Forskningen gällande hjärt-kärlsjukdom har tidigare utgått från män och överförts till kvinnor trots att det finns skillnader i sjukdomsförlopp och påverkan på livssituationen mellan kvinnor och män. Studiens syfte var att beskriva kvinnors upplevelser av hjärtinfarkt utifrån ett transitionperspektiv. Metoden var en deskriptiv litteraturstudie där tio artiklar med kvalitativ metod ingick. Fyra rubriker med tillhörande kategorier togs fram. Första rubriken Hälsa omfattar kategorierna Diffusa fysiska symptom före den akuta fasen, Sjukdomsupplevelse i den akuta fasen och Fysisk försämring i återhämtningsfasen. Andra rubriken Livsförändring omfattar rubrikerna Svårigheter med att förstå vad som hänt i den akuta fasen, Oro inför anpassningen till ett nytt liv i återhämtningsfasen, Livsstilsförändringar i återhämtningsfasen och En ny mening med livet i omvärderingsfasen. Tredje rubriken Relationer omfattar kategorierna Vill inte vara en börda i den akuta fasen och i återhämtningsfasen, Behovet av stöd i återhämtningsfasen och En förändrad roll i familjen i omvärderingsfasen. Fjärde rubriken Omgivning omfattar kategorierna Stöd från rehabiliteringsgruppen i återhämtningsfasen och Att börja arbeta igen i återhämtningsfasen. Författarna drar slutsatsen att när kvinnor drabbas av hjärtinfarkt genomgår de en transition inom flera områden, så som identitet, relationer, kroppslig kapacitet och beteendemönster i samband med att deras hälsostatus förändras. / Cardiovascular research was originally based on men and applied on women, despite differences in disease course and effect on life between women and men. The study’s aim was to describe women’s experience of myocardial infarction from a transition perspective. The method was a descriptive literature study and ten qualitative articles were included. Four titles with associated categories were found. The first title Health included the categories Diffuse physical symptoms before the acute phase, Illness experience in the acute phase and Physical deterioration. The second title Life change included the categories Difficulties with understanding what happened, Concern regarding the adaptation to a new life, Life style changes and A new meaning with life. The third title Relations included the categories Not wanting to be a burden, Need for support and A changed role in the family. The fourth title Environment included Support from the rehabilitation and Back to work. The authors concluded that when women experience a myocardial infarction, they experience a transition in several areas such as identity, relations, physical capacity and behavioral patterns as their health status change.

This literature review posits that the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an attractive candidate therapeutic target in the setting of acute myocardial infarction (AMI). This transcription factor binds to antioxidant response elements (ARE) in the promoter region of a battery of genes that collectively encode an array of antioxidant, phase II drug metabolism, metabolically stabilizing, and overall cytoprotective enzymes, facilitating their transcription at basal levels and increasing transcription in response to various cellular stressors. Following a brief background tutorial on normal cardiac myocyte cellular physiology, key events that occur early in ischemia and reperfusion are outlined and integrated. These include ionic and metabolic dysregulation, electron transport chain uncoupling, mitochondrial depolarization, and the generation of reactive oxygen species (ROS). Abrupt changes in response to ischemia prime opening of the mitochondrial permeability transition pore (MPTP) and cardiac myocytes to generate a burst of ROS upon reperfusion–two key events that contribute to the umbrella term ischemia-reperfusion injury (IRI). How ROS damage cells is then outlined, and through a ROS-centric viewpoint, a case will be made as to how exogenous upregulation of Nrf2 could protect and/or salvage at-risk tissue immediately subjected to infarction and neighboring tissue in the peri-infarct zone (PIZ). The history of how Nrf2 came to be known as the "master regulator of oxidative stress" is reviewed, as well as the discovery of the canonical mechanism of Nrf2 regulation via Kelch-like ECH-associated protein 1 (Keap1) and other alternative mechanisms of endogenous Nrf2 regulation. Finally, compiling interdisciplinary evidence from research publications around the world, the benefits of therapeutically targeting Nrf2 are considered given the timescale and context of acute MI. Drug delivery methods, potential challenges, and limitations are then considered. Cardiac tissue is a dynamic substrate that exhibits changes for up to 90 days after AMI and patient outcomes are directly related to the extent of tissue lost following infarction/reperfusion. Targeting Nrf2 addresses an unmet need, as current clinical therapies focus on precluding occlusions and prompt reperfusion of infarcted tissue, but do not explicitly target at-risk tissue following infarcts and/or present-day reperfusion methodologies.