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 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.

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.

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.

Gut Microbiome in Chronic Coronary Syndrome Patients.

Despite knowledge of classical coronary artery disease (CAD) risk factors, the morbidity and mortality associated with this disease remain high. Therefore, new factors that may affect the development of CAD, such as the gut microbiome, are extensively investigated. This study aimed to evaluate gut microbiome composition in CAD patients in relation to the control group. We examined 169 CAD patients and 166 people in the control group, without CAD, matched in terms of age and sex to the study group. Both populations underwent a detailed health assessment. The microbiome analysis was based on the V3-V4 region of the 16S rRNA gene (NGS method). Among 4074 identified taxonomic units in the whole population, 1070 differed between study groups. The most common bacterial types were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Furthermore, a higher Firmicutes/Bacteroidetes ratio in the CAD group compared with the control was demonstrated. Firmicutes/Bacteroidetes ratio, independent of age, sex, CAD status, LDL cholesterol concentration, and statins treatment, was related to altered phosphatidylcholine concentrations obtained in targeted metabolomics. Altered alpha-biodiversity (Kruskal-Wallis test, p = 0.001) and beta-biodiversity (Bray-Curtis metric, p < 0.001) in the CAD group were observed. Moreover, a predicted functional analysis revealed some taxonomic units, metabolic pathways, and proteins that might be characteristic of the CAD patients' microbiome, such as increased expressions of 6-phospho-ß-glucosidase and protein-N(pi)-phosphohistidine-sugar phosphotransferase and decreased expressions of DNA topoisomerase, oxaloacetate decarboxylase, and 6-beta-glucosidase. In summary, CAD is associated with altered gut microbiome composition and function.

Paroxysmal Atrial Fibrillation in the Course of Acute Pulmonary Embolism: Clinical Significance and Impact on Prognosis.

The relationship and clinical implications of atrial fibrillation (AF) in acute pulmonary embolism (PE) are poorly investigated. We aimed to analyze clinical characteristics and prognosis in PE patients with paroxysmal AF episode. Methods. From the 391 patients with PE 31 subjects with paroxysmal AF were selected. This group was compared with patients with PE and sinus rhythm (SR) and 32 patients with PE and permanent AF. Results. Paroxysmal AF patients were the oldest. Concomitant DVT varies between groups: paroxysmal AF 32.3%, SR 49.5%, and permanent AF 28.1% (p = 0.02). The stroke history frequency was 4.6% SR, 12.9% paroxysmal AF, and 21.9% permanent AF (p < 0.001). Paroxysmal AF comparing to permanent AF and SR individuals had higher estimated SPAP (56 versus 48 versus 47 mmHg, p = 0.01) and shorter ACT (58 versus 65 versus 70 ms, p = 0.04). Patients with AF were more often classified into high-risk group according to revised Geneva score and sPESI than SR patients. In-hospital mortality was lower in SR (5%) and paroxysmal AF (6.5%) compared to permanent AF group (25%) (p < 0.001). Conclusions. Patients with PE-associated paroxysmal AF constitute a separate population. More severe impairment of the parameters reflecting RV afterload may indicate relation between PE severity and paroxysmal AF episode. Paroxysmal AF has no impact on short-term mortality.

Matrix Metalloproteinase Neutrophil Gelatinase-Associated Lipocalin Complex Predicts Atrial Fibrillation Recurrence after Electrical Cardioversion in Obese Patients.

