Multimodal assessment of right ventricle overload-metabolic and clinical consequences in pulmonary arterial hypertension.

BACKGROUND: In pulmonary arterial hypertension (PAH) increased afterload leads to adaptive processes of the right ventricle (RV) that help to maintain arterio-ventricular coupling of RV and preserve cardiac output, but with time the adaptive mechanisms fail. In this study, we propose a multimodal approach which allows to estimate prognostic value of RV coupling parameters in PAH patients. METHODS: Twenty-seven stable PAH patients (49.5 ± 15.5 years) and 12 controls underwent cardiovascular magnetic resonance (CMR). CMR feature tracking analysis was performed for RV global longitudinal strain assessment (RV GLS). RV-arterial coupling was evaluated by combination of RV GLS and three proposed surrogates of RV afterload-pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR) and pulmonary artery compliance (PAC). 18-FDG positron emission tomography (PET) analysis was used to assess RV glucose uptake presented as SUVRV/LV. Follow-up time of this study was 25 months and the clinical end-point was defined as death or clinical deterioration. RESULTS: Coupling parameters (RV GLS/PASP, RV GLS/PVR and RV GLS*PAC) significantly correlated with RV function and standardized uptake value (SUVRV/LV). Patients who experienced a clinical end-point (n = 18) had a significantly worse coupling parameters at the baseline visit. RV GLS/PASP had the highest area under curve in predicting a clinical end-point and patients with a value higher than (-)0.29%/mmHg had significantly worse prognosis. It was also a statistically significant predictor of clinical end-point in multivariate analysis (adjusted R2 = 0.68; p < 0.001). CONCLUSIONS: Coupling parameters are linked with RV hemodynamics and glucose metabolism in PAH. Combining CMR and hemodynamic measurements offers more comprehensive assessment of RV function required for prognostication of PAH patients. TRIAL REGISTRATION: NCT03688698, 09/26/2018, retrospectively registered; Protocol ID: 2017/25/N/NZ5/02689.

Increased platelet content of SDF-1alpha is associated with worse prognosis in patients with pulmonary prterial hypertension.

Inflammatory processes and platelet activity play an important role in the pathophysiology of pulmonary arterial hypertension (PAH). Enhanced IL-6 signaling and higher concentration of stromal-derived factor alpha (SDF-1) have been previously shown to be linked with prognosis in PAH. We hypothesized that platelets of PAH patients have higher content of IL-6 and SDF-1 and thus are involved in disease progression. We enrolled into study 22 PAH patients and 18 healthy controls. Patients with PAH presented significantly higher plasma concentrations and platelet contents of IL-6, sIL-6R, and SDF-1 than healthy subjects (platelet content normalized to protein concentration: IL-6 (0.85*10-10 [0.29 - 1.37] vs. 0.45*10-10 [0.19-0.65], sIL-6R 1.54*10-7 [1.32-2.21] vs. 1.14*10-7 [1.01-1.28] and SDF-1 (2.72*10-7 [1.85-3.23] vs. 1.70*10-7 [1.43-2.60], all p < 0.05). Patients with disease progression (death, WHO class worsening, or therapy escalation, n = 10) had a significantly higher platelet SDF-1/total platelet protein ratio (3.68*10-7 [2.45-4.62] vs. 1.69*10-7 [1.04-2.28], p = 0.001), with no significant differences between plasma levels. Kaplan-Meier analysis revealed that patients with higher platelet SDF-1/total platelet protein ratio had more frequently deterioration of PAH in the follow-up (15.24 ± 4.26 months, log-rank test, p = 0.01). Concentrations of IL-6, sIL-6 receptor and SDF-1 in plasma and platelets are elevated in PAH patients. Higher content of SDF-1 in platelets is associated with poorer prognosis. Our study, despite of limitation due to small number of enrolled patients, suggests that activated platelets may be an important source of cytokines at the site of endothelial injury, but their exact role in the pathogenesis of PAH requires further investigation.

