The usefulness of sST2 and galectin-3 as novel biomarkers for better risk stratification in hypertrophic cardiomyopathy.

BACKGROUND: Estimation of sudden cardiac death (SCD) risk is an integral part of clinical management of patients with hypertrophic cardiomyopathy (HCM). Identification of novel biomarkers of this disease can provide additional criteria for SCD risk stratification. Soluble suppression of tumourigenicity (sST2) and galectin-3 (Gal-3) are useful biomarkers for prognosis of heart failure (HF). Both of them appear to mediate cardiac fibrosis - an important pathogenetic process in HCM. Data about sST2 and Gal-3 usefulness in patients with HCM are limited. AIM: The aim of this study was to evaluate sST2 and Gal-3 as potential novel biomarkers for better risk stratification in hypertrophic cardiomyopathy. METHODS: Serum sST2 and serum Gal-3 levels were measured in 57 patients with HCM and in 18 healthy controls. The patients with HCM underwent routine evaluation including medical history, physical examination, blood tests (including N-terminal pro-B-type natriuretic peptide [NT-proBNP] and high-sensitivity cardiac troponin T [hs-cTnT] measurements), 12-lead electrocardiography (ECG), 48-h Holter monitoring and two-dimensional (2D) echocardiography with the assessment of the maximal left ventricular wall thickness, left atrial diameter, maximal left ventricular outflow tract gradient, and left ventricular ejection fraction. Risk of SCD at five years according to HCM SCD-risk calculator was evaluated. The control group underwent ECG, 2D echocardiography, and NT-proBNP measurements to exclude asymptomatic heart disease. RESULTS: Concentrations of sST2 and Gal-3 were significantly higher in patients with HCM than in controls (14.9 ± 5.8 ng/mL vs. 11.7 ± 3.3 ng/mL, p = 0.03 and 8.4 ng/mL [6.8-10.0] vs. 6.2 ng/mL [5.8-7.7], p = 0.005, respectively). Levels of sST2 and Gal-3 were considerably different in the New York Heart Association (NYHA) groups (p = 0.008, p = 0.009, respectively). Patients who presented non-sustained ventricular tachycardia (nsVT) on 48-h Holter monitoring had higher levels of sST2 (19.1 ng/mL [12.2-24.2] vs. 13.2 ng/mL [10.0-17.1], p = 0.02). There were no significant relationships between sST2 and Gal-3 levels and HCM SCD-risk, history of syncope presence, family history of SCD, and echocardio-graphic parameters. CONCLUSIONS: Gal-3 levels and sST2 levels were higher in patients with HCM than in the control group. There were significant differences in Gal-3 levels between NYHA classes, but no correlations between Gal-3 levels and other parameters were found. Apart from differences in sST2 levels between NYHA classes, we demonstrated higher levels of sST2 in patients with nsVT. These findings suggest that sST2 may be useful as an additional biomarker for better risk stratification in hypertrophic cardiomyopathy.

ANP and BNP plasma levels in patients with rheumatic mitral stenosis after percutaneous balloon mitral valvuloplasty.

INTRODUCTION: Atrial (ANP) and B-type (BNP) natriuretic peptides are hormones secreted by the heart as a response to volume expansion and pressure overload. AIM: To assess the changes of ANP and BNP after percutaneous balloon mitral valvuloplasty (PBMV) and to investigate factors associated with endpoints. MATERIAL AND METHODS: The study included 96 patients (90.7% females, age 51.6 ±12.2 years) with rheumatic mitral valve stenosis (mitral valve area (MVA) 1.18 (1.01-1.33) cm2, mean mitral gradient (MMG) 8.2 (7.1-9.2) mm Hg, NYHA 2.09 (1.9-2.5)). Patients were followed up for 29.1 months for the search of endpoints. RESULTS: The PBMV was successful in all cases. After the procedure MVA increased (1.18-1.78 cm2, p < 0.01) and pulmonary capillary wedge pressure (PCWP) decreased (29.8-21.8 mm Hg, p < 0.01). Concentration of ANP significantly rose 30 min after the PBMV (79.2 vs. 134.2 pg/ml, p = 0.012) and dropped significantly after 24 h (134.2 vs. 70.4 pg/ml, p = 0.01). Furthermore, after 36 months concentration of ANP did not differ from the baseline value (p = NS). BNP concentration at day 1 was lower than at baseline (94.5 vs. 80.2 pg/ml, p = 0.032). Moreover, during the follow-up period BNP continued to fall at all time points. In univariate analysis parameters associated with endpoint occurrence were baseline PAP (p = 0.023), baseline PCWP (p = 0.022), baseline NYHA (p = 0.041) and increase in 6-minute walk test (6MWT) (p = 0.043). In multivariate analysis the only factor associated with endpoint occurrence was baseline NYHA (HR = 1.52, 95% CI: -1.3-1.91, p = 0.022). CONCLUSIONS: Patients with MS had increased levels of both BNP and ANP. Baseline NYHA class was found to be associated with outcomes after the procedure.