BACKGROUND: There is not much data on matrix metalloproteinase neutrophil gelatinase-associated lipocalin (MMP-NGAL) complex in patients with atrial fibrillation (AF). AIM: The aim of the study was to assess the value of MMP-NGAL complex in predicting AF recurrence after electrical cardioversion. METHODS: The serum levels of NGAL, cystatin C, interleukin-6, high-sensitivity C-reactive protein, copeptin, MMP-NGAL complex, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase 1, Von Willebrand factor, B-type natriuretic peptide and the urinary level of NGAL were evaluated before cardioversion. RESULTS: A total of 83 patients with persistent AF were enrolled in the study. Left atrial diameter (LA) ≥4.5 cm was significantly associated with AF recurrence at follow-up (p = 0.009). In selected 39 obese patients, MMP-NGAL complex was associated with AF recurrence (p = 0.03). If the concentration of MMP-NGAL complex increased by 1 ng/ml, the odds of AF recurrence increased by 4% (OR 1.04; CI: 1.00-1.08; p = 0.03). MMP-NGAL complex did not correlate with AF recurrence in patients with a first episode of AF, in patients ≥65 years of age and in patients with a LA ≥4.5 cm or with chronic kidney disease. CONCLUSIONS: It is known that the greater the BMI at baseline, the higher the likelihood of progression from paroxysmal to permanent AF. However, European Society of Cardiology (ESC) guidelines do not consider obese patients a population with a low likelihood of success of cardioversion. That is why we need a sensitive marker to predict sinus rhythm maintenance in such a population. We found that MMP-NGAL complex may predict AF recurrence after successful cardioversion in obese patients.

Activity of the kynurenine pathway and its interplay with immunity in patients with pulmonary arterial hypertension.

OBJECTIVE: We evaluated blood concentrations of kynurenine pathway metabolites, natural and induced regulatory T cells (nTreg, iTreg), and Th17 cells in order to examine the activity of the kynurenine pathway and its relation to immune status in patients with pulmonary arterial hypertension (PAH). METHODS: Plasma concentrations of tryptophan, kynurenine, kynurenic acid, anthranilic acid, and 3-hydroxykynurenine were quantified in 26 patients with PAH (vs 30 healthy controls) at baseline and after 6 months, and assessed them in relation to clinical parameters, frequencies of lymphocyte subsets, and outcome. RESULTS: The PAH group presented higher concentrations of tryptophan (52.9 (IQR 46.3-57.5) vs 40.3 (35.2-46.3) µmol/L, p=0.00003), kynurenine 2.8 (2.4-3.4) vs 1.9 (1.5-2.3) µmol/L, p=0.000007), kynurenine/tryptophan ratio (0.051 (0.044-0.064) vs 0.043 (0.039-0.055), p=0.03), iTreg frequencies (10.5 (8.8-13.9)% vs 6.8 (5.2-9.5)%, p=0.002) and iTreg/Th17 (1.73 (1.2-2.8) vs 0.93 (0.61-1.27), p=0.003) together with lower ratios of kynurenic acid/kynurenine, 3-hydroxykynurenine/kynurenine, and anthranilic acid/kynurenine. Kynurenine concentrations and kynurenine/tryptophan ratio correlated positively with iTreg/Th17, and inversely with Th17 subsets, whereas kynurenic acid/kynurenine and anthranilic acid/kynurenine ratios correlated positively with Th17. Adverse outcomes occurred in 9 of 26 patients and they showed higher baseline concentrations of kynurenine (3.6 (2.8-4.3) vs 2.7 (2.1-3.2) µmol/L, p=0.033). Median kynurenine values ≥3.4 µmol/L (67% sensitivity, 94% specificity) identified patients with a worse clinical course. CONCLUSIONS: PAH is characterised by upregulated tryptophan metabolism and enhanced biosynthesis of kynurenine. Elevated kynurenine concentration is associated with an adverse clinical course. Dysregulated immunity, delineated by Treg-Th17 imbalance, is directly related to diverse activation of the kynurenine pathway, indicating the potential interplay between kynurenines and the immune system in PAH.

The rs12526453 Polymorphism in an Intron of the PHACTR1 Gene and Its Association with 5-Year Mortality of Patients with Myocardial Infarction.