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / BACKGROUND: In order to improve the quality and efficacy of healthcare while reducing the overall cost to deliver that healthcare, it has become increasingly important to manage utilization of services for populations of patients. Healthcare systems are aggressively working to identify patients at risk for hospital readmissions. Although readmission rates have been studied before, parameters for identifying patients at risk for readmission appear to vary depending the patient population. We will examine existing Electronic Health Record (EHR) data at Banner Health to establish what parameters are clinical indicators for readmission risk. Three conditions were identified by the CMS to have high and costly readmissions rates; heart failure (HF), acute myocardial infarction (AMI), and pneumonia. This study will focus on attempting to determine the primary predictive variables for these three conditions in order to have maximum impact on cost savings. METHODS: A literature review was done and 68 possible risk variables were identified. Of these, 30 of the variables were identifiable within the EHR system. Inclusion criteria for individual patient records are that they had an index admission secondary to AMI, heart failure, or pneumonia and that they had a subsequent readmission within 30 days of the index admission. Pediatric populations were not studied since they have unique factors for readmission that are not generalizable. Logistics regression was applied to all data including data with missing data rows. This allowed all coefficients to be interpreted for significance. This model was termed the full model. Variables that were determined to be insignificant were subsequently removed to create a new reduced model. Chi square testing was then done to compare the reduced model to the full model to determine if any significant differences existed between the two. RESULTS: Several variables were determined to be the significant predictors of readmission. The final reduced model had 19 predictors. When analyzed using ROC analysis, the area under the curve (AUC) was 0.64. CONCLUSION: Several variables were identified that could be significant contributors to readmission risk. The final model had an AUC on it ROC of 0.64 suggesting that it would only have poor to moderate clinical value for predicting readmission.

Heart failure (HF) is one of the leading causes of death and impacts millions of people throughout the world. Recently, injectable hydrogels have been developed as a potential new therapy to treat myocardium infarction (MI). This dissertation is focused on two main topics: 1) to gain a better understanding the transmural contractility in the healthy left ventricle (LV) wall and 2) investigate the efficacy of the hydrogel injection treatment on LV wall stress and function. The results indicate that a non-uniform distribution of myocardial contractility in the LV wall provide a better representation of normal LV function. The other important study explored the influence altering the stiffness of the biomaterial hydrogel injections. These results show that a larger volume and higher stiffness injection reduce myofiber stress the most and maintaining the wall thickness during loading. The computational approach developed in this dissertation could be used in the future to evaluate the optimal properties of the hydrogel. The last study used a combination of MRI, catheterization, finite element (FE) modeling to investigate the effects of hydrogel injection on borderzone (BZ) contractility after MI. The results indicate that the treatment with hydrogel injection significantly improved BZ function and reduce LV remodeling, via altered MI properties. Additionally, the wall thickness in the infarct and BZ regions were significantly higher in the treated case. Conclusion: hydrogel injection could be a valuable clinical therapy for treating MI.

Introduction : La resynchronisation cardiaque (CRT) améliore les patients insuffisants cardiaques, symptomatiques malgré un traitement médical optimal et présentant un élargissement du QRS>120ms. Cependant, un tiers des patients ne répondent pas à cette thérapie. L'objet de cette thèse est d'identifier les mécanismes déterminant la réponse à la CRT. Méthode: Dans un premier temps, nous avons apprécié la précision des méthodes de quantification de la contraction myocardique utilisées pour caractériser l'asynchronisme. Ensuite, nous avons évalué les facteurs liés à l'asynchronisme et à la réponse à la CRT (fibrose, nécrose myocardique, réserve contractile). De plus, nous avons développé et validé un nouvel indice permettant d'évaluer les conséquences « énergétiques » de l'asynchronisme sur la contraction myocardique. Résultats: Nous avons démontré que le strain longitudinal en speckle tracking était supérieur au Doppler tissulaire pour évaluer la déformation et l'asynchronisme myocardique et qu'il était mieux corrélé au pronostic des patients insuffisants cardiaques. Ensuite nous avons mis en évidence que le retard de contraction mécanique n'était pas lié simplement à un bloc de conduction électrique mais qu'il était observé pour l'ensemble des segments myocardiques nécrosés. De plus ces zones de fibrose et de nécrose évaluées en échographie de stress influencent la réponse à la CRT. Ces résultats suggèrent l'importance de considérer le retard de contraction et la contractilité résiduelle pour prédire la réponse à la CRT. A partir de cette hypothèse, nous avons validé un indice unique associant l'asynchronisme et la contractilité résiduelle pour évaluer la perte d'énergie contractile liée au retard de contraction. Conclusion : Les travaux réalisés ont permis de développer des outils pour mieux apprécier les conséquences de l'asynchronisme myocardique. / Background: Randomized studies demonstrated that Cardiac Resynchronization Therapy (CRT) improves symptoms and survival in heart failure patients with wide QRS duration that remains symptomatic despite optimal medical treatments. However, up to 40% of patients did not response to CRT. The purpose of this work was to investigate the underlying mechanisms of mechanical cardiac dyssynchrony to optimize the identification of responder to CRT. Methods: The first part of our study was to identify the accurate echocardiography method for quantifying of myocardial deformation and dyssynchrony (Tissue Doppler Imaging and Speckle tracking analysis). Next, we studied factors (myocardial scar and contractile reserve) interacting with myocardial dyssynchrony and response to CRT. Then, we developed and validated a mathematical model (strain delay index) to assess the wasted energy related to myocardial dyssynchrony. Results: First we demonstrated that longitudinal strain computed from spec kle tracking analysis was superior to tissue Doppler imaging in assessing myocardial dyssynchrony and function with a better correlation with outcome in heart failure patients. Next, we showed that mechanical dyssynchrony was not specific of electrical delay but was prevalent in scar segments. In addition, using dobutamine stress echocardiography, we demonstrated that contractile reserve in delayed segments greatly impacts on response to CRT. Then, we proposed and validated a mathematical model, the strain delay index for assessing the wasted energy related to mechanical dyssynchrony. Conclusion: The mathematical model proposed in the present study to assess the impact of dyssynchrony on myocardial contractility allows a better identification of responder to CRT.

Background Low aerobic fitness and obesity are associated with atherosclerosis, and thereforegreatly increase the risk of cardiovascular disease (CVD) and early death. It has long been known that atherosclerosis my begin early in life. Despite this fact, it remains unknown how obesity and aerobic fitness early in life influence the risks of atherosclerosis, CVD and death. Furthermore, it is unknown whether high aerobic fitness can compensate for the risks associated with obesity, and how genetic confounding affects the relationshipsof aerobic fitness with CVD and all-cause mortality. Thus, the main aims of this thesis were to investigate the associations of aerobic fitness in late adolescence with myocardial infarction (Study I), stroke (Study II) and all-cause mortality (Study III), and how genetic confounding influences the relationshipsof aerobic fitness with CVD, diabetes and death (Study IV). Methods The study population comprised up to1.3 million men who participated in mandatory Swedish military conscription. During conscription, all conscripts underwent highly standardized tests to assess aerobic fitness, body mass index, blood pressure and cognitive function. A physician also examined all conscripts. Data on subjects’ diagnoses, death and socioeconomic status during follow-up were retrieved using record linkage. Subjects were subsequently followed until the study endpoint, date of death or date of any outcome of interest. Associations between baseline variables and the risks of adverse outcomes were assessed using Cox’s proportional hazard models. Genetic confounding of the relationships between aerobic fitness and diabetes, CVD and death was assessed using a twin population and a paired logistic regression model. Results In Study I, low aerobic fitness at conscription was associated with an increased risk of myocardial infarction (MI) during follow-up (hazard ratio [HR] 0.82 per standard deviation increase). Similarly, in Study II, high aerobic fitness reduced the risk of stroke (HR 0.84 for ischemic stroke, HR 0.82 for hemorrhagic stroke; P < 0.001 for all), and obesity was associated with an increased risk of stroke (HR 1.15 for ischemic stroke, HR 1.18 for hemorrhagic stroke; P < 0.001 for all). In Study III, high aerobic fitness was also associated with reduced all-cause mortality later in life (HR 0.49, P < 0.001). High aerobic fitness exerted the strongest protection against death from substance and alcohol abuse, suicide and trauma (HRs 0.20, 0.41 and 0.52, respectively; P < 0.001 for all). Obese individuals with aerobic fitness were at higher risk of MI and all-cause mortality than were normal-weight individuals with low fitness (Studies I and III). In Study IV, fit twins had no reduced risk of CVD or death during follow-up compared with their unfit twin siblings (odds ratio 1.11, 95% confidence interval 0.88–1.40), regardless of how large the difference in fitness was. However, the fitter twins were protected against diabetes during follow-up. Conclusions Already early in life, aerobic fitness is a strong predictor of CVD and all-cause mortality later in life. In contrast to the “fat but fit” hypothesis, it seems that high aerobic fitness cannot fully compensate for the risks associated with obesity. The associationsof aerobic fitness with CVD and all-cause mortality appear to be mediated by genetic factors. Together, these findings have implications for the view of aerobic fitness as a causal risk factor for CVD and early death.

