Investigation of the Role of BMP2 and -4 in ASD, VSD and Complex Congenital Heart Disease.

Congenital heart malformations (CHMs) make up between 2 and 3% of annual human births. Bone morphogenetic proteins (BMPs) signalling is required for chamber myocardium development. We examined for possible molecular defects in the bone morphogenetic protein 2 and 4 (BMP2, -4) genes by sequencing analysis of all coding exons, as well as possible transcription or protein expression deregulation by real-time PCR and ELISA, respectively, in 52 heart biopsies with congenital malformations (atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy ofFallot (ToF) and complex cases) compared to 10 non-congenital heart disease (CHD) hearts. No loss of function mutations was found; only synonymous single nucleotide polymorphisms (SNPs) in the BMP2 and BMP4 genes were found. Deregulation of the mRNA expression and co-expression profile of the two genes (BMP2/BMP4) was observed in the affected compared to the normal hearts. BMP2 and -4 protein expression levels were similar in normal and affected hearts. This is the first study assessing the role of BMP-2 and 4 in congenital heart malformations. Our analysis did not reveal molecular defects in the BMP2 and -4 genes that could support a causal relationship with the congenital defects present in our patients. Importantly, sustained mRNA and protein expression of BMP2 and -4 in CHD cases compared to controls indicates possible temporal epigenetic, microRNA or post-transcriptional regulation mechanisms governing the initial stages of cardiac malformation.

Long-term risk, clinical management, and healthcare resource utilization of stable patients with coronary artery disease and post-myocardial infarction in Greece - TIGREECE study.

BACKGROUND: In light of the scarcity of evidence, TIGREECE evaluated the clinical management and long-term outcomes of patients at high risk for an atherothrombotic event who have suffered a myocardial infarction (MI), managed by cardiologists/internists in routine hospital and private office settings in Greece. METHODS: TIGREECE, a multicenter, 3-year prospective cohort study, enrolled patients ≥50 years old, with a history of MI 1-3 years before enrollment and with at least one of the following risk factors: age ≥65 years, diabetes mellitus requiring medication, second prior MI, multivessel coronary artery disease, and creatinine clearance 15-60 mL/min. The primary outcome was a composite of MI, unstable angina with urgent revascularization, stroke, or all-cause death. RESULTS: Between 5 June 2014 and 25 July 2015, 305 eligible consented patients (median age: 67.3 years; 81.3% males; 14.8% active smokers; 80.7% overweight/obese) were enrolled; 52.5% had ≥2 qualifying risk factors. The median time from the index MI [ST-segment elevation myocardial infarction (STEMI) in 51.1%, non-STEMI in 33.1%] to enrollment was 1.7 years. Of the patients, 65.9% had been discharged on dual antiplatelet therapy. At enrollment, 94.4% were receiving antiplatelets: 60.0% single [acetylsalicylic acid (ASA): 43.3%; clopidogrel: 15.7%] and 34.4% dual (ASA + clopidogrel: 31.8%) therapy. The Kaplan-Meier estimated 3-year primary composite event rate was 9.3% [95% confidence interval (CI): 6.4-13.0), and the ischemic composite event rate was 6.7% (95% CI: 4.2-9.9). CONCLUSIONS: Study results indicate that in the routine care of Greece one in ten patients experience a recurring cardiovascular event or death, mainly of ischemic origin, 1-3 years post-MI.

Large eddy simulation of dispersion of hazardous materials released from a fire accident around a cubical building.

The turbulent smoke dispersion from a pool fire around a cubical building is studied using large eddy simulation at a high Reynolds number, corresponding to existing experimental measurements both in laboratory and field test scales. Emphasis of this work is on the smoke dispersion due to two different fuel pool fire accident scenarios, initiated behind the building. For the setup of fire in the first case, crude oil was used with a heat release rate of 7.8 MW, and in the second, diesel oil with a heat release rate of 13.5 MW. It is found that in both fire scenarios, the downstream extent of the toxic zone is approximately the same. This is explained in terms of the fact that the smoke concentration and dispersion are influenced mainly by the convective buoyant forces and the strong turbulence mixing processes within the wake zone of the building. It is suggested that wind is the dominating factor in these accident scenarios, which represent the conditions resulting in the highest toxicity levels.

