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.

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.

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.

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.

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.

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.

Prognostic role of PET/MRI hybrid imaging in patients with pulmonary arterial hypertension.

OBJECTIVE: Right ventricular (RV) function is a major determinant of survival in patients with pulmonary arterial hypertension (PAH). Metabolic alterations may precede haemodynamic and clinical deterioration. Increased RV fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) was recently associated with progressive RV dysfunction in MRI, but the prognostic value of their combination has not been established. METHODS: Twenty-six clinically stable patients with PAH (49.9±15.2 years) and 12 healthy subjects (control group, 44.7±13.5 years) had simultaneous PET/MRI scans. FDG uptake was quantified as mean standardised uptake value (SUV) for both left ventricle (LV) and RV. Mean follow-up time of this study was 14.2±7.3 months and the clinical end point was defined as death or clinical deterioration. RESULTS: Median SUVRV/SUVLV ratio was 1.02 (IQR 0.42-1.21) in PAH group and 0.16 (0.13-0.25) in controls, p<0.001. In PAH group, SUVRV/SUVLV significantly correlated with RV haemodynamic deterioration. In comparison to the stable ones, 12 patients who experienced clinical end point had significantly higher baseline SUVRV/SUVLV ratio (1.21 (IQR 0.87-1.95) vs 0.53 (0.24-1.08), p=0.01) and lower RV ejection fraction (RVEF) (37.9±5.2 vs 46.8±5.7, p=0.03). Cox regression revealed that SUVRV/SUVLV ratio was significantly associated with the time to clinical end point. Kaplan-Meier analysis showed that combination of RVEF from MRI and SUVRV/SUVLV assessment may help to predict prognosis. CONCLUSIONS: Increased RV glucose uptake in PET and decreased RVEF identify patients with PAH with worse prognosis. Combining parameters from PET and MRI may help to identify patients at higher risk who potentially benefit from therapy escalation, but this hypothesis requires prospective validation.

Circadian variations of interleukin 6 in coronary circulations of patients with myocardial infarction.

UNLABELLED: We hypothesize that higher morbidity of patients with ST-segment elevation myocardial infarction (STEMI) in the out-of-office hours differences in outcome after myocardial infarction may depend on the concentrations of inflammatory cytokines. The aim of the study was to determine the relation between the time of percutaneous coronary intervention (PCI) and local concentration of interleukin 6 (IL-6) and its soluble receptors (sIL-6R and sgp130) in patients with STEMI. METHODS AND RESULTS: The study included 32 patients with invasively treated left anterior descending artery occlusion and no significant co-morbidities. Blood samples were drawn from coronary sinus and aorta before and after intervention. Patients admitted in the afternoon (13-20) presented significantly higher mean IL-6 levels in all samples than patients admitted in the morning. There was a positive correlation between time of intervention and concentrations of IL-6 in all samplings, but also with transcardiac IL-6 gradient at the end of procedure and IL-6 increase during PCI. We did not find any significant association between time of PCI and concentrations of sIL-6R and sgp130, time from pain to balloon, angiographic parameters or medical history. CONCLUSIONS: Coronary concentration of IL-6 in patients with STEMI is significantly higher in the afternoon than in the morning. This might be involved in increased morbidity of those patients.

Coronary blood flow in patients with end-stage renal disease assessed by thrombolysis in myocardial infarction frame count method.

BACKGROUND: Myocardial ischaemia in patients with end-stage renal disease (ESRD) develops both due to the epicardial coronary artery stenosis and to the microvascular injury. We aimed to evaluate coronary blood flow in ESRD patients by means of the thrombolysis in myocardial infarction (TIMI) frame count method (TFC). In patients with ESRD, implementation of the TFC as a marker of the coronary flow abnormalities have not been previously investigated. METHODS: Thirty-nine ESRD patients on regular dialysis underwent elective coronary angiography. Coronary artery stenosis >75% was defined as significant. TFC for the three main coronary vessels was calculated. Higher TFC values reflected slower flow. RESULTS: In 19 patients (49%), significant epicardial coronary artery disease was found. Distribution of the TFC for the three main coronary arteries reflected prevalence for higher TFC values. Mean corrected TFC for the left anterior descending artery (LAD) was 34.7 +/- 16, for the circumflex artery (Cx) 41.5 +/- 25 and for the right coronary artery (RCA) 30.9 +/- 18 frames. For the three main coronary vessels, there were no statistically significant differences between the mean TFC values according to the presence or absence of the severe coronary artery stenoses on angiography (LAD: 30.2 +/- 12 vs 36.3 +/- 18; Cx: 41.5 +/- 20 vs 41.5 +/- 27; RCA: 34.9 +/- 16 vs 30.0 +/- 19, respectively). CONCLUSIONS: Our results demonstrate for the first time the reduction in blood flow velocity, assessed with TFC method, in the coronary arteries of ESRD patients. This phenomenon was observed regardless of the presence of the significant epicardial coronary artery stenosis. Therefore, TFC cannot be applied as a marker of significant coronary artery stenosis in ESRD population.

Apelin: a novel marker for the patients with first ST-elevation myocardial infarction.

