Targeted Proteomic Analysis of Patients with Ascending Thoracic Aortic Aneurysm.

BACKGROUND: There is a need for clinical markers to aid in the detection of individuals at risk of harboring an ascending thoracic aneurysm (ATAA) or developing one in the future. OBJECTIVES: To our knowledge, ATAA remains without a specific biomarker. This study aims to identify potential biomarkers for ATAA using targeted proteomic analysis. METHODS: In this study, 52 patients were divided into three groups depending on their ascending aorta diameter: 4.0-4.5 cm (N = 23), 4.6-5.0 cm (N = 20), and >5.0 cm (N = 9). A total of 30 controls were in-house populations ethnically matched to cases without known or visible ATAA-related symptoms and with no ATAA familial history. Before the debut of our study, all patients provided medical history and underwent physical examination. Diagnosis was confirmed by echocardiography and angio-computed tomography (CT) scans. Targeted-proteomic analysis was conducted to identify possible biomarkers for the diagnosis of ATAA. RESULTS: A Kruskal-Wallis test revealed that C-C motif chemokine ligand 5 (CCL5), defensin beta 1 (HBD1), intracellular adhesion molecule-1 (ICAM1), interleukin-8 (IL8), tumor necrosis factor alpha (TNFα) and transforming growth factor-beta 1 (TGFB1) expressions are significantly increased in ATAA patients in comparison to control subjects with physiological aorta diameter (p < 0.0001). The receiver-operating characteristic analysis showed that the area under the curve values for CCL5 (0.84), HBD1 (0.83) and ICAM1 (0.83) were superior to that of the other analyzed proteins. CONCLUSIONS: CCL5, HBD1 and ICAM1 are very promising biomarkers with satisfying sensitivity and specificity that could be helpful in stratifying risk for the development of ATAA. These biomarkers may assist in the diagnosis and follow-up of patients at risk of developing ATAA. This retrospective study is very encouraging; however, further in-depth studies may be worthwhile to investigate the role of these biomarkers in the pathogenesis of ATAA.

Management of atrial fibrillation in Greece: the MANAGE-AF study.

BACKGROUND: Although atrial fibrillation (AF) is a highly prevalent health problem with high morbidity and mortality, data regarding the clinical characteristics and management of AF in the Greek population are scarce. The "Current Clinical Practice in the MANAGEment of Atrial Fibrillation in Greece" study (MANAGEAF) aimed to assess the epidemiological features as well as the daily clinical practice in the management of Greek patients with AF. METHODS: Taking into consideration the distribution of the Greek population, 603 consecutive patients over 18 years of age, with any type of AF, presenting at the emergency departments or outpatient clinics of 27 different centers, were included in our study. RESULTS: The mean age of the patients was 68.5 ± 12.1 years, with male patients representing 52.5% of the study population. The most common AF type in our cohort was non-paroxysmal AF (60%), including the patients with permanent (24.1%), persistent (17.4%), long-standing (4.8%) and first diagnosed AF (13.8%). Hypertension was the most common comorbidity (70.3%). A history of stroke or transient ischemic attack was detected in 9.2% of the patients, while 6.2% had a history of gastrointestinal bleeding. About half of the patients (49.3%) were treated with anticoagulant drugs, mainly vitamin K antagonists (46.9%), while 34.2% were on antiplatelet drugs, aspirin and/or clopidogrel. The mean INR level (1.7 ± 0.8) was sub-therapeutic, although the mean values for CHADS2 and CHA2DS2-VASc scores were 1.6 ± 1.2 and 3.0 ± 1.7, respectively. CONCLUSION: The MANAGE-AF baseline results indicate unsatisfactory levels of compliance with the current guidelines for the management of AF in Greece. Considering the undisputed effectiveness of anticoagulant treatment for preventing AF-related strokes, MANAGE-AF demonstrates the need for optimization of our therapeutic strategies for the management of cardioembolic stroke risk.

Association of post-cardioversion transcardiac concentration gradient of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) and inflammatory biomarkers to atrial fibrillation recurrence.

OBJECTIVES: Soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) has been shown to have both pro- and anti-apoptotic activities and is associated to better prognosis in heart failure. The aim of this study was to determine the transcardiac concentration gradient of sTRAIL and inflammatory biomarkers after AF cardioversion and assess their relation to AF recurrence. DESIGN AND METHODS: We measured transcardiac gradients (coronary sinus concentration minus aortic root concentration) of sTRAIL, C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with non-valvular AF after electrical cardioversion. Six-month AF recurrence was the study endpoint. RESULTS: There were no differences in sTRAIL and hsCRP concentrations in peripheral venous blood between patients with and without AF recurrence (p=0.066 and 0.149, respectively), while IL-6 was higher in patients with recurrence (p=0.032). Only sTRAIL showed a significant transcardiac gradient [3 pg/mL (IQR 1-4 pg/mL); p=0.01]. sTRAIL gradient was 4 pg/mL (IQR 3-5 pg/mL) in patients without recurrence versus -1 pg/mL (IQR -2-1 pg/mL) in those with recurrence (p<0.001). IL-6 (p=0.281) and hsCRP (p=0.979) aortic concentrations were not significantly different from coronary sinus concentrations. In multivariate analysis, sTRAIL transcardiac gradient (beta -0.81, p=0.004) remained a negative predictor of AF recurrence. CONCLUSION: This study demonstrates the existence of a significant transcardiac sTRAIL concentration gradient in patients with non-valvular AF, inversely associated to AF recurrence. These results suggest production of sTRAIL by the heart and a protective role against substrate-altering processes in AF-prone atria. This could have implications for TRAIL-targeting therapies currently under development.