The significance of diminished sTWEAK and P-selectin content in platelets of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by proliferative changes in pulmonary arteries. There is growing evidence suggesting that soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and P-selectin could be involved in PAH development and progression. Here we investigate whether circulating platelets may be a source of sTWEAK and contribute to diminished availability of sTWEAK and P-selectin in PAH patients. We have prospectively enrolled two independent study groups of stable patients with confirmed PAH and age matched controls: derivation (10 PAH; 15 controls) and validation (20 PAH; 12 controls). P-selectin and sTWEAK concentrations were measured in platelet-poor plasma and platelet lysate. To avoid procedural bias, in each group we employed different protocols for platelet isolation. Consistently, both in derivation and validation groups PAH patients presented significantly lower sTWEAK content in platelets than control group with no significant differences in plasma levels. Similarly, patients presented comparable to controls plasma P-selectin concentrations and lower concentration in platelet lysate. Kaplan-Meier analysis revealed that patients with low platelet sTWEAK/total protein concentration ratio had more frequently detoriation of PAH in the follow-up (16.51 ±â€¯3.32 months), log-rank test, p = .03. Patients diagnosed with pulmonary arterial hypertension present diminished sTWEAK and P-selectin storage capacity in platelets. Thrombocytes appear to be a major source of sTWEAK that could be released upon local injury and its decreased availability could have an impact on pathophysiology and prognosis in PAH.

CHA2 DS2 VASc score predicts unsuccessful electrical cardioversion in patients with persistent atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia occurring in 2% of the population. It is known that AF increases morbidity and limits quality of life. The CHA2 DS2 VASc score (congestive heart failure/left ventricular dysfunction, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65-74 and sex category (female)) is widely used to assess thrombotic complications. The CHA2 DS2 VASc score was not used until now in predicting the effectiveness of electrical cardioversion. AIM: To assess the value of CHA2 DS2 VASc score in predicting unsuccessful electrical cardioversion. METHODS: We analysed 258 consecutive patients with persistent AF who underwent electrical cardioversion between January 2012 and April 2016 in a Cardiology University Centre in Poland. RESULTS: Out of 3500 hospitalised patients with AF, 258 (mean age 64 ± 11 years, 64% men) underwent electrical cardioversion. The CHA2 DS2 VASc score in analysed population (258 patients) was 2.5 ± 1.7 (range 0-8), and the HAS-BLED (hypertension, abnormal liver or renal function, stroke, bleeding, labile international normalised ratio, elderly, drugs or alcohol) was 1 ± 0.9 (range 0-4). Electrical cardioversion was unsuccessful in 12%. Factors associated with unsuccessful cardioversion were age (P = 0.0005), history of ischaemic stroke (P = 0.04), male gender (P = 0.01) and CHA2 DS2 VASc score (P = 0.002). The CHA2 DS2 VASc score in patients who had unsuccessful cardioversion was higher compared to patients who had successful cardioversion - 3.5 versus 2.4 (P = 0.001). In the logistic regression model, if the CHA2 DS2 VASc score increases by 1, the odds of unsuccessful cardioversion increase by 39% (odds ratio (OR) 1.39; confidence interval (CI): 1.12-1.71; P = 0.002). The odds of unsuccessful cardioversion are three times higher in patients with a CHA2 DS2 VASc score ≥ 2 than in patients with a CHA2 DS2 VASc score of 0 or 1 (OR 3.06; CI: 1.03-9.09; P = 0.044). CONCLUSION: The CHA2 DS2 VASc score routinely used in thromboembolic risk assessment may be a simple, easy and reliable scoring system that can be used to predict unsuccessful electrical cardioversion.

Alterations of soluble TWEAK and CD163 concentrations in patients with chronic heart failure.

UNLABELLED: Inflammatory activation plays a pivotal role in chronic heart failure with reduced ejection fraction (HF-REF). A novel mediator from TNF family: soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) along its soluble decoy receptor CD163 (sCD163) recently has been investigated in other cardiovascular pathologies. We aimed to evaluate sTWEAK and sCD163 concentrations in HF-REF patients. The study enrolled 79 patients with stable HF-REF, EF < 35%. The control population without history of heart failure included two groups: 26 comorbidities matched patients and 27 healthy volunteers. sTWEAK and sCD163 serum concentrations were determined using ELISA kits. Univariate and multivariate analysis was performed to assess variables affecting concentration of sTWEAK and sCD163. HF-REF patients were characterized by higher sTWEAK (median 374 IQR: 321-429 vs 201 IQR: 145-412pg/ml, P=0.005), sCD163 (median 744 IQR: 570-1068 vs 584 IQR: 483-665pg/ml, P=0.03) concentrations and sTWEAK/sCD163 ratio (median 0.53 IQR: 0.32-0.7 vs 0.3 IQR: 0.22-0.37, P=0.001) comparing to healthy volunteers. Comparing to comorbidities matched controls, HF-REF patients had lower sTWEAK levels (median 374 IQR: 321-429 vs 524 IQR: 384-652pg/ml; P=0.002), while sCD163 and sTWEAK/sCD163 ratio didn't differ. Concentration of sTWEAK in HF-REF was affected by white blood cell count and aspirin intake, while sCD163 by exercise capacity, LV diastolic volume, CRP and presence of arterial hypertension. CONCLUSIONS: HF-REF patients present increased sTWEAK and sCD163 levels as well as sTWEAK/sCD163 ratio when compared to healthy subjects, however CHF itself appears to be associated with down-regulation of sTWEAK.