To date, only animal studies have been concerned with apelin involvement in acute myocardial ischemia. The aim of this study was to investigate apelin measurements in low-risk patients with first ST-elevation myocardial infarction (STEMI) and to assess if apelin may feature as a marker of left ventricular (LV) injury and prognosis. In 78 consecutive patients (mean age 67 +/- 11.5 years, 24 women) with first STEMI treated with primary percutaneous coronary intervention, plasma apelin-36 concentrations were measured twice: on admission and on the 5th day of hospitalization. Left ventricle ejection fraction (LVEF) was applied as marker of LV injury. Composite endpoint (CEP), which included death, stroke, and recurrent ischemic event, was assessed after 1 year follow-up. On the first day, median apelin-36 concentration was 2138.5 pg/ml and on the 5th day was significantly lower, 2008.3 pg/ml (P = 0.002). There were no significant differences found in apelin-36 concentrations between patients with normal and low LVEF. In both groups significant reductions were found in apelin-36 concentrations measured in 5-day intervals (P = 0.04 and P = 0.008, respectively). After a 1-year follow-up, only one patient died and 19 patients (24.3%) had reached CEP. No difference in baseline apelin-36 concentrations were found in the group of patients who reached CEP compared with those without CEP. However, in both groups concentrations significantly decreased after 5 days (P = 0.04 and P = 0.013, respectively). Apelin-36 concentrations are reduced in low risk first STEMI patients during the first days regardless of the degree of LV dysfunction and prognosis.

Influence of atorvastatin on blood pressure control in treated hypertensive, normolipemic patients - An open, pilot study.

AIMS: The aim of the study was to determine whether a high dose of atorvastatin lowers blood pressure (BP) in normolipemic patients with well controlled primary arterial hypertension and if this effect is associated with alteration of biomarkers of endothelial function and oxidative stress. In this open-label study, normolipemic patients (n=56) were randomized in the proportion of 2:1 to receive atorvastatin 80 mg daily for 3 months (statin-treated, ST n=39), or to previous therapy (statin-free, SF). BP was measured using a 24-h ambulatory BP measurement device. Plasma levels of 6-keto-PGF(1alpha) (prostacyclin metabolite), serum nitric oxide (NO) and levels of autoantibodies immunoglobulin G against oxidatively modified low-density lipoprotein (ox-LDL) were measured. MAJOR FINDINGS: The mean change in systolic BP and diastolic BP for ST was - 5.7 mmHg (95% CI -4.1 to -7.2 mmHg) and -3.9 mmHg (95% CI -2.7 to -5.0 mmHg), respectively. Hypotensive statin effect was independent of lipid lowering. No change of BP in SF patients was observed. In ST, prostacyclin metabolites and NO concentrations were not significantly increased and autoantibodies against ox-LDL concentrations did not change. In ST, the decrease in BP correlated with increase in NO and decrease in autoantibodies against ox-LDL. PRINCIPAL CONCLUSION: High-dose atorvastatin resulted in reduction of BP independently of lipid-lowering effect, changes in endothelial function and oxidative stress, but it was related to the increase in NO and decrease in autoantibodies against ox-LDL. However, because of the open design of the study, these results should be carefully debated.

Endothelial dysfunction and sympathetic nervous system activation in young patients with essential arterial hypertension and without hypercholesterolaemia.

OBJECTIVE: The aim of the study was to evaluate whether measurements of hs-C-reactive protein (hs-CRP), endothelin-1 (ET-1), epinephrine (E) and norepinephrine (NE) would provide useful information for the assessment of endothelial dysfunction and sympathetic nervous system activation in a selected group of young, properly treated patients with essential arterial hypertension (HTN) and without hypercholesterolaemia. METHODS AND RESULTS: Serum hs-CRP and ET-1 as well as plasma epinephrine and norepinephrine concentrations were measured in 134 subjects (62 patients with diagnosed HTN and 72 healthy subjects from a reference group). In patients the concentrations of hs-CRP, ET-1 and NE were significantly higher, than in healthy subjects. The highest diagnostic sensitivity (87%; 95% CI 76.1-94.2) was found for serum hs-CRP; the highest diagnostic specificity (96%; 95% CI 88.3-99.1) and positive predictive value (89%) were found for ET-1 measurements. The analysis of logistic regression showed that the highest risk of HTN was found for the patients with high levels of ET-1, hs-CRP and NE, but not epinephrine. CONCLUSIONS: These results indicate that measurements of hs-CRP, ET-1 and NE may be useful in the identification of endothelial dysfunction and sympathetic activation in young patients with properly controlled essential arterial hypertension and without hyperlipidaemia.

Perfusion defects on real-time myocardial contrast echocardiography predict higher mortality in patients with end-stage renal disease - a 3-year follow-up.

AIM: The aim of this study was to assess the prognostic significance of myocardial contrast echocardiography (MCE) in patients with end-stage renal disease (ESRD) on a 3-year follow-up and to compare the value of MCE with demographic, clinical, and laboratory parameters. METHODS: Fifty-eight ESRD patients on regular dialysis were prospectively screened for coronary artery disease (CAD) using perfusion assessment on real-time MCE. We analyzed the following end points during the 3-year follow-up: death, cardiovascular complications, and combined end point, which consisted of adverse cardiac events mentioned above. All features were compared between the two groups with and without perfusion disturbances on MCE. RESULTS: No adverse events related to MCE administration have been observed. Twenty-seven (47%) patients with ESRD demonstrated perfusion defects on MCE. The patients with perfusion defects on MCE comparison with those without perfusion disturbances were older (p = 0.008) and had lower ejection fraction (EF) (p = 0.0001) and higher wall motion index (WMSI) (p = 0.0001). After the 3-year follow-up, the incidence of death (p = 0.00018), cardiovascular end points, revascularizations [both percutaneous coronary intervention (PCI) and coronary artery bypass grafts (CABG) p = 0.0016 and p = 0.004, respectively], and composite end point (p = 0.0015) was significantly higher in patients with perfusion defect on MCE. CONCLUSIONS: In patients with ESRD, MCE appears to be a safe and useful tool for risk stratification. MCE facilitates decision for coronary angiography.