Atherosclerosis is complex inflammatory disease of the arterial wall with progressive accumulation of lipids and narrowing of the vessel. Increasing evidence suggest that inflammation plays an important role in plaque stability and often accelerate cardiovascular events such as myocardial infarction (MI). Among the vast number of inflammatory cytokines, IL-1β is known to be a key modulator in vessel wall inflammation and acceleration of the atherosclerotic process. The biologically active IL-1β is regulated by a multiprotein complex known as the NLRP3 inflammasome complex. In this thesis, we have focused on polymorphisms in the NLRP3 and CARD8 genes and their possible association to atherosclerosis and/or MI. We have also investigated the expression of inflammasome components NLRP3 and CARD8 in atherosclerosis and the role of genetic variants for the expression of these genes. The expression of NLRP3, CARD8, ASC, caspase-1, IL-1β, and IL-18 were found significantly upregulated in atherosclerotic lesions compared to normal arteries. Human carotid plaques not only express the NLRP3 inflammasome, but also release IL-1β upon exposure to lipopolysaccharide (LPS), adenosine triphosphate (ATP) and cholesterol crystals, which suggest NLRP3 inflammasome activation in human atherosclerotic lesions. Also, CARD8 was found to be important in the regulation of several inflammatory markers in endothelial cells, like RANTES, IP10 and ICAM-1. We further assessed the potential association of a CARD8 polymorphism and polymorphisms located downstream of the NLRP3 gene to the risk of MI in two independent Swedish cohorts. The CARD8 variant exhibited no association to risk of MI in either of the two cohorts. Some of the minor alleles of NLRP3 variants were associated with increased IL-1β levels and to NLRP3 mRNA levels in peripheral blood monocytic cells (PBMC). Taken together, the present thesis shows that NLRP3 inflammasome activation and increased expression of CARD8 in the atherosclerotic plaque might be possible contributors to the enhanced inflammatory response and leukocyte infiltration in the pathophysiology of atherosclerosis.

Cardiac stem cells (CSCs), isolated from heart tissue explants and expanded via the formation of cardiospheres (Csp), are a promising candidate for cell therapy to prevent heart failure following myocardial infarction. To allow early administration to patients, isolation and expansion of CSCs must be performed in the shortest time possible. Hence, this project aimed to optimize culture conditions and characterize the cardiac explant-derived cells (EDCs), Csp and Csp-derived cells (CDCs) produced. Rat neonatal EDCs contained 4-7% c-kit⁺ cells, measured using flow cytometry. Optimal Csp growth conditions were determined, such that plating 3 x 10^4 EDCs per well of a 24-well plate coated with 16.7 µg/ml poly-D-lysine, in CGM containing 7% serum, improved Csp production and generated 1.5 x 10^7 CDCs in 16 days, a sufficient number for cell therapy. The CDCs expressed the stemness markers; c-kit, Oct3/4, SOX2, and Klf-4, and the cardiac differentiation markers; GATA4 and Nkx2.5. The therapeutic effect of CDCs may be limited by the low, 3 ± 0.1%, c-kit⁺ cell numbers. To increase c-kit⁺ cells in CDCs, an alternate culture method for Csp and different extracellular matrices (ECM) for cell expansion were tested. The hanging drop culture method produced Csp with higher levels of c-kit⁺ cells (9 ± 2%) than poly-D-lysine-coated and low-bind culture dishes. Of five ECM tested, collagen IV was found to enhance EDC migration and CDC proliferation, and produced 11 ± 0.4% c-kit⁺ cells, with Csp cultured in hanging drops. Intramyocardial injection of CDCs improved left ventricular ejection fractions of infarcted rat hearts by 9% and prevented the peri-infarct wall from thinning, measured in vivo using MRI over 16 weeks. To improve cell tracking using MRI, two MR positive contrast agents, gadolinium-DTPA and gadonanotubes were tested. Gd-DTPA had low sensitivity after labelling (1.4 x 10^5 cells/mm2); whereas gadonanotubes did not provide positive contrast at 11.7 T. Thus, neither contrast agent could be used for cell tracking using high magnetic field. In conclusion, CDCs were an effective source of stem cells that could be used for heart repair, although cells could not be tracked using positive MR contrast.