The influence of renal function on the association of rs854560 polymorphism of paraoxonase 1 gene with long-term prognosis in patients after myocardial infarction.

Paraoxonase 1 (PON1) is an enzyme responsible for the antioxidant properties of high density lipoprotein (HDL). The activity of PON1 is decreased in patients with coronary artery disease, myocardial infarction or chronic kidney disease. rs662 and rs854560 are single nucleotide polymorphisms (SNPs) associated with PON1 activity and 10-year cardiovascular mortality of patients with stable coronary artery disease. We investigated the association of rs662 and rs854560 SNPs of the PON1 gene with 5-year mortality in patients with ST-elevation myocardial infarction (STEMI) treated invasively. We analyzed the data of consecutive patients with STEMI treated with primary PCI. Genotyping was performed with the TaqMan method. The analyzed end-point was total 5-year mortality. Additional subgroup analysis was performed for survival of patients depending on their eGFR. The study group comprised 634 patients (mean age 62.3 ± 11.85 years; 25.2% of women, n = 160; PCI successful in 92.3%, n = 585). No clinically relevant differences in baseline characteristics were found between the genotypes. No association between either genotype and 5-year mortality was found: p = 0.4 for the rs662 SNP, p = 0.73 for the rs854560 one (log-rank test). However, in a subgroup of patients with eGFR below median value (78.6 ml/min/1.73m2) the rs854560 AA homozygotes had a significantly lower probability of survival (p = 0.047, log-rank test). The AA genotype of the rs854560 SNPs of the PON1 gene is associated with increased mortality in patients after myocardial infarction in the subpopulation of patients with lowered eGFR. This phenomenon may be explained by potentially lower PON1 activity in kidney disease.

The 9p21 polymorphism is linked with atrial fibrillation during acute phase of ST-segment elevation myocardial infarction.

The aim of the study was to find whether patients carrying polymorphic allele of the rs10757278 polymorphism from 9p21 locus have changed risk of arrhythmia (atrial fibrillation, AF; sustained ventricular tachycardia or ventricular fibrillation, sVT/VF) during acute phase of myocardial infarction. Retrospective analysis of data collected prospectively from two independent centers was performed. The clinical data were pooled from two independent cardiac registries: (1) the Warsaw ACS genetic registry (STEMI and NSTEMI/UA patients hospitalized in the years 2008-2011; only STEMI patients were analyzed); (2) the Bialystok STEMI genetic registry (STEMI patients hospitalized in years 2001-2005, who survived the first 48 h from hospital admission). Data regarding sVT/VF and AF within first 24 h were analyzed. The patients were genotyped with rs10757278 polymorphism. 1083 patients were included in the analysis; 62 (5.7 %) patients had sVT/VF during acute phase and 78 (7.2 %) patients had AF, 46 (4.2 %) patients had new-onset AF. Minor allele frequency in all patients with AF was significantly different from those without AF (0.40 vs 0.51, p = 0.0096). When only new-onset AF was analyzed, the trend was the same, with significant protective effect in recessive model [OR 0.41 (95 % CI 0.17-0.97), p = 0.025]. The effect was independent of age and GRACE score. No relationship was found between sVT/VF and rs10757278. Patients with STEMI, who survived until hospitalization with polymorphic allele of 9p21 rs10757278 SNP have less AF during acute phase of STEMI. SNP rs10757278 is not linked with sVT/VF in acute phase of STEMI.

Predictors of Long-Term Mortality in Patients Hospitalized in an Intensive Cardiac Care Unit.

