Diabetes causes cardiomyopathy and increases the risk of heart failure independent of hypertension and coronary heart disease. This condition called “Diabetic Cardiomyopathy” (DCM) is becoming a well- known clinical entity. Recently, there has been substantial research exploring its molecular mechanisms, structural and functional changes, and possible development of therapeutic approaches for the prevention and treatment of DCM. This review summarizes the recent advancements to better understand fundamental molecular abnormalities that promote this cardiomyopathy and novel therapies for future research. Additionally, different diagnostic modalities, up to date screening tests to guide clinicians with early diagnosis and available current treatment options has been outlined.

A minority of patients with end-stage disease are referred to palliative medicine for consultation in advanced heart failure. Educating stakeholders, including primary care, cardiology, and critical care of the benefits of hospice and palliative medicine for patients with poor prognosis, may increase appropriately timed referrals and improve quality of life for these patients. This article reviews multiple tools useful in prognostication in the setting of advanced heart failure.

Transcutaneous auricular vagal nerve stimulation (taVNS) is a non-invasive method of activating axons in the auricular branch of the vagus nerve through the concha of the outer ear. taVNS is under investigation as an alternative treatment option for a wide range of disorders. Vagal afferent fibers terminate in the nucleus of the solitary tract (NTS) where information is processed and relayed to higher brain regions influencing sympathetic and parasympathetic systems. Due to extensive neuronal connections, it is likely that taVNS could serve as a treatment option for many disorders, specifically cardiac, migraine, and gastric motility disorders. Human fMRI studies have indicated that taVNS elicits neuronal responses within NTS and spinal trigeminal nucleus (Sp5c). Studies have indicated that caudal NTS (cNTS) has substantial connections with the cardiac system, rostral NTS (rNTS) is relevant for gastric motility, and Sp5c is likely involved in migraine disorders due to meningeal connections. Aberrant neuronal signaling is likely responsible for the development of these disorders, and taVNS has the potential to modulate neuronal activity to reestablish homeostatic signaling. In this study, electrophysiological methods were used to interrogate neuronal activity of 50-70 neurons within cNTS, rNTS, and Sp5c following taVNS. A high-impedance tungsten electrode was placed stereotaxically in 15 male Sprague-Dawley rats anesthetized with chloralose. Changes in neuronal firing rates were investigated during and immediately following taVNS by comparing changes in neuronal activity to baseline levels using the software Spike 2 v9.14. Neurons were classified as negative responders if activity decreased more than 20%, positive responders if activity increased more than 20%, or non-responders if activity changes were less than 20%. Six different taVNS parameters were investigated using three frequencies (20, 100, 250Hz) at two intensity levels (0.5, 1.0mA). Data from this study suggest that taVNS can modulate neuronal activity in a frequency and intensity-dependent manner. The greatest positive activation for all 3 brain regions occurred at 20Hz, 1.0mA stimulation where an average of 46% ± 9% neurons showed increased firing compared to 29% ± 2% positive responders for other paradigms. The greatest negative activation for all 3 regions occurred at 100Hz, regardless of intensity, where an average of 33% ± 1% neurons showed reduced firing compared to 15% ± 2% negative responders for remaining paradigms. Based on what is known about cardiac, migraine, and gastric motility disorders, it is likely that taVNS can be used to modulate activity in NTS and Sp5c to provide beneficial treatment options to patients. Specifically, using paradigms yielding decreased activity in Sp5c could improve migraine symptoms, and paradigms increasing activity in cNTS and rNTS could improve cardiac and gastric motility disorders, respectively.

No description available.

Background: The initial systolic blood pressure (SBP) in patients with acute heart failure (AHF) can be used as a guide when choosing specific pharmacologic treatments by helping identify the underlying type of HF (e.g., HF with preserved ejection fraction). Clinical experience and research data from our medical center suggests that AHF with elevated SBP may be presenting less frequently than in the past. This may call into question the utility of initial SBP as a clinical guide. The goal of this Master’s Thesis is to test the hypothesis that the frequency of AHF patients with a SBP>160mmhg has declined over time. Methods: This observational study compares data from 4 cohorts of adult patients admitted with AHF in central MA. Data were obtained from a contemporary (2011-2013) study of patients with AHF as well as from the 1995, 2000, 2006 Worcester Heart Failure Study (WHFS) cohorts. The Framingham criteria the diagnostic criterion for AHF. The main outcome was the proportion of patients with AHF with a SBP > 160 mmHg who presented in each of the 4 study cohorts and was examined by multivariate logistic regression. Results: 2,366 patients comprised the study population. The average age was 77 years, 55% were female, 94% white, and 75% had prior HF. In 1995 33.6% of AHF patients had a SBP >160 mmHg compared to 19.5% in 2011-2013 (p160 mmHg in 2006 (0.64, (0.42-0.96)) and 2011-13 (0.46, (0.28-0.74)). Conclusion: The proportion of patients with AHF and an initial SBP >160 mmHg has significantly declined over time. This may warrant a reexamination of the utility of SBP to inform diagnosis and treatment in patients with AHF.

