T1 mapping for assessment of myocardial injury and microvascular obstruction at one week post myocardial infarction

Acknowledgements This study was supported by a Medical Research Council UK grant (grant number G0800901), as a sub-study of Nitrites in Acute Myocardial Infarction. Thanks are due to Roger Staff, for invaluable advice regarding receiver operator characteristic analysis.

Association of increasing age with receipt of specialist care and long-term mortality in patients with non-ST elevation myocardial infarction

© The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Modulation of 1HERG/1K by cellular metabolites : implication in the arrhythmogenesis during myocardial ischemia

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

The impact of late career job loss on myocardial infarction and stroke: a 10 year follow up using the health and retirement survey.

BACKGROUND: Involuntary job loss is a major life event associated with social, economic, behavioural, and health outcomes, for which older workers are at elevated risk. OBJECTIVE: To assess the 10 year risk of myocardial infarction (MI) and stroke associated with involuntary job loss among workers over 50 years of age. METHODS: Analysing data from the nationally representative US Health and Retirement Survey (HRS), Cox proportional hazards analysis was used to estimate whether workers who suffered involuntary job loss were at higher risk for subsequent MI and stroke than individuals who continued to work. The sample included 4301 individuals who were employed at the 1992 study baseline. RESULTS: Over the 10 year study frame, 582 individuals (13.5% of the sample) experienced involuntary job loss. After controlling for established predictors of the outcomes, displaced workers had a more than twofold increase in the risk of subsequent MI (hazard ratio (HR) = 2.48; 95% confidence interval (CI) = 1.49 to 4.14) and stroke (HR = 2.43; 95% CI = 1.18 to 4.98) relative to working persons. CONCLUSION: Results suggest that the true costs of late career unemployment exceed financial deprivation, and include substantial health consequences. Physicians who treat individuals who lose jobs as they near retirement should consider the loss of employment a potential risk factor for adverse vascular health changes. Policy makers and programme planners should also be aware of the risks of job loss, so that programmatic interventions can be designed and implemented to ease the multiple burdens of joblessness.

Preservation of myocardial beta-adrenergic receptor signaling delays the development of heart failure after myocardial infarction.

When the heart fails, there is often a constellation of biochemical alterations of the beta-adrenergic receptor (betaAR) signaling system, leading to the loss of cardiac inotropic reserve. betaAR down-regulation and functional uncoupling are mediated through enhanced activity of the betaAR kinase (betaARK1), the expression of which is increased in ischemic and failing myocardium. These changes are widely viewed as representing an adaptive mechanism, which protects the heart against chronic activation. In this study, we demonstrate, using in vivo intracoronary adenoviral-mediated gene delivery of a peptide inhibitor of betaARK1 (betaARKct), that the desensitization and down-regulation of betaARs seen in the failing heart may actually be maladaptive. In a rabbit model of heart failure induced by myocardial infarction, which recapitulates the biochemical betaAR abnormalities seen in human heart failure, delivery of the betaARKct transgene at the time of myocardial infarction prevents the rise in betaARK1 activity and expression and thereby maintains betaAR density and signaling at normal levels. Rather than leading to deleterious effects, cardiac function is improved, and the development of heart failure is delayed. These results appear to challenge the notion that dampening of betaAR signaling in the failing heart is protective, and they may lead to novel therapeutic strategies to treat heart disease via inhibition of betaARK1 and preservation of myocardial betaAR function.

Thrombolysis in myocardial infarction risk score in an observation unit setting.