Inadequate heart rate control is associated with worse quality of life in patients with coronary artery disease and chronic obstructive pulmonary disease. The RYTHMOS study.

INTRODUCTION: Significant evidence shows that elevated heart rate (HR) is an independent risk factor in patients with coronary artery disease (CAD) and influences their prognosis. In addition, patients with chronic obstructive pulmonary disease (COPD) have more frequent episodes of angina and their compliance with heart rate agents, such as beta blockers, is poor. The purpose of the multicenter observational RYTHMOS study was to evaluate the role of heart rate management in the prognosis and quality of life in patients with CAD and COPD. METHODS: Baseline data from 280 patients, enrolled in 22 hospitals representing all types of hospital and all geographical areas of the country, were analyzed. All patients had either a prior myocardial infarction or angiographically documented CAD, and COPD verified either after spirometry or from a clinical evaluation by pulmonologists. RESULTS: The mean age of the enrolled patients was 71.8 ± 9.3 years, 76% were males, mean body mass index was 28.6 ± 7.9 kg/m2, 76.3% had hypertension, 31% had diabetes mellitus, and 53.5% of them suffered from heart failure. About 31% of the patients had an angina episode the week before the enrollment and the Canadian Cardiovascular Society (CSS) classification was class I, II, III and IV in 55%, 30%, 14% and 1%, respectively. The mean resting HR was 72.5 bpm; 51% of the patients had resting HR>70 bpm and 22% of them had HR80 bpm. Only 52.8% of the study patients were receiving beta-blockade (BB) therapy; they were more likely to have resting HR70 bpm (57.4% vs. 42.7%, p<0.001). 16.4% of the patients were receiving ivabradine and they had a higher initial HR compared to the others (78.5 vs. 71.3, p<0.001). Multivariate analysis showed that diabetes mellitus was independently associated with HR>70 bpm. Patients with resting HR>70 bpm had significantly more frequent angina episodes (p<0.001), were less satisfied with treatment (p<0.001), and had a lower quality of life (p<0.001). CONCLUSION: The baseline data of this study showed that patients with CAD and COPD present inadequate HR control and frequent angina episodes. Apart from the special characteristics of these patients related to COPD management, underuse of BB therapy largely contributes to the inadequate control of HR. Patients with HR>70 bpm had significantly worse quality of life.

Estimation of atrial fibrillation recency of onset and safety of cardioversion using NTproBNP levels in patients with unknown time of onset.

OBJECTIVE: As shown previously in patients with new-onset atrial fibrillation (AF) without symptoms or signs of heart failure, N-terminal pro-brain natriuretic peptide (NTproBNP) increases rapidly, reaching a maximum within 24-36 h, and then decreases even if AF persists. A study was undertaken to use NTproBNP measurements in patients with AF of unknown time of onset to identify patients with presumed recent onset of the arrhythmia. DESIGN: Two-group open cross-sectional study. SETTING: Hospitalised patients in cardiology departments of four hospitals. PATIENTS: Patients presenting with AF of unknown onset and no signs or symptoms of heart failure were separated into two groups: group A with NTproBNP above the cut-off level and group B with a low NTproBNP level. INTERVENTIONS: No therapeutic intervention. All patients underwent transoesophageal echocardiography (TEE). MAIN OUTCOME MEASURES: Presence of left atrial thrombus on TEE. RESULTS: In group A (N=43) only two patients (4.7%) were found to have an atrial thrombus on TEE (negative predictive value of raised NTproBNP levels 95.3%) compared with 13 of 43 patients in group B (30.2%; p=0.002). Patients with a higher CHA(2)DS(2)VASc score (p=0.002) and a larger left atrium (p<0.001) were more likely to have an atrial thrombus. In the multivariate analysis, NTproBNP below the cut-off level was the most powerful predictor of the presence of thrombus (OR 25.0; p=0.016). CONCLUSION: The reported strong correlation between raised NTproBNP levels and the absence of atrial thrombi on TEE suggests that the short-term increase in NTproBNP levels after AF onset might be used to assess the age of the arrhythmia and thus the safety of cardioversion in patients with AF of unknown onset and no heart failure.