OBJECTIVE: The rs12526453 (C/G) is a single nucleotide polymorphism in an intron of the PHACTR1 gene (phosphatase and actin regulator 1). The C allele is associated with increased risk of coronary artery disease in an unknown mechanism. We investigated its association with long-term overall mortality in patients with ST-elevation myocardial infarction (STEMI) treated invasively. METHODS: Two independent groups of patients with STEMI were analyzed: a derivation group (n= 638) and a validation one (n=348). Genotyping was performed with the TaqMan method. The analyzed end-point was total long term mortality. Additionally, transcriptomic analysis was performed in mononuclear blood leukocytes from rs12526453 CC monozygotes or G allele carriers. RESULTS: In the study group (mean age 62.3 ± 11.9 years; 24.9% of females, n=159), percentages of CC, CG, and GG genotypes were 45.3% (n=289), 44.7% (n=285), and 10% (n=64), respectively. In the 5-year follow-up 105 patients died (16.46%). CC homozygotes had significantly lower mortality compared to other genotypes: 13.1% (n=38) vs. 18.3% in G-allele carriers (n=67), (p=0.017, Cox`s F test). In the validation group 47 patients died within 3 years (13.5%). We confirmed lower mortality of CC homozygotes: 10.1 % (n=18) vs. 16.95% in G-allele carriers (n=29), (p=0.031, Cox`s F test). Transcriptomic analysis revealed a markedly higher expression of NLRP-2 in CC homozygotes. CONCLUSIONS: The rs12526453 CC homozygotes (previously associated with increased risk of myocardial infarction) showed, in 2 independent samples, better long-term survival. The finding of such high effect size, after appropriate validation, could potentially be translated into clinical practice.

[Cardiac myxoma attached to anterior leaflet--case report]. / Sluzak o nietypowej lokalizacji u chorego po przebytym udarze niedokrwiennym mózgu.

Cardiac myxoma attached to anterior mitral leaflet - a case report. A case of a 64-year-old patient with a history of stroke and myocardial infarction is presented. Echocardiography revealed cardiac myxoma originating from anterior mitral leaflet. The patient underwent successful surgery. Differential diagnosis of cardiac myxoma is presented.

[Is Q-wave on admission associated with microvascular injury in patients with acute myocardial infarction treated with primary angioplasty?]. / Czy obecnosc patologicznego zalamka Q przy przyjeciu predysponuje do poreperfuzyjnego uszkodzenia mikrokrazenia u pacjentów ze swiezym zawalem miesnia sercowego, leczonych pierwotna angioplastyka wiencowa?

INTRODUCTION: Impaired microvascular flow, despite patent epicardial artery (no-reflow phenomenon), leads to greater left ventricular dysfunction after myocardial infarction (MI). Predictive factors associated with no-reflow remain largely unexplored. Q-wave on admission (Q(A)) is a sign of extensive ischemia probably predisposing to no-reflow. The aim of the study was to explore possible relation between Q(A) and electrocardiographic signs of no-reflow in patients with first MI. MATERIAL AND METHODS: The study group was composed of 108 patients (81 men; mean age 60+/-11 years), with first ST-segment elevation MI, treated successfully with primary angioplasty (p-PTCA). ECG tracings were obtained before and 30 minutes after p-PTCA. The sum of ST-segment elevations (sum(ST(el))) in 3 contiguous leads with the highest ST(el) was calculated. Lack of 50% reduction of the sum(ST(el)) 30 minutes after angioplasty was defined as ECG sign of no-reflow. Presence of Q(A) was estimated in leads with ST(el). RESULTS: Q(A) was found in 42 (39%) patients. Q(A) was more often observed in patients with ECG signs of no-reflow (38% vs. 18%; p<0.05). Group with Q(A) showed larger damage of left ventricle estimated with ECG QRS score (7.7+/-4.4 vs. 6.1+/-3.4; p<0.05) as well as worse ejection fraction (42% vs. 46%; p=0.05). CONCLUSIONS: Patients with Q(A) have more often ECG signs of no-reflow than other patients with MI. Previously described worse function of left ventricle in this group, may be partially caused by more frequent no-reflow occurring in those patients. This fact suggests that adjunctive therapy preventing no-reflow could be beneficial in this group of patients.

Serum adiponectin and markers of endothelial dysfunction in stable angina pectoris patients undergoing coronary artery bypass grafting (CABG).