OBJECTIVE: The Thrombolysis in Myocardial Infarction (TIMI) score is a validated tool for risk stratification of acute coronary syndrome. We hypothesized that the TIMI risk score would be able to risk stratify patients in observation unit for acute coronary syndrome. METHODS: STUDY DESIGN: Retrospective cohort study of consecutive adult patients placed in an urban academic hospital emergency department observation unit with an average annual census of 65,000 between 2004 and 2007. Exclusion criteria included elevated initial cardiac biomarkers, ST segment changes on ECG, unstable vital signs, or unstable arrhythmias. A composite of significant coronary artery disease (CAD) indicators, including diagnosis of myocardial infarction, percutaneous coronary intervention, coronary artery bypass surgery, or death within 30 days and 1 year, were abstracted via chart review and financial record query. The entire cohort was stratified by TIMI risk scores (0-7) and composite event rates with 95% confidence interval were calculated. RESULTS: In total 2228 patients were analyzed. Average age was 54.5 years, 42.0% were male. The overall median TIMI risk score was 1. Eighty (3.6%) patients had 30-day and 119 (5.3%) had 1-year CAD indicators. There was a trend toward increasing rate of composite CAD indicators at 30 days and 1 year with increasing TIMI score, ranging from a 1.2% event rate at 30 days and 1.9% at 1 year for TIMI score of 0 and 12.5% at 30 days and 21.4% at 1 year for TIMI ≥ 4. CONCLUSIONS: In an observation unit cohort, the TIMI risk score is able to risk stratify patients into low-, moderate-, and high-risk groups.

Modulation of I����/I�� by cellular metabolites : implication in the arrhythmogenesis during myocardial ischemia

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Can emerging biomarkers of myocardial remodelling identify asymptomatic hypertensive patients at risk for diastolic dysfunction and diastolic heart failure?

AIMS: Hypertension is one of the main drivers of the heart failure (HF) epidemic. The aims of this study were to profile fibro-inflammatory biomarkers across stages of the hypertensive heart disease (HHD) spectrum and to examine whether particular biochemical profiles in asymptomatic patients identify a higher risk of evolution to HF.

METHODS AND RESULTS: This was a cross-sectional observational study involving a population of 275 stable hypertensive patients divided into two different cohorts: Group 1, asymptomatic hypertension (AH) (n= 94); Group 2, HF with preserved ejection fraction (n= 181). Asymptomatic hypertension patients were further subdivided according to left atrial volume index ≥34 mL/m(2) (n= 30) and <34 mL/m(2) (n= 64). Study assays involved inflammatory markers [interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP1), and tumour necrosis factor α], collagen 1 and 3 metabolic markers [carboxy-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 3 (PIIINP), and carboxy-terminal telopeptide of collagen 1 (CITP)], extra-cellular matrix turnover markers [matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and tissue inhibitor of metalloproteinase 1 (TIMP1)], and the brain natriuretic peptide. Data were adjusted for age, sex, systolic blood pressure, and creatinine. Heart failure with preserved ejection fraction was associated with an increased inflammatory signal (IL6, IL8, and MCP1), an increased fibrotic signal (PIIINP and CITP), and an increased matrix turnover signal (MMP2 and MMP9). Alterations in MMP and TIMP enzymes were found to be significant indicators of greater degrees of asymptomatic left ventricular diastolic dysfunction.

CONCLUSION: These data define varying fibro-inflammatory profiles throughout different stages of HHD. In particular, the observations on MMP9 and TIMP1 raise the possibility of earlier detection of those at risk of evolution to HF which may help focus effective preventative strategies.

Fatigue two months after myocardial infarction may indicate risk for persistent fatigue

Fatigue two months after myocardial infarction may indicate risk for persistent fatigue

Changes of Soluble CD40 Ligand in the Progression of Acute Myocardial Infarction Associate to Endothelial Nitric Oxide Synthase Polymorphisms and Vascular Endothelial Growth Factor But Not to Platelet CD62P Expression

Reported in vitro data implicated soluble CD40 ligand (sCD40L) in endothelial dysfunction and angiogenesis. However, whether sCD40L could exert that influence in endothelial dysfunction and angiogenesis after injury in acute myocardial infarction (AMI) patients remains unclear. In the present study, we evaluated the association of sCD40L with markers of platelet activation, endothelial, and vascular function during a recovery period early after AMI. To achieve this goal, the time changes of soluble, platelet-bound, and microparticle-bound CD40L levels over 1 month were assessed in AMI patients and correlated with endothelial nitric oxide synthase (eNOS) polymorphisms, vascular endothelial growth factor (VEGF) concentrations, and platelet expression of P-selectin (CD62P). The association of soluble form, platelet-bound, and microparticle-bound CD40L with CD62P expression on platelets, a marker of platelet activation, was also assessed to evaluate the role of CD40L in the thrombosis, whereas the association with eNOS and VEGF was to evaluate the role of CD40L in vascular dysfunction. This work shows for the first time that time changes of sCD40L over 1 month after myocardial infarct onset were associated with G894T eNOS polymorphism and with the VEGF concentrations, but not to the platelet CD62P expression. These results indicate that, in terms of AMI pathophysiology, the sCD40L cannot be consider just as being involved in thrombosis and inflammation but also as having a relevant role in vascular and endothelial dysfunction.

