Bakgrund: Hjärtsvikt är en vanligt förekommande kronisk sjukdom, som ökar runt om i världen i takt med att befolkningen blir äldre. Personen som drabbas måste lära sig att leva med och hantera sjukdomen, då det dagliga livet kommer att påverkas. Syfte: Att beskriva personers upplevelser av att leva med hjärtsvikt. Metod: Litteraturöversikt baserad på 12 stycken kvalitativa vetenskapliga artiklar. Data samlades in via Medline och CINAHL samt sekundärsökning. Dataanalys utfördes enligt Fribergs metod.  Resultat: Analysen resulterade i fem kategorier som beskriver personers upplevelser av att leva med hjärtsvikt; ett förändrat liv, känna trygghet och stöd, begränsningar i vardagslivet, osäker framtid och att vara beroende av vård.  Slutsats: Personer som lever med hjärtsvikt får en förändrad livssituation som påverkar dem fysiskt, psykiskt, socialt och existentiellt. Att personerna känner trygghet i sin vardag krävs för hantering av sjukdomen.  Kliniska implikationer: Sjuksköterskan ska informera och vägleda personen i sin sjukdom, samt hjälpa personen att hitta resurser för att klara av vardagen och sin livssituation. / Background: Heart failure is a common chronic disease, increasing around the world as the population gets older. The person who is affected must learn to live with and manage the disease, since the daily life will be affected.  Aim: To describe persons’ experiences of living with heart failure. Method: A literature study based on 12 scientific qualitative articles. Medline, CINAHL and secondary search was used to collect data. Fribergs analyze method was used to analyze the data.  Results: The analysis resulted in five categories that describe persons’ experiences of living with heart failure; a changed life, feeling secure and supported, limitations in daily life, uncertain future and being dependent on care. Conclusion: People living with heart failure have a changed life situation that affects them physically, mentally, socially and existentially. For these people to feel secure in their daily life it is required of them to cope with the disease. Clinical implications: The nurse must inform and guide the person in their illness, help the person find resources to cope with everyday life and their life situation.

Introduction: Nurses and other health care professionals meet patients with heart failure (HF) who report they are thirsty. Thirst is described by the patients as a concern, and it is distressing. Currently there are no standardized procedures to identify patients with increased thirst or to help a patient to manage troublesome thirst and research in the area of thirst is scarce. In order to prevent and relieve troublesome thirst more knowledge is needed on how thirst is experienced and what factors cause increased thirst. Aim: The aim of this thesis was to describe the thirst experience of patients with HF and describe the relationship of thirst with physiologic, psychologic and situational factors. The goal was to contribute to the improvement of the care by identifying needs and possible approaches to prevent and relieve thirst in patients with HF. Methods: The studies in this thesis used a cross-sectional design (Study I) and prospective observational designs (II-IV). Studies include data from patients with HF who were admitted to the emergency department for deterioration in HF (I, IV) or visited an outpatient HF clinic for worsening of HF symptoms (III); others were patients who were following up after HF hospitalization (II), and patients with no HF diagnosis who sought care at the emergency department for other illness (I). Patients completed questionnaires on thirst intensity, thirst distress, HF self-care behaviour, feeling depressive and feeling anxious. Data on sociodemographic, clinical characteristics, pharmacological treatment and prescribed fluid restriction were retrieved from hospital medical records and by asking the patients. Data were also collected from blood, urine and saliva samples to measure biological markers of dehydration, HF severity and stress. Results: Thirst was prevalent in 1 out of 5 patients (II) and 63% of patients with worsening of HF symptoms experienced moderate to severe thirst distress at hospital admission (IV). Patients at an outpatient HF clinic who reported thirst at the first visit were more often thirsty at the follow-up visits compared to patients who did not report thirst