Patients admitted to an intensive cardiac care unit (ICCU) are a heterogeneous population with a high mortality rate. The aim of our study was to investigate which clinical, biochemical, and echocardiographic parameters routinely assessed may affect long-term mortality in a non-selected ICCU population.A total of 392 patients hospitalized between 2008-2011 (mean age, 70 ± 13.8 years, 43% women) were consecutively and prospectively assessed with the following admission diagnoses: 168 with acute coronary syndromes (ACS), 122 with acute decompensated heart failure (ADHF), and 102 with other acute cardiac disorders. Patients were treated according to the current European Society of Cardiology (ESC) guidelines.During a mean 29.3 (± 18.9) months of observation, 152 (38.8%) patients died and 7.9% of the patients needed a red blood cell transfusion (RBC Tx). Patients who died were significantly older and had lower baseline levels of hemoglobin (Hb), serum iron concentration (SIC), total iron binding capacity (TIBC), cholesterol, and left ventricular ejection fraction (LVEF), as well as lower eGFR values, and higher white blood cell (WBC) counts and C-reactive protein (CRP) levels (P < 0.05). Predictors of death in multivariate regression analysis were age, Hb, LVEF, WBC, and CRP. The most powerful factor was hospitalization for non-ACS. The risk of long-term mortality increased with decreasing levels of Hb (P < 0.001), SIC (P = 0.001), TIBC (P = 0.009), and the need for RBC Tx (P < 0.001), as well as the diagnosis of ADHF (P < 0.001) and the absence of ACS (P = 0.007).In ICCU patients, age, Hb, parameters of iron status, and LVEF are strong predictors of long-term mortality. Among the ICCU population, patients with ACS diagnosis have better survival.

Enhanced IL-6 trans-signaling in pulmonary arterial hypertension and its potential role in disease-related systemic damage.

BACKGROUND: The role of IL-6 in pulmonary arterial hypertension (PAH) has been reported but the prevalence of soluble receptors for IL-6: sIL-6R and sgp130 and its potential role in PAH have not been studied.Our aim was to examine the IL-6 together with the soluble receptors and to assess its relationship with clinical status of PAH patients as well as to assess its potential prognostic significance. METHODS: Serum concentrations of IL-6, sIL-6R and sgp130 were quantified by ELISA in 26 patients with PAH and 27 healthy controls and related to functional and biochemical parameters and clinical outcome in PAH group. The PAH patients were followed up for 1 year, noting the end point of clinical deterioration (WHO class change, the need for escalation of therapy) or death. RESULTS: The PAH group was characterized by higher median serum IL-6 [2.38 (IQR 1.56-3.75) vs 0.87 (0.63-1.3) pg/ml, p=0.000003] and sIL-6R concentrations [69.7 (IQR 60.4-84.4 vs 45.7 (34.6-70.3) ng/ml, p=0.0036] compared to control subjects. Both groups did not differ in sgp130 concentrations. There were significant correlations in PAH group between IL-6 levels and uric acid, parameters of ventilatory efficiency in cardiopulmonary exercise testing: VE/VO2, VE/VCO2, VE/VCO2 slope and peak PetCO2. sIL-6R levels inversely correlated with LDL cholesterol. After 1 year the clinical deterioration occurred in 11 patients, 15 remained stable. Patients in whom the clinical deterioration occurred showed significantly higher baseline concentrations of IL-6 [3.25 (IQR 2.46-5.4) pg/ml vs 1.68 (1.38-2.78) pg/ml, p=0.004], but not sIL-6R. Median IL-6 ⩾ 2.3 pg/ml (91% sensitivity, 73% specificity) identified subjects with worse clinical course. In the univariate analysis, higher IL-6 level at baseline was associated with increased risk and earlier occurrence of clinical deterioration (HR 1.42, 95%CI 1.08-1.85, p=0.015). CONCLUSIONS: IL-6 trans-signaling is enhanced in PAH. Elevated concentration of sIL-6R suggests its potential unfavorable role in systemic amplification of IL-6 signaling in PAH. Levels of IL-6 are associated with clinical indicators of disease severity as well as indirectly with systemic metabolic alterations. IL-6 shows prognostic value regarding predicting clinical deterioration.

Do CHA2 DS2 VASc and HAS-BLED scores influence 'real-world' anticoagulation management in atrial fibrillation? 1556 patient registry from the reference cardiology centre.

