Patients with multiple sclerosis do not necessarily consume more alcohol or tobacco than the general population

Peer reviewedPublisher PD

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Pathogenesis of chronic Chagas cardiomyopathy: the role of coronary microvascular derangements

There is ample experimental and clinical evidence of functional and structural microvascular abnormalities occurring in patients with Chagas cardiomyopathy, possibly due to the inflammatory process and/or autonomic disturbances caused by Trypanosoma cruzi infection. Those microvascular derangements are likely to constitute at least an ancillary factor that potentiates and amplifies the chronic inflammation in myocardial tissue. It is possible to devise appropriate therapeutic interventions aimed at reverting or slowing the progression of the microvascular abnormalities to positively affect the natural history of Chagas cardiomyopathy

Sustained Ventricular Tachycardia Is Associated with Regional Myocardial Sympathetic Denervation Assessed with (123)I-Metaiodobenzylguanidine in Chronic Chagas Cardiomyopathy

Cardiac sympathetic denervation and ventricular arrhythmia are frequently observed in chronic Chagas cardiomyopathy (CCC). This study quantitatively evaluated the association between cardiac sympathetic denervation and sustained ventricular tachycardia (SVT) in patients with CCC. Methods: We prospectively investigated patients with CCC and left ventricular ejection fraction (LVEF) greater than 35% with SVT (SVT group: n = 5 15; mean age +/- SD, 61 +/- 8 y; LVEF, 51% +/- 8%) and patients without SVT (non-SVT group: n = 11; mean age +/- SD, 55 +/- 10 y; LVEF, 57% +/- 10%). Patients underwent myocardial scintigraphy with (123)I-metaiodobenzylguanidine ((123)I-MIBG) for the evaluation of sympathetic innervation and resting perfusion with (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) for the evaluation of myocardial viability. A visual semiquantitative score was attributed for regional uptake of each radiotracer using a 17-segment left ventricular segmentation model (0, normal; 4, absence of uptake). A mismatch defect was defined as occurring in segments with a 99mTc-MIBI uptake score of 0 or 1 and a (123)I-MIBG score of 2 or more. Results: Compared with the non-SVT group, the SVT group had a similar (99m)Tc-MIBI summed score (6.9 +/- 7.5 vs. 4.4 +/- 5.2, respectively, P = 0.69) but a higher (123)I-MIBG summed score (10.9 +/- 7.8 vs. 22.4 +/- 9.5, respectively, P = 0.007) and a higher number of mismatch defects per patient (2.0 +/- 2.2 vs. 7.1 +/- 2.0, respectively, P < 0.0001). The presence of more than 3 mismatch defects was strongly associated with the presence of SVT (93% sensitivity, 82% specificity; P = 0.0002). Conclusion: In CCC, the amount of sympathetically denervated viable myocardium is associated with the occurrence of SVT. Myocardial sympathetic denervation may participate in triggering malignant ventricular arrhythmia in CCC patients with relatively well-preserved ventricular function.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), an official governmental research funding agency for Brazilian investigators[2008/04140-3

Improved Endothelial Function and Reversal of Myocardial Perfusion Defects after Aerobic Physical Training in a Patient with Microvascular Myocardial Ischemia

The objective of this report is to document the effects of an aerobic training program on myocardial perfusion, and endothelial function abnormalities, and on the relief of angina in a patient with microvascular myocardial ischemia. A 53-year-old female patient exhibited precordial pain on effort and angiographically normal coronaries. Her symptoms had been present for 4 yrs despite pharmacologic treatment for the control of risk factors, with myocardial perfusion scintigraphy revealing an extensive reversible perfusion defect. She was submitted to aerobic training for 4 mos, obtaining significant improvement of the anginal symptoms. Additionally, after the aerobic training program, scintigraphy revealed the disappearance of the myocardial perfusion defect, with a marked improvement of endothelium-dependent vasodilatory response and an improved quality-of-life score. These results suggest that aerobic training can improve endothelial function, leading to a reduction of ischemia and an improved quality-of-life in patients with microvascular myocardial ischemia.FAPESP[08/04140-3