Visual functioning and health-related quality of life in diabetic patients about to undergo anti-vascular endothelial growth factor treatment for sight-threatening macular edema

Purpose To examine patient-reported outcome (PRO) in a selected group of Swedish patients about to receive anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). Material and methods In this cross-sectional study, 59 patients with diabetes mellitus, who regularly visited the outpatient eye-clinics, were included. Sociodemographic and clinical data were collected and the patients completed PRO measures before starting anti-VEGF treatment. PRO measures assessed eye-specific outcomes (NEI-VFQ-25) and generic health-related quality of life (SF-36). Results The participants consisted of 30 men and 29 women (mean age, 68.5 years); 54 (92 %) patients had type 2 diabetes; Five (9%) patients had moderate or severe visual impairment; 28 (47 %) were classified as having mild visual impairment. Some of the patients reported overall problems in their daily lives, such as with social relationships, as well as problems with impaired sight as a result of reduced distance vision. Conclusions Further studies are needed to investigate PRO factors related to low perceived general health in this patient population. It is important to increase our understanding of such underlying mechanisms to promote improvements in the quality of patient care.

Anti-VEGF treatment of patients with diabetic macular edema : Studies of visual acuity, macular edema and patient-reported outcomes

The aim of this thesis was to describe and evaluate visual acuity, macular edema and patientreported outcomes (PRO) following anti-VEGF treatment of diabetic macular edema (DME) patients in a real-world setting. Using a longitudinal study design, a cohort of DME patients was followed from baseline to 1 year after treatment start. Data were collected from two eye clinics at two county hospitals. Social background characteristics, medical data and PRO were measured before treatment initiation, at four month and after 1 year. A total of 57 patients completed the study. Mean age was 69 years and the sample was equally distributed regarding sex. At baseline, the patients described their general health as low. One year after treatment initiation, 30 patients had improved visual acuity and 27 patients had no improvement in visual acuity. The patients whose visual acuity improved reported an improvement in several subscales in patient-reported outcome measures (PROM), which was in contrast to the group that experienced a decline in visual acuity, where there was no improvement in PROM. Outcomes from the study can be useful for developing and providing relevant information and support to patients undergoing this treatment.

Patient-reported outcomes and visual acuity after 12 months of anti-VEGF-treatment for sight-threatening diabetic macular edema in a real world setting

Aims To examine objective visual acuity measured with ETDRS, retinal thickness (OCT), patient reported outcome and describe levels of glycated hemoglobin and its association with the effects on visual acuity in patients treated with anti-VEGF for visual impairment due to diabetic macular edema (DME) during 12 months in a real world setting. Methods In this cross-sectional study, 58 patients (29 females and 29 males; mean age, 68 years) with type 1 and type 2 diabetes diagnosed with DME were included. Medical data and two questionnaires were collected; an eye-specific (NEI VFQ-25) and a generic health-related quality of life questionnaire (SF-36) were used. Results The total patient group had significantly improved visual acuity and reduced retinal thickness at 4 months and remains at 12 months follow up. Thirty patients had significantly improved visual acuity, and 27 patients had no improved visual acuity at 12 months. The patients with improved visual acuity had significantly improved scores for NEI VFQ-25 subscales including general health, general vision, near activities, distance activities, and composite score, but no significant changes in scores were found in the group without improvements in visual acuity. Conclusions Our study revealed that anti-VEGF treatment improved visual acuity and central retinal thickness as well as patient-reported outcome in real world 12 months after treatment start.