Serum markers of deranged myocardial collagen turnover: their relation to malignant ventricular arrhythmias in cardioverter-defibrillator recipients with heart failure

BACKGROUND: Pathologic collagen remodeling has been involved in the occurrence of ventricular arrhythmias and sudden cardiac death in heart failure. The aim of the study was to investigate the relationship between malignant ventricular arrhythmias and cardiac collagen turnover indexes, expressing specific types of derangement in collagen physiology, in stable patients with an implantable cardioverter-defibrillator (ICD). METHODS: Seventy-four patients with an ICD and heart failure were studied. They had coronary artery disease (n = 42) or dilated cardiomyopathy, New York Heart Association classes I and II, and left ventricular ejection fraction 29% +/- 1%. An ICD had been implanted for secondary (n = 36) or primary prevention of sudden cardiac death. We assessed (1) markers of collagen types I and III synthesis and their ratio: procollagen type I carboxyterminal peptide (PICP), procollagen type III aminoterminal peptide (PIIINP), and PICP/PIIINP; (2) markers of collagen degradation, degradation inhibition, and their ratio: matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase (TIMP) 1 (TIMP-1), and MMP-9/TIMP-1. Patients were prospectively followed up for 1 year. The number of episodes necessitating appropriate interventions for ventricular tachyarrhythmias (>170 beat/min) was related to the assessed parameters. RESULTS: Multivariate analysis revealed a significant relation between the number of tachyarrhythmic episodes and MMP-9/TIMP-1 (P = .007), PICP/PIIINP (P = .007), and ejection fraction (P = .04). No other significant relation was observed between arrhythmias and the remaining parameters. CONCLUSION: In heart failure, biochemical markers indicative of a deranged equilirium in myocardial collagen deposition/degradation and collagen I/III synthesis are related to ventricular arrhythmogenesis. Further studies are needed to investigate their predictive ability

Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-ligand pathway in mice

Peer reviewedPublisher PD

Prévention de la syncope chez l'homme

- Cette étude propose d'améliorer les valeurs de sensibilité et de spécificité d'un test médical de diagnostic de la syncope chez l'homme. Cette amélioration repose notamment sur l'utilisation d'un réseau de neurones

Platinum-free photoelectrochromic devices working with copper-based electrolytes for ultrastable smart windows

Photoelectrochromic systems are devices designed for large-scale manufacturing of smart windows, capable of changing their transmittance according to external environmental conditions. This communication proposes the replacement of the two most critical photoelectrochemical device components studied so far, namely the counter electrode and the redox mediator. Regarding the first, graphene nanoplatelets are used to replace platinum, maintaining both its optical and electrocatalytic properties, and at the same time reducing the device cost. Secondly, a copper-based redox pair was chosen to solve the corrosion problems typically encountered with the iodine-based mediator. The combination of the above components led to devices with high performance (coloration speeds in the order of seconds, with a maximum contrast ratio of 10.4 : 1), as well as the achievement of a long-term stability record (over 400 days) for these photoelectrochromic systems

Human Physiological Responses to Cycle Ergometer Leg Exercise During +Gz Acceleration

Spaceflight and bed-rest deconditioning decrease maximal oxygen uptake (aerobic power), strength, endurance capacity, and orthostatic tolerance. In addition to extensive use of muscular exercise conditioning as a countermeasure for the reduction in aerobic power (VO(sub 2max)), stimuli from some form of +Gz acceleration conditioning may be necessary to attenuate the orthostatic intolerance component of this deconditioning. Hypothesis: There will be no significant difference in the physiological responses (oxygen uptake, heart rate, ventilation, or respiratory exchange ratio) during supine exercise with moderate +Gz acceleration

The extent of PXE skin changes is related to cardiovascular complications and visual loss: a cross-sectional study

Pseudoxanthoma elasticum (PXE) is a genetic multisystem disorder with cutaneous, ophthalmological and cardiovascular (CV) involvement(1, 2, 3) . Having the capacity to predict the natural progression of PXE within various systems would improve preventive care in those patients at elevated risk of CV or ophthalmological complications. Yet, the means required to predict PXE progression are still lacking today. It is yet to be established whether each body system evolves at its own pace, however skin is typically involved earlier than other systems(4) . PXE skin lesions appear mainly in the first two decades of life; the initial manifestations are usually located at the neck and progressively extend to other skin areas. This extension is mostly over around 30 years old (y/o).(5) CV and ophthalmological complications may develop later. This article is protected by copyright. All rights reserved

Pseudoxanthoma elasticum – Genetics, pathophysiology, and clinical presentation

Pseudoxanthoma elasticum (PXE) is an autosomal-recessively inherited multisystem disease. Mutations in the ABCC6-gene are causative, coding for a transmembrane transporter mainly expressed in hepatocytes, which promotes the efflux of adenosine triphosphate (ATP). This results in low levels of plasma inorganic pyrophosphate (PPi), a critical anti-mineralization factor. The clinical phenotype of PXE is characterized by the effects of elastic fiber calcification in the skin, the cardiovascular system, and the eyes. In the eyes, calcification of Bruch's membrane results in clinically visible lesions, including peau d'orange, angioid streaks, and comet tail lesions. Frequently, patients must be treated for secondary macular neovascularization. No effective therapy is available for treating the cause of PXE, but several promising approaches are emerging. Finding appropriate outcome measures remains a significant challenge for clinical trials in this slowly progressive disease. This review article provides an in-depth summary of the current understanding of PXE and its multi-systemic manifestations. The article offers a detailed overview of the ocular manifestations, including their morphological and functional consequences, as well as potential complications. Lastly, previous and future clinical trials of causative treatments for PXE are discussed

Can we identify response markers to antihypertensive drugs? First results from the Ideal Trial

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.Journal of Human Hypertension advance online publication, 17 April 2014; doi:10.1038/jhh.2014.29