PURPOSE: It has been established that endothelial dysfunction (ED) occurs after coronary artery bypass grafting (CABG). The aim of the study was to assess whether adiponectin may act as a novel marker of ED and its potential relations with new markers of ED: novel cell adhesion molecule CD146, a natural anti-thrombin glycoprotein - thrombomodulin (TM) and the well-established ED marker - Von Willebrand factor (VWF) in coronary artery disease (CAD) patients undergoing CABG. MATERIAL/METHODS: 45 CAD patients undergoing elective CABG were included in the study. RESULTS: In the study group the concentration of adiponectin and CD146 before the surgery were significantly lower than in the control group - 6.06 µg/ml ± 3.06 vs. 19.0 µg/ml ± 6.4 and 303.2 ng/ml ± 28.7 vs. 328.1 ng/ml ± 22.6 (p<0.05). Significant increase of adiponectin and CD146 concentration 3 months after CABG vs. before the surgery was found. Adiponectin concentration 3 months after CABG correlated with VWF, TM, CD146, and a number of grafts. CD146 before and 3 months after CABG correlated significantly with adiponectin, VWF activity as well as the statins therapy after the surgery. CONCLUSIONS: In CAD patients undergoing CABG new markers of endothelial cell dysfunction as adiponectin and CD146 are significantly lower compared to healthy volunteers. Significant increase in adiponectin and CD146 concentration 3 months after CABG vs. before the surgery was found. However adiponectin concentrations 3 months after CABG were still significantly lower compared to healthy individuals, whereas CD146 concentration returned to the values comparable to the control.

Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction.

OBJECTIVE: The rs10757278, rs1333049 and rs4977574 are single nucleotide polymorphisms (SNPs) of chromosome 9p21 locus associated with a prevalence of acute coronary syndromes (ACS). Reports concerning their association with long-term outcome after an ACS are equivocal. The aim of our study was to investigate the association of the 9p21.3 locus with 5-year overall mortality in patients with ST-elevation myocardial infarction (STEMI). MATERIALS AND METHODS: We performed a retrospective analysis of data collected prospectively in 2 independent registries of consecutive patients with STEMI (derivation and validation group). Genotyping was performed with the TaqMan method. The analyzed end-point was total mortality. RESULTS: The derivation group comprised 589 patients: 25.3% female (n = 149), mean age 62.4 ± 12.0 years, total 5-year mortality 16.6% (n = 98). When all the study group was analyzed, no significant differences in mortality were found between the genotypes. However, in high-risk patients (GRACE risk score ≥ 155 points, n = 238), homozygotes associated with higher risk for ACS had significantly better 5-year survival compared to other genotypes. The hazard ratio associated with the high-risk genotype (a homozygote of high risk for ACS or a heterozygote) was: HR = 2.2 (1.15-4.2) for the rs10757278 polymorphism, HR = 2.7 (95% CI 1.3-5.4) for the rs4977574 one and HR = 2.3 (1.2-4.5) for the rs1333049 one (Cox proportional hazards model). Survival analysis in the validation group (n = 365) showed a clear trend towards better prognosis in GG homozygotes of the rs10757278 SNP, which confirms our initial results (p = 0.09, log-rank test). CONCLUSIONS: The 9p21.3 locus is associated with 5-year mortality in high-risk patients with STEMI. The genotypes associated with higher risk for ACS show a protective effect in terms of further survival (instead of a deteriorating prognosis, as reported previously). This finding, due to the very high size of the effect, could potentially be applied to clinical practice, if appropriate methods are elaborated.

Cardiogenic pulmonary oedema: alarmingly poor long term prognosis. Analysis of risk factors.