Bakgrund: Hjärtsvikt klassificeras som en av Sveriges folksjukdomar där 10% av populationen vid en ålder av 80 år drabbas. Att leva med hjärtsvikt innefattar en kontinuerlig kontakt med hälso- och sjukvården, samt ett omfattande personligt ansvar att utföra egenvård. För en del patienter innebär egenvård ett överväldigande ansvar, där såväl yttre som inre omständigheter kan påverka en patients egenvårdsförmåga, och i sin tur även livskvalitet.  Syfte: Syftet är att beskriva faktorer som påverkar egenvård vid hjärtsvikt ur ett patientperspektiv.  Metod: Designen är en litteraturöversikt. Resultatet grundar sig på 15 vetenskapliga artiklar hämtade från databasen CINAHL; 7 kvalitativa, 7 kvantitativa samt 1 mixed method-studie.  Resultat: Faktorer som påverkar egenvården för patienter med hjärtsvikt kunde delas in i fem huvudkategorier: Kultur, Kunskap och utbildning, Acceptans och förståelse, Emotionella upplevelser samt Motivation. Resultatet visade att såväl fysiska som psykiska och sociala faktorer ansågs påverka egenvården vid hjärtsvikt ur ett patientperspektiv.  Slutsats: Att leva med hjärtsvikt utgör olika individuella förutsättningar till egenvårdshandling, där olika faktorer påverkar patientens egenvårdsförmåga. Forskning visar att vardagliga situationer och vanor har stor betydelse för egenvårdsförmågan, där familjen och inte minst hälso- och sjukvården utgör en hörnsten till att kunskap, delaktighet och trygghet integreras. Genom en kontinuerlig vårdkontakt och att känna motivation till att leva efter de förutsättningar patienten har kan egenvårdsförmågan stärkas och därmed även livskvaliteten. / Background: Heart failure is classified as one of Sweden's public diseases and 10% of the population at the age of 80 are affected. Living with heart failure includes continuous contact with health care, as well as extensive personal responsibility to perform self-care. For some patients, self-care means an overwhelming responsibility, where both external and internal circumstances can affect a patient's self-care ability, and in turn also quality of life.  Aim: The aim is to describe factors that affect self-care in heart failure from a patient perspective.  Method: The design is a literature review. The results are based on 15 scientific articles conducted from the CINAHL database: 7 qualitative, 7 quantitative and 1 mixed method study.  Results: Factors that affect self-care for patients with heart failure could be divided into five main categories: Culture, Knowledge and education, Acceptance and understanding, Emotional experiences and Motivation. The results showed that both physical, mental and social factors were considered to affect self-care in heart failure from a patient perspective.  Conclusion: Living with heart failure constitutes different individual prerequisites for self-care, where different factors affect the patient's self-care ability. Research shows that everyday situations and habits are of great importance for the self-care ability, where the family and not least health care constitute a cornerstone for the integration of knowledge, participation and security. Through continuous health care contact and feeling motivated to live according to the conditions the patient has, self-care ability can be strengthened and thus also the quality of life.

Bakgrund: Hjärtsvikt är en vanlig sjukdom som drabbar många individer, framförallt äldre. I Sverige får ca 28 000 individer akut hjärtsvikt varje år. Den vanligaste orsaken till hjärtsvikt är ischemisk hjärtsjukdom och högt blodtryck. Syftet: Att beskriva patienters upplevelser av att leva med hjärtsvikt. Metod: Litteraturöversikt som är baserad på 12 vetenskapliga kvalitativa artiklar. Resultat: Patienter upplevde begränsningar i dagliga aktiviteter. Detta påverkade sömnrutin, socialt liv och känslor. Familj och vänner spelar en viktig roll i patienternas liv. Acceptans av sjukdomen och vara positiv upplevde som nödvändig för att hantera dagliga livet. Patienter upplevde brist på information från sjukvården. Slutsats: Symtom som andfåddhet och trötthet begränsar patientens aktiviteter. Det är viktigt att patienter bli delaktiga i sin hälsa genom att lära sig om sin sjukdom. Sjuksköterskans ansvar är att motivera och stärka patienterna samt uppmuntra dem att leva ett hälsosamt liv. Det är sjuksköterskans ansvar att lyssna på patienternas situation och främja deras välbefinnande. / Background: Heart failure is a common disease that affects many people, especially the elderly. Approximately 28 000 of Sweden´s population experience heart failure each year. The most common cause of heart failure is ischemic heart disease and high blood pressure. Purpose: To describe patients' experiences of living with heart failure. Method: Literature overview based on 12 scientific articles. Results: Patients` experienced limitations in daily activities. This affected their sleep routine, social life and emotions. Family and friends play an important role in patients' lives. Acceptance of the disease and being positive is perceived as necessary for managing daily life. Patients experienced a lack of disease information from healthcare. Conclusion: Symptoms such as shortness of breath and fatigue limit the patients activities. It is important that patients become involved in their health by learning about heart failure. The nurse's responsibility is to motivate, strengthen the patients and give self-confidence to live a healthy life. It is important for the nurses to listen to the patients 'situation and promote the patients' well-being.