INTRODUCTION: Although recommendations for the antithrombotic management of atrial fibrillation (AF) are based on strong evidence, the European guidelines are not fully implemented into practice. OBJECTIVES: The objective of this study is to analyse antithrombotic treatment in AF in Poland after the publication of the European Society of Cardiology Guidelines in 2012. PATIENTS AND METHODS: We retrospectively studied 1556 patients with AF from the Reference Cardiology University Centre in Poland in 2012-2014. RESULTS: CHA2 DS2 VASc and HAS-BLED scores were 3.5 ± 1.7 and 2.4 ± 1.1. Anti-vitamin K agent were prescribed in 59%, with non-vitamin K antagonist oral anticoagulants in 12%, acetylsalicylic acid (ASA) alone in 18%. Older patients (p < 0.0001) and with paroxysmal AF were less likely to receive oral anticoagulation (OAC, p < 0.0001). The risk of stroke according to CHA2 DS2 VASc score was higher in patients who did not receive OAC (p < 0.0001). The use of OAC increased with increasing CHA2 DS2 VASc score but was less frequent in score ≥ 4. The risk of bleeding was higher in patients without OAC (p < 0.0001). The odds of non-vitamin K antagonist oral anticoagulants use were lower for older patients, patients with ischaemic heart disease, chronic heart failure, anaemia, HAS-BLED ≥ 3 and valvular AF. ASA was given in 39% of the patients, especially in paroxysmal AF (p < 0.0001). The odds of ASA alone were higher for older patients, with ischaemic heart disease and history of myocardial infarction (p < 0.0001). The odds of use of ASA as the only treatment were 5.5 times higher for HAS-BLED ≥ 3 (p < 0.0001). CONCLUSIONS: Antithrombotic management in AF is well implemented in Polish conditions, but we show the lack of pattern concerning who is being treated with OAC and ASA when it comes to the risk of stroke and bleeding.

Is real time contrast echocardiography useful for assessment of the right ventricular morphology, function, and perfusion?

BACKGROUND: Contrast-enhanced echocardiography (CE) is recommended to assess left ventricular function and perfusion but is rarely used to assess the right ventricle (RV). We used CE to assess RV function and perfusion and evaluated whether RV perfusion defects varied in different patient groups with RV failure due to pressure overload. METHODS: We studied 17 patients with acute pulmonary embolism (PE), 19 patients with chronic pulmonary arterial hypertension (CPH), and 7 healthy volunteers. The examination included RV opacification (RVO) and myocardial CE. RV end-diastolic area (RVEDA), RV end-systolic area (RVESA), fractional area change (FAC), and wall-motion score index (WMSI) were assessed before and after contrast agent administration. Perfusion was evaluated qualitatively and quantitatively. RESULTS: RVEDA, RVESA, FAC, and regional contractility were comparable before and after contrast agent injection. Significant perfusion defects were seen in PE and CPH (18/39 segments and 37/51 segments, respectively, vs. 0/21 segments in healthy volunteers; P < 0.0001). Wall-perfusion score index (WPSI) was higher in PE and CPH compared to healthy volunteers (1.5 ± 0.3 and 1.8 ± 0.4 vs. 1.0 ± 0.0; P = 0.02 and P = 0.0003, respectively). Linear correlations were noted between WMSI, FAC and WPSI (r = 0.5, P = 0.014 and r = -0.55, P = 0.005, respectively). Quantitative perfusion assessment revealed perfusion defects in the apical segment in the PE group. The mean region of interest value was insignificantly reduced in PE and CPH groups. CONCLUSION: Contrast-enhanced echocardiography is feasible and may be useful for RVO and perfusion assessment in patients with RV dysfunction due to systolic overload. The SonoVue contrast agent was well tolerated by stable patients with PE and CPH.

Serum levels of CD163 and TWEAK in patients with pulmonary arterial hypertension.

