Search

Aims Depression is an important issue in heart failure (HF). The study investigated whole-brain and regional brain glucose metabolism in HF patients and its association with depression comorbidity. Methods and results Twenty-nine hospitalized patients with symptomatic systolic HF (left ventricular ejection fraction 0.93) or 'real' (≤0.93) depression. Conclusion Heart failure patients with more severe disease showed whole-brain and regional brain hypometabolism in 18 F-FDG PET/CT. Depressed HF patients (Beck Depression Inventory score >13) exhibited different metabolic patterns that could be used to differentiate between 'epiphenomenal' and 'real' depression. Namely, presence of whole-brain hypometabolism suggested 'epiphenomenal' depression, whereas absence suggested 'real' depression. Presence of significant relative regional brain hypometabolism enhanced the likelihood of 'real' depression diagnosis.

Background/Introduction Depression comorbidity is an important issue in heart failure (HF) disease. Results from the recent prospective randomized trial MOOD-HF did not provide a rationale for the indiscriminate use of antidepressants in depressed HF patients. Purpose The study investigated whole-brain and regional-brain glucose metabolism in HF patients with 18F-FDG PET/CT and its association with depression comorbidity. Methods Twenty-nine hospitalized patients with symptomatic systolic HF disease (LVEF Results HF patients had lower average whole-brain SUVmean (3.90±1.49 vs 5.10±1.35, p=0.001), average regional-brain SUVmean (4.57±2.31 vs 9.96±3.58, p Whole-brain SUVmean had a statistically significant correlation to patient age (r=−0.39, p=0.031), NYHA class (p=0.027), LVEF in the major group of 21 NYHA III-IV patients (p=0.018), diabetes comorbidity (p=0.001), creatinine levels (r=−0.49, p=0.005) and depression (r=−0.36, p=0.049). Regional-brain SUVmean was correlated to whole-brain SUVmean (r=0.53, p=0.002) and depression (r=0.46, p=0.011). The standardized SUVmean, in particular, was found to be a robust index that could differentiate HF patients with “epiphenomenal” (>0.93) or “real” (≤0.93) depression. Conclusion HF patients with more severe disease showed whole-brain and regional-brain hypometabolism in 18F-FDG PET/CT scan, which is consistent with impaired cerebral perfusion. Depressed HF patients (Beck Depression Inventory score >13) exhibited different metabolic patterns that could be used to differentiate between “epiphenomenal” and “real” depression. Namely, presence of whole-brain hypometabolism suggested “epiphenomenal” depression. Absence of whole-brain hypometabolism suggested “real” depression. When the pattern of whole-brain hypometabolism included significant relative, depression-related regional hypometabolism (standardized SUVmean ≤0.93), “real” depression was the most likely diagnosis. The distinction is important, as different types of comorbid depression suggest different treatment approach. Summarizing figure Funding Acknowledgement Type of funding source: None

Renal impairment and worsening renal function (WRF) are risk factors for adverse outcomes in patients with acute heart failure (AHF). The utilization of novel renal biomarkers that can estimate more accurately glomerular filtration rate (GFR) may provide new insights concerning renal effects of AHF

Background We investigated the effectiveness of perconditioning (Perc) applied at different time points along with the role of RISK, SAFE, STAT5 and eNOS pathways. Methods and results Anesthetized rabbits were subjected to 30-min ischemia/3-hour reperfusion. Perc, consisted of 4cycles of 1-min ischemia/reperfusion, was applied in the carotid artery at different time points. Perc was started and ended during ischemia, started during ischemia and ended at the beginning of reperfusion, started at the end of ischemia and ended at reperfusion and started and ended during reperfusion. The PI3K inhibitor wortmannin, or the JAK-2 inhibitor AG490, was also applied and the infarct size was assessed. In another series assigned to the previous groups, the phosphorylation of Akt, PI3K, ERKs1/2, GSK3β, STAT3, and STAT5 was evaluated. All Perc groups had smaller infarction compared to those without Perc, independently of PI3K or JAK-2 inhibition. STAT5 was the only molecule that was phosphorylated in parallel with cardioprotection. Since Src and angiotensin II mediate the STAT5 pathway, we administered the Scr inhibitor PP1 and the angiotensin II receptor antagonist valsartan. PP1 and valsartan prevented STAT5 phosphorylation, but did not abrogate the effect of Perc. Furthermore, the NOS inhibitor L-NAME was administered and abrogated the infarct size limiting effect of Perc. In parallel, the expression of cleaved caspase-3 was elevated only in the control and Perc-A-L-NAME groups. Conclusion Perc reduces infarction independently of RISK, SAFE and STAT5 pathways. Src kinase and angiotensin II play a predominant role in STAT5 activation. eNOS may protect the myocardium through inhibition of apoptosis.

Background— We investigated the effects of anakinra, an interleukin-1 receptor antagonist, on coronary and left ventricular function in coronary artery disease (CAD) patients with rheumatoid arthritis. Methods and Results— In a double-blind crossover trial, 80 patients with rheumatoid arthritis (60 with CAD and 20 without) were randomized to a single injection of anakinra or placebo and after 48 hours to the alternative treatment. At baseline and 3 hours after treatment, we assessed (1) flow-mediated dilation of brachial artery; (2) coronary flow reserve, ejection fraction, systemic arterial compliance, and resistance by echocardiography; (3) left ventricular global longitudinal and circumferential strain, peak twisting, untwisting velocity by speckle tracking; and (4) interleukin-1β, nitrotyrosine, malondialdehyde, protein carbonyl, and Fas/Fas ligand levels. At baseline, patients with CAD had 3-fold higher interleukin-1β, protein carbonyl, higher nitrotyrosine, malondialdehyde, and Fas/Fas ligand than non-CAD ( P P Conclusions— Interleukin-1 inhibition causes a greater improvement in endothelial, coronary aortic function in addition to left ventricular myocardial deformation and twisting in rheumatoid arthritis patients with CAD than in those without. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01566201.

Objective To determine the presence of depressive symptoms in adolescent and adult patients with CHD and their impact on prognosis, using self-rating depression scales. Design Prospective study. Setting Outpatient clinic of a tertiary center. Patients Sixty ambulatory adolescent and adult patients admitted at the outpatient clinic for regular evaluation. Methods Self-rating depression questionnaires (Beck Depression Inventory [BDI] and Zung Self-Rating Depression Scale [Zung SDS]) were administered on admission. Patients were characterized as having depressive symptoms when scores on both questionnaires were above cutoff levels and were subsequently followed for 5.1 ± 1.1 years for major adverse cardiovascular events (MACEs; death or hospitalization for cardiac reasons). Results Seventeen patients (mean age 28.9 ± 11.4 years) were characterized as having depressive symptoms. According to univariate Cox regression analysis, the presence of depressive symptoms was independently associated with adverse clinical outcome. During the follow-up period, patients with depressive symptoms had a shorter event-free survival (1559 ± 92 days vs. 1077 ± 188 days, P = .00215) and a twofold higher risk of getting a MACE, compared with patients without (95% CI 1.630 to 3.616, P < .05). Based on receiver operator characteristics, the BDI had a better prognostic value for future MACEs (area under curve = 0.662, 95% CI 0.5442 to 0.7792; P < .05) compared with the Zung SDS. Mean event-free survival for patients with BDI ≥ 10 was 986 ± 179 days vs. 1624 ± 83 days for patients with BDI < 10. Conclusions The incidence of depressive symptomatology in patients with CHD is rather high and is associated with poorer prognosis. The BDI seems to independently predict adverse clinical outcome. Standardized screening tools and psychosocial interventions to improve the well being of these patients should be a priority in the overall care of this population.