Une stimulation β-adrénergique (β-AR) aigue, par exemple au cours d’un exercice physique, accroît le second messager AMPc dans les cardiomyocytes aboutissant à une cascade d’évènements permettant d’augmenter la fonction cardiaque. Une élévation chronique des taux de catécholamines est délétère puisqu’elle participe au remodelage pathologique du cœur et à la progression vers l’insuffisance cardiaque (IC). L'IC correspond à l'incapacité du cœur à répondre aux besoins hémodynamiques de l'organisme. Si la majorité des patients meurt de défaillance cardiaque, une part importante décède d'arythmies.Les phosphodiestérases (PDEs) sont des enzymes essentielles puisqu’elles permettent non seulement la terminaison des signaux AMPc en dégradant ce nucléotide cyclique en 5’AMP inactif mais aussi l’organisation spatiale de ces signaux dans des compartiments subcellulaires spécifiques. L'IC s'accompagne de profonds remaniements de la voie β-AR et l'expression des PDEs est modifiée en conditions pathologiques, perturbant ainsi la compartimentation intracellulaire de l’AMPc. Il a été notamment démontré que l’expression d’une isoforme de PDE particulière, la PDE4B, diminue dans l'hypertrophie cardiaque et que l’invalidation du gène codant pour celle-ci favorise les arythmies ventriculaires chez la souris lors d’une stimulation β-AR. À l’inverse, l'expression d'une autre enzyme, la PDE2A, est augmentée dans l’IC, chez l’homme et différents modèles animaux. Ceci constituerait un mécanisme de défense lors d'un stress cardiaque puisqu’il a été montré que sa surexpression atténue l’hypertrophie induite par la noradrénaline ou la phényléphrine et limite les arythmies chez la souris.L’objectif de mon travail était de tester l’hypothèse qu’une augmentation de l’activité des PDEs pourrait constituer une alternative aux traitements classiques de l’IC, pour limiter le remodelage hypertrophique, la progression vers l’IC et les arythmies associées. Pour cela, j’ai réalisé une thérapie génique dans des modèles murins d'IC grâce à des virus adéno-associé de type 9 (AAV9) codant pour la PDE4B ou la PDE2A. Mes résultats suggèrent que cette approche pourrait constituer une nouvelle stratégie thérapeutique prometteuse de l'IC en limitant le dysfonctionnement cardiaque, l’hypertrophie du ventricule gauche, et la survenue des arythmies ventriculaires mais seulement lorsque la PDE2A est surexprimée. / Acute stimulation of β-adrenergic receptors (β-ARs), for example during physical activity, leads to the synthesis of the second messenger cAMP in cardiomyocytes, which triggers a cascade of events leading to the increase of cardiac function. While acute β-AR stimulation is beneficial to the heart, chronic β-AR activation is detrimental because it promotes cardiac remodeling and ultimately leads to heart failure (HF). HF is defined by the heart's inability to overcome hemodynamic needs of the body. While the majority of patients die of worsening heart function, a significant proportion dies suddenly of cardiac arrhythmias.Phosphodiesterases (PDEs) are crucial enzymes since they allow not only to terminate cAMP signals by degrading this second messenger into inactive 5’AMP but permit their spatial organization in subcellular compartments. HF is accompanied by profound rearrangements of the β-AR pathway and the expression of PDEs is modified under pathological conditions, thus disrupting cAMP intracellular compartmentation. The expression of one of these enzymes, PDE4B, is decreased in cardiac hypertrophy and the invalidation of the gene encoding PDE4B promotes ventricular arrhythmias under β-AR stimulation in mice. Conversely, the expression of another enzyme, PDE2A, is up-regulated in human and animal models of HF which may constitute an important defense mechanism during cardiac stress since its overexpression attenuates hypertrophy induced by norepinephrine or phenylephrine and limits cardiac arrhythmias.The purpose of my work was to test the hypothesis that an increase of PDE activity could constitute an alternative to conventional HF treatments to limit cardiac remodeling, HF progression and associated arrhythmias. To do so, I performed a cardiac gene therapy in mouse models of HF using serotype 9 adeno-associated viruses (AAV9) encoding for PDE4B or PDE2A. My results suggest that this approach may be a promising new therapeutic strategy during HF by limiting cardiac dysfunction, left ventricular hypertrophy, and could protect ventricular arrhythmias only when PDE2A is overexpressed.

