Brilliant violet fluorochromes in simultaneous multicolor flow cytometry-fluorescence in situ hybridization measurement of monocyte subsets and telomere length in heart failure.

Conventional analytical methods to determine telomere length (TL) have been replaced by more precise and reproducible procedures, such as fluorescence in situ hybridization coupled with flow cytometry (flow-FISH). However, simultaneous measurement of TL and cell phenotype remains difficult. Relatively expensive and time-consuming cell-sorting purification is needed to counteract the loss, due to stringent FISH conditions, of prehybridization fluorescence by the organic fluorochromes conventionally used in the phenotyping step. Here, we sought to assess whether the newly developed Brilliant Violet (BV) dyes are valuable to specifically and simultaneously assess the distribution and telomere attrition of monocyte subsets circulating in the blood of a cohort of patients with heart failure. We performed flow-FISH on blood samples from 28 patients with heart failure. To differentiate among monocyte subsets, we used BV and conventional fluorochromes conjugated to antibodies against CD86, CD14, CD16, and CD15. We simultaneously assessed the TLs of the monocyte subsets with a telomere-specific peptide nucleic acid probe labeled with fluorescein isothiocyanate. The BV dyes completely tolerated the harsh conditions required for adequate DNA denaturation and simultaneously provided accurate identification of monocyte subpopulations and respective TLs. The presented protocol may be faster and less expensive than those used currently for purposes such as establishing associations among patient categories, disease progression, monocyte heterogeneity, and aging in the context of heart failure.

Fragility is a key determinant of survival in heart failure patients.

BACKGROUND: Heart failure (HF) is a chronic condition with poor prognosis, and has a high prevalence among older adults. Due to older age, fragility is often present among HF patients. However, even young HF patients show a high degree of fragility. The effect of fragility on long-term prognosis in HF patients, irrespective of age, remains unexplored. The aim of this study was to assess the influence of fragility on long-term prognosis in outpatients with HF. METHODS AND RESULTS: At least one abnormal evaluation among four standardized geriatric scales was used to identify fragility. Predefined criteria for such scales were: Barthel Index, <90; OARS scale, <10 in women and <6 in men; Pfeiffer Test, >3 (± 1, depending on educational grade); and ≥ 1 positive response for depression on the abbreviated Geriatric Depression Scale (GDS). We assessed 1314 consecutive HF outpatients (27.8% women, mean age years 66.7 ± 12.4 years with different etiologies. Fragility was detected in 581 (44.2%) patients. 626 deaths occurred during follow-up; the median follow-up was 3.6 years [P25-P75: 1.8-6.7] for the total cohort, and 4.9 years [P25-P75: 2.5-8.4] for living patients. Fragility and its components were significantly associated with decreased survival by univariate analysis. In a comprehensive multivariable Cox regression analysis, fragility remained independently associated with survival in the entire cohort, and in age and left ventricular ejection fraction subgroups. CONCLUSION: Fragility is a key determinant of survival in ambulatory patients with HF across all age strata.

Educational level and self-care behaviour in patients with heart failure before and after nurse educational intervention.

BACKGROUND: Self-care is important for heart failure (HF) management and may be influenced by the patient's educational level. AIM: We assessed the relationship of educational level with baseline self-care behaviour and changes one year after a nursing intervention in HF outpatients attending a HF unit. PATIENTS AND METHOD: Three hundred and thirty-five HF patients were studied, with a median age of 67 years (P(25-75) 57-75) and a median HF duration of six months (P(25-75) 1-36). HF aetiology was mainly ischaemic heart disease (53.4%). Median ejection fraction was 30% (P(25-75) 24-37%). The functional class was mainly II (66.3%) and III (25.7%). Educational levels were: very low 17.3%; low 62.1%; medium-high 20.6%. Patients were evaluated at the first visit (baseline) and one year after the educational intervention with the nine-item European Heart Failure Self-care Behaviour Scale. RESULTS: Median patient scores differed in the baseline (19 (P(25-75) 15-26) vs. 16 (P(25-75) 13-21) vs. 15 (P(25-75) 12.5-15.5)) and the one-year evaluation (15 (P(25-75) 13-17) vs. 13 (P(25-75) 11-15) vs. 12 (P(25-75) 10-14)) for the three educational levels, respectively, with statistically significant differences between levels (p=0.007 to p<0.001) except between low and medium-high education at one year (p=0.057). In the one-year evaluation, self-care behaviour significantly improved in the three educational groups (p<0.001), with a similar, albeit not statistically significant, magnitude of improvement in all groups. CONCLUSIONS: Self-care behaviour at baseline and one year after a nursing intervention was better in patients with a higher education, although the improvement with the intervention was similar irrespective of the educational level.

