With the introduction of antiretroviral therapy (ART), human immunodeficiency virus (HIV) has progressed to a chronic inflammatory disease with accelerated, subclinical end-organ damage, specifically cardiovascular disease (CVD). People with HIV (PWH) have higher incidence, risk, and mortality from CVD, such as atherosclerosis, diastolic dysfunction, and heart failure. Several recent clinical reports have shown that PWH have a predisposition to developing heart failure with preserved ejection fraction (HFpEF), presenting with pathological concentric hypertrophy, diffuse fibrosis, and diastolic dysfunction. As such, an investigation into immunological and molecular mechanisms promoting pathological changes in the heart is necessary. Recent clinical reports show that people living with HFpEF have elevated plasma osteopontin (Opn), and plasma Opn is a powerful predictor of HFpEF severity, HFpEF-related hospitalizations, and mortality. Second, several animal models of HFpEF phenotypes have suggested Opn is involved in driving or perpetuating diastolic dysfunction and cardiac fibrosis. Therefore, we investigated changes in Opn in a cohort of PWH and two translationally relevant models of HIV infection (non-human primates and humanized mice) to identify the pathological role of Opn in cardiac fibrosis and detail the adjunctive potential of Opn for PWH presenting with HFpEF. In Chapter 2, twenty asymptomatic, antiretroviral-treated women with HIV (WHIV) and fourteen women without HIV (HIV-women) matched on age and body mass index underwent cardiac magnetic resonance imaging (MRI) and immune phenotyping. First, we compared a number of immunological parameters to the extensive cardiac MRI parameters in WHIV. Secondly, we analyzed relationships between plasma Opn with cardiac structure and function and markers of immune activation among WHIV, HIV- women, and the whole cohort. Multivariable modeling among the whole group was performed using myocardial fibrosis and myocardial steatosis, respectively, as the dependent variable and HIV status, atherosclerotic cardiovascular disease (ASCVD) risk score, and plasma Opn as independent variables. Among WHIV, multi-variable modeling was performed using plasma Opn as the dependent variable and CD4+ T cell count, HIV viral load, and the respective immune parameter, relating to plasma OPN in bivariate analyses, as an independent variable. In Chapter 3, we investigated bulk transcriptomic changes in the left ventricle of the heart in a model of HIV infection. We utilize the highly translatable simian immunodeficiency virus (SIV)-infected rhesus macaque model to identify changes in the myocardium with and without ART. Animals were selected by viral load, with SIV-infected animals having a high titer of plasma viral load and the SIV-infected animals with ART having a reduction in viral load by several logs. We performed total RNA-Seq on left ventricle tissue from uninfected animals, SIV-infected animals, and SIV-infected animals receiving a clinically relevant ART regimen. SIV infection led to high plasma viral load, but little to no SIV RNA was detectable in the left ventricle, shown by minimal of SIV RNA+ cells in the heart and no SIV sequences identified from RNA-Seq. SIV infection produced a highly inflammatory reaction in the heart, predominated by interferon and pathogen response. Additionally, interferon gamma (IFNg) and lipopolysaccharide (LPS) were both identified as potential upstream drivers of transcriptomic changes in the heart from SIV infection. Reduction of viral load by ART reduced the interferon and cytokine response in the heart; however, SIV-infected animals receiving ART exhibited decreased expression of integral genes directly involved in fatty acid (FA) metabolism, carnitine shuttling, and beta-oxidation. In Chapter 4, we use both in vitro and in vivo modeling to identify molecular mechanisms involved in the development of cardiac fibrosis. We utilized mouse embryonic fibroblasts (MEFs) modeled cardiac fibroblasts and were stimulated with IFNg, LPS, and TGF-b for phenotypic changes in contraction and cytokine production. The interplay of Opn and cardiac fibrosis was investigated in SIV-infected macaques with/without ART and HIVinfected humanized mice with/without an Opn-inhibiting RNA aptamer. LPS-stimulated MEFs retained myofibroblast-like contractility from TGF-b stimulation, secreted inflammatory cytokines/chemokines, and produced Opn (Spp1 transcripts). SIV-infected animals had elevated plasma Opn at necropsy, accumulation of full-length Opn in the ventricle, and ventricular interstitial fibrosis. Multivariate regression identified growth differentiation factor (GDF)-15, inflammatory CD14+CD16+ monocytes, and CD163 expression on CD14+ CD16+ monocytes as independent predictors of plasma Opn during SIV infection. HIV-infected humanized mice showed increased interstitial fibrosis compared to uninfected/untreated animals, and systemic inhibition of Opn by RNA aptamer reduced left ventricle fibrosis in HIV-infected humanized mice. These studies combined a clinical cohort of WHIV, SIV-infected rhesus macaques, and HIV-infected humanized mice to determine the role of Opn in the pathophysiology of cardiac deficits from HIV infection. Our primary goals were to begin to unravel the role of Opn in the development of HFpEF phenotypes seen in PWH, detail Opn as a converging biomarker of cardiac stress and remodeling and immune dysfunction in HIV infection, and investigate the therapeutic potential of Opn to reduce cardiac fibrosis from HIV infection. While Opn has a broad spectrum of physiological and pathological functions, we aimed to frame Opn as an important protein of interest in future studies into HFpEF in PWH. / Biomedical Sciences