Prognostic value of novel biomarkers compared with detailed biochemical evaluation in patients with heart failure.

INTRODUCTION: The assessment of prognosis is crucial for the clinical management of patients with heart failure (HF). OBJECTIVES: The aim of the study was to evaluate the usefulness of novel biomarkers for the assessment of prognosis in patients with HF, compared with a detailed assessment based on routine laboratory tests. PATIENTS AND METHODS: The study included 179 patients with HF. In all patients, routine laboratory tests were performed and selected biomarkers were measured (N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, growth hormone, myeloperoxidase, metaloproteinase 9, procollagen type III, soluble toll like receptor 2, insulin growth factor, and neutrophil gelatinase-associated lipocain). The primary endpoint was death or urgent heart transplantation, while the secondary endpoints encompassed primary endpoints plus cardioverter intervention or hospitalization for HF. RESULTS: The mean age of the study group was 52.5 years (91% were men). Most patients had advanced HF. During a 6-month follow-up, 21 primary endpoints and 63 secondary endpoints were recorded. A multiple regression analysis showed that of all laboratory variables and biomarkers, only uric acid and sodium were independent predictors of primary endpoints, and only estimated glomerular filtration rate had a predictive value for secondary endpoints. None of the biomarkers were a significant prognostic factor in the study population. CONCLUSIONS: Biomarkers do not outweigh the value of standard laboratory tests. Routine laboratory workup allows to assess multiorgan damage and provides the most significant prognostic data. Biochemical tests should remain the gold standard for the assessment of prognosis in patients with HF.

Usefulness of Somatostatin Receptor Scintigraphy (Tc-[HYNIC, Tyr3]-Octreotide) and 123I-Metaiodobenzylguanidine Scintigraphy in Patients with SDHx Gene-Related Pheochromocytomas and Paragangliomas Detected by Computed Tomography.

AIMS: The aim of this study was to assess the usefulness of somatostatin receptor scintigraphy (SRS) using (99m)Tc-[HYNIC, Tyr3]-octreotide (TOC) and 123I-metaiodobenzylguanidine (mIBG) in patients with SDHx-related syndromes in which paragangliomas were detected by computed tomography and to establish an optimal imaging diagnostic algorithm in SDHx mutation carriers. METHODS: All carriers with clinical and radiological findings suggesting paragangliomas were screened by SRS and 123I-mIBG. Lesions were classified by body regions, i.e. head and neck, chest, abdomen with pelvis and adrenal gland as well as metastasis. RESULTS: We evaluated 46 SDHx gene mutation carriers (32 index cases and 14 relatives; 28 SDHD, 16 SDHB and 2 SDHC). In this group, 102 benign tumors were found in 39 studied patients, and malignant disease was diagnosed in 7 patients. In benign tumors, the sensitivity of SRS was estimated at 77% and of 123I-mIBG at 22.0%. The SRS and mIBG sensitivity was found to be clearly region dependent (p < 0.001). The highest SRS sensitivity was found in head and neck paragangliomas (HNP; 91.4%) and the lowest was found in abdominal paragangliomas and pheochromocytomas (40 and 42.9%, respectively). The highest 123I-mIBG sensitivity was found in pheochromocytomas (sensitivity of 100%) and the lowest in HNP (sensitivity of 3.7%). In metastatic disease, SRS was superior to mIBG (sensitivity of 95.2 vs. 23.8%, respectively). CONCLUSION: SRS and 123I-mIBG single photon emission computed tomography (SPECT) sensitivity in SDHx patients is highly body region dependent. In malignant tumors, SRS is superior to 123I-mIBG SPECT.

Relationship between primary aldosteronism and obstructive sleep apnoea, metabolic abnormalities and cardiac structure in patients with resistant hypertension.