Do we reperfuse those in most need? Clinical characteristics of ST-elevation myocardial infarction patients receiving reperfusion therapy in the countrywide registry HELIOS.

INTRODUCTION: we analysed the clinical profile of patients with an ST-elevation myocardial infarction (STEMI) who arrived in hospital within 12 hrs from pain onset and either received reperfusion therapy (PCI or fibrinolytic therapy) or remained without reperfusion. METHODS: the Hellenic Infarction Observation Study (HELIOS) was a countrywide registry of acute myocardial infarction, conducted during 2005-2006. The registry enrolled 1840 patients with myocardial infarction from 31 hospitals, with a proportional representation of all types of hospitals and all geographical areas. RESULTS: of 870 patients with STEMI who were admitted within 12 hrs from pain onset, Group A received no reperfusion (n=289, 33.2%), group B underwent primary PCI (n=84, 9.7%) and group C received fibrinolysis (n=497, 57.1%). In groups A, B and C, respectively, mean age was 73 ± 13, 61 ± 12 and 62 ± 13 years (p<0.001). The prevalence of female sex was 33%, 14%, 18%, of diabetes 40%, 23%, 21%, of prior MI 23%, 10%, 11% and of Killip class 2-4 at admission 32%, 11%, 13%, respectively (all p<0.001). In a multivariate analysis, advanced Killip class, age, diabetes and pain to admission time >3 hrs were all independent variables related to no reperfusion therapy. CONCLUSION: reperfusion therapies are applied to relatively lower-risk patients. If a survival advantage is to be expected at the national level, more high-risk patients, such as the elderly, women, diabetics, and mainly those with advanced Killip class, should be considered for reperfusion strategies.

Outcome of patients with acute myocardial infarction admitted in hospitals with or without catheterization laboratory: results from the HELIOS registry.

AIMS: To compare the treatment and outcomes of myocardial infarction patients in hospitals with and without catheterization laboratory. METHODS AND RESULTS: The Hellenic Infarction Observation Study was a countrywide registry of acute myocardial infarction, conducted during 2005-2006. The registry enrolled 1840 patients with myocardial infarction from 31 hospitals with a proportional representation of all types of hospitals and of all geographical areas. Out of these patients, 645 (35%) were admitted in 11 hospitals with and 1195 (65%) in 20 hospitals without catheterization laboratory. Patients admitted in hospitals with catheterization laboratory in comparison with patients admitted in hospitals without were younger (66+/-14 vs. 68+/-13, P<0.004) with less diabetes (27 vs. 33%, P<0.001), but without other baseline differences (female 27 vs. 25%, prior myocardial infarction 20 vs. 17%, Killip class>1 22 vs. 23%). Reperfusion rates for ST-segment elevation myocardial infarction were 67% (43% lytic, 24% primary percutaneous coronary interventions) versus 56% (55% lytic, 1% percutaneous coronary interventions; P<0.01). In-hospital outcomes in hospitals with versus in hospitals without laboratory were: mortality 6.5 versus 8.3% (NS), stroke 2.2 versus 1.1% (NS), major bleeding 1.1 versus 0.6% (NS), and heart failure 11 versus 16% (P<0.01). In multivariate regression analysis, being admitted in a hospital without catheterization laboratory was not an independent predictor of increased in-hospital mortality (odds ratio=1.18, 95% confidence interval: 0.72-1.93, P=0.505). CONCLUSION: Although the majority of acute myocardial infarction patients was admitted in hospitals without catheterization laboratory, these patients do not have a survival disadvantage, provided they are treated with lytic therapy, medical secondary prevention drugs, and eventual revascularization according to current guidelines.

Association between plasma levels and immunolocalization of cytokines in heart valve lesions: a possible target for treatment?

OBJECTIVE: To compare the distribution of pro-inflammatory cytokines in heart valve lesions with their plasma levels. METHODS: Plasma levels of TNF-alpha and IL-10 were determined in 70 patients with heart valve lesions. TNF-alpha and IL-6 levels were also quantified in tissue specimens obtained from these patients after valve replacement. RESULTS: Plasma concentrations of TNF-alpha and the extent of calcium deposits were significantly higher in patients with aortic valve stenosis compared with individuals with mitral valve stenosis. A direct relationship was demonstrated between TNF-alpha blood and tissue levels. There was an increase in TNF-alpha and IL-6 tissue immunoreactivity with the progression of heart valve disease from mild to advanced inflammation. The increased accumulation of calcium deposits in damaged heart valves correlated with plasma TNF-alpha and IL-10 levels. CONCLUSIONS: The association between plasma and tissue sample cytokine concentrations suggests that plasma cytokine levels reflect the extent and severity of valvular lesions. Statins may attenuate progressive calcific valve stenosis. Statins also affect TNF-alpha and IL-10 plasma levels. These associations may help not only predict the progression but also attenuate the deterioration of valvular lesions. Verification of these results in larger scale studies is required before definite conclusions can be drawn.