up of twelve months were assessed. Acute coronary syndromes occurred in 36.1% of the Registry patients including 14.3% with ST-elevated myocardial infarction (STEMI), 10.2% with NSTEMI and 9,9% with unstable angina (UA). The highest LDL-C concentration on admission was observed in the STEMI subgroup (mean level: 127.0 mg/dL [3.28 mmol/L]). In 76.6% of the Registry patients LDL-C concentration was lower than 130 mg/dL and in 20.7% was lower than 70 mg/dL at baseline. The patients with baseline LDL < 70 mg/dL were usually presented with the worst clinical profile. In 91,6% of the patients admitted due to acute coronary syndrome, statin treatment was administered at discharge. Among them, 37.6% received intensive statin therapy. In the 12-month follow-up, in 32.4% of patients admitted due to STEMI, LDL-C concentration was lower than 70 mg/dL, compared to 29.9% in patients with NSTEMI and 27.8% in patients with UA. In conclusion, STEMI patients are less clinically burdened with concomitant risk factors and comorbidities, but present significantly worse baseline lipid profile values. Among the patients already treated with statins, patients with ACS regardless of its type have significantly higher LDL-C than patients with SA. Despite discrepancies in the clinical profile on admission, achievement of the therapeutic target equalizes the outcomes in 12-month follow-up, however with the best results for STEMI patients.