at the first visit (II). Thirst intensity was significantly higher in patients hospitalized with decompensated HF compared to patients with no HF (median 75 vs. 25 mm, visual analogue scale [VAS] 0-100 mm; P < 0.001) (I). During optimization of pharmacological treatment of HF, thirst intensity increased in 67% of the patients. Thirst intensity increased significantly more in patients in the high thirst intensity group compared to patients in the low thirst intensity group (median +18 mm vs. -3 mm; P < 0.001) (III). Patients who were admitted to the hospital with high thirst distress continued to have high thirst distress over time (IV). A large number of patients were bothered by thirst and feeling dry in the mouth when they were thirsty (III, IV). Patients with a fluid restriction had high thirst distress over time and patients who were feeling depressed had high thirst intensity over time (IV). Thirst was associated with fluid restriction (III-IV), a higher serum urea (IIIII), and depressive symptoms (II). Conclusions: A considerable amount of patients with HF experiences thirst intensity and thirst distress. Patients who reported thirst at the first follow-up more often had thirst at the subsequent follow-ups. The most important factors related to thirst intensity or thirst distress were a fluid restriction, a higher plasma urea, and depressive symptoms. Nurses should ask patients with HF if they are thirsty and measure the thirst intensity and thirst distress, and ask if thirst is bothering them. Each patient should be critically evaluated if a fluid restriction really is needed, if the patient might be dehydrated or needs to be treated for depression.

Résumé: Une des maladies cardiaques les plus sévères est l’insuffisance cardiaque (IC). Un facteur important à la base de l’IC est la mort des cardiomyocytes suite à un déséquilibre du métabolisme énergétique. Une meilleure compréhension des voies signalétiques à la base de ces déséquilibres aiderait donc à comprendre un des mécanismes à la base du développement de l’IC. La protéine ADAP1, reconnue pour être abondante au cerveau, est également présente dans d’autres organes. ADAP1 possède un domaine ArfGAP capable d’inactiver les protéines de la famille Arf et deux domaines PH de liaison aux phosphatidylinositols. ADAP1 est connue pour changer de localisation intracellulaire par l’action de facteurs de croissance. Son action entraîne l’ouverture du pore de transition de perméabilité mitochondriale (mPTP), menant directement à la mort cellulaire. Il est connu que la protéine AKT est sous le contrôle des mêmes facteurs de croissance qu’ADAP1 et qu'elle contrôle également l'ouverture des mPTPs. Nous avons émis l’hypothèse que dans les cardiomyocytes, ADAP1 transloque vers les mitochondries avec un effet conjoint d’AKT et que ce changement de localisation entraîne la mort cellulaire en stimulant l’ouverture des mPTPs. Afin de vérifier cette hypothèse, plusieurs expérimentations ont eu lieu. Tout d’abord, un immunobuvardage et une PCR quantitative ont révélé la forte expression d’ADAP1 au cœur de rat adulte. L’isolation des cellules cardiaques démontre qu’ADAP1 est majoritairement exprimée chez les cardiomyocytes. Contrairement à ce qui est rapporté chez les neurones, un immunobuvardage de fractions cellulaires a démontré que la forme humaine d’ADAP1 surexprimée est très peu localisée aux mitochondries des cardiomyocytes. Une analyse bio-informatique a permis de postuler que les sites de phosphorylation connus ADAP1 ont un grand potentiel pour être la cible d’AKT. Un essai MTT à démontrer que la double surexpression d’ADAP1 et d’un mutant constitutivement actif d’AKT (AKTca) diminue la viabilité des cardiomyocytes infectés, et ce de façon indépendante du domaine ArfGAP et dépendante de la présence de sérum. Un immunobuvardage sur des fractions cellulaires a démontré qu’AKTca ne modifie pas la localisation d’ADAP1 surexprimée et ne favorise pas sa translocation aux mitochondries. Un immunobuvardage a démontré que l’effet de la double surexpression n’est pas dépendant de la phosphorylation d’ADAP1 par AKTca. Bien qu’ADAP1 a le potentiel de mettre à jour un nouveau mécanisme moléculaire contribuant au développement de l’IC, notre hypothèse ne s’est pas vérifiée, car AKT n’influence pas la localisation d’ADAP1. Le rôle de la protéine ADAP1 chez les cardiomyocytes reste à déterminer et d'autres