BACKGROUND: Inflammation may play a pivotal role in the pathogenesis of pulmonary arterial hypertension (PAH). We evaluated the concentrations of serum sTWEAK, its scavenger receptor sCD163 and sTWEAK/sCD163 ratio in patients with PAH. DESIGN: The study enrolled 26 stable patients with PAH confirmed by right heart catheterization and 24 healthy volunteers matched for age, sex and body weight. All patients underwent transthoracic echocardiography, cardiopulmonary exercise test, 6-min walk test, measurement of lung diffusing capacity for the carbon monoxide (DLCO) and venous blood tests. Concentrations of sTWEAK and sCD163 were determined using ELISA kits. RESULTS: The PAH patients were characterized by significantly higher median serum sCD163 levels (1072 vs 890ng/ml, p=0.04) together with lower serum sTWEAK concentrations (200 vs 278.1pg/ml, p=0.003) comparing to control subjects. sTWEAK/sCD163 ratio was therefore significantly lower in PAH group (0.18 vs 0.33, p=0.0005). No correlation was found between sTWEAK and sCD163 concentrations in both groups. We observed statistically significant inverse correlation between peak VO2 consumption and sCD163 concentrations (r=-0.52, p<0.05) and positive with sTWEAK/sCD163 ratio (r=0.45, p<0.05) in PAH group. Moreover, sTWEAK/sCD163 ratio positively correlated with % of predicted values of DLCO (r=0.42, p<0.05). CONCLUSIONS: Patients with PAH present altered serum sTWEAK and sCD163 levels. The sTWEAK/sCD163 ratio appears to be a better indicator of the severity of PAH as compared to sTWEAK or sCD163 alone. The exact role of sCD163 or interaction between CD163 and sTWEAK in the initiation or progression of PAH as well as their potential prognostic significance remains to be established.

Is there association between changes in eGFR value and the risk of permanent type of atrial fibrillation? Analysis of valvular and non-valvular atrial fibrillation population.

BACKGROUND/AIMS: There are no data concerning renal function in population with valvular and non-valvular atrial fibrillation (AF). To assess renal function in patients with AF, the association between eGFR and AF perpetuation, in-hospital mortality. METHODS: We studied 1523 patients with AF. Patients with chronic kidney disease (CKD) were compared to population with preserved renal function. RESULTS: CKD was more frequently observed in patients with valvular AF(p=0.009). In non-valvular AF patients eGFR <60 ml/min./1,73 m2 had more often permanent AF (p<0.0001). In patients with CKD CHA2DS2VASc score was 4.1±1.5 and HAS-BLED score was 2.1±1.2 and it was higher as compared to population with preserved renal function (p<0.0001 vs. p<0.0001). The odds of permanent AF in patients with non-valvular AF and CKD were increased 1.82 times (OR=1.82, p<0.0001, 95% CI:1.46-2.27). The odds of permanent AF in patients with valvular AF and CKD were not significantly increased (OR=1.46, p=0.2,95% CI:0.86-2.5). In non-valvular AF, if eGFR decrease by 10 ml/min, odds of permanent AF are increased by 10% (OR=1.1 p<0.0001, 95% CI 1.05-1.15). In multivariate logistic regression, in non-valvular AF, odds of in-hospital death were higher for patients >75 years old (OR=3.70, p=0.01, 95% CI 1.33-10.28), with CKD (OR=2.61, p=0.03, 95% CI 1.09-6.23). The type of AF had no significant influence on in-hospital mortality(OR=0.71, p=0.45,95% CI 0.30-1.70). CONCLUSIONS: CKD is more often observed in patients with valvular AF. In population with non-valvular AF decreased eGFR is associated with permanent type of AF and with higher CHA2DS2VASc and HAS-BLED score. Among valvular AF patients there are no differences in type of AF between patients with and without CKD. There is the correlation between CKD and AF perpetuation but only in non-valvular population.

Sustained decrease in plasma sphingosine-1-phosphate concentration and its accumulation in blood cells in acute myocardial infarction.

Sphingosine-1-phosphate (S1P) is a cardioprotective sphingolipid present at high concentration in plasma and blood cells. However, effect of the myocardial infarction on S1P metabolism in blood is poorly recognized. Therefore, we aimed to examine the dynamics of changes in concentration of sphingolipids in blood of patients with acute ST-segment elevation myocardial infarction (STEMI). The study was performed on two groups of subjects: healthy controls (n=32) and patients with STEMI (n=32). In the latter group blood was taken upon admission to intensive heart care unit, and then on the second, fifth and thirtieth day, and approximately two years after admission. STEMI patients showed decreased plasma S1P concentration and accumulation of free sphingoid bases and their 1-phosphates in erythrocytes. This effect was already present upon admission, and was maintained for at least thirty days after the infarction. Interestingly, two years post-infarction plasma S1P level recovered only partially, whereas the content of erythrocyte sphingolipids decreased to the values observed in the control subjects. The most likely reason for the observed reduction in plasma S1P level was its decreased release or increased degradation by vascular endothelial cells, as we did not find any evidence for downregulation of S1P synthesis or release by blood cells. We conclude that patients with STEMI are characterized by marked alterations in sphingolipid metabolism in blood which could be a consequence of the infarction itself, the antiplatelet treatment given or both. Our data suggest that cardioprotective action of S1P may be diminished in patients with acute myocardial infarction.