Effect of fragility on quality of life in patients with heart failure.

Heart failure (HF) is a chronic disease that frequently causes quality of life (QoL) impairment. We aimed to evaluate whether fragility affects QoL perception in outpatients with HF across age strata. The Minnesota Living with Heart Failure Questionnaire (MLWHFQ) was used to assess QoL, and fragility was defined according to basic standardized geriatric scales. Predefined criteria for such scales were scores of Barthel index <90, Older Americans' Resources and Services scale <10 in women and <6 in men, and Pfeiffer test >3 (±1 depending on educational grade) and ≥1 positive depression response on the abbreviated Geriatric Depression Scale. We evaluated 1,405 consecutive outpatients with HF (27.8% women, median age 69 years [twenty-fifth to seventy-fifth percentiles: 59 to 76 years]). Fragility, defined as at least 1 abnormal evaluation, was detected in 621 patients (44.2%). A positive depression response on the abbreviated Geriatric Depression Scale was the most prevalent (31.2%) component of fragility. We found a strong correlation between MLWHFQ score and the presence of fragility and all fragility components (all p <0.001). These associations prevailed in both younger (<75 years) and older patients (≥75 years; all p values <0.001 except for Pfeiffer test in younger patients [p = 0.007]). In multivariate regression analysis, QoL remained significantly associated with fragility after adjustment for age, gender, etiology of HF, left ventricular ejection fraction, New York Heart Association functional class, co-morbidities, and HF treatment, in both younger and older patients (p <0.001). In conclusion, MLWHFQ, a specific HF QoL questionnaire, is significantly influenced by fragility regardless of age.

Depression, antidepressants, and long-term mortality in heart failure.

BACKGROUND: This study was designed to assess whether depression and the use of antidepressants were related to long-term mortality in heart failure. METHODS: Heart failure outpatients (n=1017) from a specialized tertiary unit in Spain were prospectively studied for a median follow-up of 5.4 years (IQR 3.1-8.1). Depressive symptoms were assessed using an abbreviated version of the geriatric depression scale. Survival rates during the study period (August 2001 until December 2010) and hazard ratios (HR) for mortality were adjusted by several demographic and clinical variables. RESULTS: Depressive symptoms were detected in 302 patients (29.7%) at baseline and 222 (21.8%) de novo during follow-up; 304 patients (29.9%) received at least one prescription of antidepressants, mainly selective serotonin reuptake inhibitors (92.8%); 441 patients (43.4%) died. In a multivariate Cox proportional hazard model, depression was associated with an increased all-cause (HR, 1.39; 95% CI, 1.15-1.68), but not cardiovascular, mortality risk after adjustment for several demographic and clinical confounders. The use of any antidepressant was not independently associated with mortality (HR, 0.89; 95% CI, 0.71-1.13), but benzodiazepines showed a protective role (HR, 0.70; 95% CI, 0.57-0.87). On the contrary, fluoxetine prescriptions, but not duration of fluoxetine treatment, were associated with increased mortality (HR, 1.66; 95% CI, 1.13-2.44). CONCLUSIONS: Depressive symptoms are associated with long-term mortality, but the use of antidepressants and benzodiazepines is safe regarding survival in HF patients, although further research is needed considering individual antidepressants separately.

Quality of life monitoring in ambulatory heart failure patients: temporal changes and prognostic value.