INTRODUCTION: The aim of this study was to evaluate in patients with resistant hypertension (RHTN) enrolled in the RESIST-POL study the relationship between primary aldosteronism (PA) and obstructive sleep apnoea (OSA) and their effect on metabolic abnormalities and cardiac structure. MATERIAL AND METHODS: We included 204 patients (123 M, 81 F, mean age 48.4 yrs) with true RHTN, eGFR > 60 mL/min/1,73 m(2) and no known diabetes. OSA was defined as an apnoea/hypopnoea index of 15/h or more. Metabolic syndrome components were assessed. On echocardiography, left ventricular hypertrophy (LVH), concentric remodelling (RWT > 0.45), E' velocity, E/E' index and global strain (GLS) were evaluated. RESULTS: PA was diagnosed in 32 patients (15.7%). OSA occurred more frequently in patients with PA (59.4 v. 42.4%; p = 0.058). Patients were divided into four groups: PA+ OSA+ , PA+ OSA-, PA-OSA+ and PA-OSA-. Newly diagnosed diabetes, impaired glucose tolerance and increased fasting glucose were most frequent in the PA+ OSA+ group compared to other groups. The presence of OSA was associated with concentric remodelling, and the presence of PA was associated with higher left ventricular mass and higher frequency of left ventricular hypertrophy. In the PA+ OSA+ and PA+ OSA- groups, the most frequent geometry patterns were concentric hypertrophy (68.4%) and eccentric hypertrophy (54.5%) respectively. E' velocity was lowest and E/E' was highest in PA+ OSA+ compared to other groups. GLS was lower in patients with OSA compared to those without OSA. CONCLUSIONS: Both metabolic abnormalities and target organ damage are more pronounced in patients with RHTN, PA and OSA. OSA and PA influence differently left ventricular geometry.

Impact of percutaneous coronary intervention on biomarker levels in patients in the subacute phase following myocardial infarction: the Occluded Artery Trial (OAT) biomarker ancillary study.

BACKGROUND: The purpose of the Occluded Artery Trial (OAT) Biomarker substudy was to evaluate the impact of infarct related artery (IRA) revascularization on serial levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and dynamics of other biomarkers related to left ventricular remodeling, fibrosis and angiogenesis. METHODS: Patients were eligible for OAT-Biomarker based on the main OAT criteria. Of 70 patients (age 60.8 ± 8.8, 25% women) enrolled in the substudy, 37 were randomized to percutaneous coronary intervention (PCI) and 33 to optimal medical therapy alone. Baseline serum samples were obtained prior to OAT randomization with follow up samples taken at one year. The primary outcome was percent change of NT-proBNP from baseline to 1 year. The secondary outcomes were respective changes of matrix metalloproteinases (MMP) 2 and 9, tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), Vascular Endothelial Growth Factor (VEGF), and Galectin-3. RESULTS: Paired (baseline and one-year) serum samples were obtained in 62 subjects. Baseline median NT-proBNP level was 944.8 (455.3, 1533) ng/L and decreased by 69% during follow-up (p < 0.0001). Baseline MMP-2 and TIMP-2 levels increased significantly from baseline to follow-up (p = 0.034, and p = 0.027 respectively), while MMP-9 level decreased from baseline (p = 0.038). Levels of VEGF and Galectin-3 remained stable at one year (p = NS for both). No impact of IRA revascularization on any biomarker dynamics were noted. CONCLUSIONS: There were significant changes in measured biomarkers related to LV remodeling, stress, and fibrosis following MI between 0 and 12 month. Establishing infarct vessel patency utilizing stenting 24 hours-28 days post MI did not however influence the biomarkers' release.

Hepatocyte growth factor - the earliest marker of myocardial injury in ST-segment elevation myocardial infarction.

BACKGROUND: Hepatocyte growth factor (HGF) concentration increases in the first few hours of myocardial infarction (MI). AIM: (1) To illustrate human HGF (hHGF) plasma concentration during the first 24 h of ST segment elevation myocardialinfarction (STEMI); (2) To estimate the odds ratio of STEMI in the context of hHGF measurements; (3) To describe the normalconcentration of hHGF in healthy subjects. METHODS: The study groups consisted of 73 STEMI patients and 11 healthy volunteers. In all the patients, we took bloodsamples for hHGF twice, i.e. on admission to hospital and 24 h later. RESULTS: The median value of hHGF in healthy volunteers was 666 pg/mL (576; 760 pg/mL). In STEMI, the highest values of hHGF were observed in the first measurement. An increase of 1 pg/mL in hHGF level increased STEMI odds ratio by 0.2%. CONCLUSIONS: In acute MI, of the known biomarkers, hHGF rises the earliest and very promptly returns to normal values.