études sont ainsi requises. / Abstract: One of the most severe heart disease is heart failure. An important factor in the development of this disease is cardiomyocyte death cause d by an imbalance of energy metabolism. A better understanding of the signalling pathway at the base of these imbalances would therefore help to understand the mechanisms underlying the development of this disease. The ADAP1 protein, known to be abundant in the brain, is also present in other organs. This protein, with an enzymatic domain ArfGAP capable of inactivating proteins of the Arf family and two phosphatidylinositols binding domains, is known for changing its intracellular localization by the action of growth factor. ADAP1 mitochondrial localization leads to the formation of mPTP which directly lead to cell death. It is known that the AKT protein is under the control of the same growth factors than ADAP1 and is also control the opening of the mPTPs. We hypothesized that in cardiomyocytes, ADAP1 translocates to the mitochondria with a combined effect of AKT and that this change in localization leads to cell death by stimulating the opening of mPTPs. To test this hypothesis, many experiments were conducted. First of all, an immunoblotting and a quantitative PCR demonstrated that ADAP1 has a strong expression in the heart of adult rats. The isolation of cardiac cells demonstrates that ADAP1 is predominantly expressed in cardiomyocytes. Contrary to what is reported in neurons, an immunoblotting on cellular fractions demonstrated that the overexpression of the human form of ADAP1 is not localized to mitochondria in cardiomyocytes. A bioinformatic analysis, postulated that ADAP1 known phosphorylation sites have a great potential to be the target of AKT. An MTT assay demonstrated that a dual overexpression of ADAP1 and a constitutively active mutant of AKT (AKTca) decreases the viability of infected cardiomyocytes, and this, independently of the ArfGAP domain and dependent on the presence of serum. An immunoblotting on cellular fractions demonstrated that the presence of AKTca does not change the location of overexpressed ADAP1 and does not promotes its translocation to mitochondria. An immunoblotting demonstrated that the effect of the double overexpression is not dependent on the phosphorylation of AKT ca by ADAP1. Although ADAP1 has the potential to be implicated in a new molecular mechanism contributing to the development of heart failure, our hypothesis does not hold, because AKT does not influence the location of ADAP1. The role of ADAP1 in cardiomyoccyte is yet to be determined and so further study are needed

BACKGROUND:Heart failure is sometimes incorrectly listed as the underlying cause of death (UCD) on death certificates, thus compromising the accuracy and comparability of mortality statistics. Statistical redistribution of the UCD has been used to examine the effect of misclassification of the UCD attributed to heart failure, but sex- and race-specific redistribution of deaths on coronary heart disease (CHD) mortality in the United States has not been examined.METHODS:We used coarsened exact matching to infer the UCD of vital records with heart failure as the UCD from 1999 to 2010 for decedents 55years old and older from states encompassing regions under surveillance by the Atherosclerosis Risk in Communities (ARIC) Study (Maryland, Minnesota, Mississippi, and North Carolina). Records with heart failure as the UCD were matched on decedent characteristics (five-year age groups, sex, race, education, year of death, and state) to records with heart failure listed among the multiple causes of death. Each heart failure death was then redistributed to plausible UCDs proportional to the frequency among matched records.RESULTS:After redistribution the proportion of deaths increased for CHD, chronic obstructive pulmonary disease, diabetes, hypertensive heart disease, and cardiomyopathy, P<0.001. The percent increase in CHD mortality after redistribution was the highest in Mississippi (12%) and lowest in Maryland (1.6%), with variations by year, race, and sex. Redistribution proportions for CHD were similar to CHD death classification by a panel of expert reviewers in the ARIC study.CONCLUSIONS:Redistribution of ill-defined UCD would improve the accuracy and comparability of mortality statistics used to allocate public health resources and monitor mortality trends.