Exercise training is an established modality in chronic heart failure. Functional electrical stimulation (FES) is an effective alternative mode of training in patients unwilling or unable to exercise; however, it has not been investigated in elderly patients. We sought to investigate the effects of FES on functional status, quality of life, emotional status and endothelial function in chronic heart failure patients aged 70 years or higher.Thirty patients with stable systolic chronic heart failure (mean age 75 ± 3 years, New York Heart Association (NYHA) class II/III, 37%/63%) randomly underwent a six-week FES training programme or placebo. Questionnaires addressing quality of life (Kansas City Cardiomyopathy Questionnaire (KCCQ), functional and overall) and emotional stress (Zung self-rating depression scale (SDS), Beck Depression Inventory (BDI)), as well as endothelial function (flow-mediated dilatation) were assessed at baseline and upon protocol completion.A significant improvement in NYHA class (p=0.005), KCCQ-functional (F=68.6, p for interaction0.001), KCCQ-overall (F=66.9, p0.001), BDI (F=66.3, p0.001) and Zung SDS (F=95.1, p0.001) was observed in the FES group compared to placebo. Patients in the FES group also had a significant increase in flow-mediated dilatation compared with placebo (F=59.1, p0.01). FES-induced per cent change in flow-mediated dilatation was significantly correlated with respective per cent change in KCCQ functional (r=0.386, p=0.039).In this pilot study, FES effectively improved functional status, quality of life, motional stress and endothelial function in elderly chronic heart failure patients and warrants further investigation in this particular group of patients.

Background β-thalassemia major is a unique disease characterized by early severe diastolic dysfunction, due to iron myocardial deposition alone, while left ventricular systolic dysfunction and failure seem to be multifactorial in aitiology. Objectives The purpose of this study was to investigate left ventricular diastolic dysfunction using a new echo index as speckle tracking in comparison with the conventional methods. Material and methods Eighty-eight consecutive patients (38 male, 50 female) aged 36 ± 8.2 yr with β-thalassemia major and preserved LV ejection fraction (LVEF>55%) were studied. Patients were divided into two groups according to the E mitral/E mitral annulus ratio (E/E′): group A patients with E/E′ ratio ≤8 and group B patients with E/E′ >8. Cutoff value of eight was used to separate patients with normal and abnormal diastolic function. All subjects were studied thoroughly by tissue Doppler echocardiography as also by 2D left ventricular and atrial strain imaging 2–4 d following blood transfusion. Blood samples were also taken for plasma BNP measurements at the same time. Results Left atrial volumes(LAV max, LAV min) as also left atrial index were significantly higher in patients with diastolic dysfunction compared with patients without diastolic dysfunction(LAV max: 57.6 ± 19.4 vs. 71.3 ± 22.9, P

Sleep disordered breathing (SDB) is highly prevalent in patients with chronic heart failure (CHF) and is associated with adverse effects on cardiac geometry and function. Continuous positive airway pressure (CPAP) has been proved an effective treatment modality for obstructive sleep apnoea (OSA), whereas adaptive servoventilation (ASV) is more effective in patients with central sleep apnoea (CSA). The impact of selection of therapy and effective apnoea alleviation on cardiac performance and reverse left ventricular remodelling (r-LVR) has not yet been evaluated.Eighty five patients with stable CHF were screened for SDB and underwent polysomnography and treatment according to the type of SDB. Clinical evaluation and a comprehensive echocardiographic study was performed before initiation of therapy and after six months of effective treatment (ventilator use5h/day with AHI5 events/h).Seventeen compliant patients under effective treatment were included in the analysis (8 OSA under Autoset CPAP and 9 CSA under ASV). In both groups, a significant improvement in all measured, conventional and TDI LV systolic indexes was recorded, including LVEF (32% ± 6% vs. 27% ± 6%, p0.001). A decrease in LV end-systolic volume (189 ± 94 ml vs. 211 ± 88 ml, p=0.015, difference10%) was indicative of r-LVR. Furthermore, RV systolic parameters were also increased (TAPSE, p0.001; systolic TDI wave from lateral tricuspid annular aspect, p=0.001), whereas right heart dimensions and areas were diminished, indicating better pulmonary haemodynamics. Moreover, a significant improvement in patients' clinical status, as evaluated by New York Heart Association Class was also documented at the end of six months follow-up.Effective alleviation of SDB in CHF patients is associated with significant improvements in LV and RV systolic function and r-LVR. Longitudinal studies are needed to evaluate effects on morbidity and mortality.

Cardiopulmonary fitness is associated with reduced cardiovascular risk. Abnormal systolic blood pressure (SBP) response during recovery has been found to have diagnostic role for detecting cardiovascular risk. Aim of the study was to determine whether increased arterial stiffness associates with reduced aerobic exercise capacity after maximal cardiopulmonary exercise test (CPET) in a cohort of recently diagnosed hypertensive patients with a delayed decline in SBP during recovery.Eighty-four hypertensive patients with recently diagnosed I-II essential hypertension and under treatment with RAAS antagonists ± HCTZ, underwent pulse wave velocity (PWV) estimation and a maximal CPET. Fifty-four healthy normotensive subjects served as a control group. Blood pressure recovery ratio (BPRR) was defined as the SBP after 3 min recovery divided by SBP at peak exercise.PWV was significantly increased in hypertensives vs normotensives (p0.001). A non-independent, reverse association between PWV and VO2PEAK was revealed in hypertensives with delayed BPRR (r = - 0.49, p0.05). Age and sex independently predicted VO2PEAK in hypertensives with delayed BPRR.Delayed blood pressure response detected during recovery in treated hypertensives implies a reverse relationship between any given impaired aerobic exercise capacity and expected persistent peripheral vascular resistance during exercise.

This randomized, placebo-controlled trial showed that levosimendan administration causes a significant reduction of circulating proinflammatory cytokine interleukin-6 and soluble apoptosis mediators, such as soluble Fas and Fas ligand in patients with decompensated heart failure. These immunomodulatory effects may lead to improvement of symptoms and echocardiographic markers of cardiac contractile performance in these patients.

Chronic heart failure (CHF) is characterized by hemodynamic compromise, neurohormonal and immune activation. We sought to examine the presence and severity of immunosenescence and its relation with the stages of CHF.We enrolled 86 consecutive stable systolic CHF patients and examined the relationship of leukocyte and lymphocyte subpopulation counts by flow cytometry with their functional status according to New York Heart Association (NYHA) class.Patients with advanced heart failure were characterized by significantly increased neutrophil and reduced lymphocyte counts. T-helper cells were increased, whereas B-cells and T cytotoxic cells were decreased. T-helper cells exhibited significant differentiation and aging across the NYHA classes; naïve T-cells, CD4 + CD45RA +, were significantly reduced in NYHA Class IV and memory T-cells, CD4 + CD45RO +, were significantly increased.Patients with CHF develop intense T-cell differentiation and aging. The presence of significant immunosenescence in advanced CHF may indicate a population at increased risk for adverse events.

Introduction: Hypertension links to a prothrombotic state driven by endothelial dysfunction, reduced fibrinolytic potential and platelet hyperactivity. We hypothesized that ramipril treatment would favourably modify the haemostatic response to a submaximal aerobic exercise session in hypertensives. Methods: Twenty-four hypertensive patients underwent a submaximal exercise test before and after 13±2 months of treatment with ramipril ± hydrochlorothiazide. Hypercoagulability (prothrombin fragments [PF1+2], thrombin– antithrombin complex [TAT] and D-dimers [Dd]), fibrinolytic activity (plasmin–a2-antiplasmin complex [PAP]), endothelial function (von Willebrand factor [vWf] and soluble thrombomodulin [sTM]), and platelet function (soluble P-selectin [sPsel]) were measured before, at peak and one hour after exercise. Results: Antihypertensive treatment resulted in an increase of PAP, vWf and sTM. During the first exercise, PF1+2 were mildly increased at peak exercise ( p

Novel purine analogues bearing nitrate esters were designed and synthesized in an effort to develop compounds triggering endogenous cardioprotective mechanisms such as ischemic preconditioning (IPC) or postconditioning (PostC). The majority of the compounds reduced infarct size compared to the control group in anesthetized rabbits, whereas administration of the most active analogue 16 at a dose of 3.8 μmol/kg resulted on a significant reduction of infarct size, compared to PostC group (13.4 ± 1.9% vs 26.4 ± 2.3%). These findings introduce a novel class of promising pharmacological compounds that could be used as mimics or enhancers of PostC.