Evaluation of hepatobiliary excretion and enterobiliary reflux in rats with biliary obstruction submitted to bilioduodenal or biliojejunal anastomosis

Bilioduodenal and biliojejunal anastomoses are effective for the treatment of biliary obstruction. The objective of this study was to compare the effects of these anastomoses on hepatobiliary excretion and enterobiliary reflux. Enterobiliary reflux and biliary excretion were evaluated respectively after oral administration of technetium (Tc-99m) in combination with sodium phytate and intravenous infusion of Tc-99m with diisopropyl-iminodiacetic acid. Enterobiliary reflux occurred to an equal degree in the bilioduodenal and biliojejunal groups. Maximum hepatic activity time (T-max) and radiotracer clearance half-time (T-1/2) were similar in both groups. However, when compared with that found for the sham-operated group, T-max, and T-1/2 were higher in the biliojejunal group (P = 0.02 and P = 0.01, respectively). Histopathological analysis showed marked reduction in ductal proliferation in both groups. These data undermine the theoretical advantages attributed to biliojejunal anastomosis and further the understanding of the pathophysiology of cholangitis that occurs even with patent anastomosis

Interictal hyperemia correlates with epileptogenicity in polymicrogyric cortex

Objective: To investigate pathophysiological factors underlying the presence of interictal hyper-perfusion within the limits of the polymicrogyric (PMG) cortex in epileptic patients. Methods: Retrospective observational study on interictal perfusion by Single Photon Emission Computed Tomography (SPECT) in 16 patients with PMG and its correlations with a number of clinical and neurophysiological variables. Patients underwent video-EEG monitoring, neurological and psychiatric assessments, invasive EEG, and the interictal SPECT coregistered to Magnetic Resonance Imaging (MRI). Results: Patients with interictal hyperperfusion within the PMG cortex had a significantly higher spike rate on interictal EEG than patients with normal perfusion. Interictal hyperperfusion was not correlated to sex, age at epilepsy onset, age at evaluation, number of seizures per month, presence of initial precipitating insult (IPI), abnormal neurological examination, EEG findings, ictal serniology, and seizure outcome. The high interictal spike rate did not correlate to a high frequency of seizures per month. Conclusions: Our work provides further evidences for an intrinsic epileptogenesis of the PMG cortex during the interictal state, which accounts for the major rote of PMG tissue in seizure generation. These results might help to increase our understanding about epileptogenesis related to the PMG cortex, providing new toots for more tailored epilepsy surgery in PMG patients. (c) 2008 Elsevier B.V. All rights reserved

Multimodality imaging evaluation of Chagas disease: an expert consensus of Brazilian Cardiovascular Imaging Department (DIC) and the European Association of Cardiovascular Imaging (EACVI)

International audienceAims To develop a document by Brazilian Cardiovascular Imaging Department (DIC) and the European Association of Cardiovascular Imaging (EACVI) to review and summarize the most recent evidences about the non-invasive assessment of patients with Chagas disease, with the intent to set up a framework for standardized cardiovascular imaging to assess cardiovascular morphologic and functional disturbances, as well as to guide the subsequent process of clinical decision-making. Methods and results Chagas disease remains one of the most prevalent infectious diseases in Latin America, and has become a health problem in non-endemic countries. Dilated cardiomyopathy is the most severe manifestation of Chagas disease, which causes substantial disability and early mortality in the socially most productive population leading to a significant economical burden. Prompt and correct diagnosis of Chagas disease requires specialized clinical expertise to recognize the unique features of this disease. The appropriate and efficient use of cardiac imaging is pivotal for diagnosing the cardiac involvement in Chagas disease, to stage the disease, assess patients' prognosis and address management. Echocardiography is the most common imaging modality used to assess, and follow-up patients with Chagas disease. The presence of echocardiographic abnormalities is of utmost importance, since it allows to stage patients according to disease progression. In early stages of cardiac involvement, echocardiography may demonstrate segmental left ventricuar wall motion abnormalities, mainly in the basal segments of inferior, inferolateral walls, and the apex, which cannot be attributed to obstructive coronary artery arteries. The prevalence of segmental wall motion abnormalities varies according to the stage of the disease, reaching about 50% in patients with left ventricular dilatation and dysfunction. Speckle tracking echocardiography allows a more precise and quantitative measurement of the regional myocardial function. Since segmental wall motion abnormalities are frequent in Chagas disease, speckle tracking echocardiography may have an important clinical application in these patients, particularly in the indeterminate forms when abnormalities are more subtle. Speckle tracking echocardiography can also quantify the heterogeneity of systolic contraction, which is associated with the risk of arrhythmic events. Three-dimensional (3D) echocardiography is superior to conventional two-dimensional (2D) echocardiography for assessing more accurately the left ventricular apex and thus to detect apical aneurysms and thrombus in patients in whom ventricular foreshortening is suspected by 2D echocardiography. In addition, 3D echocardiography is more accurate than 2D Simpson s biplane rule for assessing left ventricular volumes and function in patients with significant wall motion abnormalities, including aneurysms with distorted ventricular geometry. Contrast echocardiography has the advantage to enhancement of left ventricular endocardial border, allowing for more accurate detection of ventricular aneurysms and thrombus in Chagas disease. Diastolic dysfunction is an important hallmark of Chagas disease even in its early phases. In general, left ventricular diastolic and systolic dysfunction coexist and isolated diastolic dysfunction is uncommon but may be present in patients with the indeterminate form. Right ventricular dysfunction may be detected early in the disease course, but in general, the clinical manifestations occur late at advanced stages of Chagas cardiomyopathy. Several echocardiographic parameters have been used to assess right ventricular function in Chagas disease, including qualitative evaluation, myocardial performance index, tissue Doppler imaging, tricuspid annular plane systolic excursion, and speckle tracking strain. Cardiac magnetic resonance (CMR) is useful to assess global and regional left ventricular function in patients with Chagas diseases. Myocardial fibrosis is a striking feature of Chagas cardiomyopathy and late gadolinium enhancement (LGE) is used to detect and quantify the extension of myocardial fibrosis. Myocardial fibrosis might have a role in risk stratification of patients with Chagas disease. Limited data are available regarding right ventricular function assessed by CMR in Chagas disease. Radionuclide ventriculography is used for global biventricular function assessment in patients with suspected or definite cardiac involvement in Chagas disease with suboptimal acoustic window and contraindication to CMR. Myocardial perfusion scintigraphy may improve risk stratification to define cardiac involvement in Chagas disease, especially in the patients with devices who cannot be submitted to CMR and in the clinical setting of Chagas patients whose main complaint is atypical chest pain. Detection of reversible ischemic defects predicts further deterioration of left ventricular systolic function and helps to avoid unnecessary cardiac catheterization and coronary angiography. Conclusion Cardiac imaging is crucial to detect the cardiac involvement in patients with Chagas disease, stage the disease and stratify patient risk and address management. Unfortunately, most patients live in regions with limited access to imaging methods and point-of-care, simplified protocols, could improve the access of these remote populations to important information that could impact in the clinical management of the disease. Therefore, there are many fields for further research in cardiac imaging in Chagas disease. How to better provide an earlier diagnosis of cardiac involvement and improve patients risk stratification remains to be addressed using different images modalities

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report

Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naive patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico`[CNPq-Brazil-554490/2005-6]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[FAPESP-02/13197-2]CNPq (Brazil)FAPESP (Brazil)THC-Pharm (Frankfurt, Germany)STI-Pharm (Brentwood, UK