Potential prevention of pacing-induced heart failure using simple pacemaker programming algorithm.

INTRODUCTION: Right ventricular pacing (RVP) causes ventricular desynchronization and may lead to the development of heart failure (HF). Prolongation of atrioventricular delay (AVD) in DDDR pacemakers reduces unnecessary RV stimulation. The aim of the study was to verify the influence of RVP reduction on HF symptoms. METHODS: The study comprised 31 patients (17 men, mean age: 71.6 ± 8 yrs) with DDDR pacemaker implanted due to sinus node dysfunction (SND). At baseline, 28 patients did not present any symptoms of HF. Three patients were in NYHA class II. Patients were randomized either to 150 ms AVD or to minimizing right ventricular pacing (MRVP). Crossing over to the alternate mode took place after 4 months. Cardiopulmonary exercise test (CPX), echocardiography (ECHO) and BNP measurements were done before pacemaker implantation, after 4 and 8 months. RESULTS: The percentage of RVP was significantly higher in 150 ms AVD than in MRVP: 81.7 ± 22.6 versus 14.2±20.5%, P < 0.0001. Patients with 150 ms mode had worse CPX parameters than those with MRVP mode: peak oxygen uptake was 14.2±4.3 versus 19.9±6.3 ml/kg per min, P = 0.0001, higher BNP concentrations: 72.3±48.3 versus 49.4±43.9 pg/ml, P = 0.001 and worse left ventricle [LV] function: ejection fraction: 53.2±6.7 versus 57.3±5.5%, P < 0.0001; LV diastolic diameter: 4.86±0.52 versus 4.66±0.5 cm, P < 0.01. CONCLUSION: Predominant RVP in patients without symptoms of HF at baseline may be responsible for worse performance in cardiopulmonary exercise test, higher BNP concentrations and impairment of LV function. Specific DDDR pacemaker programming promotes intrinsic AV conduction and may prevent the development of pacing-induced HF.

Ischaemia modified albumin in patients with acute coronary syndrome and negative cardiac troponin I.

BACKGROUND: Approximately 40-60% of patients with acute coronary syndrome (ACS) have normal cardiac troponin I (cTnI) concentrations on admission. Ischaemia modified albumin (IMA) has been suggested as a new biomarker of myocardial ischaemia. METHODS: A total of 43 patients presenting with symptoms suggestive of ACS but with normal (< 0.1 µg/L) cTnI concentrations and 45 healthy subjects were studied. The patients from the study group were divided into two groups: STEMI (n = 28) and NSTEMI (n = 15). All these patients were undergoing percutaneous coronary intervention (PCI) with stenting. The concentrations of cTnI, myoglobin and IMA were determined on admission and 4 h after PCI. RESULTS: Mean (SD) IMA concentrations were higher in patients with ACS (114.39 ± 25.18 U/ml) as compared to the control group (96.24 ± 6.28 U/ml, p < 0.005). IMA concentrations ≥ 104.0 U/ml demonstrated 72.1% sensitivity and 75.6% specificity for the diagnosis of ACS. The area under the receiver operator characteristic curve was 0.766 (95% CI 0.664-0.868) for ACS patients (NSTEMI + STEMI). In both groups increased median (IQR) cTnI concentration after PCI was observed (STEMI patients to 65.4 (10.9-106.9) µg/L and NSTEMI to 17.6 (0.77-84.0) µg/L). In contrast, no increase in IMA concentration was observed. CONCLUSIONS: IMA may be a useful biomarker for the identification of ACS patients presenting with typical acute chest pain and/or abnormal electrocardiograms but negative cTnI.

Concentration of vascular endothelial growth factor in patients with acute coronary syndrome.

