The pathological changes of ubiquitination and deubiquitination following myocardial infarction (MI) and chronic heart failure (CHF) have been sparsely examined. We investigated the expression of muscle-specific E3 ubiquitin ligases and deubiquitinases in MI and CHF. Therefore, mice were assigned to coronary artery ligation for 3 days or 10 weeks as well as for sham operation (each n = 10). Expression of E3 ligases (MAFBX, MURF1, CHIP, ITCH, MDM2) and deubiquitinases (A20, CYLD, UCH-L1, USP14, USP19) was determined. After MI and in CHF, the mRNA expression of MURF1, CHIP and MDM2 (all p < 0.05) was decreased. Protein expression analyses revealed that ITCH expression decreased in CHF (p = 0.01), whereas MDM2 expression increased in MI (p = 0.02) and decreased in CHF (p = 0.02). Except for USP19 mRNA expression that decreased at 3 days and 10 weeks (both p < 0.01), the expression of other deubiquitinases remained unaffected after MI and CHF. The expression of myocardial E3 ligases is differentially regulated following MI, raising the question of whether an upstream regulation exists that is activated by MI for tissue protection or whether the downregulation of E3 ligases enables myocardial hypertrophy following MI.

Aims To characterize the prevalence and clinical relevance of malnutrition in patients undergoing transcatheter tricuspid valve edge-to-edge repair (TTVR). Methods and results Overall, 86 consecutive patients (mean age 78 ± 7 years) with moderate-to-severe tricuspid regurgitation (TR) at prohibitive surgical risk were analysed. Mini Nutritional Assessment (MNA), quality of life assessment, 6-min walk test distance and laboratory analyses were performed before and 1 month after TTVR. A total of 43 patients (50%) underwent concomitant transcatheter mitral valve repair. According to MNA, 81 patients (94%) were malnourished or at risk of malnutrition before TTVR. Following TTVR, MNA improved in 64 patients (74%). As compared to patients without MNA improvement, patients with increased MNA score had greater reductions in TR [regurgitation volume −17.0 (interquartile range, IQR −25.0; −7.0) mL vs. −26.4 (IQR −40.3; −14.5) mL, P < 0.001] and inferior vena cava diameter. Only patients with increased MNA score displayed a decrease in N-terminal pro-brain natriuretic peptide levels [−320 (IQR −1294; 105) pg/mL vs. +708 (IQR −342; 2708) pg/mL, P = 0.009], improvements in cholinesterase levels (0.0 ± 11.9 μmoL/L vs. +10.9 ± 16.7 μmoL/L, P < 0.001) and renal function during follow-up. Beneficial effects on quality of life scores and 6-min walk test distance following TTVR were observed exclusively in patients with improvement in MNA. During a median follow-up of 6 months, patients with worsened MNA had an increased risk of death and rehospitalization for heart failure. Conclusion Nutritional impairment is common and of prognostic importance in patients undergoing TTVR. Hepatorenal function modestly improves after successful TTVR. Further study of extracardiac implications of TR-associated right heart failure is warranted to improve care in this vulnerable patient population.

Endpoints of large-scale trials in chronic heart failure have mostly been defined to evaluate treatments with regard to hospitalizations and mortality. However, patients with heart failure are also affected by very severe reductions in exercise capacity and quality of life. We aimed to evaluate the effects of heart failure treatments on these endpoints using available evidence from randomized trials. Interventions with evidence for improvements in exercise capacity include physical exercise, intravenous iron supplementation in patients with iron deficiency, and – with less certainty – testosterone in highly selected patients. Erythropoiesis-stimulating agents have been reported to improve exercise capacity in anaemic patients with heart failure. Sinus rhythm may have some advantage when compared with atrial fibrillation, particularly in patients undergoing pulmonary vein isolation. Studies assessing treatments for heart failure co-morbidities such as sleep-disordered breathing, diabetes mellitus, chronic kidney disease and depression have reported improvements of exercise capacity and quality of life; however, the available data are limited and not always consistent. The available evidence for positive effects of pharmacologic interventions using angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists on exercise capacity and quality of life is limited. Studies with ivabradine and with sacubitril/valsartan suggest beneficial effects at improving quality of life; however, the evidence base is limited in particular for exercise capacity. The data for heart failure with preserved ejection fraction are even less positive, only sacubitril/valsartan and spironolactone have shown some effectiveness at improving quality of life. In conclusion, the evidence for state-of-the-art heart failure treatments with regard to exercise capacity and quality of life is limited and appears not robust enough to permit recommendations for heart failure. The treatment of co-morbidities may be important for these patient-related outcomes. Additional studies on functional capacity and quality of life in heart failure are required.

Bakgrund: Hjärtsvikt är en folksjukdom som ökar kraftigt vid stigande ålder och kräver ökade behov av hälso- och sjukvårdsinsatser. För att bibehålla hälsan och inte belasta sjukvården kan interventioner av egenvård förebygga, underhålla och hantera den kroniska hjärtsvikten. Även livsstilsförändringar är viktiga bitar i egenvårdsinterventionen för att minska risken för sjukdomsförsämring. För att kunna sköta sin egenvård på ett optimalt sätt behövs utbildning och kunskap om effektiva interventioner som stärker förmågan att utföra egenvård. Syftet: Syftet var att belysa interventioner som kan förbättra egenvård hos personer med hjärtsvikt. Metod: En litteraturstudie valdes som metod. Sökningarna i omvårdnadsdatabaserna CINAHL och PubMed genererade totalt 16 omvårdnadsvetenskapliga artiklar publicerade mellan 2013 och 2023 som svarade på studiens syfte. Artiklarna kvalitetsgranskades och analyserades genom integrerad analys. Resultat: Olika typer av interventioner kan förbättra egenvården hos personer med hjärtsvikt. Resultatet sorterades in i tre kategorier. Utbildningsintervention som stärker kunskap, Interventioner med teknisk support och socialt stöd och Interventioner med olika samtalstekniker.   Slutsats: Studien visar på hur strukturerade insatser av egenvårdsinterventioner stärker egenvårdsbeteendet för att förebygga, hanterar och underhåller hjärtsviktssymtom vilken inverkan på hur personen behåller hälsan. Personens självkännedom kan förbättras genom individanpassad information och utbildningsprogram för att öka kunskapen på ett sätt som passar bäst utifrån sina resurser och behov. Därför har personcentrerad vård en central roll när det gäller att stärka egenvård och delaktighet hos personer med hjärtsvikt. / Background: Heart failure is a common disease that increases sharply with increasing age and requires additional needs for health care interventions. In order to maintain health and avoid burdening the healthcare system, self-care interventions can prevent, maintain and manage chronic heart failure. Lifestyle changes are also important compondents of the self-care intervention to reduce the risk of disease worsening. In order to manage self-care in an optimal way, education and knowledge about effective interventions that strengthen the ability to perform self-care are needed. Purpose: The aim was to highlight interventions that can improve self-care in people with heart failure. Method: A literature study was chosen as the method. The searches in the nursing databases CINAHL and PubMed generated a total of 16 nursing science articles published between 2013 and 2023 that responded to the study objective. The articles are quality checked and analyzed through integrated analysis. Results: Different types of interventions can improve self-care in people with heart failure. The results were sorted into three categories. Educational intervention that strengthens knowledge, Interventions with technical support and social support and Interventions with different conversation techniques. Conclusion: The study shows how structured interventions focusing on self-care  strengthens self-care behaviours to prevent, manage and maintain heart failure symptoms which impact on how the person maintains their health. A person's self-awareness can be improved through individually tailored information and training programs to increase knowledge in a way that best suits their resources and needs. Therefore, person-centered care has a central role when it comes to strengthening self-care and participation in people with heart failure.

Acute congestive heart failure is a leading cause of morbidity and mortality. Patients often undergo repeated hospitalizations with an annual cost in excess of $32B dollars. Early detection of impending acute congestion allows for pharmaceutical interdiction that prevents hospitalization, improves outcomes, and reduces healthcare spending. A subcutaneous implantable monitoring device that detects impending acute congestive heart failure by using heart sounds may provide a valuable tool that can be used to titrate heart failure medications to prevent acute heart failure requiring hospitalization. The device may be used to measure changes in the intervals between the R-wave and S1 and S2 heart sounds, and to detect evolving S3 and S4 heart sounds consistent with volume overload. The amplitudes of S1 and S3 heart sounds change as heart failure patients' symptoms worsen. Designing a non-invasive, external device, capable of recording heart sounds and EKGs in patients undergoing pharmaceutical regression of acute congestive heart failure in a hospital setting may give important insight into the nature of heart sound and EKG changes that occur in patients during progression of acute heart failure while they lead their day-to-day lives. This thesis details the design of a portable, non-invasive device, worn externally on the left-pectoral muscle, capable of continuously recording human EKG signals and heart sounds (through custom MEMS accelerometer technology) over a period of two days. Hardware testing for the scope of this thesis exclusively involved healthy volunteers.

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) accounts for half of all clinical heart failure presentations, but unfortunately lacks effective therapies. Therefore, it has become more urgent to elucidate the pathophysiology underlying this disease, both by using patient data and the development of more accurate animal models. With clinical evidence suggesting that skeletal muscle abnormality is a significant factor in the development of exercise intolerance, this thesis investigates whether the salty drinking water, unilateral nephrectomy, and aldosterone (SAUNA) HFpEF mouse model also demonstrates similar skeletal muscle abnormality as seen in patients. METHODS: Eight-weeks old C57BL/6J mice were subjected to a left nephrectomy and given a mini-osmotic pump to deliver a continuous infusion of either saline (Sham) or aldosterone (HFpEF). The mice were then maintained on a standard rodent chow and a 1% sodium chloride solution. After 4 weeks, the soleus and gastrocnemius muscles were harvested. Histological analyses were performed to examine fiber composition, cross-sectional area of fiber, capillary density, and fibrosis. Quantitative PCR (qPCR) and western blot analyses were performed to examine the expression changes in mitochondrial oxidative phosphorylation, vasculature, fibrosis and inflammation. RESULTS: HFpEF mice showed significant increase in systolic and diastolic blood pressure, increased heart/tibia length ratio, increased wet/dry lung ratio, decreased bodyweight as well as decreased weight of soleus and gastrocnemius muscle relative to tibia length. In oxidative soleus muscle, histological analyses showed a reduction in the abundance of type 1 and type 2A oxidative fiber, reduced cross-sectional area of type 2A fiber, decreased capillary density and increased fibrosis. Molecular analyses showed alterations that are consistent with histological data as well as increased gene expression of inflammatory mediators. In glycolytic gastrocnemius muscle, histological analysis indicated cross-sectional area was reduced for type 2B fibers and increased in type 1 fibers, and decreased capillary density. However, no changes in fiber abundance or in fibrosis was observed. Molecular data was consistent with these findings and revealed an increased gene expression of inflammatory mediators CONCLUSION: Skeletal muscle in SAUNA HFpEF mice displayed significant abnormalities relative to their sham counterparts. These results thus support that SAUNA HFpEF mouse model is suitable and relevant to study skeletal muscle abnormalities and could contribute to the development of novel therapies for HFpEF. / 2025-06-21T00:00:00Z

Mutations in mitochondrial aminoacyl-tRNA synthetases (mtARSs) have been reported in patients with mitochondriopathies: most commonly encephalopathy, but also cardiomyopathy. Through a GWAS, we showed possible associations between mitochondrial valyl-tRNA synthetase (VARS2) dysregulations and non-ischemic cardiomyopathy. We aimed to investigate the possible consequences of VARS2 depletion in zebrafish and cultured HEK293A cells. Transient VARS2 loss-offunction was induced in zebrafish embryos using Morpholinos. The enzymatic activity of VARS2 was measured in VARS2-depleted cells via northern blot. Heterozygous VARS2 knockout was established in HEK293A cells using CRISPR/Cas9 technology. BN-PAGE and SDS-PAGE were used to investigate electron transport chain (ETC) complexes, and the oxygen consumption rate and extracellular acidification rate were measured using a Seahorse XFe96 Analyzer. The activation of the integrated stress response (ISR) and possible disruptions in mitochondrial fatty acid oxidation (FAO) were explored using RT-qPCR and western blot. Zebrafish embryos with transient VARS2 loss-of-function showed features of heart failure as well as indications of CNS and skeletal muscle involvements. The enzymatic activity of VARS2 was significantly reduced in VARS2-depleted cells. Heterozygous VARS2-knockout cells showed a rearrangement of ETC complexes in favor of complexes III2, III2 + IV, and supercomplexes without significant respiratory chain deficiencies. These cells also showed the enhanced activation of the ISR, as indicated by increased eIF-2 phosphorylation and a significant increase in the transcript levels of ATF4, ATF5, and DDIT3 (CHOP), as well as disruptions in FAO. The activation of the ISR and disruptions in mitochondrial FAO may underlie the adaptive changes in VARS2-depleted cells.

Despite concerted efforts to decrease costs and increase public health, the embattled U.S. health care system continues to struggle to alleviate these widespread issues. Because the problem of hospital utilizations among patients with heart failure is posited to increase as the population ages, innovative methodologies need to be explored to mitigate adverse events. Remote monitoring harnesses the strength of advanced information and communication technology to affect positive changes in health care quality and cost. By reaching across geographical boundaries, remote monitoring may support increased access to less costly services and improve the quality of home health care. The purpose of the study was to examine the home care quality effects of remote monitoring technology in patients with heart failure and to provide an economic justification for its adoption and diffusion. It compared remote monitoring as a potential intervention strategy to a standard no-intervention group (without remote monitoring). Specifically, it analyzed remote monitoring as a viable strategy to decrease hospital readmissions and emergency department visits. It also compared the cost of remote monitoring against the current standard-of-care. The theoretical framework of Donabedian's Quality Model was used in the evaluation of remote monitoring. A retrospective posttest only, case control study design was used to test the degree which remote monitoring was effective in promoting health care quality (hospital readmissions and decreased emergency department visits). Retrospective chart reviews were performed using electronic medical records (EMR). Analysis of Variance, Path Analysis, Automatic Interaction Detector Analysis (Dtreg), and Cost Outcomes Ratio were used to test the hypotheses and validate the proposed theoretical model. No significant difference was noted in remote monitoring and usual care groups. Results suggested that remote monitoring does not statistically lead to a decrease in heart failure-related hospital readmissions and all-cause emergency department visits. Results of the cost ratio analysis suggested that there was no statistically significant difference in the net income between usual care and remote monitoring; however, data suggest that there were significant increases in cost and intensity of nursing utilization for the remote monitoring intervention. The Automatic Interaction Detector Analysis showed that the unfavorable results in hospital readmissions were due to a decrease in collaborative care and patient education prior to the recommendation for hospitalization. The role of nursing care, whether in hospital or community-based care, in heart failure management is critical to quality outcomes. As the field continues to consider the use of technology in health care, decision makers should think through the process of patient care such that preventable hospital readmissions are decreased and patients received quality care.

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