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.

Mean platelet volume is associated with serum 25-hydroxyvitamin D concentrations in patients with stable coronary artery disease.

There is little published data on the association of platelet function and 25(OH)D concentration. We investigated the associations between mean platelet volume (MPV) and 25(OH)D concentration in patients with stable coronary artery disease. Study population was divided into three groups: group 1-25(OH)D < 10 ng/mL (N = 22), group 2-25(OH)D 10-20 ng/mL (N = 42), and group 3-25(OH)D > 20 ng/mL (N = 14). Study groups shared similar demographics. MPV values were the highest in group 1, moderate in group 2, and the lowest in group 3 (11.1 vs 10.4 vs 9.8 fL P < 0.001). There was a negative correlation between MPV and 25(OH)D (R = - 0.38, P = 0.001). ROC analysis demonstrated a moderate predictive value (AUC 0.70) in identifying the discrimination thresholds of MPV (> 10.5 fL) for vitamin D deficiency and a weak predictive value (AUC 0.65) in identifying the discrimination thresholds of 25(OH)D concentration (≤ 15.5 ng/mL) for the presence of large platelets (MPV over the upper limit of normal). In conclusion, even though the effect of vitamin D on platelet size and function is probably multifactorial, our study provides further evidence linking vitamin D to thrombosis and hemostasis. Platelets are another potential element through which vitamin D deficiency could exert adverse cardiovascular outcomes.

Interaction of myosin VI and its binding partner DOCK7 plays an important role in NGF-stimulated protrusion formation in PC12 cells.

DOCK7 (dedicator of cytokinesis 7) is a guanidine nucleotide exchange factor (GEF) for Rac1 GTPase that is involved in neuronal polarity and axon generation as well in Schwann cell differentiation and myelination. Recently, we identified DOCK7 as the binding partner of unconventional myosin VI (MVI) in neuronal-lineage PC12 cells and postulated that this interaction could be important in vivo [Majewski et al. (2012) Biochem Cell Biol., 90:565-574]. Herein, we found that MVI-DOCK7 interaction takes also place in other cell lines and demonstrated that MVI cargo domain via its RRL motif binds to DOCK7 C-terminal M2 and DHR2 domains. In MVI knockdown cells, lower Rac1 activity and a decrease of DOCK7 phosphorylation on Tyr1118 were observed, indicating that MVI could contribute to DOCK7 activity. MVI and DOCK7 co-localization was maintained during NGF-stimulated PC12 cell differentiation and observed also in the outgrowths. Also, during differentiation an increase in phosphorylation of DOCK7 as well as of its downstream effector JNK kinase was detected. Interestingly, overexpression of GFP-tagged MVI cargo domain (GFP-GT) impaired protrusion formation indicating that full length protein is important for this process. Moreover, a transient increase in Rac activity observed at 5min of NGF-stimulated differentiation of PC12 cells (overexpressing either GFP or GFP-MVI) was not detected in cells overexpressing the cargo domain. These data indicate that MVI-DOCK7 interaction could have functional implications in the protrusion outgrowth, and full length MVI seems to be important for delivery and maintenance of DOCK7 along the protrusions, and exerting its GEF activity.

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.

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.

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.

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.

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).

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.

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.

Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure.

BACKGROUND: Iron is an indispensable element of hemoglobin, myoglobin, and cytochromes, and, beyond erythropoiesis, is involved in oxidative metabolism and cellular energetics. Hence, iron deficiency (ID) is anticipated to limit exercise capacity. We investigated whether ID predicted exercise intolerance in patients with systolic chronic heart failure (CHF). METHODS AND RESULTS: We prospectively studied 443 patients with stable systolic CHF (age 54 ± 10 years, males 90%, ejection fraction 26 ± 7%, New York Heart Association Class I/II/III/IV 49/188/180/26). ID was defined as: serum ferritin <100 µg/L or serum ferritin 100-300 µg/L with serum transferrin saturation <20%. Exercise capacity was expressed as peak oxygen consumption (VO(2)) and ventilatory response to exercise (VE-VCO(2) slope). ID was present in 35 ± 4% (±95% confidence interval) of patients with systolic CHF. Those with ID had reduced peak VO(2) and increased VE-VCO(2) slope as compared to subjects without ID (peak VO(2): 13.3 ± 4.0 versus 15.3 ± 4.5 mL•min•kg, VE-VCO(2) slope: 50.9 ± 15.8 versus 43.1 ± 11.1, respectively, both P < .001, P < .05). In multivariable models, the presence of ID was associated with reduced peak VO(2) (ß = -0.14, P < .01 P < .05) and higher VE-VCO(2) slope (ß = 0.14, P < .01 P < .05), adjusted for demographics and clinical variables. Analogous associations were found between serum ferritin, and both peak VO(2) and VE-VCO(2) slope (P < .05). CONCLUSIONS: ID independently predicts exercise intolerance in patients with systolic CHF, but the strength of these associations is relatively weak. Whether iron supplementation would improve exercise capacity in iron-deficient subjects requires further studies.

