Iron Overload and Myocardial Restriction

Heart failure still remains the main cause of death in β-thalassemia, despite the progress, which was made by intensification of iron chelation therapy. Iron myocardial deposition, due to regular blood transfusions, can cause congestive heart failure as a result of left- or right-sided heart failure combined with left ventricular myocardial restriction. Regular and intense chelation therapy has improved quality of life and survival by decreasing secondary hemochromatosis. However, heart failure has not been prevented despite the intensification of iron chelation therapy.             Acute myocarditis in β-thalassemia major has been reported to contribute to heart failure in addition to iron overloading. However, apart from myocarditis which may lead to immune mediated chronic left ventricular dysfunction and failure, other factors acting through immunologic or genetically defined mechanisms might also affect the development of left sided heart failure. Multiple transfusions represent a repetitive antigenic stimulus together with iron chelation therapy itself. In this brief overview, the pathogenetic mechanisms of myocardial involvement and heart failure in β-thalassemia major are discussed

Ischemic preconditioning: Protection against myocardial necrosis and apoptosis

The phenomenon of ischemic preconditioning has been recognized as one of the most potent mechanisms to protect against myocardial ischemic injury. In experimental animals and humans, a brief period of ischemia has been shown to protect the heart from more prolonged episodes of ischemia, reducing infarct size, attenuating the incidence, and severity of reperfusion-induced arrhythmias, and preventing endothelial cell dysfunction. Although the exact mechanism of ischemic preconditioning remains obscure, several reports indicate that this phenomenon may be a form of receptor-mediated cardiac protection and that the underlying intracellular signal transduction pathways involve activation of a number of protein kinases, including protein kinase C, and mitochondrial KATP channels. Apoptosis, a genetically programmed form of cell death, has been associated with cardiomyocyte cell loss in a variety of cardiac pathologies, including cardiac failure and those related to ischemia/reperfusion injury. While ischemic preconditioning significantly reduces DNA fragmentation and apoptotic myocyte death associated with ischemia-reperfusion, the potential mechanisms underlying this effect have not been fully clarified. A comprehensive understanding of these mechanisms and application to clinical scenarios will provide new directions in research and translate this information into new treatment approaches for reducing the extent of ischemia/reperfusion injury

Vasovagal syncope: a prospective, randomized, crossover evaluation of the effect of propranolol, nadolol and placebo on syncope recurrence and patients’ well-being

AbstractObjectivesWe sought to assess the relative therapeutic efficacy of propranolol, nadolol and placebo in recurrent vasovagal syncope (VVS).BackgroundCentral and peripheral mechanisms have been implicated in the pathogenesis of VVS. Propranolol, nadolol and placebo have different sites of action on central and/or peripheral mechanisms. It has not yet been clarified whether one of the aforementioned treatments is more efficient than the others in reducing clinical episodes and exerting a beneficial effect on patients’ well-being.MethodsWe studied 30 consecutive patients with recurrent VVS and a positive head-up tilt test. All were serially and randomly assigned to propranolol, nadolol or placebo. Therapy with each drug lasted three months. On the day of drug crossover, patients reported the total number of syncopal and presyncopal attacks during the previous period. They also gave a general assessment of their quality of life, taking into account: 1) symptom recurrence; 2) drug side effects; and 3) their personal well-being during therapy (scale 0 to 4: 0 = very bad/discontinuation; 1 = bad; 2 = good; 3 = very good; 4 = excellent). At the end of the nine-month follow-up period, they reported whether they preferred a specific treatment over the others.ResultsSpontaneous syncopal and presyncopal episode recurrence during each three-month follow-up period was reduced by all drugs tested (analysis of variance [ANOVA]: chi-square = 67.4, p < 0.0001 for syncopal attacks; chi-square = 60.1, p < 0.0001 for presyncopal attacks) No differences were observed in the recurrence of syncope and presyncope among the three drugs. All drugs improved the patients’ well-being (ANOVA: chi-square = 61.9, p < 0.0001).ConclusionsPropranolol, nadolol and placebo are equally effective treatments in VVS, as demonstrated by a reduction in the recurrence of syncope and presyncope, as well as an improvement in the patients’ well-being

Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

Introduction Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown. Methods and Results We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox\u27s proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C-reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P\u3c0.0001) and its severity (P\u3c0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden\u27s index) predicted future risk of MI (hazard ratio [HR]=3.2; P\u3c0.0001), cardiac death (HR=2.62; P\u3c0.0001), and the combined endpoint of death and MI (HR=1.9; P\u3c0.0001), even after adjustment of covariates. The C-statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR. Conclusion Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD

A case-control validation of Type D personality in Greek patients with stable coronary heart disease

BACKGROUND: Type D personality has been associated with a variety of emotional and social difficulties as well as with poor prognosis in patients with established coronary heart disease (CHD). We examined the psychometric properties and validity of the Type D Scale-14 (DS14) and the prevalence of Type D personality among Greek patients with CHD while taking into account demographic; clinical, such as diabetes mellitus, hypertension, and hypercholesterolemia; as well as psychological variables such as depression, anxiety, and psychological stress. METHODS: Ninety-six patients with stable coronary heart disease and 80 healthy participants from the general population completed the Greek version of the DS14 and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Cronbach's α coefficient for the negative affectivity (NA) and social inhibition (SI) subscales was 0.83 and 0.72 for the CHD and 0.88 and 0.76 for the control group, respectively. Internal-structural validity was assessed by a factor analysis (two-factor solution), and the factor structure of the original DS14 was replicated. Using the standardized cutoff point of NA ≥10 and SI ≥10, instead of the median scores, in order to have compatible results with the majority of studies, the prevalence of Type D personality was 51% for the CHD patients and 13% for the control group. Higher NA and SI were connected with higher anxiety, depression, and total psychological stress. Finally, more patients with CHD and Type D personality than those without were diagnosed with type 2 diabetes; however, no differences were observed in hypertension or hypercholesterolemia. CONCLUSIONS: These results indicate that the Type D construct is reliable and valid in a Greek population. The prevalence of Type D personality was higher in patients with stable coronary heart disease than in people from the general population. The DS14 subscales were positively correlated with higher anxiety, depression, and total psychological stress. Regarding other CHD risk factors, only diabetes mellitus was found more frequently in CHD patients with Type D personality

Quantitative analysis of left atrial function in asymptomatic patients with b-thalassemia major using real-time three-dimensional echocardiography

<p>Abstract</p> <p>Background</p> <p>There is strong evidence that left atrial (LA) size is a prognostic marker in a variety of heart diseases. Recently, real-time three-dimensional echocardiography (RT3DE) has been reported as a useful tool for studying the phasic changes of the left atrial volumes. The aim of this study was to investigate the performance of the left atrium in beta-thalassemic patients with preserved left ventricular ejection fraction (EF) and no iron overload, using RT3DE.</p> <p>Methods</p> <p>Twenty-eight asymptomatic b-thalassemic patients (32.2 ± 4.3 years old, 17 men) who were on iron chelating therapy, as well as 20 age- and sex-matched healthy controls underwent transthoracic RT3DE. The patient group had normal echocardiographic systolic and diastolic indices, while there was no myocardial iron disposition according to MRI. Apical full volume data sets were obtained and LA volumes were measured at 3 time points of the cardiac cycle: (1) maximum volume (LAmax) at end-systole, just before mitral valve opening; (2) minimum volume (LAmin) at end-diastole, just before mitral valve closure; and (3) volume before atrial active contraction (LApreA) obtained from the last frame before mitral valve reopening or at time of the P wave on the surface electrocardiogram. From the derived values, left atrial active and passive emptying volumes, as well as the respective emptying fractions were calculated.</p> <p>Results</p> <p>Left ventricular EF (59.2 ± 2.5% patients vs. 60.1 ± 2.1% controls), E/A, E/E' were similar between the two groups. Differences in the LAmax, LAmin and LApreA between b-thalassemic patients and controls were non-significant, LAmax:(35.5 ± 13.4 vs 31.8 ± 9.8)cm³, LAmin:(16.0 ± 6.0 vs. 13.5 ±4.2)cm³, and LApreA:(25.4 ± 9.8 vs. 24.3 ± 7.2)cm³. However, left atrial active emptying fraction was reduced in the patient group as compared to the healthy population (34.3 ± 16.4% vs. 43.2 ± 11.4%, p < 0.05).</p> <p>Conclusion</p> <p>RT3DE may be a novel technique for the evaluation of LA function in asymptomatic patients with b-Thalassemia Major. Among three-dimensional volumes and indices, left atrial active emptying fraction may be an early index of LA dysfunction in the specific patient population.</p