AIMS: Heart failure (HF) is a chronic condition that typically affects a patient's quality of life (QoL). Little is known about long-term QoL monitoring in HF. This study aimed to evaluate the temporal changes and prognostic value of QoL assessment in a real-life cohort of HF patients. METHODS AND RESULTS: The Minnesota Living with Heart Failure Questionnaire was used to monitor QoL at baseline and at 1, 3, and 5 years for 1151 consecutive patients {71.7% men, median age 69 years [25th-75th percentiles (P(25)-P(75)) 59-76]} in an HF unit. Follow-up for prognosis assessment was extended to 6 years. The number of answered questionnaires was 1151 at baseline, 746 at 1 year, 268 at 3 years, and 240 at 5 years. QoL scores showed a steep decrease (indicating QoL improvement) during the first year [29 (P(25)-P(75) 16-43) at baseline vs. 15 (P(25)-P(75) 8-27) at 1 year, P < 0.001], which was tempered, yet significant up to 5 years [12 (P(25)-P(75) 7-23) at 3 years vs. 10 (P(25)-P(75) 5-21) at 5 years, P = 0.012]. We recorded 457 deaths during follow-up. In a comprehensive multivariable Cox regression analysis, baseline QoL remained a significant prognosticator during follow-up [hazard ratio (HR)(Cox) for death 1.012, 95% confidence interval 1.006-1.018, P < 0.001]. QoL monitoring showed that a score increase ≥10% between consecutive assessments stratified high-risk patients within the next 12 months (P = 0.008). CONCLUSION: Both baseline and follow-up QoL monitoring were useful for patient risk stratification in a real-life HF cohort. Worse QoL may warn of a worse prognosis. Widespread QoL monitoring in routine clinical practice is recommended.

Combined use of high-sensitivity ST2 and NTproBNP to improve the prediction of death in heart failure.

AIMS: To address the incremental usefulness of biomarkers from different disease pathways for predicting risk of death in heart failure (HF). METHODS AND RESULTS: We used data from consecutive patients treated at a structured multidisciplinary HF unit to investigate whether a combination of biomarkers reflecting ventricular fibrosis, remodelling, and stretch [ST2 and N-terminal pro brain natriuretic peptide (NTproBNP)] improved the risk stratification of a HF patient beyond an assessment based on established mortality risk factors (age, sex, ischaemic aetiology, left ventricular ejection fraction, New York Heart Association functional class, diabetes, glomerular filtration rate, sodium, haemoglobin, and beta-blocker and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatments). ST2 was measured with a novel high-sensitivity immunoassay. During a median follow-up time of 33.4 months, 244 of the 891 participants in the study (mean age 70.2 years at baseline) died. In the multivariable Cox proportional hazards model, both ST2 and NTproBNP significantly predicted the risk of death. The individual inclusion of ST2 and NTproBNP in the model with established mortality risk factors significantly improved the C statistic for predicting death [0.79 (0.76-0.81); P < 0.001]. The net improvement in reclassification after the separate addition of ST2 to the model with established risk factors and NTproBNP was estimated at 9.90% [95% confidence interval (CI) 4.34-15.46; P < 0.001] and the integrated discrimination improvement at 1.54 (95% CI 0.29-2.78); P = 0.015). CONCLUSIONS: Our data suggest that in a real-life cohort of HF patients, the addition of ST2 and NTproBNP substantially improves the risk stratification for death beyond that of a model that is based only on established mortality risk factors.

Mortality and cause of death in patients with heart failure: findings at a specialist multidisciplinary heart failure unit.