Iron deficiency: an ominous sign in patients with systolic chronic heart failure.

AIMS: Beyond erythropoiesis, iron is involved in numerous biological processes crucial for maintenance of homeostasis. Patients with chronic heart failure (CHF) are prone to develop iron deficiency (ID), and iron supplementation improves their functional status and quality of life. We sought to examine the relationship between ID and survival in patients with systolic CHF. METHODS AND RESULTS: In a prospective observational study, we evaluated 546 patients with stable systolic CHF [age: 55 +/- 11 (mean +/- standard deviation) years, males: 88%, left ventricular ejection fraction: 26 +/- 7%, New York Heart Association (NYHA) class (I/II/III/IV): 57/221/226/42]. Iron deficiency was defined as: ferritin <100 microg/L, or 100-300 microg/L with transferrin saturation <20%. The prevalence of ID was 37 +/- 4% [+/-95% confidence intervals (CI)] in the entire CHF population (32 +/- 4 vs. 57 +/- 10%-in subjects without vs. with anaemia defined as haemoglobin level <12 g/dL in women and <13 g/dL in men, P < 0.001). In a multiple logistic model, ID was more prevalent in women, those in the advanced NYHA class, with higher plasma N-terminal pro-type B natriuretic peptide and higher serum high-sensitivity C-reactive protein (all P < 0.05). At the end of follow-up (mean duration: 731 +/- 350 days), there were 153 (28%) deaths and 30 (6%) heart transplantations (HTX). In multivariable models, ID (but not anaemia) was related to an increased risk of death or HTX (adjusted hazard ratio 1.58, 95% CI 1.14-2.17, P < 0.01). CONCLUSION: In patients with systolic CHF, ID is common and constitutes a strong, independent predictor of unfavourable outcome. Iron supplementation may be considered as a therapeutic approach in these patients to improve prognosis.

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.

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.

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.

Therapeutic window for calcium-channel blockers in the management of dilated cardiomyopathy: a prospective, two-centre study on non-advanced disease.

OBJECTIVE: This study aimed to investigate the usefulness of the calcium-channel blocker verapamil in non-advanced dilated cardiomyopathy (DCM). METHODS: This was a randomised trial of 70 DCM patients treated with carvedilol (36 patients) and verapamil (instead of ß-blocker; 34 patients) for 12 months. The remaining heart failure (HF) therapy was constant in both groups. The primary outcomes were to determine selected echocardiography parameters and functional status of patients. The secondary outcome included death, heart transplantation and re-hospitalisation due to HF progression. RESULTS: Of the primary outcomes, only the mean ratio of early to late transmitral flow velocities increased significantly in the verapamil-treated patients as compared with the carvedilol-based therapy (1.1 ± 0.3 vs. 0.7 ± 0.2; 95% CI -0.6 to -0.1; p = 0.015). Simultaneously, the Minnesota Quality of Life improved significantly in the verapamil group (95% CI 5.2-19.9; p = 0.002). It was accompanied by the favourable effect of verapamil therapy on exercise capacity in the 6-min walk test (95% CI 21.3-110.7; p = 0.005). CONCLUSION: The addition of verapamil to angiotensin-converting enzyme and aldosterone inhibitors in non-advanced DCM patients has been shown to have a neutral or even positive effect in a few patients.

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.