UNLABELLED: Vascular endothelial growth factor (VEGF) is a regulator of vascular formation in physiological and pathological conditions. The aim of our study was to evaluate the value of VEGF as a surrogate marker of myocardial injury in acute ischemic conditions. MATERIALS AND METHODS: In 104 consecutive patients with acute coronary syndrome (ACS) with and without ST segment elevation (STEMI and NSTEMI) the plasma and serum human VEGF (hVEGF) concentration was measured two times i.e. immediately after admission due to ACS and 24h later. According to ECG findings and coronary angiography results, patients were divided into three groups. Group A represented major myocardial injury due to ST-segment elevation in precordial leads and/or in I and aVL leads and with left anterior descending (LAD) artery responsible for STEMI symptoms or additionally with significant atherosclerotic lesions (lumen vessel narrowed>50%) in other than LAD coronary arteries. Group B (medium myocardial injury) consisted of patients with ST-segment elevation in II, III and aVF leads and/or ST-segment depression in V2-V3 leads with one-vessel disease and the culprit artery was not LAD. Group C included patients with changes in ECG other than ST-segment elevation independently of the site of atherosclerotic lesions in coronary arteries. RESULTS: In all 104 patients with ACS the highest values of serum hVEGF were observed in second measurement (357.9 ± 346 pg/ml, p<0.01). Although in the first measurement, plasma and serum hVEGF concentration did not differentiate groups, the difference between deltas for serum hVEGF was observed (p<0.05). Increased number of neutrophils in the first measurement increased the OR of the high serum hVEGF concentration in the first measurement (OR=1.155; 95%CI: 1.011; 1.32) (p<0.05). The number of neutrophils in the second measurement also revealed significant relationship with high serum hVEGF in the first assessment (OR=1.318, 95%CI: 1.097; 1.583) (p<0.01). Increased values of triglycerides (exceeding the upper limit) were connected with decreased OR of high serum hVEGF concentrations in the first measurement (OR=0.152, 95%CI: 0.033; 0.695, p<0.05). CONCLUSIONS: In acute coronary syndrome, serum VEGF concentrations are elevated and can serve as a surrogate marker of myocardial injury. The elevated number of neutrophils increases odds ratio of high VEGF concentrations in ACS. In patients with high concentrations of triglycerides, odds ratio of low level of hVEGF is expected.

The role of B-type natriuretic peptide in the evaluation of left atrioventricular valve regurgitation following surgical repair of partial atrioventricular canal.

BACKGROUND: Left atrioventricular valve (LAVV) regurgitation usually follows surgical repair of partial atrioventricular canal (PAVC). Although measurements of B-type natriuretic peptide (BNP) levels are useful for the monitoring and prediction of outcomes in chronic mitral regurgitation, no data are available on the role of BNP measurements in the assessment of LAVV regurgitation in patients after surgical correction of PAVC. AIM: To determine the role of plasma BNP determination in the assessment of LAVV regurgitation in patients after surgical repair of PAVC. METHODS: We evaluated 41 patients who had undergone surgery for PAVC between 1968 and 2005 with preserved left ventricular ejection fraction (LVEF, mean age at follow-up: 39.2 ± 14.0 years, mean age at the time of surgery: 31.3 ± 15.6 years, 32 females) and 13 healthy controls (mean age: 38.9 ± 13.2 years, 9 females). All the subjects had undergone transthoracic echocardiography and had their plasma BNP levels determined. LAVV regurgitation was assessed qualitatively on 1+ to 4+ grading scale and quantitatively by calculating the effective regurgitant orifice area (EROA). RESULTS: LAVV regurgitation was present in 40 (97.6%) patients. Compared to patients with mild-to-moderate LAVV regurgitation (grade 1+ to 2+/EROA 〈 0.4 cm²) evaluated qualitatively and quantitatively, the group with severe regurgitation (grade 3+ to 4+/EROA ≥ 0.4 cm²) had higher values of left atrial volume (LAvol) and right ventricular (RV) systolic pressure, although there was no significant difference in plasma BNP levels. There were significant correlations between BNP levels and LAvol (r = 0.54, p = 0.0001), age at follow-up (r = 0.61, p=0.0001), age at the time of surgery (r = 0.58, p = 0.0001), RV diastolic diameter (r = 0.38, p = 0.02) and RV systolic pressure (r = 0.48, p = 0.002). Multivariate logistic regression analysis showed that only LAvol and age at the time of surgery but not the degree of LAVV regurgitation were independently associated with elevated plasma BNP levels. CONCLUSIONS: In patients late after surgical repair of the PAVC with preserved LVEF, plasma BNP levels reflect the consequences of the shunt at atrial level and LAVV regurgitation expressed by LAvol but it does not allow to estimate the severity of regurgitation.

Clinically overt and silent cerebral embolism in the course of infective endocarditis.