BACKGROUND: Acute heart failure (AHF) is a life-threatening condition associated with poor prognosis. AIM: To investigate the long term prognosis and identify prognostic factors among patients who were discharged after an episode of cardiogenic pulmonary oedema. METHODS: We enrolled 84 patients (M: 56%, n = 47) who were discharged with cardiogenic pulmonary oedema as a diagnosis. Clinical, biochemical and echocardiographic variables were collected and analysed. The completeness of two- and five-year follow-up was 100% and 96%, respectively. RESULTS: The median (IQR) age was 74 years (64-81), left ventricular ejection fraction was 35% (27-45), blood pressure on admission was 140/90 mm Hg (115-180/70-100), estimated glomerular filtration rate was 60 mL/min/1.73 m2 (45-73). Forty per cent (n = 34) of the patients had a history of atrial fibrillation (AF), however, AF was directly involved with pulmonary oedema only in 4% (n = 3) of the cases. Acute myocardial infarction (AMI) accounted for 34% (n = 29) of all the causes of pulmonary oedema and was associated with a better two-year prognosis compared to other causes of pulmonary oedema (p = 0.018). Two- and five-year mortality was 45% (n = 38) and 72% (n = 58), respectively. Co-morbidities were common. Ischaemic heart disease and arterial hypertension were present in 83% and 70% of the patients, respectively. Multivariable analysis identified increased left ventricular mass (RR 3.609, 95% CI 1.235-10.547, p = 0.017) and treatment with long-acting vasodilator drugs (LAVDs) (RR 4.881, 95% CI 1.618-14.727, p = 0.004) as independent negative prognostic factors, whereas in-hospital therapy with beta-blockers created a distinctly protective effect (RR 0.123, 95% CI 0.033-0.457, p = 0.002) in the two-year follow-up. Five-year mortality was independently associated with older age (RR 1.08, 95% CI 1.02-1.14, p = 0.005) and treatment with LAVDs (RR 6.4, 95% CI 1.47-28.14, p = 0.012), while percutaneous coronary intervention (RR 0.17, 95% CI 0.05-0.58, p = 0.004) significantly decreased the risk. CONCLUSIONS: AHF is a heterogeneous syndrome with a very high remote mortality. LAVDs administered during the hospital stay as well as older age on admission correlate with higher long-term overall mortality. In the age of percutaneous coronary intervention, AMI aetiology of pulmonary oedema is no longer a negative prognostic factor for the long-term prognosis.

Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction.

OBJECTIVE: The rs1333049, rs10757278 and rs4977574 are single nucleotide polymorphisms (SNPs) of chromosome 9p21 locus that are associated with prevalence of acute coronary syndromes (ACS). The rs1333049 SNP was also associated with cardiac outcome 6 months post ACS. No data concerning their association with long term prognosis after myocardial infarction is available. The aim of our study was to investigate the association of the 9p21.3 locus with 5-year overall mortality in patients with ST-elevation myocardial infarction (STEMI) treated invasively. MATERIALS AND METHODS: We performed a retrospective analysis of data collected prospectively in a registry of consecutive patients with STEMI treated with primary PCI. Genotyping was performed with a TaqMan method. The analyzed end-point was total 5-year mortality. RESULTS: The study group comprised 589 patients: 25.3% of females (n = 149), mean age 62.4±11.9 years, total 5-year mortality 16.6% (n = 98). When all the study group was analyzed, no significant differences in mortality were found between the genotypes. However, in high-risk patients (Grace risk score ≥155 points, n = 238), low-risk homozygotes had significantly better 5-year survival compared to other genotypes. The hazard ratio associated with high-risk genotype (high-risk homozygote or heterozygote) was: HR = 2.9 (95%CI 1.4-6.1) for the rs4977574 polymorphism, HR = 2.6 (1.25-5.3) for the rs1333049 one and HR = 2.35 (1.2-4.6) for the rs10757278 one (Cox proportional hazards model). CONCLUSIONS: The 9p21.3 locus is associated with 5-year mortality in high-risk patients with STEMI. This finding, due to very high effect size, could potentially be applied into clinical practice, if appropriate methods are elaborated.

GRACE, TIMI, Zwolle and CADILLAC risk scores--do they predict 5-year outcomes after ST-elevation myocardial infarction treated invasively?