Die chronische Herzinsuffizienz gehört zu den häufigsten internistischen Krankheitsbildern in Europa. Eine wichtige Rolle in der Therapie der chronischen Herzinsuffizienz spielt das moderate körperliche Ausdauertraining. HDL ist als Vasoprotektor bekannt und ist in der Lage, über die Regulation der endothelialen Stickstoffmonoxidsynthase (eNOS) die Dilatationsfähigkeit von Gefäßen zu regulieren. Da eine gestörte Endothelfunktion verbunden mit einer geringeren eNOS-Expression einen wichtigen Aspekt in der Pathophysiologie der Herzinsuffizienz darstellt, war das Ziel dieser Arbeit zunächst, die HDL-induzierte eNOS-Aktivierung und NO-Produktion in Endothelzellen bei chronisch Herzinsuffizienten mit der von Gesunden zu vergleichen. Des Weiteren wurde der Einfluss körperlichen Ausdauertrainings auf die HDL-Funktion bei chronischer Herzinsuffizienz untersucht. Dafür wurde HDL jeweils aus Blutserum von herzgesunden Probanden und Herzinsuffizienten vor und nach körperlichem Ausdauertraining isoliert. Damit wurden humane aortale Endothelzellen inkubiert und anschließend mittels Western Blot die HDL-induzierte Phosphorylierung der endothelialen Stickstoffmonoxidsynthase (Regulation der eNOS-Aktivierung), der Proteinkinase C-βII sowie der p70S6K ermittelt. Des Weiteren wurde ESR-spektroskopisch die HDL-induzierte NO-Produktion in Endothelzellen gemessen. Letztendlich bestand die Frage, worin der Unterschied zwischen HDL von Gesunden und HDL von Herzinsuffizienten besteht, der die funktionalen Differenzen erklären kann. Dazu wurde die Menge des HDL-gebundenen Malondialdehyds ermittelt. Die Endothelfunktion wurde sonographisch als Fluss-vermittelte Vasodilatation bestimmt. Die Ergebnisse der Untersuchungen belegen, dass die HDL-induzierte eNOS-Aktivierung bei Patienten mit chronischer Herzinsuffizienz im Vergleich zu Gesunden vermindert ist. Des Weiteren kann der Einfluss von HDL auf die eNOS-Aktivierung durch körperliches Ausdauertraining bei Patienten mit chronischer Herzinsuffizienz verbessert werden. Die Verbesserung der HDL-induzierten NO-Produktion korreliert dabei mit der verbesserten Fluss-vermittelten Vasodilatation. Als Unterschied zwischen HDL von Gesunden und dem von chronisch Herzinsuffizienten konnte bei den Letztgenannten eine höhere Menge von gebundenem Malondialdehyd nachgewiesen werden.