The data on cerebral embolism prevalence in the course of infective endocarditis (IE) are most probably underestimated. Part of the cerebral embolism episodes are clinically silent. The objective of this study was to assess the prevalence of clinically silent cerebral embolism in the course of IE and to correlate hematological, inflammatory, and echocardiography parameters with the presence of clinically overt or silent cerebral embolisms. For this purpose, we examined 65 patients with IE by blood test, cultures, echocardiography, and MRI/CT imaging. Clinically overt cerebral embolism was found in 13 patients; 52 patients had no clinically overt cerebral embolism. MRI/CT examinations revealed that among patients with no clinically overt cerebral embolism, 24 had clinically silent cerebral embolism. Thus, 37 patients in all were diagnosed with a cerebral embolism episode (overt + clinically silent). Clinically silent cerebral embolism was diagnosed in 36.9% of all patients, being as high as 64.8% of cerebral embolism cases. Silent or overt embolism development did not depend on the localization of the inflammatory process in either native or artificial valves. The type of cerebral embolism was not found to be influenced by leukocytosis, platelet count, ESR, or hsCRP levels. Neither was the type of embolism found to be influenced by the etiologic factor. Nine patients died. In three patients, the cause of death was hemorrhage from a cerebral apoplectic focus. These results suggest that clinically silent central nervous system embolism is a common complication of infective endocarditis and each patient should undergo a neuroimaging examination.

Gender differences in angiotensin II and aldosterone secretion in patients with pressure overloaded systemic right ventricles are similar to those observed in systemic arterial hypertension.

BACKGROUND: There are very few and inconclusive data concerning the renin-angiotensin-aldosterone system activity in adults with systemic right ventricles, compared to classic heart failure patients. Therefore, we prospectively evaluated angiotensin II and aldosterone levels in a series of patients following Mustard or Senning procedures for complete transposition of the great arteries. METHODS: Forty-two patients (31 male and 11 female, mean age 20.8 ± 3.7 years), 18.2 ± 2.8 years following atrial switch procedures, were included in the analysis. All the patients underwent comprehensive echocardiographic examinations. Angiotensin II and aldosterone levels were measured with immunoradiometric assays. RESULTS: The mean angiotensin II level was 11.9 ± 9.4 pg/mL; 15 patients (35.7%) had angiotensin II levels exceeding the upper limit of normal values. There was a negative correlation between angiotensin II levels and treatment with angiotensin enzyme inhibitors (r = -0.33, P = 0.03). The mean aldosterone level was 217.7 ± 160.2 pg/mL; 26 patients (61.9%) had aldosterone levels exceeding the upper limit of normal values. Female patients had significantly higher aldosterone levels than male patients (321 ± 248 vs 180 ± 95 pg/mL, P = 0.01). A negative correlation between angiotensin II levels and fractional area change (r = -0.65, P=0.03), and a positive correlation between aldosterone levels and right ventricular end-diastolic area (r = 0.66, P = 0.03) were observed in female but not in male patients. CONCLUSIONS: Renin-angiotensin-aldosterone axis activation in patients with systemic right ventricles was similar to reported values in other studies of stable heart failure. The gender differences in aldosterone levels in patients with systemic right ventricles were similar to that associated with left ventricular remodeling in systemic arterial hypertension.

Adrenomedullin concentrations at two time points following myocardial infarction and prediction of mid-term outcomes.

INTRODUCTION: Adrenomedullin (ADM) is a vasopeptide with multiple actions in the cardiovascular system and a potentially powerful tool in comparison to some of the well-established unimodal biomarkers of risk stratification in myocardial infarction (MI). Previous studies on ADM in acute MI were based on single assessment. Therefore the aim of the study was to examine the relation between ADM plasma concentrations assessed at different time points following MI and outcomes. MATERIAL AND METHODS: The study included 127 patients with acute MI treated with percutaneous coronary intervention and 60 healthy individuals as controls. Adrenomedullin concentration was assessed at baseline in all study subjects and 48 h after admission in patients with MI. The primary endpoint consisted of all-cause death, nonfatal myocardial infarction, stroke and the need of target vessel revascularization at 6-month follow-up. RESULTS: Mean ADM plasma concentration on admission was higher in patients with MI than in controls (30.3 ±14.3 pmol/l vs. 14.6 ±4.7 pmol/l, p < 0.0001). There was no significant difference between ADM concentration after 48 h (30.6 ±12.3 pmol/l) and on admission. The primary endpoint occurred in 9.4% of patients with MI. Multivariable analysis showed that ADM concentration at 48 h after admission (OR = 2.121, 95% CI 1.180-3.810 for every increase of 10 pmol/l, p = 0.012) was the only independent predictor of the primary endpoint. CONCLUSIONS: In patients with acute MI adrenomedullin plasma concentration assessed at 48 h after admission, but not ADM concentration at baseline, is an independent predictor of major adverse cardiovascular events at mid-term follow-up.