Mobile phones and applications in the management of patients with arterial hypertension.

The use of mobile health (mHealth) in the field of medicine is constantly evolving and advancing. Arterial hypertension, a major modifiable cardiovascular risk factor with a high prevalence in the general population, frequently remains underdiagnosed and thus untreated. Furthermore, the majority of hypertensive patients fail to achieve blood pressure target levels. The purpose of this review is to identify and evaluate current use of mHealth strategies, with focus on mobile phones, smartphones and applications, in the management of patients with arterial hypertension. Current mobile technology has the capacity to inform and motivate the general public for timely diagnosis of hypertension, to facilitate communication between physicians and patients, to aid in the monitoring of blood pressure levels and the optimization of treatment and to promote, in general, a healthy lifestyle and assist in the management of other cardiovascular risk factors. There is potential for positive impact of mHealth technology in the management of arterial hypertension, as well as probable detrimental effects that warrant caution. The research in this field is ongoing and future well-conducted studies are needed in order to establish the use of mobile technology in arterial hypertension management.

Outcomes of coronary artery bypass grafting versus percutaneous coronary intervention with second-generation drug-eluting stents for patients with multivessel and unprotected left main coronary artery disease.

OBJECTIVES: To compare the efficacy and safety of percutaneous coronary intervention using second-generation drug-eluting stents with those of coronary artery bypass grafting among patients with multivessel disease and/or unprotected left main coronary artery disease in terms of mortality, myocardial infarction, repeat revascularization, and angina. BACKGROUND: Although coronary artery disease is a leading cause of death in the Western world and in many developing countries, its optimal treatment is still a matter of controversy. Several studies have examined the clinical safety and efficacy of percutaneous coronary intervention using first-generation drug-eluting stents over coronary artery bypass grafting in patients with multivessel disease and/or unprotected left main coronary artery disease. However, this study compared the efficacy of percutaneous coronary intervention using second-generation drug-eluting stents to that of coronary artery bypass grafting for multivessel disease and/or unprotected left main coronary artery disease. METHODS: This was a prospective single-center cohort study conducted from September 2012 to November 2014 at the Nicosia General Hospital. In total, 140 patients (94% men and 6% women) with chronic coronary artery disease undergoing revascularization with either percutaneous coronary intervention using second-generation drug-eluting stents or coronary artery bypass grafting were evaluated. We examined the differences in clinical outcomes between coronary artery bypass grafting and percutaneous coronary intervention at 1-year follow-up. RESULTS: Percutaneous coronary intervention with second-generation drug-eluting stents as opposed to coronary artery bypass grafting resulted in similar rates of mortality (5.7% vs 11.4%, respectively; p = 0.135), myocardial infarction (0% vs 4.3%, respectively), repeat revascularization (4.3% vs 8.6%, respectively; p = 0.115) and angina (10% vs 18.6%, respectively; p = 0.153). CONCLUSION: In this patient population, percutaneous coronary intervention with second-generation drug-eluting stents was not inferior to coronary artery bypass grafting in terms of mortality, myocardial infarction, repeat revascularization, or angina.

Heart Score Estimation by Specialized Nurses in a Greek Urban Population.

AIMS: Specialized nurses estimated the HeartScore in an urban Greek population by recognizing cardiovascular disease (CVD) risk factors in the setting of the Onassis Cardiovascular Prevention Program (OCPP). They also provided nursing consultation and assessed the clinical and biochemical characteristics of the studied population. METHODS AND RESULTS: Individuals were recruited through TV announcements and via the website of the Onassis Cardiac Surgery Centre. All participants visited the Onassis Cardiac Centre from 20 September to 30 October 2011. Overall, 2,145 individuals were included in the study. CVD risk was calculated by the HeartScore and serum total cholesterol was measured (mean: 193±43 mg/dl). Although 33% of the participants reported dyslipidaemia, only 17% were on hypolipidaemic treatment. Hypertension and dyslipidaemia frequency increased with age. CONCLUSION: In the present study, specialized nurses estimated the HeartScore in a Greek urban population. The majority of the studied population was undiagnosed and untreated. These results highlight the necessity for both primary and secondary prevention programs that can be carried out by specialized nurses. Such programs may improve the diagnosis and treatment of CVD risk factors; early initiation and optimization of therapy as well as management of drug intolerance (e.g. statins) can contribute to CVD risk reduction.

