In vivo characterization of myocardial tissue post myocardial infarction using combined fluorescence and diffuse reflectance spectroscopy

Accurately assessing the extent of myocardial tissue injury induced by Myocardial infarction (MI) is critical to the planning and optimization of MI patient management. With this in mind, this study investigated the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to characterize a myocardial infarct at the different stages of its development. An animal study was conducted using twenty male Sprague-Dawley rats with MI. In vivo fluorescence spectra at 337 nm excitation and diffuse reflectance between 400 nm and 900 nm were measured from the heart using a portable fiber-optic spectroscopic system. Spectral acquisition was performed on (1) the normal heart region; (2) the region immediately surrounding the infarct; and (3) the infarcted region—one, two, three and four weeks into MI development. The spectral data were divided into six subgroups according to the histopathological features associated with various degrees/severities of myocardial tissue injury as well as various stages of myocardial tissue remodeling, post infarction. Various data processing and analysis techniques were employed to recognize the representative spectral features corresponding to various histopathological features associated with myocardial infarction. The identified spectral features were utilized in discriminant analysis to further evaluate their effectiveness in classifying tissue injuries induced by MI. In this study, it was observed that MI induced significant alterations (p < 0.05) in the diffuse reflectance spectra, especially between 450 nm and 600 nm, from myocardial tissue within the infarcted and surrounding regions. In addition, MI induced a significant elevation in fluorescence intensities at 400 and 460 nm from the myocardial tissue from the same regions. The extent of these spectral alterations was related to the duration of the infarction. Using the spectral features identified, an effective tissue injury classification algorithm was developed which produced a satisfactory overall classification result (87.8%). The findings of this research support the concept that optical spectroscopy represents a useful tool to non-invasively determine the in vivo pathophysiological features of a myocardial infarct and its surrounding tissue, thereby providing valuable real-time feedback to surgeons during various surgical interventions for MI.

In vivo tissue diagnosis for myocardial infarction using optical spectroscopy with novel spectral interpretation algorithms

In recent decades, the rapid development of optical spectroscopy for tissue diagnosis has been indicative of its high clinical value. The goal of this research is to prove the feasibility of using diffuse reflectance spectroscopy and fluorescence spectroscopy to assess myocardial infarction (MI) in vivo. The proposed optical technique was designed to be an intra-operative guidance tool that can provide useful information about the condition of an infarct for surgeons and researchers. ^ In order to gain insight into the pathophysiological characteristics of an infarct, two novel spectral analysis algorithms were developed to interpret diffuse reflectance spectra. The algorithms were developed based on the unique absorption properties of hemoglobin for the purpose of retrieving regional hemoglobin oxygenation saturation and concentration data in tissue from diffuse reflectance spectra. The algorithms were evaluated and validated using simulated data and actual experimental data. ^ Finally, the hypothesis of the study was validated using a rabbit model of MI. The mechanism by which the MI was induced was the ligation of a major coronary artery of the left ventricle. Three to four weeks after the MI was induced, the extent of myocardial tissue injury and the evolution of the wound healing process were investigated using the proposed spectroscopic methodology as well as histology. The correlations between spectral alterations and histopathological features of the MI were analyzed statistically. ^ The results of this PhD study demonstrate the applicability of the proposed optical methodology for assessing myocardial tissue damage induced by MI in vivo. The results of the spectral analysis suggest that connective tissue proliferation induced by MI significantly alter the characteristics of diffuse reflectance and fluorescence spectra. The magnitudes of the alterations could be quantitatively related to the severity and extensiveness of connective tissue proliferation.^

In Vivo Characterization of Myocardial Tissue Post Myocardial Infarction Using Combined Fluorescence and Diffuse Reflectance Spectroscopy

Accurately assessing the extent of myocardial tissue injury induced by Myocardial infarction (MI) is critical to the planning and optimization of MI patient management. With this in mind, this study investigated the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to characterize a myocardial infarct at the different stages of its development. An animal study was conducted using twenty male Sprague-Dawley rats with MI. In vivo fluorescence spectra at 337 nm excitation and diffuse reflectance between 400 nm and 900 nm were measured from the heart using a portable fiber-optic spectroscopic system. Spectral acquisition was performed on - (1) the normal heart region; (2) the region immediately surrounding the infarct; and (3) the infarcted region - one, two, three and four weeks into MI development. The spectral data were divided into six subgroups according to the histopathological features associated with various degrees / severities of myocardial tissue injury as well as various stages of myocardial tissue remodeling, post infarction. Various data processing and analysis techniques were employed to recognize the representative spectral features corresponding to various histopathological features associated with myocardial infarction. The identified spectral features were utilized in discriminant analysis to further evaluate their effectiveness in classifying tissue injuries induced by MI. In this study, it was observed that MI induced significant alterations (p < 0.05) in the diffuse reflectance spectra, especially between 450 nm and 600 nm, from myocardial tissue within the infarcted and surrounding regions. In addition, MI induced a significant elevation in fluorescence intensities at 400 and 460 nm from the myocardial tissue from the same regions. The extent of these spectral alterations was related to the duration of the infarction. Using the spectral features identified, an effective tissue injury classification algorithm was developed which produced a satisfactory overall classification result (87.8%). The findings of this research support the concept that optical spectroscopy represents a useful tool to non-invasively determine the in vivo pathophysiological features of a myocardial infarct and its surrounding tissue, thereby providing valuable real-time feedback to surgeons during various surgical interventions for MI.

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.

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