BACKGROUND Arterial stiffness and carotid intima-media thickness (IMT) constitute validated cardiovascular prognostic markers. Adiponectin and its receptors 1 (AdipoR1) and 2 (AdipoR2) are involved in coronary artery disease (CAD). We investigated whether AdipoR1 and R2 mRNA and protein expression are associated with arterial stiffness, IMT and extent of coronary atherosclerosis. METHODS We studied 71 patients (61 men, 10 women) with angiographically proven CAD. We measured: (i) monocyte expression of AdipoR1 and AdipoR2 mRNA (quantitative real-time PCR) and protein expression (flow cytometry) (iii) adiponectin, metalloproteinase-9 (MMP-9) and C-reactive protein (CRP) blood levels, (iv) carotid-femoral artery pulse wave velocity (PWV) and carotid IMT. RESULTS Patients with multi-vessel CAD had higher AdipoR1 and AdipoR2 mRNA than those with single-vessel (P < 0.05). PWV was associated with AdipoR1 mRNA (r = 0.474), AdipoR1 protein (r = 0.228), AdipoR2 mRNA (r = 0.716), AdipoR2-protein (r = 0.261), adiponectin (r = 0.236), and MMP-9 (r = 0.350) (P < 0.05, for all correlations). After adjustment for age, sex, waist-hip ratio, and mean blood pressure both AdipoR1 and AdipoR2 mRNA remained independent determinants of PWV (R(2) = 0.35 and R(2) = 0.57, P < 0.05). IMT was also associated with AdipoR2 mRNA, AdipoR2 protein, and MMP-9 (P < 0.05). Increased expression of ADR2 mRNA significantly related to MMP-9 (r = 0.210), and CRP (r = 0.531) (P < 0.05). CONCLUSION Increased mRNA and protein expression of adiponectin receptors is related with increased aortic stiffness, coronary and peripheral atherosclerosis in patients with CAD. The interrelation of AdipoR2 with inflammatory markers, PWV and IMT suggests a compensatory increase of these receptors to counteract the excess inflammatory and atherogenic process in CAD. Thus, adiponectin receptors may provide a potential therapeutic target of agents activating their beneficial action.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.42.

Aims The effectiveness of postconditioning (POC) in hypercholesterolaemia is in dispute. We investigated the effects of 3-day lipophilc (simvastatin) or hydrophilic (pravastatin) statin treatment, without or with POC in normocholesterolaemic (Norm) and hypercholesterolaemic (Chol) rabbits. Methods and results Norm or Chol rabbits were subjected to 30 min ischaemia and randomized in two series of 12 groups each: control, simvastatin (Sim), pravastatin (Prav), POC, Sim-POC, Prav-POC, Chol, Sim-Chol, Prav-Chol, POC-Chol, Sim-POC-Chol, Prav-POC-Chol. After ischaemia, rabbits of the first series underwent 3 h reperfusion, followed by infarct size, total cholesterol, and low density lipoprotein plasma level evaluation; animals of the second series underwent 10 min reperfusion followed by tissue sampling for nitrotyrosine (NT), malondialdehyde, endothelial nitric oxide synthase (eNOS), and Akt analyses. N -nitro-l-arginine methylester (L-NAME) was given in two additional groups (POC-L-NAME and Prav-Chol-L-NAME) for infarct size assessment. All interventions reduced infarction in Norm (24.3 ± 1.3, 25.9 ± 2.8, 27.9 ± 3.1, 23.3 ± 2.3, and 33.4 ± 2.5%, in POC, Sim, Prav, Sim-POC, and Prav-POC groups, respectively, vs. 49.3 ± 1.9% in control, P < 0.05), but only Prav did so in Chol animals (25.7 ± 3.3 and 25.3 ± 3.9% in Prav-Chol and Prav-POC-Chol vs. 50.9 ± 1.7, 44.8 ± 4.3, 41.5 ± 3.5, and 49.3 ± 5.5% in Chol, Sim-Chol, POC-Chol, and Sim-POC-Chol, respectively, P < 0.05). L-NAME abolished the infarct size-limiting effect of POC and Prav-Chol. Prav induced the greatest reduction in NT, while it was the only intervention that increased myocardial eNOS and Akt in Chol rabbits ( P < 0.05 vs. all others). Conclusion Prav, in contrast to same-dose Sim or POC, reduces infarction in Chol rabbits independently of lipid lowering, potentially through eNOS activation and nitro-oxidative stress attenuation.

Reactive oxygen and nitrogen species are critical in preconditioning (PC). We sought to determine the effect of N-2-mercaptopropionyl glycine (MPG) on infarct size and on the oxidative status. Rabbits were exposed to 30-minute regional ischemia of the heart, which was followed by 3-hour reperfusion: (1) a control group without further intervention, (2) a PC1 group that was subjected to one cycle of PC, (3) a PC4 group that was subjected to 4 cycles of PC, (4) an MPG group that was treated with MPG for 60 minutes, starting 10 minutes before reperfusion, (5) MPG-PC1, and (6) the MPG-PC4 groups that were treated with the same dose of MPG and with 1 or 4 cycles of PC, respectively. Blood samples were drawn and collected for metabonomic analysis. In another series of experiments, 6 groups respective to the described ones were subjected to 30-minute regional ischemia of the heart and 20 minutes of reperfusion, after which pieces of heart tissue were quickly excised for malondialdehyde, nitrotyrosine, and glutathione content assessment. All PC and MPG groups developed smaller infarct size compared with control (16.5% ± 3.9%, 13.7% ± 3.1%, 18.6% ± 5.0%, 9.7% ± 2.0%, 15.0% ± 2.8% vs. 48.05% ± 7.2%; P < 0.05). MPG did not prevent lipid peroxidation and nitrotyrosine formation but enhanced the glutathione content. PC and MPG induced similar nuclear magnetic resonance changes. Long MPG infusion reduces the infarct size without abolishing the effect of PC, providing novel insights into the activity of MPG in PC.

The endothelium holds a pivotal role in cardiovascular health and disease. Assessment of its function was until recently limited to experimental designs due to its location. The advent of novel techniques has facilitated testing on a more detailed basis, with focus on distinct pathways. This review presents available in-vivo and ex-vivo methods for evaluating endothelial function with special focus on more recent ones. The diagnostic modalities covered include assessment of epicardial and microvascular coronary endothelial function, local vasodilation by venous occlusion plethysmography and flow-mediated dilatation, arterial pulse wave analysis and pulse amplitude tonometry, microvascular blood flow by laser Doppler flowmetry, biochemical markers and bioassays, measurement of endothelial-derived microparticles and progenitor cells, and glycocalyx measurements. Insights and practical information on the theoretical basis, methodological aspects, and clinical application in various disease states are discussed. The ability of these methods to detect endothelial dysfunction before overt cardiovascular disease manifests make them attractive clinical tools for prevention and rehabilitation.