Introduction: Heart failure remains a major public health problem, with recent estimates indicating that end-stage heart failure with two-year mortality rates of 70-80% affects over 60,000 patients in the US each year. Medical management can be used but success declines for patients with end stage heart failure. Although cardiac transplantation is optimal, less than 2500 cardiac transplants are performed annually due to the severely limited supply of donor organs. Mechanical circulatory support (MCS) devices are now routinely used to bridge patients with end-stage heart failure who become critically ill until a donor heart is available. The use of stem cell therapy to treat heart failure has been gaining significant ground in recent years, specifically due to its regenerative properties, and both animal and human models have shown significant improvements in ventricular mass, ejection fraction, vascularization, wall thickness, and infarct size reduction. Using the patients' HeartWare HVAD device diagnostics, we were able to acquire our response variable; pulsatility. Pulsatility is a variable measure of the differential between minimum and maximum flow and is dependent on device motor speed, power, current, and fluid viscosity. This measurement is important as it relates to the contractility of the heart and could potentially be used as an end point in determining when a patient is healthy enough to have their HVAD explanted. We set out to develop a low cost and effective predictive model to determine amniotic mesenchymal stem cell's ability to repair compromised cardiac tissue of patients using the Total Artificial Heart (TAH) and Donovan Mock Circulation Tank (DMC). Methods: Predictive modelling was performed using the TAH and DMC. The system was set to a range from critical heart failure to a normal operating conditions through the variation of preload, afterload, and ventricular drive pressures with the intent of comparing the results to our patient population. Patients (n=7, 3 dilated, 4 ischemic) received intravenous and intra-myocardial injections of a heterogeneous amniotic mesenchymal stem cells mixture and liquid matrix (MSCs+LM) at HVAD implant. Groups were analyzed based on treatment; control (HVAD only, n=7) versus stem cells (HVAD + MSCs+LM). HeartWare log files were acquired from patients' devices and analyzed in SAS and Matlab. Results from the patient study were compared to the predictive model to determine levels of stem cell response. Results: Pulsatility was found to increase with left drive pressure and afterload. Lower drive pressures resulted in a drop off in pulsatility at higher afterloads while higher drive pressures were able to compensate for any afterload. Pulsatility also increased with preload but lower drive pressures were unable to fully eject at the highest preloads, resulting in a reduced pulsatility. We observed the effects of the stem cell injections on pulsatility and found that patients receiving therapy demonstrated statistically significant increases in pulsatility at 15-20 (p=.0487), 25-30 (p=.0131), 35-40 (p=.0333), and 75-80 (p=0.0476) days post implant. At minimum, when comparing the patient results to the in vitro model, the therapy resulted in a progression from end stage HF conditions to medium cardiac function conditions. At maximum, the therapy resulted in a progression from end stage HF to normal healthy operating cardiac function. Conclusions: Stem cells demonstrated a significantly increased rate of change in pulsatility within the first 40 days and at 80 days post implant when compared to control. They also demonstrated progression from end stage HF to normal healthy cardiac function at two time periods (Days 40, 90). These results justify expansion of the study to encompass a larger patient population to verify the results of the in vitro model to predict cardiac regeneration with multiple functional status indicators.

Personer med hjärtsvikt behöver enligt nationella riktlinjer för hjärtsjukvård få individanpassad som är effektiv, jämlik, patientsäker, kunskapsbaserad och tillgänglig. De är i behov av information om behandling, symtom och förebyggande åtgärder. Syftet med studien var att undersöka vilka komponenter som sjuksköterskor vid en sjuksköterskebaserad hjärtsviktsmottagning kan använda för att bedriva evidensbaserad vård. I den systematiska litteraturstudien granskades 21 artiklar där två komponenter framkom, utbildning och e-hälsa, där utbildning var den viktigaste komponenten. Som stöd till komponenterna påvisades ett flertal redskap i artiklarna såsom telefonuppföljning, hembesök, grupputbildning, telemonitorering, dagbok, skriftlig information/bok och video/ dataprogram. När komponenterna och redskapen användes av sjuksköterskor sågs nyttan med hjärtsviktsmottagning med signifikant eller bättre resultat för egenvård, livskvalitet, kostnader, nyttjande av vård samt mortalitet. / People with heart failure should according to Swedish national guidelines for heart care get personalized care that is efficient, equitable, patient safety, knowledgeable and accessible. They should receive information about treatment, symptoms and prevention. The purpose of this study was to explore components that nurses at an office nursing heart failure clinic can use to conduct evidence-based care. This systematic literature study reviewed 21 articles in which two components emerged, education and e-support, where education was the most important component. To maintain the components, several tools were found in the articles, these were; telephone follow-up, home visits, group education, telemonitoring, diary, written information/book and video/computer programs. When the components and tools was used together by nurses at nursing office heart failure clinics, significantly or better results were found for self-care, quality of life, costs, utilization of care and mortality.