Does neutrophil gelatinase-asociated lipocalin have prognostic value in patients with stable angina undergoing elective PCI? A 3-year follow-up study.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), a widely accepted diagnostic marker of acute renal injury (AKI) may be involved in the development of atherosclerosis. PURPOSE: To assess the prognostic significance of serum and urinary NGAL and serum cystatin C in patients with stable angina undergoing percutaneous coronary intervention (PCI) on a 3-year follow-up. METHODS: We included patients with stable angina undergoing PCI. Serum NGAL and cystatin C were evaluated before and 4h, 8h after PCI. Urinary NGAL was evaluated before and 12h and 24h after the procedure. The primary end-point was all-cause mortality on a 3-year follow-up. RESULTS: Among 132 patients there were 63% of males (mean age 64,5±9,8 years). Mean eGFR was 86.2±28.5 ml/min. During follow-up 8% of the patients died. All-cause mortality was significantly higher in patients with increased urinary NGAL concentration 12h after PCI (p=0.04). Urinary NGAL 12h after PCI correlated with eGFR (p<0.05), with serum NGAL evaluated before and 4h and 8h after PCI (p<0.05) and with increased serum cystatin C evaluated 4 hours after PCI (p<0.05). CONCLUSIONS: Increased urinary NGAL concentration is a strong predictor of mortality in patients with stable angina who undergo PCI and may be used for the risk stratification in this population.

Pharmacologic treatment in dialysis patients hospitalized for cardiovascular reasons: do we follow the guidelines?

AIM: The aim was to assess if the pharmacological treatment due to cardiovascular causes in dialysis patients is compliant with the European Guidelines. METHODS: In total, 110 consecutive end-stage renal disease (ESRD) patients on regular dialysis were enrolled into the study. We divided the population into subgroups with coronary artery disease (CAD), chronic heart failure (CHF) and diabetes mellitus (DM). RESULTS: We gathered information about drugs from 99 patients. The mean age was 61.8 ± 12.9 years (70% of males). There were 37 patients with CAD. Acetylsalicylic acid (ASA) was taken by 89% of the patients with CAD, clopidogrel by 25%, beta-blockers by 70%, angiotensin converting enzyme inhibitors (ACEIs) by 50%, angiotensin receptor blockers (ARBs) by 8%, and statins by 41%. Dual antiplatelet therapy was used after stent implantation (35%). There were 24 patients with CHF. Beta-blockers were taken by 71% of the patients, ACEIs by 45%, statins by 54%, and diuretics by 21% with CHF. There were 36 patients with DM. ASA was taken by 89% of the patients, clopidogrel and ticlopidine by 34%, beta-blockers were taken by 67%, ACE-inhibitors by 55%, and statins by 38% of the population with DM. The patients with DM were taking more ACEIs than those without DM (p = 0.033). DM was associated with a statistically 21% higher odds of ACEI/ARB use, but CHF was associated with no increase in the odds of beta-blocker use and no increase in ACEI/ARB use. CONCLUSIONS: Dialysis patients with cardiovascular diseases are given less cardioprotective drugs such as ASA, beta-blockers, ACEIs, ARBs, and statins than they should be given according to the guidelines.

Impact of diabetes mellitus on survival in patients with end-stage renal disease: a three-year follow-up.

BACKGROUND/AIMS: To assess the impact of diabetes mellitus (DM) on clinical outcome in patients with end-stage renal disease (ESRD) on a 3-year follow-up. METHODS: 58 ESRD patients were divided into 2 groups according to the presence of DM. We analyzed following end points: death, cardiac arrest, myocardial infarction, stroke, hospitalizations due to cardiovascular causes, revascularization, and combined end point. RESULTS: Among diabetics, 14 (77.8%) had significant atherosclerotic changes, in the group without DM only 8 (38.1%), p = 0.01. In the group without DM, 14 (46.7%) patients reached combined end point, while in the group with DM 16 (53.3%) patients, p = 0.0013. There were no statistical differences in mortality (p = 0.423). CONCLUSION: Survival of hemodialyzed diabetic patients is not inferior to nondiabetics; however, morbidity is significantly higher due to adverse cardiac events.