Expert consensus on the rational clinical use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab and alirocumab, have recently been approved by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of hypercholesterolemia. These fully human monoclonal antibodies selectively block PCSK9, thus permitting the low-density lipoprotein (LDL) receptor to effectively recycle to the surface of liver cells. The administration of these antibodies leads to robust LDL cholesterol (LDL-C) lowering by 50-60% on top of maximum hypolipidemic treatment. At least 4 randomized, placebo-controlled studies are under way and will address the question of whether the administration of these PCSK9 inhibitors is associated with a significant reduction of cardiovascular events. Because of the high cost associated with the use of these medications it is very important to consider which patients may gain the most benefit, at least until the results of outcome studies are available. In this Consensus paper, 34 clinicians/scientists define 3 groups of patients that should be currently considered as candidates for the use of these novel drugs. These include: 1a. Adults with established cardiovascular disease and LDL-C≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 1b. Adults with diabetes and established cardiovascular disease or chronic kidney disease or target organ damage and LDL-C ≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 2. Adults with familial hypercholesterolemia (FH) without established cardiovascular disease and LDL-C ≥130 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe (evolocumab is also indicated in children above 12 years with homozygous FH), and 3. Adults at high or very high cardiovascular risk who are statin intolerant and have an LDL-C ≥100 and ≥130 mg/dL, respectively, while on any tolerated hypolipidemic treatment.

Churg-Strauss syndrome masquerading as an acute coronary syndrome.

Churg-Strauss Syndrome (CSS) is a rare vasculitis with multiorgan involvement. Cardiac manifestations are common causing serious complications. We report a case of CSS masquerading as a non-ST elevation myocardial infarction with heart failure. CSS should be considered in the differential diagnosis of an acute coronary syndrome(ACS)with normal coronary arteries when history of asthma, peripheral eosinophilia and multisystemic involvement is present.

Assessment of left ventricular and atrial diastolic function using two-dimensional (2D) strain imaging in patients with ß-thalassemia major.

BACKGROUND: ß-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 ß-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 < 0.01,LAV min: 20.2 ± 11.4 vs. 33.9 ± 18, P < 0.01, LAVI: 37.66 ± 12.18 vs. 47.13 ± 14.77, P < 0.01). Radial 2D strain (RS) and peak atrial 2D strain (AS) were significantly reduced in patients with suspected diastolic dysfunction compared with patients without diastolic dysfunction (RS: 43.48 ± 13.92 vs. 35.58 ± 11.32, P < 0.05; AS: 36.36 ± 8.45 vs. 29.85 ± 9.25, P < 0.01). Using ROC analysis, peak atrial 2D strain at a cutoff of 41.1 cm/s was highly accurate (AUC: 0.66, P < 0.05 in ruling out diastolic dysfunction (E/E'<8) with a sensitivity of 90% and a specificity of 81%. CONCLUSIONS: B-thalassemic major patients with preserved left ventricular systolic function had impaired left atrial function at the longitudinal axis and left ventricular function at the radial axis. The new echo markers have better prognostic value than the traditional echo indexes in detecting latent diastolic dysfunction in ß-thalassemia major, earlier than E/E' ratio.

Beta-sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells.