Influence of exercise training on leptin levels in patients with stable coronary artery disease: A pilot study.

BACKGROUND: This study was designed to examine the influence of exercise training on leptin levels in patients with stable coronary artery disease (CAD). METHODS: Sixty-four male patients, mean age 55.6 ± 6.0 years, were randomized either to six weeks of aerobic training, three times a week, at 60-80% of maximal heart rate (training group, Ex, n = 32) or to a control group (n = 32). Exercise stress test was performed and body mass index (BMI), waist-to-hip ratio (WHR), waist circumference and plasma leptin levels were measured at the beginning and end of the study. RESULTS: Physical capacity increased significantly only in Ex patients (max workload in METs from 7.7 ± 1.4 to 8.2 ± 1.4, p < 0.05). There were no significant differences between initial and final results in either group in terms of BMI, WHR or waist circumference. Although, at the end of the study, leptin levels did not change in Ex patients (6.7 ± 3.2 vs 6.9 ± 3.6 ng/mL, NS), they did increase significantly in the control group (8.0 ± 4.0 vs 9.3 ± 5.2 ng/mL, p < 0.02). CONCLUSIONS: A short period of exercise training in CAD patients improved their physical capacity, but did not influence BMI, WHR and waist circumference. Exercise training prevented an increase in leptin levels during the study period.

Determinants of the reduction in B-type natriuretic peptide after mitral valve replacement in patients with rheumatic mitral stenosis.

BACKGROUND: Plasma B-type natriuretic peptide (BNP) levels are closely related to symptoms in left ventricle (LV) systolic heart failure, although marked regarding heterogeneity levels among subjects are reported. AIMS: To assess the influence of right ventricle on plasma BNP in the patients with different grades of its overload secondary to severe mitral valve stenosis (MVS). METHODS: Plasma BNP was evaluated in MVS patients (n = 27) before valve replacement and during follow-up (FUV) 401 ± 42 days after operation. RESULTS: Initial examination showed severe MVS (0.9 ± 0.2 cm²), left atrial enlargement (LAI 30 ± 4.5 mm m⁻²), right ventricle diastolic dilatation (RVDI 16 ± 3.6 mm m⁻²), normal LV size/function and elevated BNP levels (166 ± 137 pg ml⁻¹). FUV examination revealed a significant reduction in LAI (27 ± 2.2 mm m⁻²), RVDI (14 ± 1.6 mm m⁻²) and BNP levels (80 ± 35 pg ml⁻¹). The regression analysis of the initial parameters found RVDI to be the strongest predictor (R² = 0.61; P<0.0001) for BNP level, whereas RVDI reduction was the strongest factor for BNP decrease (R² = 0.65; P<0.0001) during FUV. CONCLUSIONS: Right ventricle should be taken into account as a potential important source of plasma BNP owing to the fact that LV size and function are well preserved in MVS patients. RVDI determines BNP plasma levels whereas after MVS removal, the RVDI reduction predicts BNP level decrease.

High concentrations of B-type natriuretic peptide and left ventricular diastolic dysfunction in patients with paroxysmal/persistent atrial fibrillation as possible markers of conversion into permanent form of arrhythmia: 1-year prospective evaluation.

BACKGROUND: Atrial fibrillation (AF) may cause electrical and structural atrial remodelling, leading to progression from paroxysmal to permanent form of arrhythmia. Predictors of such a transition have not yet been well established. AIM: To assess the role of B-type natriuretic peptide (BNP) and left ventricular (LV) diastolic impairment in prediction of progression from paroxysmal/persistent AF to permanent AF. METHODS: The study group consisted of 154 patients (84 males, mean age 65.8 +/- 10 years) with paroxysmal (51%) or persistent (49%) AF and normal LV systolic function. All patients had BNP level and echocardiographic parameters of diastolic LV dysfunction measured at baseline and after one-year follow up. RESULTS: After one-year follow-up, 15 (9.5%) patients developed permanent AF. These patients had significantly higher baseline and one-year BNP values than the remaining patients (96.0 v. 41 pg/mL, p < 0.005, and 151.1 v. 32.5 pg/mL, p < 0.0001, respectively). Also echocardiographic indices of LV diastolic dysfunction were abnormal in patients who developed permanent AF. Stepwise logistic regression analysis revealed that baseline BNP level had independent prognostic value in predicting permanent AF development (OR 1.06, CI 1.01-1.12, p < 0.0162). The area under ROC curve was 0.787. CONCLUSIONS: Patient with normal systolic LV function and paroxysmal or persistent AF are likely to progress into permanent AF when they have increased BNP levels and echocardiographic signs of LV diastolic dysfunction.