Which method of GFR estimation has the best prognostic value in patients treated with primary PCI: Cockcroft-Gault formula, MDRD, or CKD-EPI equation?--A 6-year follow-up.

BACKGROUND/AIMS: The aim of this study was to determine the correlation between renal function and 6-year mortality in patients with acute myocardial infarction (AMI), treated successfully with primary percutaneous coronary intervention (PCI), and to examine whether Cockcroft-Gault (C-G) formula or Modification of Diet in Renal Disease (MDRD) study equation or CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation is the best predictor of very late mortality. METHODS: A prospective cohort study with 6-year follow-up of a homogenous group of 193 patients, with ST-segment elevation AMI treated with successful primary PCI. Glomerular filtration rate (GFR) estimated by C-G formula, MDRD, and CKD-EPI equation were analyzed. RESULTS: The patients with chronic kidney disease (CKD) had a much lower cumulative survival rate than those without it (p < 0.05). A larger area under the receiver-operating characteristic curve for death with respect to GFR for C-G formula was observed. In the multivariate analysis, only GFR ≥ 55 mL/min according to C-G formula was independently associated with lower mortality. CONCLUSION: CKD is associated with higher mortality after a successful primary PCI during a 6-year follow-up. C-G formula is better than MDRD and CKD-EPI equations at predicting mortality after AMI.

[The role of matrix metalloproteinases in cardiovascular diseases]. / Metaloproteinazy macierzy zewnatrzkomórkowej w chorobach ukladu krazenia.

Matrix metalloproteinases (MMPs) belong to a large family of multidomain zinc endopeptidases. They are one of the most important proteolytic enzymes which digest components of the extracellular matrix and take part in many physiological processes, such as apoptosis or angiogenesis. It was shown that MMPs are also involved in the pathogenesis of many diseases such as malignant tumors and cardiovascular diseases. The discovery of the mechanisms of MMPs' action can have significant influence on therapeutic strategy, especially in cardiovascular diseases.

Prognostic value of late gadolinium enhancement mass index in patients with pulmonary arterial hypertension.

PURPOSE: Dysfunction of the right ventricle (RV) is an important determinant of survival in patients with pulmonary arterial hypertension (PAH). The presence of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) at RV insertion points (RVIPs) has been found in majority of PAH patients and was associated with parameters of RV dysfunction. We hypothesize, that more detailed quantification of LGE may provide additional prognostic information. MATERIAL AND METHODS: Twenty-eight stable PAH patients (mean age 49.9 â€‹± â€‹15.9 years) and 12 healthy subjects (control group, 44.8 â€‹± â€‹13.5 years) were enrolled into the study. Septal LGE mass was quantified at the RVIPs and subsequently indexed by subject's body surface area. Mean follow-up time of this study was 16.6 â€‹± â€‹7.5 months and the clinical end-point (CEP) was defined as death or clinical deterioration. RESULTS: Median LGE mass index (LGEMI) at the RVIPs was 2.75 â€‹g/m2 [1.41-4.85]. We observed statistically significant correlations between LGEMI and hemodynamic parameters obtained from right heart catheterization - mPAP (r â€‹= â€‹0.61, p â€‹= â€‹0.001); PVR (r â€‹= â€‹0.52, p â€‹= â€‹0.007) and from CMR - RVEF (r â€‹= â€‹-0.54, p â€‹= â€‹0.005); RV global longitudinal strain (r â€‹= â€‹0.42, p â€‹= â€‹0.03). Patients who had CEP (n â€‹= â€‹16) had a significantly higher LGEMI (4.49 [2.75-6.17] vs 1.67 [0.74-2.7], p â€‹= â€‹0.01); univariate Cox analysis confirmed prognostic value of LGEMI. Furthermore, PAH patients with LGEMI higher than median had worse prognosis in Kaplan-Meier analysis (log-rank test, p â€‹= â€‹0.0006). CONCLUSIONS: The body surface indexed mass of LGE at RV septal insertion points are suggestive of RV hemodynamic dysfunction and could be a useful non-invasive marker of PAH prognosis.