beta-Sitosterol, normally present in vegetable-containing diets, comprises an important component of cholesterol controlling functional foods. It has been associated with cardiovascular protection, exerting its effect mainly through increasing the antioxidant defense system and effectively lowering the serum cholesterol levels in humans. However, its anti-inflammatory effect on endothelium is unknown. Attachment of leukocytes to the vascular endothelium and the subsequent migration of cells into the vessel wall are early events in atherogenesis, this process requiring the expression of endothelial adhesion molecules. We examined the effect of beta-sitosterol (0.1-200 microM) on (i) the expression of vascular adhesion molecule 1 and intracellular adhesion molecule 1 by cell ELISA and (ii) the attachment of monocytes (U937 cells) in tumor necrosis factor-alpha (TNF-alpha)-stimulated human aortic endothelial cells (HAECs) by adhesion assay. The effect on nuclear factor-kB phosphorylation was also examined via a cell-based ELISA kit. Results showed that beta-sitosterol inhibits significantly vascular adhesion molecule 1 and intracellular adhesion molecule 1 expression in TNF-alpha-stimulated HAEC as well as the binding of U937 cells to TNF-alpha-stimulated HAEC and attenuates the phosphorylation of nuclear factor-kB p65. This study extends existing data regarding the cardioprotective effect of beta-sitosterol and provides new insights into understanding the molecular mechanism underlying the beneficial effect of beta-sitosterol on endothelial function.

G-455A polymorphism of beta-fibrinogen gene and the risk of premature myocardial infarction in Greece.

INTRODUCTION: There are limited and controversial data regarding the impact of G-455A polymorphism of beta-fibrinogen gene in the pathogenesis of premature myocardial infarction (MI). We examined whether the G-455A polymorphism of beta-fibrinogen gene is associated with the development of MI< or =35 years of age. METHODS: We recruited 181 consecutive patients who had survived their first acute MI< or =35 years of age (mean age=32.2+/-3.4 years). The control group consisted of 129 healthy individuals matched with cases for age and sex, without a family history of premature coronary heart disease. G-455A polymorphism of beta-fibrinogen was tested with polymerase chain reaction and reverse hybridization. RESULTS: There was a higher prevalence of carriers of the A allele (GA+AA genotype) in controls than in patients (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.36 to 0.91, p=0.02). G-455A polymorphism of beta-fibrinogen gene was associated with lower risk for acute MI (OR 0.46, 95% CI 0.25 to 0.83, p=0.01) after adjusting for major cardiovascular risk factors. Fibrinogen levels were higher in patients compared to controls [332 (292-385) vs. 311 (262-373) mg/dL, p=0.01], but the adjusted for classical risk factors fibrinogen levels did not differ (OR 1.003, 95% CI 0.99 to 1.01, p=0.37). Patients possessing the A allele did not differ in their fibrinogen and lipid levels compared to patients with the -455GG genotype. CONCLUSIONS: Our data indicate that the presence of the G-455A polymorphism of beta-fibrinogen gene has a "protective effect" against the development of non-fatal acute MI< or =35 years of age in Greece.

Bilateral adrenal hyperplasia complicated with severe ischemic stroke in a young patient.

A young patient suffered from acute right hemiparesis, facial weakness and Broca's aphasia with multiple brain lesions due to severe hypertension. His evaluation for secondary causes of hypertension revealed hyperaldosteronism due to bilateral adrenal hyperplasia. Treatment is based primarily on spironolactone and ACE inhibitors. Two years later he was in an outstanding clinical condition with few remained neurological symptoms and his blood pressure well controlled.

Chios mastic gum extract and isolated phytosterol tirucallol exhibit anti-inflammatory activity in human aortic endothelial cells.

Chios mastic gum (CMG) is a white, semitransparent, natural resin that is obtained as a trunk exudate from mastic trees. Triterpenic compounds and phytosterols like tirucallol are among its major components. CMG has been associated with cardiovascular protection, exerting its effect mainly through increasing the antioxidant defense system, and effectively lowering the levels of serum cholesterol in human subjects. However, data on its anti-inflammatory effect on endothelium are scarce. Attachment of leukocytes to the vascular endothelium and the subsequent migration of cells into the vessel wall are early events in atherogenesis, and this process requires the expression of endothelial adhesion molecules. In this study, we examined the effect of CMG neutral extract (25-200 microg/ml) and tirucallol (0.1-100 microM) on the following: 1) the expression of adhesion molecules (VCAM-1 and ICAM-1) by Cell ELISA and 2) the attachment of monocytes (U937 cells) in TNF-alpha stimulated Human Aortic Endothelial Cells (HAEC) by Adhesion assay. The impact of treatment with CMG neutral extract and tirucallol in NFkB phosphorylation was also examined by a cell-based ELISA kit. Both CMG extract and tirucallol inhibit significantly VCAM-1 and ICAM-1 expression in TNF-alpha-stimulated HAEC. They also inhibit significantly the binding of U937 cells to TNF-alpha-stimulated HAEC and attenuate the phosphorylation of NFkB p65. This study extends existing data regarding the cardioprotective effect of CMG, expands the spectrum of known phytosterols with potent antiatheromatic activity, provides new insight into the mechanisms underlying the beneficial effect of CMG on endothelial function, and may aid in design of new therapy for intervention in atherosclerosis.

