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.

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.

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.

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.

Hepatocyte growth factor--a new marker for prognosis in acute coronary syndrome.

UNLABELLED: This study was designed to check the properties of hepatocyte growth factor (HGF) as a new marker of myocardial necrosis. MATERIALS AND METHOD: In one hundred and four patients with acute coronary syndrome (ACS), plasma human HGF (hHGF) concentrations were assessed twice, i.e. just after admission to hospital and 24 h afterwards. The primary composite endpoint was assessed at three-month follow-up. RESULTS: The maximal concentration of hHGF (1902 pg/ml) was reached at the time of admission to hospital due to ACS with significant decrease 24 h after the first measurement (705 pg/ml p < 0.0001). hHGF levels in ST segment elevation myocardial infarction (STEMI) were higher than in non-ST segment elevation myocardial infarction (NSTEMI) and in patients who reached composite primary endpoint (33 patients-4211 pg/ml) vs. event-free 71 patients (1013 pg/ml p < 0.01). The correlation between values of hHGF and N-terminal prohormone B-type natriuretic peptide and cardiac troponin I was revealed. CONCLUSION: HGF is a very early, good marker of myocardial necrosis and a sensitive short- and long-term prognostic factor in ACS.

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.

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.

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.

Antioxidative activity of sulodexide, a glycosaminoglycan, in patients with stable coronary artery disease: a pilot study.

BACKGROUND: Oxidative stress may promote chronic inflammation and contribute to accelerated atherogenesis in patients with coronary artery disease (CAD). Sulodexide, a glycosaminoglycan consisting primarily of heparin, has been shown to affect oxidative stress in experimental settings. The purpose of this pilot study was to determine the effect of sulodexide administration on oxidative stress, inflammation and plasma lipids in patients with proven stable CAD. MATERIAL/METHODS: Fifty-six optimally treated male CAD patients (pts), mean age 57+/-6 yrs, were randomized to either 8 weeks of sulodexide treatment (SUL, n=28), or to a control group (n=28). At baseline and at the end of the study, all pts underwent full clinical and standard laboratory plasma level assessment of lipids, markers of inflammation, and 8-isoprostane, as a sensitive index of oxidative stress. RESULTS: At entry the 2 groups did not differ significantly in terms of age, coronary risk factors, clinical status and concomitant medication. SUL treatment appeared to be safe and caused a significant decrease in the level of plasma 8-isoprostane (77.4 vs 44.5 pg/ml, p<0.0001) compared with controls (75.7 vs 68.3 pg/ml, p=NS). In contrast, neither LDL cholesterol (2.71 vs 2.72 mmol/l) and triglycerides (1.38 vs 1.43 mmol/l), nor markers of inflammation - fibrinogen (3.7 vs 3.6 g/l), C-reactive protein (0.14 vs 0.13 mg/l), leukocyte count (6.33 vs 6.32x10(9)/l) - were affected by SUL treatment. CONCLUSIONS: Sulodexide administration resulted in significant reduction in oxidative stress in stable CAD patients, and neither the changes in cholesterol metabolism nor in systemic inflammation underlay this effect.

Alterations in calcium regulatory protein expression in patients with preserved left ventricle systolic function and mitral valve stenosis.

BACKGROUND: In heart failure, alterations in the expression of proteins relevant to calcium homeostasis are involved in depressed contractility and diminished relaxation. However the regulation of genes expression is only partially known. The aim was to assess expression of calcium regulatory proteins in left ventricle (LV) myocardium characterised by a preserved global function in mitral valve stenosis (MVS) model but increased neurohumoral/cytokine (N/C) activation. METHODS AND RESULTS: Plasma N/C activation was evaluated in MVS-patients (n = 27), where expression of calcium regulatory proteins (L-type channel, sarcoplasmic reticulum Ca2+-ATPase type2 - SERCA2, Na+/Ca2+ exchanger -NCX, calsequestrin, phospholamban) in LV myocardium was assessed (Western Blot) in comparison with non-failing hearts (NFH). Out of all proteins assessed in MVS, only SERCA2 and NCX expression revealed highly variable changes between subjects, with significant reduction of SERCA2 (15%) level compared to NFH. Moreover, SERCA2 was negatively correlated with BNP (univariate/regression analysis r = -0.63, P = 0.005/r2 = 0.74, P <0.001, respectively), whereas NCX was positively correlated only with noradrenaline (univariate/stepwise analysis r = 0.59 P = 0.002/r2 = 0.59; P = 0.003). CONCLUSIONS: In MVS-patients LV becomes remodelled, although its global function is preserved. It seems that apart from alterations in LV load and wall stress, also such neurohumoral factors as BNP/noradrenaline may influence the Ca2+ handling proteins expression.

Role of the rat gastrointestinal mucosa in catabolism of endothelin peptides.

Endothelin-1 is involved in physiology and pathophysiology of the alimentary tract. The peptide modulates blood flow in the gastrointestinal microvasculature and regulates contractility of smooth muscles and, when present in excess, may be an important factor contributing to pathogenesis of various forms of mucosal injury and peristaltic disorders. Mechanisms that regulate endothelin concentration in the gastrointestinal tissues are unknown. Therefore, the aim of our study was to identify and characterize endothelin inactivating peptidases in the rat gastrointestinal mucosa and smooth muscle cells. We have found three high affinity and efficient endothelin-1 inactivating peptidases. The acidic (pH optimum 5.5), membrane-bound, thiorphan- (ED(50) 1.2+/-0.2 nM) and phosphoramidon (ED(50) 150+/-25 pM) sensitive, endothelin-1 inactivating peptidase (K(M) 0.12+/-0.03 microM) was present in the mucosal cells of duodenum and small intestine. The enzyme exhibited high molecular weight (>100 kDa) and characteristics similar to that of the rat and human kidney, acidic metalloendopeptidase that was recently described. Two forms of the unique, low molecular weight (100>MW>30 kDa), alkaline (pH optimum 8.5), specific (K(M) 0.5+/-0.2 microM), thiorphan- and phosphoramidon insensitive, 1,10 phenanthroline inhibitable (ED(50) 0.65+/-0.20 mM, mean+/-S.E.M.) endothelin-1 inactivating peptidase were present exclusively in the duodenal mucosal cells; soluble form in cytosol and membrane-bound form exhibiting an abundance ratio 5:1, respectively. Mucosa of the stomach and large intestine, and gastrointestinal smooth muscle cells do not contain the specific endothelin-1 inactivating peptidases. The enzymes may play a crucial role in regulation of endothelin concentration in the gastrointestinal tissues. Whether impairment of activity of the mucosal endothelin inactivating peptidases, resulting in the increase of concentration of endothelin peptides in gastrointestinal tissues, occurs in various pathological conditions is actually studied in our laboratory.

Cardiovascular risk factors in hypertensive patients with coronary artery disease and coexisting renal artery stenosis.

OBJECTIVE: The aim of our study was to examine the association between the presence of atherosclerotic renal artery stenosis (RAS) and coexisting cardiovascular risk factors in hypertensive patients with coronary artery disease (CAD). METHODS: A total of 333 consecutive hypertensive patients (239 men, 94 women) with CAD underwent clinically indicated non-emergency coronary angiography, followed by renal angiography. Before catheterization clinical examination was performed to determine demographics, cardiac history, known duration of hypertension, cardiovascular risk factors, features of extracoronary vascular disease and related comorbidities. Blood samples for all biochemical evaluations--including highly sensitive C-reactive protein (hsCRP), fibrinogen and homocysteine--were taken. Ambulatory blood pressure monitoring (ABPM), echocardiography and carotid and femoral ultrasound followed by a duplex colour Doppler examination were performed. RESULTS: Significant RAS (> 50% lumen narrowing) was identified in 40 patients (12%) and non-significant RAS (< 50%) was found in 45 (13.5%) subjects. Patients with significant RAS were older (59.8 versus 56.6 years, P < 0.05) and were characterized by higher systolic ambulatory blood pressure level. Patients with RAS had significantly higher levels of creatinine, hsCRP, fibrinogen and homocysteine and lower creatinine clearance than patients without RAS. Multivessel coronary artery disease (MVD) was more frequent in patients with significant RAS. Patients with significant RAS had significantly higher left ventricular mass index (LVMI) and lower ejection fraction (EF) as compared with those without RAS. Patients with RAS were more often characterized by the presence of carotid and femoral artery atherosclerosis and significantly more pronounced increase in carotid intima-media thickness (IMT) as compared with non-RAS subjects. In a multivariate stepwise logistic regression model carotid IMT [odds ratio (OR) 1.15; 95% confidence interval (CI) 1.03-1.29, P < 0.05], number of coronary arteries stenosed (OR 1.61; 95% CI 1.01-2.56, P < 0.05), creatinine concentration (for 10 micromol/l increase, OR 1.15; 95% CI 1.04-1.28, P < 0.01), body mass index (BMI) (OR 0.86; 95% CI 0.75-0.97, P < 0.05) and number of antihypertensive drugs (OR 1.76; 95% CI 1.18-2.62, P < 0.05) were independently associated with RAS. The areas under receiver operating characteristic curves for carotid IMT, number of coronary arteries stenosed, creatinine concentration, BMI and number of antihypertensive drugs were 0.749, 0.633, 0.703, 0.350 and 0.677, respectively (P < 0.01 for all values). CONCLUSIONS: In conclusion, renal artery stenosis is prevalent in a significant proportion of patients undergoing cardiac catheterization. Renal angiography should be considered particularly in hypertensive patients with multivessel coronary disease coexisting with cardiovascular risk factors, even moderately impaired renal function and increased carotid IMT or vascular disease elsewhere.

Alteration of myocardial sarcoplasmic reticulum Ca2+-ATPase and Na+-Ca2+ exchanger expression in human left ventricular volume overload.

BACKGROUND: Reduced myocardial contractility is often attributed to altered Ca(2+) transients and expression of Ca(2+)-ATPase of the SR (SERCA) and Na+/Ca(2+)exchanger (NCX) genes. AIMS: To assess myocardial expression of SERCA and NCX protein levels in left ventricular (LV) remodelling due to chronic severe mitral regurgitation (MR). METHODS: Myocardial expression of SERCA/NCX in biopsy specimens obtained during mitral surgery was assessed in 36 MR patients with LV remodelling and plasma neurohumoral/cytokine activation and in four non-failing hearts (NFH). RESULTS: Myocardial protein levels of SERCA were significantly (20%) lower in the MR group than in NFH group (p=0.016). No significant changes in NCX were observed. However, a lack of homogeneity with regard to SERCA/NCX proteins was observed. Moreover, SERCA was negatively correlated with BNP (r=-0.49, p=0.02), TNFalpha (r=-0.68, p=0.0005) and IL-6 (r=-0.52, p=0.02), whereas NCX was only negatively correlated with TNFalpha (r=-0.62, p=0.002). CONCLUSIONS: MR patients showed wide variations in SERCA/NCX protein expression. Myocardial protein levels of SERCA were significantly lower in the MR population. Moreover, a correlation between BNP, cytokines (IL-6, TNFalpha) and the expression of SERCA/NCX proteins was observed.

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.

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.

Reduced myocardial expression of calcium handling protein in patients with severe chronic mitral regurgitation.

OBJECTIVE: Left ventricle (LV) function was shown to be a principal determinant of morbidity and mortality in both uncorrected and surgically corrected mitral regurgitation (MR). However, the cellular mechanisms that develop in the LV remodeling secondary to volume overload in chronic severe MR is still not well defined. In single ventricular myocyte, a reduced contraction and slowed relaxation have been mainly attributed to defective intracellular Ca2+ currents. Between several Ca2+ handling proteins, sarcoplasmic reticulum Ca2+-ATPase 2 (SERCA2) expression and activity determines not only the extent and rate of relaxation, but also the rate and amplitude of contraction. The aim of the study was to determine whether modifications of SERCA2 gene expression occurs in LV wall remodeling process secondary to chronic severe MR. METHODS: The LV samples were obtained from 12 patients presented LV wall remodeling (LV: diastolic/systolic diameter-70+/-7 mm vs 46+/-10 mm; diastolic/systolic volume-260+/-65 ml vs 102+/-68 ml) due to chronic, severe MR. Expressions of SERCA2 isoforms-SERCA2a and 2b mRNAs were estimated by semiquantitative RT-PCR and normalized to GAPDH. The protein levels of SERCA2 were determined by Western blot after normalization to actin. Results were compared with samples from non-failing human hearts (NFH). RESULTS: On SERCA2 mRNA levels, important reduction on both SERCA isoforms SERCA2a (-40%) and SERCA2b (-49%) compared to NFH, together with significant correlation between isoforms (r = 0.89; p = 0.01) were observed. SERCA2 protein levels were decreased (-38%) in MR compared to NFH. Also significant correlations between SERCA2a/2b and SERCA2 protein expression (r = 0.83, p = 0.017; r = 0.68, p = 0.05, respectively) were observed. Moreover, a negative correlation between protein levels of SERCA2 (r = -0.64, p = 0.053) and left ventricular diastolic diameter was observed. CONCLUSIONS: In chronic volume overload the down-regulation of SERCA2a and 2b at the mRNA and SERCA2 protein levels exist. Moreover, protein levels of SERCA2 tend to correlate to the grade of left ventricular diastolic dilatation and suggest an important role LV remodeling.

[Homocysteine level, relationship with cardiovascular risk factors in selected Polish population]. / Stezenie homocysteiny, zwiazek z czynnikami ryzyka chorób ukladu krazenia w wybranych polskich populacjach.

The aim of the study was to evaluate the concentration and distribution of homocysteine in random samples of men and women aged 20-74 from two populations: urban (Warsaw) and industrial-rural (former Tarnobrzeg Province), and the estimation of relationship between selected cardiovascular risk factors and homocysteine concentration. In 2001 in 617 men and 657 women homocysteine level, lipids profile, glucose, folic acid, vitamin B12 concentration, blood pressure and alcohol intake were determined. The mean (geometric) homocysteine concentration was 10.9 micro mol/L in men and 9.6 micro mol/L in women. There were no differences in the homocysteine concentration and distribution between regions according to sex. The homocysteine level was connected with folic acid and vitamin B12 concentration in both genders. Moreover, in men was recorded relationship between homocysteine and body mass index, cholesterol level, alcohol intake, and in women between homocysteine and daily number of cigarettes smoked.

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.

Decreased plasma concentration of a novel anti-inflammatory protein--adiponectin--in hypertensive men with coronary artery disease.

AIMS: Recent studies indicate that adiponectin may have anti-inflammatory and anti-atherogenic properties, suggesting that hypoadiponectinemia can play a role in the pathogenesis of cardiovascular disease. Therefore the aim of the study was to assess plasma adiponectin concentration in hypertensive male patients with coronary artery disease (CAD). Associations of adiponectinemia with other cardiovascular risk factors were also analysed. METHODS AND RESULTS: The study included 99 consecutive male patients (median age 57 years) with hypertension and CAD who at the same time underwent coronary and renal angiography. The control group consisted of 62 BMI-matched healthy male blood donors (median age 48 years). Plasma adiponectin level was significantly lower in the CAD group as compared to the control group (4.01 +/- 0.18 vs. 4.88 +/- 0.24 microg/ml; p<0.01). There were no differences in plasma adiponectin concentration between hypertensive CAD patients with and without atherosclerotic renal artery stenosis. In the CAD group plasma adiponectin concentration correlated with levels of creatinine (r=0.56; p<0.001), HDL cholesterol (r=0.24; p<0.05), BMI (r=-0.33; p<0.001), glucose (r=-0.22; p<0.05) and triglycerides (r=-0.25; p<0.05). No correlation was found between plasma adiponectin and homocysteine concentrations. In a multivariate stepwise logistic regression model increasing concentrations of adiponectin were independently and significantly associated with a lower risk of CAD (OR 0.58 95% CI 0.42-0.81 p<0.001). CONCLUSIONS: Our results showed decreased plasma adiponectin concentration in the studied group of hypertensive men with CAD as compared to normotensive healthy subjects. This may suggest that decreased plasma adiponectin concentration is associated with a higher risk of CAD.