This study compares the relative efficacy of systolic and diastolic biofeedback in lowering the systolic and diastolic blood pressures of normotensives. The importance of testing these biofeedback procedures lies in assessment of their potential as blood pressure self-control techniques for the treatment of essential hypertension.

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No description available.

Heart disease is one of the primary causes of morbidity and mortality for the adult population over the age of 65. Furthermore, ailments such as hypertension can affect as many as 50% of the adult population over the age of 45. If left untreated, these ailments eventually precipitate the onset of diastolic dysfunction and heart failure. Diastolic dysfunction is the alteration or impairment of performance in either the left or right ventricle of the heart. Although there has been a marked increase in study of this disease, there is still an apparent difficulty to diagnose patients. Flow visualization techniques have been commonly employed to study the development of these diseases as they relate to the filling process of the ventricles. One method, Echo Particle Image Velocimetry (Echo-PIV) is a relatively new method for cardiac flow chamber visualization, with the potential to provide physicians with a cost-effective and safe method for obtaining high temporal resolution recordings for extending knowledge on the filling processes in cardiac chamber flow. This work presents a new approach to extending the capabilities of Echo-PIV for more accurate measurement of cardiac flows for patients with poor quality recordings. Currently, much of the literature notes that temporal resolution and poor acoustic windows results in exclusion from study. These recordings are more representative of the contrast-enhancement studies used by physicians to better identify chamber walls. When applying standard PIV cross-correlation techniques, measurements tend to fail due to image noise and artifacts. By implementing a Moving Ensemble (MWE) with Product of Correlation (PoC) processing scheme, measurement accuracy, reliability, and robustness can be obtained for measurement in left ventricular filling assessment. / Master of Science

Non-cardiac surgeries conducted globally each year often lead to cardiac complications,with myocardial injury commonly occurring within 30 days post-surgery. This thesis investigates the correlation between intra-operative signals and myocardial injuryusing machine learning models. The study focuses on analyzing intra-operative STelevation, heart rate, diastolic blood pressure, and pulse pressure variation. Multiplemachine learning models, including decision tree and random forest classifiers, weredeveloped and evaluated using two approaches: the sequence of event times and comprehensive event features.The results indicate that intra-operative physiological signals are valuable predictorsof myocardial injury, with random forest models generally outperforming decision treemodels. However, limited and unbalanced data posed challenges, affecting model performance variability. This research establishes a framework for enhancing predictivemodels and monitoring strategies to improve patient outcomes. / Icke-kirurgiska operationer som genomförs globalt varje år leder ofta till hjärtrelaterade komplikationer, där myokardskada vanligtvis uppstår inom 30 dagar efteroperationen. Denna avhandling undersöker sambandet mellan intraoperativa signaleroch myokardskada med hjälp av maskininlärningsmodeller. Studien fokuserar påatt analysera intraoperativa ST-höjning, hjärtfrekvens, diastoliskt blodtryck ochpulstrycksvariation. Flera maskininlärningsmodeller, inklusive beslutsträd- ochrandom forest-klassificerare, utvecklades och utvärderades med hjälp av två tillvägagångssätt: sekvensen av händelsetider och omfattande händelseegenskaper.Resultaten visar att intraoperativa fysiologiska signaler är värdefulla prediktorer förmyokardskada, där random forest-modeller generellt presterar bättre än beslutsträdmodeller. Begränsad och obalanserad data utgjorde dock utmaningar som påverkademodellens prestandavariabilitet. Denna forskning etablerar en ram för att förbättraprediktiva modeller och övervakningsstrategier för att förbättra patientutfall.

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A cardiomiopatia dilatada idiopática (CMD) é a segunda cardiopatia mais prevalente na espécie canina, acometendo principalmente raças grandes e gigantes, bem como o Cocker Spaniel. É uma doença que possui alta letalidade, além de comprometer substancialmente a qualidade de vida do animal. O diagnóstico definitivo é realizado por meio da ecocardiografia, onde se observam dilatação das cavidades cardíacas, mais freqüentemente do ventrículo e átrio esquerdos, e diminuição da função sistólica. Estudos realizados em seres humanos com CMD mostram que, além da sistólica, a função diastólica está comprometida, e que a análise do fluxo transmitral, importante para a detecção de alterações de relaxamento e/ou distensibilidade tem importante valor prognóstico para a sobrevida e evolução dos sintomas. O tratamento da CMD tradicionalmente baseia-se na utilização de digitálicos, diuréticos, e vasodilatadores. Contudo, nos últimos anos, visto a importância da ativação do sistema nervoso simpático sobre a fisiopatologia desta doença, os β-bloqueadores têm sido empregados. Muitos trabalhos mostram que estes fármacos melhoram a função sistólica e/ou diastólica do ventrículo esquerdo, e com isso aumentam a sobrevida e diminuindo a progressão dos sintomas. Estudaram-se 45 cães com cardiomiopatia dilatada, que foram divididos em dois grupos (A e B). O grupo A (n=25) recebeu o tratamento convencional, ou seja, digitálicos, diuréticos e vasodilatadores, e o grupo B (n=20) recebeu estes mesmos medicamentos acrescidos do carvedilol, um β-bloqueador de terceira geração. Os animais foram submetidos aos exames clínico e ecocardiográfico antes e após três, 13, 26 e 52 semanas do início do tratamento ou até o óbito. Não foram observadas diferenças nos valores dos índices de função sistólica e diastólica entre os grupos. Verificou-se que o grupo tratado com carvedilol apresentou maior tempo médio de sobrevida, porém esta diferença não foi estatisticamente significante. Quanto aos sintomas (classe funcional), observou-se que o grupo tratado com carvedilol apresentou evolução mais favorável, com maior número de animais classificados como "sintomas leves" após três meses de tratamento. Assim, embora o carvedilol tenha se mostrado benéfico, principalmente com relação aos sintomas, não se pode correlacionar esta melhora à ação do fármaco sobre as funções sistólica e diastólica / Dilated Cardiomyopathy (DCM) is the second more common heart disease in dogs, wherein large and giant breeds, as well as Cockers Spaniels, are predisposed. Such disease has a high mortality rate besides reducing the quality of life of the affected animals. The definitive diagnosis is based upon echocardiography which is characterized by dilation of cardiac chambers, mainly the left ones, and by reduced systolic function. Human medicine studies have reported that the diastolic dysfunction also plays an important role; so, an abnormal transmitral flow pattern, which represents the ventricular diastolic filling, has a great prognostic value in terms of survival and symptoms status (heart failure functional class) The management of DCM traditionally consists of digitalis, diuretics and vasodilators, however, in the late years, some attention has being paid to the importance of the sympathetic nervous system on the pathophysiology of this disorder; being so, β-blockers have been included in the therapy. Many authors have reported that these drugs improve the left ventricle systolic and diastolic function, and so they increase the survival rate and reduce the symptoms progression. Forty-five dogs with idiopathic dilated cardiomyopathy, divided into two groups (A and B), were studied. The group A (n=25) consisted of dogs that were put on the traditional therapy (digitalis, diuretics and vasodilators) and the group B (n=20) included those who were treated with all these drugs plus carvedilol, a third generation β-blocker. The animals went through clinical and echocardiographic assesment before and 3, 13, 26 and 52 weeks after starting the treatment or until death. The variables of systolic and diastolic function were not statistically different between the two groups. The median survival time of the dogs treated with carvedilol was higher, but the difference was not statistically significant. Concerning to the symptoms (heart failure funcional class), dogs who were put on carvedilol had a better progression, as more of them were classified as "mild symptoms" after three months of therapy. In conclusion, despite the beneficial effects of carvedilol on the symptoms, these can not be correlate with the systolic and diastolic functions

L’augmentation de l’obésité durant les dernières décennies expose la population à un risque accru de problèmes métaboliques et des maladies cardiovasculaires. Ce travail étudiait, d’une part, l’association de l’obésité avec la dysfonction diastolique et la rigidité artérielle aortique vingt ans plus tard chez des adultes initialement en bonne santé. Cette étude montrait que l’obésité générale mesurée par l’indice de masse corporelle et l’adiposité abdominale mesurée par le tour de taille étaient associées positivement à la dysfonction diastolique. Mais elles semblaient jouer un rôle protecteur sur la rigidité artérielle. Le ratio “tour de taille/indice de masse corporelle” semblait mieux isoler l’adiposité abdominale/viscérale de l’obésité générale, et était associé positivement à la rigidité artérielle. Il permettrait de montrer un rôle néfaste à long terme de l’adiposité abdominale/viscérale sur la rigidité artérielle même quand le poids est normal. La présence combinée de l’obésité abdominale (mesurée par le tour de taille) et d’un taux plus élevé de triglycérides était associée à un risque élevé de dysfonction diastolique. Dans la deuxième partie, nous nous sommes intéressés aux individus ayant déjà une hypertension artérielle. Ce travail montrait que, parmi les sujets ayant une hypertension, ceux ayant une hypertension non-diagnostiquée avaient un profil spécifique (plus souvent de sexe masculin, un tour de taille moins élevé, et moins souvent de maladies cardiovasculaires/diabète, antécédents familiaux d’hypertension et consultations de soins primaires moins fréquents). La présence concomitante d’un nombre élevé de ces critères renforçait fortement l’absence de primo-diagnostic. Nos résultats peuvent aider dans l’identification précoce des sujets à risque, la prévention et le management thérapeutique / Worldwide increasing obesity over the last decades expose the population to an increased risk of metabolic perturbations and cardiovascular diseases. This research investigated first the association of obesity with diastolic dysfunction and aortic stiffness observed 20 years later in initially healthy adults. General obesity measured with body mass index and abdominal adiposity measured with waist circumference were positively associated with diastolic dysfunction. But, these anthropometric parameters played a protective role in aortic stiffness. The ratio “waist circumference / body mass index” appeared to better isolate abdominal adiposity from general obesity and was then positively associated with aortic stiffness. It allowed to evidence a harmful role of abdominal adiposity in aortic stiffness, even in subjects with normal body weight. The presence of abdominal adiposity (measured with waist circumference) combined with an elevated level of triglycerides was associated with a higher risk of diastolic dysfunction. In the second part, our research focused on hypertensive individuals. It showed that among hypertensive subjects, those having undiagnosed-hypertension had specific features (being more often male, having less elevated waist circumference, and having fewer cardiovascular diseases/diabetes, familial hypertension history, and primary care uses). The concomitant presence of a higher number of these criteria appeared to strongly reinforce the absence of diagnosis. Our findings may help to early identify subjects at risk, and to establish prevention and therapeutic management

Bakgrund: I hälso-och sjukvården är blodtrycksmätning en viktig och grundläggande metod vid korrekt diagnostik och hantering av högt blodtryck. Forskning har under flera år påvisat att olika komponenter påverkar noggrannheten av blodtrycksmätningen. Eftersom auskultatorisk och oscillometrisk blodtrycksmätning utförs på två olika sätt finns en risk att blodtrycksvärdet kan variera mellan metoderna. Syfte: Syftet med studien var att undersöka om det finns någon skillnad mellan auskultatorisk och oscillometrisk blodtrycksmätning utfört i både vila och efter ansträngning. Material och metod: Studien bestod av 20 slumpmässigt utvalda studenter från Hälsohögskolan i Jönköping. Blodtrycksmätning utfördes med hjälp av auskultatorisk blodtrycksmanschett med handmanometer och stetoskop samt oscillometrisk modalitet (OMRON M7). Resultat: Statistisk signifikant skillnad observerades mellan auskultatorisk och oscillometrisk modalitet, både i vila och efter ansträngning. Skillnaden är som störst efter ansträngning för auskultatorisk och oscillometrisk mätmetod, i både systoliskt och diastoliskt blodtrycksvärde. Diskussion: I vården har användning av oscillometrisk blodtrycksmodalitet ökat och därmed finns en risk för minskad reliabilitet och validitet av blodtrycksvärdet. Slutsatser: Statistisk signifikant skillnad föreligger mellan modaliteterna, både i vila och efter ansträngning. / Background: Blood pressure measurement is an important and fundamental method for correct diagnosis and management of high blood pressure, in healthcare. For several years, research has shown that different components affect the accuracy of blood pressure measurement. There is a risk that the blood pressure value may vary between auscultatory and oscillometric measurements because they are performed in two different ways. Purpose: The purpose was to investigate whether there is any difference between auscultatory and oscillometric blood pressure values performed in both rest and after stress. Material and method: The study consists of 20 randomly selected students from the School of Health and Welfare of Jönköping. The measurement was performed using auscultatory blood pressure cuff, sphygmomanometer with stethoscope and oscillometric modality (OMRON M7). Result: Statistically significant difference was observed between auscultatory and oscillometric values, both in rest and stress. The difference is greater after stress for both methods, in systolic and diastolic values. Discussion: In healthcare, use of oscillometric modality has increased thus there is a risk of reduced reliability and validity of the blood pressure value. Conclusion: Statistically significant difference was observed between auscultatory and oscillometric values, both in rest and after stress.