BACKGROUND: GRACE, TIMI, Zwolle, and CADILLAC are risk scores designed for predicting short-term outcome after acute coronary syndromes. The aim of our study was to test their utility for a prognosis of 5-year survival in a "real-life" population of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (pPCI). METHODS: Our registry consisted of consecutive patients with STEMI treated with pPCI. Five-year follow-up was performed with all-cause mortality as the end-point. RESULTS: Out of 505 patients (mean age 58.6±11.3 years) 32 died during the first 30 days (6.3%) and an additional 74 within 5 years (15.6%). PCI was successful in 95.2% (n=481). Prognostic values (c statistics) for predicting 5-year mortality equaled: 0.742 (CI 0.69-0.79) for the GRACE risk score, 0.727 (CI 0.67-0.78) for TIMI, 0.72 (CI 0.67-0.77) for Zwolle, and 0.687 (CI 0.63-0.74) for CADILLAC. In a univariate analysis all the scores were associated with the 5-year outcome. CONCLUSIONS: GRACE, TIMI, and Zwolle risk scores predicted well 5-year all-cause mortality in patients with STEMI treated with pPCI. Our data show that the usefulness of initial bedside risk assessment can be further extended for long-term follow-up.

The influence of renal function and selected cardiovascular risk factors on the thickness of the intima-media complex in the peripheral arteries.

BACKGROUND: Measurement of the intima-media thickness (IMT) in the peripheral arteries leads to better stratification of cardiovascular risk. This is of great importance in patients with chronic renal insufficiency, who are particularly vulnerable to developing atherosclerotic lesions. The aim of the study was to evaluate whether parameters of renal insufficiency and selected risk factors of atherosclerosis influence IMT in the peripheral arteries. METHODS: The study population comprised 231 patients submitted to coronary angiography with ultrasonographic assessment of the common carotid artery (CCA), carotid artery bulb (CB) and common femoral artery (CFA) made contemporaneously with evaluation of IMT and atherosclerotic plaques. Renal function as well as selected clinical and biochemical risk factors of atherosclerosis were assessed. Two subgroups were analysed: 200 patients with coronary heart disease confirmed angiographically (study group) and 31 patients without coronary lesions (control group). RESULTS: Significant negative correlation was found between glomerular filtration rate and IMT values in CCA (p < 0.001) as well as in CB (p < 0.05). Patients with abnormal glucose metabolism had significantly higher IMT values in CCA (0.95 +/- 0.30 vs. 0.87 +/- 0.20; p = 0.034). Hypercholesterolaemia did not influence the IMT values in CCA and CFA. There was no correlation between body mass index and IMT. CONCLUSIONS: Patients with chronic renal insufficiency presented higher values of IMT in CCA. The measurement of IMT appears to be a valuable non-invasive method of diagnosing preclinical stages of atherosclerosis in the described group of patients. (Cardiol J 2007; 14: 59-66).

Lack of ST-segment depression normalization after PCI is a predictor of 5-year mortality in patients with ST-elevation myocardial infarction.

BACKGROUND: The significance of dynamic changes in a depressed ST-segment in the reciprocal changes after percutaneous coronary intervention (PCI) of patients with ST-elevation myocardial infarction (STEMI) is unknown, so the aim of this study was to evaluate the significance of reciprocal ST-segment depression normalization (STN) on long-term mortality in patients with STEMI treated with primary PCI. METHODS AND RESULTS: Data for 247 consecutive patients with STEMI were analyzed; 84 patients were excluded because of exclusion or incomplete inclusion criteria, so finally, 163 patients successfully treated with primary PCI were included. The study group was divided into 3 subgroups according to percentage of STN: poor STN (<30%), partial STN (30-70%), complete STN (>70%). Complete STN occurred in 63%, partial in 24% and poor in 13% of patients. STN correlated with late mortality (15% vs 28% vs 38% respectively, p=0.012). Patients who died during the follow-up period had a lower mean percentage reduction of initial ST-segment depression after PCI (50% vs 75%, p=0.001). Percentage reduction of initial ST-segment depression after PCI was a significant and independent risk factor of long-term mortality (odds ratio 1.01; 95% confidence interval: 1.00-1.02; p=0.02). CONCLUSIONS: These data revealed the use of reciprocal changes normalization as a novel tool for assessment of long-term risk of death in patients after successful primary PCI for STEMI.