Inflammatory response and postoperative kidney failure in patients with diabetes type 2 or impaired glucose tolerance undergoing heart valve surgery.

BACKGROUND: Diabetes type 2 (DM) or impaired glucose tolerance (IGT) are linked with a 3-fold increased risk of renal failure after heart valve surgery. The increase of proinflammatory cytokines is detected in patients with DM or IGT, moreover cardiac surgery promotes the proinflammatory response, which may be responsible for the development of postoperative kidney failure. AIM: To assess the impact of perioperative pro- and antiinflammatory reaction after heart valve surgery and other clinical parameters on the risk of postoperative acute kidney injury in patients with DM or IGT. METHODS: Thirty patients with DM or IGT, without fibrate or statin treatment, with a mean LDL-cholesterol below 129 mg/dL, ejection fraction > 45%, in NYHA class II and III, referred for surgery due to acquired heart valve disease entered the study. Patients with acute or chronic inflammatory conditions, coronary artery disease or creatinine clearance below 50 mL/min were excluded. Serum creatinine, glycosylated hemoglobin, LDL-cholesterol and interleukin-10 as well as TNF-alpha were assessed before surgery. Interleukin-10 and TNF-alpha were also measured 4 hours after weaning from cardiopulmonary bypass. Moreover, serum creatinine and hemoglobin were measured 18 +/- 2 hours after surgery. The relationship between postoperative creatinine clearance, its postoperative change and other parameters was assessed. These parameters included: age, weight and body mass index, pre- and postoperative serum level of TNF-alpha and interleukin-10, preoperative concentration of LDL-cholesterol and glycosylated hemoglobin, duration of cardiopulmonary bypass and postoperative hemoglobin. RESULTS: The significant postoperative decrease of creatinine clearance was noted in the study group. Eight (27%) patients developed postoperative kidney failure, of them 2 (6.5%) patients required hemodialysis. The level of TNF-alpha and interleukin-10 increased significantly postoperatively. A significant correlation between duration of cardiopulmonary bypass and postoperative decrease of creatinine clearance was noted (R = 0.43, p = 0.02). A non-significant trend towards correlation between preoperative TNF-alpha and postoperative decrease of creatinine clearance was observed (R = -0.36, p = 0.05). CONCLUSIONS: Postoperative kidney failure with the incidence of 27% is a frequent finding in patients with DM or IGT operated due to acquired heart valve disease. The postoperative proinflammatory response is not involved in the development of this complication. The correlation between postoperative decrease of creatinine clearance and duration of cardiopulmonary bypass was noted. The trend toward the link between postoperative kidney failure and preoperative proinflammatory status was seen.

Usefulness of 6-minute walk test, plasma neurohumoral and cytokine activation in the assessment of symptomatic patients with left ventricle dysfunction caused by chronic severe mitral valve regurgitation.

OBJECTIVE: The aim of our study was to select the most relevant markers of impaired left ventricle (LV) function in patients with heart failure (HF) symptoms due to severe chronic mitral regurgitation (MR). METHODS AND RESULTS: Thirty-six patients with decompensated HF due to severe MR underwent echocardiography, 6-minute walk test (6MWT) and measurements of plasma renin activity, angiotensin II, aldosterone, noradrenaline (NA), brain natriuretic peptide (BNP), tumour necrosis factor alpha (TNFalpha) with its receptors, and interleukine-6. Patients presented with significant neurohumoral/cytokine activation. By stepwise multiple regression analysis the strongest prediction model for 6MWT included LVEDVI (R2 = 0.95, P = 0.024), BNP (R2 = 0.67, P = 0.0006), IL-6 (R2 = 0.90, P = 0.044); for BNP: 6MWT (R2 = 0.36, P = 0.003), LA (R2 = 0.56, P = 0.0077), LVESVI (R2 = 0.83, P = 0.0072); for NA: EF (R2 = 0.4 1, P = 0.036), and for TNFalpha: LVESVI (R2 = 0.65, P = 0.003). CONCLUSIONS: 6MWT and neurohumoral markers (mainly BNP, but also NA and TNFalpha) are good predictors of the degree of LV remodelling, showing an independent correlation with the level of LV dilatation/dysfunction in chronic severe MR.These assessments may supplement standard echocardiography in LV decompensation due to severe MR.