Heart failure is a chronic illness requiring self-management to prolong individual lifespan while improving quality of life. The intent of this doctoral project was to conduct a quality improvement (QI) program focused on systematically educating patients about a two gram sodium diet, by using an educational pamphlet, provider-based patient-centered teaching, and follow up during the transition period between hospital discharge and first outpatient visit. This QI project provided systematic education for newly diagnosed heart failure patients to increase knowledge about a two gram sodium diet and facilitate translation of knowledge into self-management. The QI project used the plan, do, study, act model and was implemented by the Heart Failure Educator at Banner University Medical Center-Tucson. Patients were given the Sodium Restriction Questionnaire, to determine baseline knowledge and behavior, then educated on a two gram sodium diet and given a pamphlet with the same information for home reference. At home, patients were expected to document daily sodium intake and weight and received a phone call twice a week to obtain these values. Twice a week, patients received visual feedback to illustrate their self-management from a graph that represented personal sodium and weight values. After two weeks the same questionnaire was given to determine possible improvement. The average pre assessment questionnaire score was 19 and the average post assessment score was 21.2, showing an average improvement score of 2.2. All five patients, 100%, consumed less sodium and ingested less than two grams during the second week of monitoring sodium intake and daily weight compared to week one. Three patients, 60%, had lower average daily weight during week two by three to five pounds compared to week one. On average the patients consumed 307.18 milligrams less sodium and weighed 2.56 pounds less during week two. Results suggest that educating patients on a two gram sodium diet and providing transitional support from hospital to home, using individualized graphs and patient recording of daily sodium intake and weight, improved self-management behavior and knowledge as evidenced by improved average weight and sodium consumption and an average two point increase on the post assessment questionnaire.

Bakgrund: Hjärtsvikt medför en förkortad överlevnad där andfåddhet och trötthet är de vanligaste symtomen.  Distriktssköterskan arbetar utifrån en helhetssyn som respekterar patientens autonomi, integritet och att patienten ska vara delaktig i sin vård för att skapa förutsättningar för egenvård. Syftet var att beskriva vad som kunde påverka egenvården för patienter med diagnosen hjärtsvikt. Metod: Den metod som användes var metasyntes. De tolv inkluderade artiklarna granskades och teman och kategorier bildades. Resultat: Fem nyckelteman sammanställdes; viktigt att få tidig hjälp för att känna igen symtom och förebygga med egenvård, informationen har betydelse för egenvården, bemötande och kommunikation emellan vårdgivare och patient har betydelse för följsamheten vid egenvård, medverkan/engagemang stärker egenvården hos patienten samt depression ett hinder för egenvård. Patienter önskade ökade kunskaper och stöd, som stärkt och hjälpte deras förmåga till att övervinna hinder i egenvården. Slutsats: Kommunikation, tid och engagemang är faktorer som ökade välbefinnandet och livskvalitet hos patienter med diagnosen hjärtsvikt, dessa faktorer bör distriktssköterskan ta med sig i sin fortsatta yrkesutövning. / Background:  Heart failure results in a shortened survival where breathlessness and fatigue are the most common symptoms. District nurses work from a holistic approach that respects patient's autonomy, integrity and wish involvement from patients in order to create conditions for self-care. The aim of this study was to describe the experience and what can affect self-care for patients diagnosed with heart failure. Method: The method used was a metasynthesis. The twelve inculded articles were reviewed and themes and categories was formed. Results: Five key themes were created and presented as:  Important to get early help to recognize the symptoms and prevent with self-care, information has significance for self-care, treatment and communication between healthcare provider and patient is important for compliance in self-care, involvement / commitment strengthens the self-care of the patient and the depression is a barrier to self-care. Patients desired to have more knowledge and support to strengthen their capacity in order to help them to overcome obstacles in their self-care. Conclusion: Communication, time and commitment are factors that increase the well-being and quality of life in patients diagnosed with heart failure, these factors should be the district nurse bring in its continued occupation.

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy