The illness experiences of patients and their family members living with congestive heart failure

Purpose. To investigate and understand the illness experiences of patients and their family members living with congestive heart failure (CHF). ^ Design. Focused ethnographic design. ^ Setting. One outpatient cardiology clinic, two outpatient heart failure clinics, and informants' homes in a large metropolitan city located in southeast Texas. ^ Sample. A purposeful sampling technique was used to select a sample of 28 informants. The following somewhat overlapping, sampling strategies were used to implement the purposeful method: criterion; typical case; operational construct; maximum variation; atypical case; opportunistic; and confirming and disconfirming case sampling. ^ Methods. Naturalistic inquiry consisted of data collected from observations, participant observations, and interviews. Open-ended semi-structured illness narrative interviews included questions designed to elicit informant's explanatory models of the illness, which served as a synthesizing framework for the analysis. A thematic analysis process was conducted through domain analysis and construction of data into themes and sub-themes. Credibility was enhanced through informant verification and a process of peer debriefing. ^ Findings. Thematic analysis revealed that patients and their family members living with CHF experience a process of disruption, incoherence, and reconciling. Reconciling emerged as the salient experience described by informants. Sub-themes of reconciling that emerged from the analysis included: struggling; participating in partnerships; finding purpose and meaning in the illness experience; and surrendering. ^ Conclusions. Understanding the experiences described in this study allows for a better understanding of living with CHF in everyday life. Findings from this study suggest that the experience of living with CHF entails more than the medical story can tell. It is important for nurses and other providers to understand the experiences of this population in order to develop appropriate treatment plans in a successful practitioner-patient partnership. ^

Factors affecting the symptom burden in chronic heart failure

Background. Heart failure (HF) is a health problem of epidemic proportions and a clinical syndrome that leads to progressively severe symptoms, which contribute significantly to the burden of the disease. Several factors may affect the symptom burden of patients with HF, including physiological, psychological, and spiritual factors. This study was designed to examine the inter-relationship of physiological, psychological, and spiritual factors affecting symptoms for patients with HF. ^ Objectives. The aims of this study were to examine symptom burden of heart failure patients related to: (1) the physiological factor of brain natriuretic peptide (BNP); (2) the psychological factor of depression; (3) the spiritual factors of self transcendence and purpose in life; and (4) combined effects of physiological, psychological and spiritual factors. One additional aim was to describe symptom intensity related to symptom burden. ^ Methods. A cross-sectional non-experimental correlational design was used to examine factors affecting symptom burden in 105 patients with HF from a southwestern medical center outpatient heart failure clinic. Both men and women were included; average age was 56.6 (SD = 16.86). All measures except BNP were obtained by patient self-report. ^ Results. The mean number of symptoms present was 8.17 (SD = 3.34) with the three most common symptoms being shortness of breath on exertion, fatigue, and weakness. The mean symptom intensity was 365.66 (SD = 199.50) on a summative scale of visual analogue reports for 13 symptoms. The mean BNP level was 292.64 pg/ml (SD = 57 1.11). The prevalence rate for depression was 43.6% with a mean score of 3.48 (SD = 2.75) on the Center for Epidemiological Studies - Depression scale (CES-D 10) scale. In a multivariate analysis, depression was the only significant predictor of symptom burden (r = .474; P < .001), accounting for 18% of the variance. Spirituality had an interaction effect with depression (P ≤ .001), serving as a moderator between depression and symptom burden. ^ Conclusion. HF is a chronic and progressive syndrome characterized by severe symptoms, hospitalizations and disability. Depression is significantly related to symptom burden and this relationship is moderated by spirituality. ^

The role of transforming growth factor beta signaling in cardiac hypertrophy and fibrosis in heart failure

Objective. To determine whether transforming growth factor beta (TGF-β) receptor blockade using an oral antagonist has an effect on cardiac myocyte size in the hearts of transgenic mice with a heart failure phenotype. ^ Methods. In this pilot experimental study, cardiac tissue sections from the hearts of transgenic mice overexpressing tumor necrosis factor (MHCsTNF mice) having a phenotype of heart failure and wild-type mice, treated with an orally available TGF-β receptor antagonist were stained with wheat germ agglutinin to delineate the myocyte cell membrane and imaged using fluorescence microscopy. Using MetaVue software, the cardiac myocyte circumference was traced and the cross sectional area (CSA) of individual myocytes were measured. Measurements were repeated at the epicardial, mid-myocardial and endocardial levels to ensure adequate sampling and to minimize the effect of regional variations in myocyte size. ANOVA testing with post-hoc pairwise comparisons was done to assess any difference between the drug-treated and diluent-treated groups. ^ Results. There were no statistically significant differences in the average myocyte CSA measured at the epicardial, mid-myocardial or endocardial levels between diluent treated littermate control mice, drug treated normal mice, diluent-treated transgenic mice and drug-treated transgenic mice. There was no difference between the average pan-myocardial cross sectional area between any of the four groups mentioned above. ^ Conclusions. TGF-β receptor blockade using oral TGF-β receptor antagonist does not alter myocyte size in MHCsTNF mice that have a phenotype of heart failure. ^

Ambulatory blood pressure and physical activity in heart failure

Background. Ambulatory blood pressure (ABP) measurement is a means of monitoring cardiac function in a noninvasive way, but little is known about ABP in heart failure (HF) patients. Blood pressure (BP) declines during sleep as protection from consistent BP load, a phenomenon termed "dipping." The aims of this study were (1) to compare BP dipping and physical activity between two groups of HF patients with different functional statuses and (2) to determine whether the strength of the association between ambulatory BP and PA is different between these two different functional statuses of HF. ^ Methods. This observational study used repeated measures of ABP and PA over a 24-hour period to investigate the profiles of BP and PA in community-based individuals with HF. ABP was measured every 30 minutes by using a SpaceLabs 90207, and a Basic Motionlogger actigraph was used to measure PA minute by minute. Fifty-six participants completed both BP and physical activity for a 24-hour monitoring period. Functional status was based on New York Heart Association (NYHA) ratings. There were 27 patients with no limitation of PA (NYHA class I HF) and 29 with some limitation of PA but no discomfort at rest (NYHA class II or III HF). The sample consisted of 26 men and 30 women, aged 45 to 91 years (66.96 ± 12.35). ^ Results. Patients with NYHA class I HF had significantly greater dipping percent than those with NYHA class II/III HF after controlling their left ventricular ejection fraction (LVEF). In a mixed model analysis (PROC MIXED, SAS Institute, v 9.1), PA was significantly related to ambulatory systolic and diastolic BP and mean arterial pressure. The strength of the association between PA and ABP readings was not significantly different for the two groups of patients. ^ Conclusions. These preliminary findings demonstrate differences between NYHA class I and class II/III of HF in BP dipping status and ABP but not PA. Longitudinal research is recommended to improve understanding of the influence of disease progression on changes in 24-hour physical activity and BP profiles of this patient population. ^ Key Words. Ambulatory Blood Pressure; Blood Pressure Dipping; Heart Failure; Physical Activity. ^

Persistently elevated troponin I in heart failure patients - a suitable prognosticator and a possible boon to public health?

Baseline elevation of troponin I (TnI) has been associated with worse outcomes in heart failure (HF). However, the prevalence of persistent TnI elevation and its association with clinical outcomes has not been well described. HF is a major public health issue due to its wide prevalence and prognosticators of this condition will have a significant impact on public health. Methods: A retrospective study was performed in 510 patients with an initial HF admission between 2002 to 2004, and all subsequent hospital admissions up to May 2009 were recorded in a de-identified database. Persistent TnI elevation was defined as a level ≥0.05 ng/ml on ≥3 HF admissions. Baseline characteristics, hospital readmissions and all cause mortality were compared between patients with persistent TnI elevation (Persistent), patients with no persistence of TnI (Nonpersistent) and patients who had less than three hospital admissions (admission <3) groups. Also the same data was analyzed using the mean method in which the mean value of all recorded troponin values of each patient was used to define persistence i.e. patients who had a mean troponin level ≥0.05 ng/ml were classified as persistent. Results: Mean age of our cohort was 68.4 years out of which 99.6% subjects were male, 62.4% had ischemic HF. 78.2% had NYHA class III to IV HF, mean LVEF was 25.9%. Persistent elevation of TnI was seen in 26% of the cohort and in 66% of patients with more than 3 hospital admissions. Mean TnI level was 0.67 ± 0.15 ng/ml in the 'Persistent' group. Mean TnI using the mean method was 1.11 ± 7.25 ng/ml. LVEF was significantly lower in persistent group. Hypertension, diabetes, chronic renal insufficiency and mean age did not differ between the two groups. 'Persistent' patients had higher mortality (HR = 1.26, 95% CI = 0.89–1.78, p = 0.199 when unadjusted and HR = 1.29, 95% CI = 0.89–1.86, p = 0.176 when adjusted for race, LVEF and ischemic etiology) HR for mortality in persistent patients was 1.99 (95% CI = 1.06–3.73, p = 0.03) using the mean method. The following results were found in those with ischemic cardiomyopathy (HR = 1.44034, 95% CI = 0.92–2.26, p = 0.113) and (HR = 1.89, 95% CI = 1.01–3.55, p = 0.046) by using the mean method. 2 out of three patients with HF who were readmitted three or more times had persistent elevation of troponin I levels. Patients with chronic persistence of troponin I elevation showed a trend towards lesser survival as compared to patients who did not have chronic persistence, however this did not reach statistical significance. This trend was seen more among ischemic patients than non ischemic patients, but did not reach statistical significance. With the mean method, patients with chronic persistence of troponin I elevation had significantly lesser survival than those without it. Also ischemic patients had significantly lesser survival than non ischemic patients. ^

Secondary left ventricular ejection fraction response to beta blocker therapy in heart failure patients

Chronic β-blocker treatment improves survival and left ventricular ejection fraction (LVEF) in patients with systolic heart failure (HF). Data on whether the improvement in LVEF after β-blocker therapy is sustained for a long term or whether there is a loss in LVEF after an initial gain is not known. Our study sought to determine the prevalence and prognostic role of secondary decline in LVEF in chronic systolic HF patients on β-blocker therapy and characterize these patients. Retrospective chart review of HF hospitalizations fulfilling Framingham Criteria was performed at the MEDVAMC between April 2000 and June 2006. Follow up vital status and recurrent hospitalizations were ascertained until May 2010. Three groups of patients were identified based on LVEF response to beta blockers; group A with secondary decline in LVEF following an initial increase, group B with progressive increase in LVEF and group C with progressive decline in LVEF. Covariate adjusted Cox proportional hazard models were used to examine differences in heart failure re-hospitalizations and all cause mortality between the groups. Twenty five percent (n=27) of patients had a secondary decline in LVEF following an initial gain. The baseline, peak and final LVEF in this group were 27.6±12%, 40.1±14% and 27.4±13% respectively. The mean nadir LVEF after decline was 27.4±13% and this decline occurred at a mean interval of 2.8±1.9 years from the day of beta blocker initiation. These patients were older, more likely to be whites, had advanced heart failure (NYHA class III/IV) more due to a non ischemic etiology compared to groups B & C. They were also more likely to be treated with metoprolol (p=0.03) compared to the other two groups. No significant differences were observed in combined risk of all cause mortality and HF re-hospitalization [hazard ratio 0.80, 95% CI 0.47 to 1.38, p=0.42]. No significant difference was observed in survival estimates between the groups. In conclusion, a late decline in LVEF does occur in a significant proportion of heart failure patients treated with beta blockers, more so in patients treated with metoprolol.^

Trastuzumab use and risk of congestive heart failure in older breast cancer patients

Trastuzumab is a humanized-monoclonal antibody, developed specifically for HER2-neu over-expressed breast cancer patients. Although highly effective and well tolerated, it was reported associated with Congestive Heart Failure (CHF) in clinical trial settings (up to 27%). This leaves a gap where, Trastuzumab-related CHF rate in general population, especially older breast cancer patients with long term treatment of Trastuzumab remains unknown. This thesis examined the rates and risk factors associated with Trastuzumab-related CHF in a large population of older breast cancer patients. A retrospective cohort study using the existing Surveillance, Epidemiology and End Results (SEER) and Medicare linked de-identified database was performed. Breast cancer patients ≥ 66 years old, stage I-IV, diagnosed in 1998-2007, fully covered by Medicare but no HMO within 1-year before and after first diagnosis month, received 1st chemotherapy no earlier than 30 days prior to diagnosis were selected as study cohort. The primary outcome of this study is a diagnosis of CHF after starting chemotherapy but none CHF claims on or before cancer diagnosis date. ICD-9 and HCPCS codes were used to pool the claims for Trastuzumab use, chemotherapy, comorbidities and CHF claims. Statistical analysis including comparison of characteristics, Kaplan-Meier survival estimates of CHF rates for long term follow up, and Multivariable Cox regression model using Trastuzumab as a time-dependent variable were performed. Out of 17,684 selected cohort, 2,037 (12%) received Trastuzumab. Among them, 35% (714 out of 2037) were diagnosed with CHF, compared to 31% (4784 of 15647) of CHF rate in other chemotherapy recipients (p<.0001). After 10 years of follow-up, 65% of Trastuzumab users developed CHF, compared to 47% in their counterparts. After adjusting for patient demographic, tumor and clinical characteristics, older breast cancer patients who used Trastuzumab showed a significantly higher risk in developing CHF than other chemotherapy recipients (HR 1.69, 95% CI 1.54 - 1.85). And this risk is increased along with the increment of age (p-value < .0001). Among Trastuzumab users, these covariates also significantly increased the risk of CHF: older age, stage IV, Non-Hispanic black race, unmarried, comorbidities, Anthracyclin use, Taxane use, and lower educational level. It is concluded that, Trastuzumab users in older breast cancer patients had 69% higher risk in developing CHF than non-Trastuzumab users, much higher than the 27% increase reported in younger clinical trial patients. Older age, Non-Hispanic black race, unmarried, comorbidity, combined use with Anthracycline or Taxane also significantly increase the risk of CHF development in older patients treated with Trastuzumab. ^

Elevated cystatin C & heart failure prognosis a systematic review

Renal insufficiency is one of the most common co-morbidities present in heart failure (HF) patients. It has significant impact on mortality and adverse outcomes. Cystatin C has been shown as a promising marker of renal function. A systematic review of all the published studies evaluating the prognostic role of cystatin C in both acute and chronic HF was undertaken. A comprehensive literature search was conducted involving various terms of 'cystatin C' and 'heart failure' in Pubmed medline and Embase libraries using Scopus database. A total of twelve observational studies were selected in this review for detailed assessment. Six studies were performed in acute HF patients and six were performed in chronic HF patients. Cystatin C was used as a continuous variable, as quartiles/tertiles or as a categorical variable in these studies. Different mortality endpoints were reported in these studies. All twelve studies demonstrated a significant association of cystatin C with mortality. This association was found to be independent of other baseline risk factors that are known to impact HF outcomes. In both acute and chronic HF, cystatin C was not only a strong predictor of outcomes but also a better prognostic marker than creatinine and estimated glomerular filtration rate (eGFR). A combination of cystatin C with other biomarkers such as N terminal pro B- type natriuretic peptide (NT-proBNP) or creatinine also improved the risk stratification. The plausible mechanisms are renal dysfunction, inflammation or a direct effect of cystatin C on ventricular remodeling. Either alone or in combination, cystatin C is a better, accurate and a reliable biomarker for HF prognosis. ^

Analysis, monitoring, and management of quality of experience in video delivery services over IP

Esta tesis estudia la monitorización y gestión de la Calidad de Experiencia (QoE) en los servicios de distribución de vídeo sobre IP. Aborda el problema de cómo prevenir, detectar, medir y reaccionar a las degradaciones de la QoE desde la perspectiva de un proveedor de servicios: la solución debe ser escalable para una red IP extensa que entregue flujos individuales a miles de usuarios simultáneamente. La solución de monitorización propuesta se ha denominado QuEM(Qualitative Experience Monitoring, o Monitorización Cualitativa de la Experiencia). Se basa en la detección de las degradaciones de la calidad de servicio de red (pérdidas de paquetes, disminuciones abruptas del ancho de banda...) e inferir de cada una una descripción cualitativa de su efecto en la Calidad de Experiencia percibida (silencios, defectos en el vídeo...). Este análisis se apoya en la información de transporte y de la capa de abstracción de red de los flujos codificados, y permite caracterizar los defectos más relevantes que se observan en este tipo de servicios: congelaciones, efecto de “cuadros”, silencios, pérdida de calidad del vídeo, retardos e interrupciones en el servicio. Los resultados se han validado mediante pruebas de calidad subjetiva. La metodología usada en esas pruebas se ha desarrollado a su vez para imitar lo más posible las condiciones de visualización de un usuario de este tipo de servicios: los defectos que se evalúan se introducen de forma aleatoria en medio de una secuencia de vídeo continua. Se han propuesto también algunas aplicaciones basadas en la solución de monitorización: un sistema de protección desigual frente a errores que ofrece más protección a las partes del vídeo más sensibles a pérdidas, una solución para minimizar el impacto de la interrupción de la descarga de segmentos de Streaming Adaptativo sobre HTTP, y un sistema de cifrado selectivo que encripta únicamente las partes del vídeo más sensibles. También se ha presentado una solución de cambio rápido de canal, así como el análisis de la aplicabilidad de los resultados anteriores a un escenario de vídeo en 3D. ABSTRACT This thesis proposes a comprehensive approach to the monitoring and management of Quality of Experience (QoE) in multimedia delivery services over IP. It addresses the problem of preventing, detecting, measuring, and reacting to QoE degradations, under the constraints of a service provider: the solution must scale for a wide IP network delivering individual media streams to thousands of users. The solution proposed for the monitoring is called QuEM (Qualitative Experience Monitoring). It is based on the detection of degradations in the network Quality of Service (packet losses, bandwidth drops...) and the mapping of each degradation event to a qualitative description of its effect in the perceived Quality of Experience (audio mutes, video artifacts...). This mapping is based on the analysis of the transport and Network Abstraction Layer information of the coded stream, and allows a good characterization of the most relevant defects that exist in this kind of services: screen freezing, macroblocking, audio mutes, video quality drops, delay issues, and service outages. The results have been validated by subjective quality assessment tests. The methodology used for those test has also been designed to mimic as much as possible the conditions of a real user of those services: the impairments to evaluate are introduced randomly in the middle of a continuous video stream. Based on the monitoring solution, several applications have been proposed as well: an unequal error protection system which provides higher protection to the parts of the stream which are more critical for the QoE, a solution which applies the same principles to minimize the impact of incomplete segment downloads in HTTP Adaptive Streaming, and a selective scrambling algorithm which ciphers only the most sensitive parts of the media stream. A fast channel change application is also presented, as well as a discussion about how to apply the previous results and concepts in a 3D video scenario.

Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct

We tested whether severe congestive heart failure (CHF), a condition associated with excess free-water retention, is accompanied by altered regulation of the vasopressin-regulated water channel, aquaporin-2 (AQP2), in the renal collecting duct. CHF was induced by left coronary artery ligation. Compared with sham-operated animals, rats with CHF had severe heart failure with elevated left ventricular end-diastolic pressures (LVEDP): 26.9 ± 3.4 vs. 4.1 ± 0.3 mmHg, and reduced plasma sodium concentrations (142.2 ± 1.6 vs. 149.1 ± 1.1 mEq/liter). Quantitative immunoblotting of total kidney membrane fractions revealed a significant increase in AQP2 expression in animals with CHF (267 ± 53%, n = 12) relative to sham-operated controls (100 ± 13%, n = 14). In contrast, immunoblotting demonstrated a lack of an increase in expression of AQP1 and AQP3 water channel expression, indicating that the effect on AQP2 was selective. Furthermore, postinfarction animals without LVEDP elevation or plasma Na reduction showed no increase in AQP2 expression (121 ± 28% of sham levels, n = 6). Immunocytochemistry and immunoelectron microscopy demonstrated very abundant labeling of the apical plasma membrane and relatively little labeling of intracellular vesicles in collecting duct cells from rats with severe CHF, consistent with enhanced trafficking of AQP2 to the apical plasma membrane. The selective increase in AQP2 expression and enhanced plasma membrane targeting provide an explanation for the development of water retention and hyponatremia in severe CHF.

Preservation of myocardial β-adrenergic receptor signaling delays the development of heart failure after myocardial infarction

When the heart fails, there is often a constellation of biochemical alterations of the β-adrenergic receptor (βAR) signaling system, leading to the loss of cardiac inotropic reserve. βAR down-regulation and functional uncoupling are mediated through enhanced activity of the βAR kinase (βARK1), the expression of which is increased in ischemic and failing myocardium. These changes are widely viewed as representing an adaptive mechanism, which protects the heart against chronic activation. In this study, we demonstrate, using in vivo intracoronary adenoviral-mediated gene delivery of a peptide inhibitor of βARK1 (βARKct), that the desensitization and down-regulation of βARs seen in the failing heart may actually be maladaptive. In a rabbit model of heart failure induced by myocardial infarction, which recapitulates the biochemical βAR abnormalities seen in human heart failure, delivery of the βARKct transgene at the time of myocardial infarction prevents the rise in βARK1 activity and expression and thereby maintains βAR density and signaling at normal levels. Rather than leading to deleterious effects, cardiac function is improved, and the development of heart failure is delayed. These results appear to challenge the notion that dampening of βAR signaling in the failing heart is protective, and they may lead to novel therapeutic strategies to treat heart disease via inhibition of βARK1 and preservation of myocardial βAR function.