Role of methylenetetrahydrofolate reductase 677C->T polymorphism in the development of premature myocardial infarction.

BACKGROUND: The pathogenetic mechanism of premature myocardial infarction (MI) remains unknown. We explored the association of homocysteine and its main genetic modulator methylenetetrahydrofolate reductase (MTHFR) 677C->T polymorphism with the development of MI T polymorphism. RESULTS: Patients with premature MI had higher homocysteine levels (13.9+/-8.6 vs. 11.8+/-4.9 mmol/l, p=0.02) and higher prevalence of TT homozygocity compared to controls (27.1% vs. 14.6%, p=0.02). Thirty-four patients (23.6%) had angiographically "normal" coronary arteries. Subgroup analysis according to angiographic findings ("normal" coronary arteries versus significant coronary heart disease) showed that only patients with MI and "normal" coronary arteries (MINCA) had higher homocysteine levels compared to controls (17.6+/-12.2 vs. 11.8+/-4.9 mmol/l, p<0.001). The prevalence of TT genotype was higher only in patients with MINCA compared to controls (44.1% vs. 14.6%, p=0.001) (odds ratio 4.6, 95% confidence interval (CI), 1.9-11, p=0.001). This association remained after adjusting for conventional risk factors (odds ratio 3.4, 95% CI, 1.1-10.4, p=0.03). The adjusted odds ratio for MINCA of young individuals with MTHFR TT genotype and folate levels in the lowest quartile (T mutation of MTHFR is independently associated with the development of premature MINCA.

Chronic administration of an angiotensin II receptor antagonist resets the hypothalamic-pituitary-adrenal (HPA) axis and improves the affect of patients with diabetes mellitus type 2: preliminary results.

Diabetes mellitus type 2 (DM type 2) is associated with depressive symptomatology and intermittent hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis. DM type 2 is also accompanied by increased tissue levels of angiotensin II (Ang II), which stimulates the HPA axis through the Ang II type 1 receptors (AT1). We investigated the effect of candesartan, an angiotensin receptor blocker (ARB) that crosses the blood brain barrier, on the activity of the HPA axis and on the affect of 17 patients with DM type 2, aged 40-65 years, who were treated with 4 mg/day candesartan per os for at least 3 months. Before and after candesartan administration, a corticotropin-releasing hormone (CRH) stimulation test and psychological tests were performed. In response to hCRH, time-integrated secretion of ACTH was not altered by candesartan administration, however, the cortisol response was decreased significantly compared to baseline (mean +/- SEM, 2327 +/- 148.3 vs. 1943 +/- 131.9 microg/dl, P = 0.005) suggesting reduced sensitivity of the adrenals to ACTH. In parallel, there was a significant improvement in interpersonal sensitivity (0.91 +/- 0.16 vs. 0.70 +/- 0.15, P = 0.027) and depression scores (0.96 +/- 0.15 vs. 0.71 +/- 0.10, P = 0.026). We suggest that candesartan resets the HPA axis of patients with DM type 2 and improves their affect.

Amiodarone-induced epididymitis: a case report and review of the literature.

Epididymitis, as an unusual side-effect of amiodarone use, in a patient with dilated cardiomyopathy is reported along with a pertinent literature review. The diagnosis was one of exclusion after the patient received several regimens of antimicrobials and was only established after a dose reduction of the amiodarone regimen. Cardiologists should be aware of this rare but existing side effect of amiodarone, in order promptly intervene with dose adjustment or discontinuation of amiodarone and to avoid prolonged use of unnecessary antimicrobial regimens.