Background: Acute myocardial infarction (AMI) is a major public health concern. There are limited recent national-level population-based epidemiological data on AMI in England. As a result, the current burden of disease is difficult to quantify. Aim: This thesis addresses gaps in knowledge on AMI in England. It aims to provide a comprehensive analysis of AMI epidemiology over the last decade. Methods: This is a population-based study using person-linked routine hospital and mortality data for England for the period from 1 April 1998 to 31 March 2008. Main outcome measures include: trends in event rate, case fatality, and mortality for AMI, as well as trends in characteristics of, and hospital care for, the AMI patient population between 1999 and 2007; rates of occurrence and case fatality for first and recurrent AMI in 2007; and five-year survival and risk of a second AMI for 2003 to 2007. Results: Total age-standardised AMI mortality rate fell by around half, while the age-standardised event rate and case fatality rate each declined by around one third between 1999 and 2007. Approximately half of the decline in AMI mortality was attributed to a decline in event rate and half to improved survival. During the 2000s, the hospitalised AMI patient population became increasingly elderly, presented with more comorbidities, underwent more revascularisation procedures, and spent less time in hospital. In 2007, approximately 90,000 AMIs occurred in England, of which around one third were fatal, one in seven were reinfarctions, and three quarters were AMIs in those aged 65 years and older. Among 30-day survivors of a first AMI, around one in three men and one in four women died within five years, and about one in eight men and one in six women experienced a second AMI in the same time period. Conclusions: There have been substantial improvements in AMI occurrence, survival, and mortality over the last decade in England. This was driven by improvements in prevention and acute medical treatment. The results in this thesis emphasise the importance of both.

Bakgrund: Hjärt- och kärlsjukdomar är en vanlig dödsorsak i världen och i Sverige. Hjärtinfarkt orsakas av ateroskleros som i sin tur leder till syrebrist i hjärtmuskulaturen. Symtombilden är individuell och symtom som bröstsmärta, illamående och andningspåverkan kan förekomma. Förekomsten av att drabbas av hjärt- och kärlsjukdom skiljer sig mellan män och kvinnor. Syfte: Syftet med denna litteraturstudie var att beskriva och jämföra kvinnor och mäns symtombild vid hjärtinfarkt samt att granska undersökningsgrupper i de valda studierna. Metod: En beskrivande litteraturstudie. 13 kvantitativa artiklar valdes ut till den föreliggande litteraturstudien. Huvudresultat: Bröstsmärta var det vanligaste och mest förekommande symtomet hos både män och kvinnor vid hjärtinfarkt. Kvinnor beskrev mer ryggsmärta, smärta lokaliserat till skulderbladen och nacksmärta. Män rapporterade mer smärta i höger sida av bröstkorgen och arm. Illamående, andningsbesvär och svaghetskänsla visade sig mer förekommande hos kvinnor medan män presenterade mer svettningar. Tydliga skillnader fanns i antal rapporterade symtom i samband med hjärtinfarkt, kvinnor rapporterade fler än män. Slutsats: Det framkom både likheter och skillnader i män och kvinnors symtombild vid hjärtinfarkt, symtomen var varierande och individuella. För att sjuksköterskan ska kunna tillgodose patientens individuella omvårdnadsbehov krävs kunskap om hjärtinfarktens varierande symtombild. Detta är viktigt för att i god tid kunna handla korrekt för att förhindra komplikationer och bestående men hos patienter som drabbas av hjärtinfarkt. Mer forskning inom området skulle öka kunskapen hos sjuksköterskan och bidra till en bättre omvårdnad för patienter som drabbas av hjärtinfarkt. / Background: Cardiovascular disease is a common cause of death in the world and in Sweden. Myocardial infarction is caused by atherosclerosis, which in turn leads to hypoxia in the heart muscles. The symptoms are individual and symptoms such as chest pain, nausea and respiratory effects may occur. The existence of suffering from cardiovascular disease differ between men and women. Purpose: The purpose of this study was to describe and compare women's and men's symptoms of myocardial infarction and to review the study groups in the selected studies. Method: A descriptive literature. 13 quantitative articles were selected to the present literaturestudy. Main Results: Chest pain was the most common symptom in both men and women with myocardial infarction. Women described more frequent back pain, pain localized to the shoulder blades and neck pain. Men reported more pain in the right side of the chest and arm. Nausea, dyspnea and weakness proved to be more common in women, while men presented more sweating. Distinct differences were found in the number of reported symptoms associated with a myocardial infarction, women reported more symptoms than men. Conclusion: The litteraturstudy revealed both similarities and differences in men's and women's symptoms of myocardial infarction, symptoms were variable and individual. For the nurse to meet individual patient care needs requires knowledge of myocardial infarctions varying symptoms. This is important in order to act properly and in an early stage to prevent complications and permanent damage in patients who suffer from myocardial infarction. More research in this area would empower the nurse and contribute to better care for patients who suffer from myocardial infarction.