Alors que l’entrée SOC (store-operated Ca2+ entry) portée par les canaux calciques TRPCs (transient receptor potential canonical) et Orai1 est essentielle dans les cellules non-excitables, son rôle physiologique dans les cardiomyocytes adultes reste à élucider. Néanmoins, il est largement admis qu’une entrée SOC exacerbée dépendante des canaux TRPCs et de la protéine régulatrice STIM1 participe à la pathogenèse de l’hypertrophie et de l’insuffisance cardiaque (IC) par induction de voies pro-hypertrophiques telles que la CaMKII (Ca2+/calmoduline-dépendante kinase II ) et la calcineurine (CaN)/NFAT (Nuclear factor of activated T-cells). Au contraire, une inhibition fonctionnelle ou une extinction génique des canaux TRPCs et de la protéine STIM1 serait cardioprotectrice contre le stress hypertrophique. Cependant, le rôle physiopathologique des canaux calciques Orai1 dans le cœur reste, à ce jour, méconnu et débattu puisque son extinction in vitro présente un effet bénéfique contre l’hypertrophie des cardiomyocytes alors que son extinction in vivo présente des effets délétères avec le développement d’une cardiomyopathie dilatée. De plus amples investigations quant au rôle d’Orai1 dans la physiopathologie cardiaque apparaissent donc primordiales. De ce fait, les objectifs de ma thèse sont d’explorer le rôle de la signalisation calcique dépendante d’Orai1 dans le cœur dans des conditions physiologiques et pathologiques grâce à un modèle de souris transgéniques exprimant un mutant non fonctionnel d’Orai1, spécifiquement dans le cœur (dn-Orai1R91W/tTa) et un inhibiteur pharmacologique sélectif, le JPIII. Tout d’abord, nous montrons que les souris dn-Orai1R91W/tTa présentent une fonction cardiaque normale et une homéostasie calcique impliquée dans le couplage excitation-contraction conservée suggérant qu’Orai1 n’a pas de rôle majeur dans le coeur adulte en condition physiologique. Cependant, nous avons démontré une augmentation de l’expression et de l’activité d’Orai1 dans un modèle murin d’hypertrophie cardiaque induite par surcharge de pression, qui serait délétère pour la fonction ventriculaire. Au contraire, l’inhibition fonctionnelle d’Orai1 par manipulation génétique ou par l’outil pharmacologique (JPIII) semble protéger le coeur des dysfonctions ventriculaires au cours de l’hypertrophie. Cet effet bénéfique passerait par une restauration de l’homéostasie calcique et notamment par un maintien de l’expression de la pompe ATPase SERCA2a. Nous avons également mis en évidence que la voie de l’aldostérone/récepteurs aux minéralocorticoïdes modulait l’expression des canaux TRPC1, -C4, -C5 et notamment Orai1 via la protéine SGK1 (Serum and Glucocorticoid-regulated Kinase 1) dans les cardiomyocytes ventriculaires de rat nouveaux-nés. L’activation de cette voie de signalisation pourrait être à l’origine de la surexpression des canaux TRPCs/Orai1 retrouvée au cours de l’hypertrophie cardiaque. Ces travaux décrivent donc Orai1 comme une cible thérapeutique potentielle dans le traitement de l’hypertrophie cardiaque et de l’IC. / While the SOCE (store-operated Ca2+ entry), carried by TRPCs (transient receptor potential canonical) and Orai1 channels, is essential in non-excitable cells, its physiological role in adult cardiomyocytes remains elusive. Nevertheless, it is well established that exacerbated TRPCs/STIM1-dependent Ca2+ entry participates in the pathogenesis of hypertrophy and heart failure (HF) via the induction of pro-hypertrophic signaling pathways, such as CaMKII (Ca2+/calmodulin-kinase II) and calcineurin (CaN)/ NFAT (nuclear factor of activated T-cells). By contrast, functional inhibition or gene silencing of TRPCs and STIM1 is cardioprotective against hypertrophic insults. As for Orai1 Ca2+ channels, their pathophysiological roles in the heart remain unknown and under debate, since in vitro Orai1 silencing has a beneficial effect against cardiomyocyte hypertrophy, whereas in vivo silencing has deleterious effects with the development of dilated cardiomyopathy. Further investigations are necessary to determine the pathophysiological role of Orai1 in the heart. My thesis objectives are to explore the role of Orai1-dependent Ca2+ signaling in the heart under physiological and pathological conditions using a transgenic mouse model expressing a non functional mutant of Orai1, specifically in the heart (dn-Orai1R91W/tTa) and a selective pharmacological inhibitor, JPIII. First, we showed that dn-Orai1R91W/tTa mice have normal cardiac function and conserved Ca2+ homeostasis involved in the excitation-contraction coupling suggesting that Orai1 is not instrumental in regulating cardiac function under physiological conditions. However, we demonstrated an increased Orai1 expression and activity in a mouse model of cardiac hypertrophy induced by pressure overload, which is a maladaptive alteration involved in pathological ventricular dysfunction. By contrast, functional inhibition of Orai1 by genetic manipulation or by the pharmacological tool (JPIII) protects the heart from ventricular dysfunction after pressure overload-induced cardiac hypertrophy. This beneficial effect is related to a restoration of Ca2+ homeostasis and more specifically, is due to preserved ATPase SERCA2a pump expression. We also showed that the aldosterone/mineralocorticoid receptor signaling pathway modulates the expression of TRPC1, -C4, -C5 channels and also the Orai1 channels expression via the SGK1 (Serum and Glucocorticoid-regulated Kinase 1) protein, in neonatal rat ventricular cardiomyocytes. The activation of this signaling pathway could be the cause of the TRPCs/Orai1 channels overexpression found during cardiac hypertrophy. In conclusion, our studies highlighted that Orai1 Ca2+ channels could constitute potential therapeutic target in the treatment of cardiac hypertrophy and HF.

Bakgrund: I Sverige är det cirka 250 000 som lever med hjärtsvikt och sjukdomen fortsätter att öka i hela världen. Hjärtsvikt är ett kroniskt sjukdomstillstånd som idag inte går att bota och är förenad med morbiditet samt en för tidig död. Men genom god följsamhet till egenvård kan sjukdomen bli mer hanterbar. Syfte: Beskriva hjärtsviktspatienters upplevelser av sin egenvård.   Metod: Kvalitativ metod med deduktiv ansats har använts till litteratur-översikten. Totalt 10 stycken vetenskapliga artiklar granskats och analyserats enligt Fribergs femstegsmodell. Alla artiklar har kvalitetsgranskats.      Resultat: Två huvudteman tillsammans med tre subteman utformades. Huvudteman var resurser och stöd samt förstå information. Subteman blev socialt stöd och professionellt stöd samt patientutbildning. I resultatet beskrivs vikten av att patienter får individanpassad information som kan ges både muntligt och skriftligt om sin hjärtsvikt samt hur patienter upplever sin egenvård. Slutsats:  Information är en viktig källa till motivation och delaktighet i patienters egenvård. Patientutbildning från sjuksköterska samt stöd från familj och närstående ökar motivation till följsamhet till egenvård hos hjärtsviktspatienter. Kunskap och förståelse om patientens inre känslor för sin sjukdom är betydelsefull att ha när denna patientgrupp möts i samhället. Informationen bör ges individanpassat och gärna med stöd från närstående. / Background: In Sweden, there are approximately 250,000 living with heart failure and the disease continues to increase worldwide. Heart failure is a chronic disease condition that today cannot be cured and is associated with morbidity and premature death. But through good adherence to self-care, the disease can become more manageable. Aim: The purpose was to describe the experiences of heart failure patient’s self-care. Method: A qualitative method with a deductive approach has been used for the literature review. A total of 10 scientific articles were reviewed according to Friberg's five-step model. All articles have been quality checked.      Results: Two main themes together with three subthemes were designed. Main themes were resources and support as well as understanding information. Sub-themes became social support and professional support as well as patient education. The result describes the importance of patients receiving personalized information that can be given both orally and in writing about their heart failure as well as how patients experience their self-care. Conclusion: Information is an important source of motivation and participation in patients' self-care. Patient education from the nurse as well as support from family and close relatives increases motivation for adherence to self-care in heart failure patients. Knowledge and understanding of the patient's inner feelings for their illness are important to have when this patient group meets in the community. The information should be provided individually and preferably with the support of close relatives.