The cardiomyopathies are heart muscle diseases of primary or secondary origin. Primary cardiomyopathies are often of unknown cause, hence their treatment is limited to general heart failure management. In secondary cardiomyopathies, in contrast, the identification of the underlying cause allows for a more specific, hence effective, approach that, when applied early, may prevent the development of heart failure. The term iron overload cardiomyopathy (IOC) recently has been introduced to describe a secondary form of cardiomyopathy resulting from the accumulation of iron in the myocardium mainly because of genetically determined disorders of iron metabolism or multiple transfusions.1,2 This condition, although previously overlooked, has lately attracted the attention of investigators because iron overload is, on one hand, a frequently encountered condition, especially in association with certain hematologic conditions, and on the other hand, its accurate identification and effective management have now become possible. IOC has been recently described as a dilated cardiomyopathy, characterized by left ventricular (LV) remodeling with chamber dilatation and reduced LV ejection fraction (LVEF).1 However, primary hemochromatosis, a genetically determined condition leading to iron overload, is classically categorized as an infiltrative cause of restrictive cardiomyopathy.3 Moreover, secondary hemochromatosis may lead to severe diastolic LV dysfunction in the early stages of the disease, before LVEF is affected.4,5 In the present review, we describe the forms, pathophysiology, and phenotypic expression of IOC, focusing on ventricular geometry and function and describing the early diastolic abnormalities that lead ultimately to heart muscle dysfunction and heart failure. The clinical implications of the condition are also discussed. Iron overload is the accumulation of excess body iron in different organs as a result of increased intestinal absorption, parenteral administration, or increased dietary intake.6 Besides being a crucial component of hemoglobin with a key role in erythropoiesis, oxygen …

Background— In patients with heart failure (HF), increased arginine vasopressin concentrations are associated with more severe disease, making arginine vasopressin an attractive target for therapy. However, AVP is difficult to measure due to its in vitro instability and rapid clearance. Copeptin, the C-terminal segment of preprovasopressin, is a stable and reliable surrogate biomarker for serum arginine vasopressin concentrations. Methods and Results— The Biomarkers in Acute Heart Failure (BACH) trial was a 15-center, diagnostic and prognostic study of 1641 patients with acute dyspnea; 557 patients with acute HF were included in this analysis. Copeptin and other biomarker measurements were performed by a core laboratory at the University of Maryland. Patients were followed for up to 90 days after initial evaluation for the primary end point of all-cause mortality, HF-related readmissions, and HF-related emergency department visits. Patients with copeptin concentrations in the highest quartile had increased 90-day mortality ( P P r =0.047). Conclusions— This study showed significantly increased 90-day mortality, readmissions, and emergency department visits in patients with elevated copeptin, especially in those with hyponatremia. Copeptin was highly prognostic for 90-day adverse events in patients with acute HF, adding prognostic value to clinical predictors, ser um sodium, and natriuretic peptides. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00537628.

Objective The localization of coronary atherosclerotic lesions in patients with coronary artery disease is important. We investigated the relationship between individual cardiovascular risk factors and lesion localization in the coronary arteries. Methods We studied 200 consecutive patients with suspected or known coronary artery disease who were referred for coronary angiography because of chest pain. We assessed the following cardiovascular risk factors: male gender, hypercholesterolemia, smoking, arterial hypertension, positive family history, and diabetes. We evaluated atherosclerotic lesions creating a stenosis ≥ 50% in the 3 coronary arteries and lesions creating a stenosis ≥ 30% in the left main stem. Results Of the 200 study patients, 155 (78%) showed at least 1 coronary artery lesion with a luminal stenosis ≥ 50%. With an increasing number of risk factors, there was a significant progressive increase of diseased arteries ( P 001). There was a differential association between individual risk factors and lesions in the 3 coronary arteries. Male gender, hypercholesterolemia, and diabetes were predictors of lesions in the left anterior descending artery (odds ratios 2.365, 2.510, and 1.998, respectively). Predictors of left circumflex artery lesions were male gender, smoking, and diabetes (odds ratios 2.581, 1.913, and 2.280, respectively), whereas the only independent predictor of right coronary artery lesions was male gender (odds ratio 2.995). Diabetes was also significantly associated with lesions in the diagonal branches of the left anterior descending artery and the marginal branches of the left circumflex artery. Conclusion Individual cardiovascular risk factors are associated with the localization of atherosclerotic lesions in the coronary circulation.

Aims To identify potential genetic associations of five cytokine gene polymorphisms with disease severity and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). Methods and results Eighty patients with DCM were genotyped for transforming growth factor beta1 (TGF-β1) +869 T/C (codon10 Leu → Pro), TGF-β1 +915 G/C (codon25 Arg → Pro), interleukin (IL)-6 −174G/C, tumor necrosis factor-alpha (TNF-α) −308A/G, interferon-gamma (IFN-γ) +874T/A, IL-10 −1082A/G, IL-10 −819T/C and IL-10 −592A/C gene polymorphisms. In homozygous TT patients for TGF-β1 +869 T/C polymorphism mean VO 2 max was significantly higher than in CC homozygous patients (25.67 ± 6.73 ml/kg/min vs. 20.29 ± 6.35 ml/kg/min, p = 0.046), which remained significant only for patients younger than 39 years old after adjusting for age and sex ( p = 0.009). C carriers of TGF-β1 +915 G/C polymorphism are 4.2 times more likely to be in a worse NYHA stage (III–IV) than non C carriers [OR: 4.25, 95% CI (1.53–11.80), p = 0.006]. Patients GG homozygous for IL-6 −174G/C polymorphism presented greater left ventricle end-systolic ( p = 0.018) and end-diastolic ( p = 0.04) diameters in comparison to the CC homozygous. The AA homozygote for IFN-γ +874T/A polymorphism ( p = 0.02) and the combination of the TGF-β1 +869 T/C and TGF-β1 +915 G/C genotypes were associated with adverse outcome ( p = 0.014). Conclusion Specific cytokine gene polymorphisms seem to be associated with worse prognosis as well as with measures of disease severity in DCM.

BACKGROUND Subclinical organ damage represents an intermediate stage in the continuum of vascular disease and a determinant of overall cardiovascular risk. We investigated the associations of pulse wave velocity (PWV), ambulatory arterial stiffness index (AASI), and office pulse pressure (PP) with several target organ damages (TODs) in newly diagnosed and never-treated patients with essential hypertension with respect to their dipping profile. METHODS One hundred sixty-eight hypertensive patients with recently diagnosed and never-treated stage I-II essential hypertension were evaluated with respect to the relationship of PWV, AASI, and office PP with TOD including microalbumin (MAU) levels, cognitive function, intima-media thickness (IMT), coronary flow reserve (CFR), left ventricular mass (LVM), left ventricular filling pressures, diastolic dysfunction, and left atrium (LA) enlargement. RESULTS Simultaneous estimation of AASI, PWV, and office PP independently associated with the following: (i) CFR (P < 0.01), 24-h urine albumin excretion rates (P < 0.05), left ventricular diastolic dysfunction (P < 0.01), and LA enlargement (P < 0.01) in never-treated hypertensive patients; (ii) CFR (P < 0.05), IMT (P < 0.01 ), left ventricular diastolic dysfunction (P < 0.05), and LA enlargement (P < 0.05) in dippers; and (iii) CFR (P < 0.05) and LA enlargement (P < 0.01) in nondippers. Nonindependent relationships revealed between (i) AASI and left ventricular filling pressures and (ii) PWV and cognitive dysfunction in never-treated hypertensive patients. CONCLUSIONS The simultaneous estimation of three noninvasive indexes of arterial stiffness leads to valuable information regarding their association with TOD including CFR, MAU levels, IMT, left ventricular diastolic dysfunction, and LA enlargement in never-treated hypertensive patients regarding their dipping status.

Aims Acute pulmonary oedema (APE) is the second, after acutely decompensated chronic heart failure (ADHF), most frequent form of acute heart failure (AHF). This subanalysis examines the clinical profile, prognostic factors, and management of APE patients (n = 1820, 36.7%) included in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). Methods and results ALARM-HF included a total of 4953 patients hospitalized for AHF in Europe, Latin America, and Australia. The final diagnosis was made at discharge, and patients were classified according to European Society of Cardiology guidelines. Patients with APE had higher in-hospital mortality (7.4 vs. 6.0%, P = 0.057) compared with ADHF patients (n = 1911, 38.5%), and APE patients exhibited higher systolic blood pressures (P < 0.001) at admission and higher left ventricular ejection fraction (LVEF, P < 0.01) than those with ADHF. These patients also had a higher prevalence of diabetes (P < 0.01), arterial hypertension (P < 0.001), peripheral vascular disease (P < 0.001), and chronic renal disease (P < 0.05). They were also more likely to receive intravenous (i.v.) diuretics (P < 0.001), i.v. nitrates (P < 0.01), dopamine (P < 0.05), and non-invasive ventilation (P < 0.001). Low systolic blood pressure (P < 0.001), low LVEF (

Rotational angiography is a novel method for three-dimensional reconstruction of the left atrium and pulmonary veins during catheter ablation for atrial fibrillation, but is still hampered by suboptimal reconstructions in a considerable number of patients. We describe the results of rapid pacing of the right ventricle for optimization of image acquisition during rotational angiography.

Background: Selective serotonin re-uptake inhibitors (SSRIs) have been associated with better psychiatric status, functional capacity, and fewer arrhythmias in depressive patients with heart failure (HF). In this study, we tested the impact of sertraline (an SSRI) on patients with HF, but not clinical depression. Methods: We studied 62 clinically stable, nondepressive patients with ischemic HF (New York Heart Association class: I-II), and implantable cardioverter-defibrillator (ICD). Following psychiatric evaluation and quality of life (QoL) assessment, 24-hour electrocardiogram recordings including heart rate variability (HRV) and ICD interrogation were performed every 4 months for 1 year. Ventricular effective refractory period (ERP) at 600-, 500-, and 400-ms cycle length and the inducibility of ventricular tachycardia (VT) were assessed via the ICD. After that, sertraline 50 mg/day was administered for 12 months and the whole evaluation was repeated. Results: Sertraline was associated with fewer ventricular extrasystoles per 24 hours and a significant change in HRV (increase in mean R-R, 5-minute standard deviation of RR intervals, and root mean-square difference of successive RR intervals, and reduction in ultra and very low frequency). It was also followed by an improvement in patients’ QoL. A trend toward a decrease was observed in the number of recalled nonsustained VTs. The episodes of sustained VT were not significantly reduced. Ventricular ERPs and VT inducibility remained unaltered. Conclusion: In clinically stable, nondepressive patients with ischemic HF and ICD, sertraline is associated with reduced ventricular extrasystoles, better QoL, and a possible improvement in some HRV indexes. This suggests that SSRIs may have a favorable clinical impact on these patients, independent of the improvement in depressive symptoms. (PACE 2010; 33:1217–1223)

Objectives Our purpose was to assess the diagnostic utility of mid-regional pro–atrial natriuretic peptide (MR-proANP) for the diagnosis of acute heart failure (AHF) and the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) in patients with AHF. Background There are some caveats and limitations to natriuretic peptide testing in the acute dyspneic patient. Methods The BACH (Biomarkers in Acute Heart Failure) trial was a prospective, 15-center, international study of 1,641 patients presenting to the emergency department with dyspnea. A noninferiority test of MR-proANP versus B-type natriuretic peptide (BNP) for diagnosis of AHF and a superiority test of MR-proADM versus BNP for 90-day survival were conducted. Other end points were exploratory. Results MR-proANP (≥120 pmol/l) proved noninferior to BNP (≥100 pg/ml) for the diagnosis of AHF (accuracy difference 0.9%). In tests of secondary diagnostic objectives, MR-proANP levels added to the utility of BNP levels in patients with intermediate BNP values and with obesity but not in renal insufficiency, the elderly, or patients with edema. Using cut-off values from receiver-operating characteristic analysis, the accuracy to predict 90-day survival of heart failure patients was 73% (95% confidence interval: 70% to 77%) for MR-proADM and 62% (95% confidence interval: 58% to 66%) for BNP (difference p Conclusions MR-proANP is as useful as BNP for AHF diagnosis in dyspneic patients and may provide additional clinical utility when BNP is difficult to interpret. MR-proADM identifies patients with high 90-day mortality risk and adds prognostic value to BNP. (Biomarkers in Acute Heart Failure [BACH]; NCT00537628)

Aims Adrenomedullin (ADM) is a vasodilatory peptide. Its plasma levels or its precursors have not been evaluated in large populations of patients with chronic heart failure (CHF). We sought to explore mid-regional proADM (MR-proADM). Methods and results We assessed MR-proADM in 501 CHF patients [age 63 ± 11 years, New York Heart Association (NYHA) class I/II/III/IV 9/44/39/8%, median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 878 pg/mL (interquartile range—IQR 348–2480 pg/mL), median left ventricular ejection fraction (LVEF) 31% (IQR 25–37%)]. Mid-regional pro-adrenomedullin levels (median 0.64 nmol/L, IQR 0.49–0.87 nmol/L) increased with NYHA class (P < 0.0001). During 1-year follow-up, 70 patients (14%) died. Increasing MR-proADM was a predictor of poor survival at 12 months (hazard ratio 1.82, 95% confidence interval 1.24–2.66, P = 0.002) after multivariable adjustment. In receiver-operating characteristic curve analysis of 12-month survival, the area under the curve for MR-proADM and NT-proBNP was similar (P = 0.3). Comparison of Cox proportional hazard models using the likelihood ratio χ2 statistic showed that both NT-proBNP and MR-proADM added prognostic value to a base model of LVEF, age, creatinine, and NYHA class. Adding MR-proADM to the base model had stronger prognostic power than adding NT-proBNP (both P < 0.01). Conclusion Mid-regional pro-adrenomedullin is an independent predictor of mortality in CHF patients, which adds prognostic information to NT-proBNP.

Osteopontin (OPN) is a glycoprotein, which may play a major role in the regulation of biological phenomena. Increased levels of OPN have been linked to the presence and to the severity of atherosclerosis. This study was undertaken to assess the prognostic significance of plasma OPN levels in patients with stable ischaemic heart disease (IHD).In 101 patients with stable IHD and angiographically documented significant coronary artery stenosis, plasma OPN levels were measured at baseline (time of coronary arteriography). Patients were prospectively followed for a median time of 3 years (minimum 2.25, maximum 3.9 years). The primary study endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, need for revascularization and hospitalization for cardiovascular reasons.Baseline lnOPN levels were directly related to age (r = 0.27, P0.001) and inversely to left ventricular ejection fraction (r = -0.32, P0.01). Left ventricular ejection fraction was an independent predictor of plasma OPN levels after adjustment for age and gender (beta = -0.013, P = 0.02). Median OPN value was 55 ng mL(-1). In the univariate Cox-regression analysis, OPN levels55 ng mL(-1) (n = 50) were significantly related to adverse cardiac outcome (HR = 2.40, 95% CI: 1.11-5.23, P = 0.027). In multivariate model, OPN levels55 ng mL(-1) remained statistically significant independent predictor of adverse outcome after adjustment for age, gender, left ventricular ejection fraction and the number of diseased coronary arteries (HR = 2.88, 95% CI: 1.09-7.58, P = 0.032).OPN may provide significant prognostic information independent of other traditional prognostic markers in patients with stable IHD.

Introduction: The aim of this study was to establish an optimized fast and safe protocol for the pharmacological screening of AT1 antagonists. Materials and methods : The pharmaceutical prototype AT1 antagonist losartan, its active metabolite EXP3174 and the synthetic compound MMK1 were analysed in order to validate the protocol. Ang II was continuously infused while the animals received the drugs in two procedures. Results: In the post-treatment procedure drugs were administered either in a single bolus dose or in a sequential manner. When losartan was administered in a single bolus dose, efficacy was evident until the 7th min ( p=0.012) whilst EXP3174 infusion extended the efficiency up to the end of the study ( p=0.006). In addition, the sequential injections of losartan prolonged the inhibitory time interval until the end of the study ( p=0.045). In the pre-treatment procedure, results suggested a dose-dependent inhibitory effect for both antagonists. The pressor response to Ang II was unchanged after MMK1 administration either in the post- or in the pre-treatment mode. Conclusions: The proposed protocol appears to be safe, simple and fast for the pharmacological screening of AT1 antagonists and enables the evaluation of new antagonists using lower doses than any other reported in the literature.

Selective serotonin reuptake inhibitors (SSRIs) exert cardioprotective effects. We examined whether SSRIs a) modulate endothelial cell expression of vascular cell adhesion molecule (VCAM-1), intracellular adhesion molecule (ICAM-1) and adhesiveness to U937 monocytes, b) reduce the circulating levels of these adhesion molecules in vivo.We assessed the effect of SSRIs, (citalopram, fluvoxamine and fluoxetine), on TNF-alpha-induced expression of VCAM-1 and ICAM-1 in human aorta endothelial cells and adhesiveness to U937 monocytes. Cells were incubated with TNF-alpha in the absence and in the presence of SSRIs concentrations from 10(-7) M to10(-4) M and the VCAM-1 and ICAM-1 expression was quantified by cell-ELISA. The TNF-alpha-stimulated adhesiveness to U937 monocytes was also assessed. Twenty five patients with chronic heart failure and depression were randomized to receive sertaline 50 mg, p.o., o.d. (n=13) or placebo. At baseline and 3-months after treatment, we measured VCAM-1 and ICAM-1 plasma levels.SSRIs decreased the TNF-alpha-induced endothelial expression of VCAM-1 at concentration range 10(-7) M to 10(-4) M (p0.05). ICAM-1 expression was decreased in the presence of fluvoxamine and fluoxetine at concentrations from 10(-7) M to 10(-4) M (p0.05) and in the presence of citalopram at concentrations from 10(-7) M to 10(-5) M (p0.05). All SSRIs inhibited the TNF-alpha-stimulated adhesiveness to U937 cells at 10(-5) M and 10(-4) M (p0.05). Compared to baseline, there was a greater reduction in ICAM-1 and VCAM-1 levels post-sertaline than post placebo in heart failure patients (p0.05).SSRIs may exhibit an anti-inflammatory activity on endothelial cells and reduce circulating VCAM-1 and ICAM-1 in vivo, a mechanism which may partly mediate their cardioprotective effects.

Microcirculation (2010) 17, 303–310. doi: 10.1111/j.1549–8719.2010.00023.x Abstract Objectives: We investigated whether HIV-1 infected patients receiving highly active antiretroviral therapy (HAART) and HIV-1 infected patients who had never received HAART had differences in their vascular microcirculatory function. Methods: We assessed the forearm blood flow before and after four minutes of ischemic occlusion of the brachial artery using venous occlusion strain gauge plethysmography. The hyperaemic forearm blood flow was recorded for three minutes at 15 second intervals. We calculated the maximal percent increase of the forearm blood flow during hyperemia. Forty HIV-infected male patients receiving HAART were compared to 20 age- and BMI- matched, male HIV-infected patients who had never received HAART (control group). Results: Patients on HAART had similar baseline forearm blood flow but lower maximal and percentage (%) change in forearm blood flow than control patients (4.2 ± 1.7 vs. 4.1 ± 1.7 l/ 100mL/min P = 0.8, 32 ± 11.2 vs. 38.9 ± 10.5 l/100 mL/min. P = 0.04 and 714 ± 255 vs. 907 ± 325%, P = 0.01, respectively). Patients receiving HAART had higher cholesterol than control patients (221 ± 58 vs. 163 ± 38 mg/dL, P = 0.001). HAART was associated with the percentage change in the blood flow during hyperemia (coefficient regression B = −0.32, P = 0.02) after adjustment for age, cholesterol and viral load. Conclusions: HIV-infected patients receiving HAART present abnormalities of arterial microcirculation in comparison with never-treated patients.

The mechanisms of the N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) release in intensive care unit (ICU) patients with preserved ejection fraction (EF) are unclear. We investigated whether left ventricular (LV) dysfunction, as assessed by tissue Doppler imaging (TDI), is related to NT-pro-BNP levels in ICU patients with preserved EF and has a complementary value to NT-pro-BNP in the determination of in-hospital mortality. We examined 58 mechanically ventilated patients with no history of heart failure (age, 60 +/- 18 years; EF, 63% +/- 7%). The systolic (S) and early diastolic (E') velocity of the mitral annulus by TDI and the E/E' as well as NT-pro-BNP, troponin, lactate acid, blood oxygen (P(O2)/Fi(O2)), sepsis, and ICU mortality were assessed. Systolic, E', and E/E' correlated with age, P(O2)/Fi(O2), lactate acid, NT-pro-BNP, troponin, history of arterial hypertension, and diabetes (P < 0.05). By multivariate analysis, the determinants of NT-pro-BNP were S (P = 0.024), E/E' (P = 0.017), and sepsis (P = 0.015). An NT-pro-BNP greater than 941 pg/mL was a reliable predictor of LV diastolic dysfunction defined as a composite of E' less than or equal to 8 cm/s and/or mean E/E greater than or equal to 13 (area under the curve, 75%; P = 0.03). Patients with combined NT-pro-BNP greater than 941 pg/mL and abnormal TDI markers had increased creatinine levels and a lower MAP, P(O2)/Fi(O2), and survival rate than those with abnormal TDI or NT-pro-BNP alone or patients with normal TDI markers and NT-pro-BNP (25%, 60%, 70%, and 84%, respectively; P < 0.05). The addition of abnormal TDI in a model including NT-pro-BNP and sepsis increased the model's value for in-hospital mortality (P for change = 0.01). In ICU patients with preserved EF, LV diastolic dysfunction and sepsis determine NT-pro-BNP levels. Tissue Doppler imaging markers and NT-pro-BNP have a complementary value for in-hospital mortality.

Postconditioning (POC) reduces lethal reperfusion injury under normal conditions, but its effectiveness under certain pathological states is in dispute. In the present study, we sought to determine the effect of chronic simvastatin treatment in hyperlipidemic animals with or without POC. Anesthetized rabbits were randomized into eight groups, as follows, and were subjected to 30-min myocardial ischemia followed by 3-h reperfusion. Normally fed animals: a Control group with no additional intervention, a Sim group treated with simvastatin for 3 weeks at a dose of 3 mg kg(-1), a POC group subjected to POC with eight cycles of 30-s ischemia/reperfusion, a Sim-POC group treated with simvastatin, and POC. Cholesterol fed (6 weeks) animals: a Chol group with no additional interventions, a Chol-Sim group treated with simvastatin for 3 weeks, a Chol-POC group subjected to POC, and a Chol-Sim-POC group treated with simvastatin and POC. Infarct size and plasma levels of malondialdehyde (MDA), nitrotyrosine (NT), NOx, total cholesterol, and LDL were evaluated. In a second series of experiments, heart tissue samples were taken for MDA, NT, and NOx assessment. Infarct size, circulating MDA, NT, NOx and cardiac MDA, NT, and NOx levels declined in POC and all Sim groups compared with Control, Chol, and Chol-POC (p0.05). Simvastatin also reduced total cholesterol and LDL plasma levels. In conclusion, a 3-week simvastatin treatment limits the infarct size and attenuates the oxidative and nitrosative stress both in normo- and in hyper-cholesterolemic rabbits subjected to ischemia-reperfusion irrespective of the presence of POC, while POC is effective only in normocholesterolemic animals.

Beta-thalassemia major is a unique disease characterized by early diastolic dysfunction, related exclusively to iron myocardial deposition. N-terminal-proBNP(amino-terminal) (NT-proBNP) and B-type natriuretic peptide (BNP) are sensitive biomarkers for the detection of asymptomatic left ventricular (LV) dysfunction, and they have important diagnostic and prognostic implications. Using beta-thalassemia as a model disease with isolated diastolic dysfunction, we sought to investigate the predictive value of NT-proBNP and BNP levels in comparison with the conventional and new Doppler echocardiography indexes in detecting this disorder.Seventy beta-thalassemia major patients (mean age 27.2 +/- 12.5 years) with normal LV systolic function (mean LV ejection fraction = 59% +/- 6.8%), and 50 healthy age-matched adults (control group: mean age 25.5 +/- 10.1 years, mean LV ejection fraction = 60% +/- 4.5%) were included. All subjects were studied thoroughly by tissue Doppler echocardiography and blood samples were taken for plasma NT-proBNP and BNP measurements at the same time. To examine LV diastolic function, patients were divided in 3 groups according to the E mitral/E mitral annulus ratio (E/E'): group A, patients without diastolic dysfunction: E/E' ratio8; group B, patients with suspected diastolic dysfunction: E/E' ratio 8 to 15; group C, patients with documented diastolic dysfunction: E/E' ratio,15.NT-proBNP and BNP levels were higher in thalassemic patients compared with the control group (NT-proBNP levels: 80 +/- 19 vs 21 +/- 4 pg/mL, P.001; BNP levels: 34 +/- 6 vs 9 +/- 3 pg/mL, P.001). NT-proBNP levels showed a statistically significant increase in group C in comparison to groups A and B, which was also detected between groups A and B (A vs B: P.05). BNP levels were also significantly increased in group C in comparison to the other 2 groups, but there was no statistically significant difference between groups A and B. Using receiver operating characteristic analysis, NT-proBNP at a cut point of 49.2 pg/mL was highly accurate (area under curve: 0.97, P.001) in ruling out diastolic dysfunction (E/E'8) with a sensitivity of 93.7% and a specificity of 89.6%.BNP and NT-proBNP levels are significantly increased in documented left ventricular diastolic dysfunction, while NT-proBNP seems to have better predictive value in detecting latent left ventricular diastolic dysfunction in beta-thalassemia major.

Right ventricular (RV) dysfunction adversely affects prognosis in patients with chronic heart failure (CHF) due to left ventricular (LV) dysfunction. However, little evidence exists regarding the prognostic role of RV systolic and diastolic function indexes in combination with plasma B-type natriuretic peptide (BNP) in advanced CHF. Thus, 102 consecutive hospitalized patients with advanced CHF (New York Heart Association classes III to IV) due to LV systolic dysfunction (LV ejection fraction35%) were studied by 2-dimensional conventional and tissue Doppler imaging (TDI) echocardiography of the left and right ventricles. Plasma BNP was also measured. Patients were followed for 6 months for major cardiovascular events (cardiovascular death and/or CHF-related hospitalization). During follow-up, 13 patients died and 63 patients reached the combined end point of cardiovascular death or CHF-related hospitalization. By univariate analysis, RV TDI systolic velocity, dilated cardiomyopathy, digoxin treatment (all p values0.01), and female gender (p0.05) were associated with increased cardiovascular death. Transmitral Doppler to mitral annular TDI early diastolic velocity ratio, RV TDI early diastolic velocity (p0.05), and ratio of early to late RV diastolic TDI velocities (p0.01) predicted the combined end point. In multivariate analysis, decreased RV systolic velocity, dilated cardiomyopathy, and female gender (all p values0.05) were independent predictors of cardiovascular death, whereas increased ratio of early to late RV diastolic TDI velocities (p0.01) and increased BNP (p0.05) predicted the combined end point. In conclusion, RV TDI indexes combined with increased plasma BNP additively predict adverse cardiac outcomes in advanced CHF.

The muscle LIM protein (MLP) and cofilin 2 (CFL2) are important regulators of striated myocyte function. Mutations in the corresponding genes have been directly associated with severe human cardiac and skeletal myopathies, and aberrant expression patterns have often been observed in affected muscles. Herein, we have investigated whether MLP and CFL2 are involved in common molecular mechanisms, which would promote our understanding of disease pathogenesis. We have shown for the first time, using a range of biochemical and immunohistochemical methods, that MLP binds directly to CFL2 in human cardiac and skeletal muscles. The interaction involves the inter-LIM domain, amino acids 94 to 105, of MLP and the amino-terminal domain, amino acids 1 to 105, of CFL2, which includes part of the actin depolymerization domain. The MLP/CFL2 complex is stronger in moderately acidic (pH 6.8) environments and upon CFL2 phosphorylation, while it is independent of Ca(2+) levels. This interaction has direct implications in actin cytoskeleton dynamics in regulating CFL2-dependent F-actin depolymerization, with maximal depolymerization enhancement at an MLP/CFL2 molecular ratio of 2:1. Deregulation of this interaction by intracellular pH variations, CFL2 phosphorylation, MLP or CFL2 gene mutations, or expression changes, as observed in a range of cardiac and skeletal myopathies, could impair F-actin depolymerization, leading to sarcomere dysfunction and disease.

Aims To assess the prognostic value of a wide spectrum of neurohormonal and inflammatory markers along with functional status and exercise capacity, in hospitalized chronic heart failure (CHF) patients with depressive symptoms. Methods and results A total of 300 consecutive hospitalized CHF patients were screened for depressive symptomatology using the Zung self-rated depression scale (SDS). Patients with depressive symptoms (Zung SDS ≥40) underwent a 6 min walking test, and evaluation of left ventricular ejection fraction, B-type natriuretic peptide (BNP), and plasma inflammatory/anti-inflammatory factors [interleukin (IL)-6, IL-10, tumour necrosis factor-α, soluble intercellular adhesion molecule-1, and vascular cell adhesion molecule-1]. Patients were subsequently followed for up to 1 year for major adverse cardiovascular events (MACE, death or hospitalization due to cardiovascular causes). One hundred and fourteen patients (38%) had a Zung SDS ≥40. One-year event-free survival of these patients was 19% (mean ± SE, 150 ± 12 days). In multivariate analysis, only BNP (HR = 1.001, P = 0.002) and IL-10 (HR = 0.864, P = 0.049) were independent predictors of MACE. Using receiver operator characteristics analysis-derived cut-offs, a BNP value of 290 pg/mL predicted MACE with 86% sensitivity and 69% specificity, whereas an IL-10 value of 5 pg/mL predicted MACE with 61% sensitivity and 78% specificity. Event-free survival differed significantly between patients with BNP 5 pg/mL (261 ± 44 days) and those with BNP > 290 pg/mL and IL-10 < 5 pg/mL (79 ± 11 days, P = 0.0001). Conclusion Neurohormonal activation and defective anti-inflammatory properties are independent predictors of long-term outcome in hospitalized CHF patients with depressive symptoms.

Ischemic postconditioning has emerged as a clinically feasible intervention for limiting infarction in the setting of percutaneous intervention. In ischemic postconditioning, a number of cycles of a brief period of reperfusion followed by a brief period of occlusion are applied immediately upon reperfusion of the ischemic heart. Although ischemic postconditioning is protective in both animals and man, the animal studies reveal that the algorithm used in selecting the duration of the occlusion and reperfusion periods is critical to the degree of protection realized and it varies with species. The question then arises what is the best algorithm for man? The available animal and clinical data are examined in an attempt to shed light on this perplexing problem.

We aimed at evaluating the combined use of heart rate variability (HRV), baroreflex sensitivity (BRS), and MIBG imaging in the risk stratification for sudden cardiac death (SCD) of patients with mild to moderate heart failure. Twenty-five patients (17 male and 8 female, mean age 63 ± 5 years, mean LVEF 36 ± 3%) with a recently implanted defibrillator (ICD) and mild (NYHA I-II) heart failure due to either ischemic (n = 15) or dilated (n = 10) cardiomyopathy were studied. One week after ICD implantation they underwent (a) baroreflex sensitivity (BRS) evaluation to bolus phenylephrine by the Oxford method, (b) 24-h heart rate variability (HRV) assessment, and (c) MIBG imaging. The mean patient follow-up was 32 ± 10 months. Simple correlation and stepwise multiple regression analysis was performed to evaluate (a) if the number of sustained ventricular tachycardia (cycle length

Background Although there is evidence that inflammation and oxidative stress might contribute to the pathogenesis of atrial fibrillation (AF), the predictive value of inflammatory and oxidative stress markers in patients with AF has not been fully assessed. The aim of this study is to evaluate these markers as predictors of sinus rhythm (SR) maintenance, in patients with persistent lone AF. Methods Among 268 patients with symptomatic AF, we studied 46 patients with a first episode of recently established persistent lone AF. We measured the circulating levels of hs-CRP, TNF-α, IL-6, IL-10, sICAM-1, sVCAM-1, malondialdehyde (MDA) and nitrotyrosine (NT) before, 1 h, 24 h, 1, 2, 4 and 6 weeks after cardioversion. During a 12-month follow-up period, AF recurrence was evaluated by Holter ECG recordings every month and when symptoms were reported. Results Baseline levels of CRP, TNF-α, sICAM-1, MDA, and NT were elevated in patients with AF compared to controls, and higher in patients with than in those without persistent AF recurrence, while IL-6 levels were equally elevated in the two subgroups. SR maintenance was associated with lower baseline MDA values and faster decrease in IL-6, sICAM-1 and NT levels within the first 2 weeks following SR restoration. Conclusions Increased markers of inflammation and oxidative stress are found in patients with lone AF, implying that inflammation and oxidative stress may be associated with the presence of the arrhythmia. IL-6, sICAM-1, MDA and NT, assessed prior to and after the first cardioverted episode of persistent arrhythmia, appear to be reliable, early predictors of SR maintenance during the following year.

Ischemic postconditioning, a simple mechanical maneuver at the onset of reperfusion, reduces infarct size after ischemia/reperfusion. After its first description in 2003 by Zhao et al. numerous experimental studies have investigated this protective phenomenon. Whereas the underlying mechanisms and signal transduction are not yet understood in detail, infarct size reduction by ischemic postconditioning was confirmed in all species tested so far, including man. We have now reviewed the literature with focus on experimental models and protocols to better understand the determinants of protection by ischemic postconditioning or lack of it. Only studies with infarct size as unequivocal endpoint were considered. In all species and models, the duration of index ischemia and the protective protocol algorithm impact on the outcome of ischemic postconditioning, and gender, age, and myocardial temperature contribute.

We examined whether angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism is associated with the development of myocardial infarction (MI) ator = 35 years of age. The study sample consisted of 201 patients with premature MI and 140 age- and sex-matched healthy individuals. No difference was found in the distribution of ACE genotypes between the patients and controls. A higher prevalence of the DD genotype among hypertensives was found compared with the non-hypertensive patients (62.5% vs 35.6%, p = 0.01). ACE polymorphism is not associated with the development of premature MI and this might be due to the low prevalence of hypertension in young coronary patients.

Background: Right ventricular (RV) apical pacing deteriorates left ventricular (LV) function. RV nonoutflow (low) septal pacing may better preserve ventricular performance, but this has not been systematically tested. Our aim was to assess (1) whether long-term RV lower septal pacing is superior to RV apical pacing regarding LV volumes and ejection fraction (EF), and (2) if the changes in LV dyssynchrony imposed by pacing are related to the long-term changes in LV volumes and EF. Methods: In thirty-six patients with atrioventricular (AV) block, a dual-chamber pacemaker was implanted. The ventricular electrode was placed either at the apex or at the lower septum, in a randomized sequence. Twenty-four to 48 hours following implantation, we measured LV volumes, EF, and LV dyssynchrony (by tissue Doppler imaging), both with and without pacing. Patients were reassessed echocardiographically after 12 months. Results: Lower septal pacing induced a more synchronized pattern of LV contraction changes (P < 0.05). Following 12 months, differences were observed between groups regarding LV volumes and EF. EF increased within the septal group (from 52 ± 3.3% to 59 ± 3.0%, P < 0.05). A significant inverse relation was documented between changes in LV dyssynchrony and changes in EF (r =−0.64, P < 0.05). Conclusions: In patients with AV block, RV nonoutflow septal pacing represents an attractive alternative, since it preserves better and may even improve LV volumes and EF. Late changes in EF are associated with the changes in LV dyssynchrony imposed by pacing.

Summary Background We investigated whether dietary habits can discriminate young individuals with myocardial infarction (MI) from age–sex-matched controls. Methods We enrolled 100 consecutive patients who had survived their first MI before the age of 36 years and 100 age- and sex-matched controls without a history of cardiovascular disease. Dietary habits were assessed through a semi-quantitative food frequency questionnaire, and a diet score that evaluates quality of diet was developed (ranging 14–60). Smoking habits, physical activity status, body mass index, clinical history and blood lipid levels were also measured. Results Data analysis revealed that MI patients had less healthy dietary as compared to their matched controls (23 ± 4 vs. 31 ± 4; p Conclusions The present work provides scientific evidences that promotion of healthy eating from the youth may prevent the development of CHD.

The aim of this study was to assess the prevalence of several polymorphisms in genes that are involved in several pathways such as hemostasis, fibrinolysis, platelet membrane receptor activity, endothelial integrity and function, lipid metabolism, and regulation of blood pressure in healthy subjects of Greek origin. Most of these polymorphisms are mainly associated with conditions such as venous thromboembolism and atherothrombosis, and their prevalence has not been studied yet in Greece. We tested 140 healthy individuals for factor V (FV)1691G/A, FV4070G/A, FII 20210G/A, factor XIII (FXIII) exon 2G/T, fibrinogen beta-455G/A, plasminogen activator inhibitor-1 (PAI-1)-675 4G/5G, human platelet antigens 1 (HPA1) a/b, apolipoprotein B (ApoB) 10708 G/A, apolipoprotein E (ApoE) E2, E3, and E4, angiotensin-converting enzyme (ACE) D/I, 5,10 methylenetetrahydrofolate reductase (MTHFR) 677C/T, and MTHFR 1298A/C polymorphisms using a PCR and reverse hybridization technique that detects all of them simultaneously. The allele frequencies observed are in accordance with those reported in other Caucasian populations and almost identical to those of East Mediterranean populations. This first report from Greece may serve as a baseline for planning further investigations of these polymorphisms in association with several clinical entities and for launching guidelines for patient testing of various disease settings in this population.

Levosimendan reduces symptoms and improves hemodynamics in patients with acutely decompensated chronic heart failure (ADCHF). The aim of this study was to investigate (1) the association of changes induced by low-dose dobutamine stress echocardiography in 2-dimensional strain parameters with the corresponding changes in the left ventricular (LV) ejection fraction (EF) and LV outflow tract velocity time integral (VTI) in patients with ADCHF and (2) whether LV contractile reserve assessed by conventional and speckle-tracking echocardiography is associated with clinical and neurohumoral improvement after levosimendan treatment. Twenty-eight consecutive patients with ADCHF (mean age 65 +/- 10 years, mean New York Heart Association class 3.6 +/- 0.3, mean EF 22 +/- 6%) were studied using dobutamine stress echocardiography before 24-hour infusion of levosimendan. The LV EF, VTI, and mean longitudinal, circumferential, and radial strain and strain rate using speckle-tracking imaging were measured. Twenty-one patients (75%) had evidence of contractile reserve (LV EF increase10% and VTI increase20% after peak dobutamine dose). Patients with versus without contractile reserve demonstrated greater improvements in New York Heart Association class (mean change -1.0 +/- 0.5 vs -0.5 +/- 0.3, p = 0.01) and reductions in B-type natriuretic peptide levels (-34 +/- 30% vs +4 +/- 31%, p0.01) 48 hours after treatment. On multivariate analysis, mean longitudinal systolic strain rate reserve (peak longitudinal strain rate minus longitudinal strain rate at rest) was the best predictor of improvement in New York Heart Association class (p = 0.039) and B-type natriuretic peptide level (p = 0.042) after levosimendan among the reserve of LV fractional shortening, the EF, VTI, and longitudinal, circumferential, and radial strain and strain rate. In conclusion, dobutamine-induced changes in longitudinal systolic strain rate are associated with clinical and neurohumoral improvement after levosimendan treatment in patients with ADCHF.