INTRODUCTION AND OBJECTIVES: Heart failure mortality is similar to or even higher than that due to various cancers. It is usually associated with disease progression, though sudden death has also been reported as a frequent cause of mortality. The objectives of this study were to investigate mortality and its causes in outpatients with heart failure of different etiologies who were treated in a specialist multidisciplinary unit, and to identify associated factors. METHODS: The follow-up cohort study (median duration 36 months) involved 960 patients (70.9% male; median age 69 years; ejection fraction 31%; and the majority had an ischemic etiology and were in functional class II or III). RESULTS: Overall, 351 deaths (36.5%) occurred: 230 due to cardiovascular causes (65.5%), mainly heart failure (33.2%) and sudden death (16%); 94 due to non-cardiovascular causes (26.8%), mainly malignancies (10.5%) and septic processes (6.8%); and 27 (7.7%) due to unknown causes. Mortality was independently associated with age, sex, functional class, ejection fraction, time since symptom onset, ischemic etiology, diabetes, creatinine clearance rate, peripheral vascular disease, fragility, and the absence of treatment with an angiotensin-converting enzyme inhibitor or angiotensin-II receptor blocker, beta-blockers, statins or antiplatelet agents. The principal factor associated with cardiovascular death was an ischemic etiology. No factor studied clearly predicted sudden death. CONCLUSIONS: Even though mortality in patients treated at a specialist heart failure unit was not low, a quarter died from non-cardiovascular causes. The principal factor associated with cardiovascular death was an ischemic etiology. Only 5.8% of the study population experienced sudden death.

Mortalidad y causas de muerte en pacientes con insuficiencia cardiaca: experiencia de una unidad especializada multidisciplinaria / Mortality and cause of death in patients with heart failure: findings at a specialist multidisciplinary heart failure unit

Introducción y objetivos. La mortalidad de la insuficiencia cardiaca es similar o incluso superior a la de muchos cánceres. Suele ocurrir por progresión de la enfermedad, aunque la muerte súbita se ha descrito como una causa frecuente. El objetivo es evaluar la mortalidad y sus causas en una población ambulatoria de pacientes con insuficiencia cardiaca de etiología diversa tratados en una unidad especializada multidisciplinaria y analizar los factores asociados con ellas. Métodos. Estudio de seguimiento de cohorte (mediana, 36 meses) de 960 pacientes (el 70,9% varones; mediana de edad, 69 años; mayoritariamente de etiología isquémica, con fracción de eyección del 31% y en clase funcional fundamentalmente II y III). Resultados. Se registraron 351 fallecimientos (36,5%): 230 de causa cardiovascular (65,5%), fundamentalmente por insuficiencia cardiaca (33,2%) y muerte súbita (16%), 94 de causa no cardiovascular (26,8%), fundamentalmente neoplasias (10,5%) y procesos sépticos (6,8%), y 27 (7,7%) de causa desconocida. Mostraron relación independiente con la mortalidad: edad, sexo, clase funcional, fracción de eyección, tiempo de evolución, etiología isquémica, diabetes mellitus, aclaramiento de creatinina, vasculopatía periférica, fragilidad y ausencia de tratamiento con inhibidores de la enzima de conversión de angiotensina o antagonistas de los receptores de la angiotensina II, bloqueadores beta, estatinas y antiagregantes. El factor principal asociado a muerte cardiovascular fue la etiología isquémica. No hallamos ningún factor predictor claramente determinante de muerte súbita. Conclusiones. Aunque la mortalidad de los pacientes atendidos en una unidad especializada de insuficiencia cardiaca no fue baja, una cuarta parte falleció de causa no cardiovascular. El principal factor asociado a muerte cardiovascular fue la etiología isquémica. La muerte súbita afectó sólo al 5,8% de la población (AU)

Introduction and objectives. Heart failure mortality is similar to or even higher than that due to various cancers. It is usually associated with disease progression, though sudden death has also been reported as a frequent cause of mortality. The objectives of this study were to investigate mortality and its causes in outpatients with heart failure of different etiologies who were treated in a specialist multidisciplinary unit, and to identify associated factors. Methods. The follow-up cohort study (median duration 36 months) involved 960 patients (70.9% male; median age 69 years; ejection fraction 31%; and the majority had an ischemic etiology and were in functional class II or III). Results. Overall, 351 deaths (36.5%) occurred: 230 due to cardiovascular causes (65.5%), mainly heart failure (33.2%) and sudden death (16%); 94 due to noncardiovascular causes (26.8%), mainly malignancies (10.5%) and septic processes (6.8%); and 27 (7.7%) due to unknown causes. Mortality was independently associated with age, sex, functional class, ejection fraction, time since symptom onset, ischemic etiology, diabetes, creatinine clearance rate, peripheral vascular disease, fragility, and the absence of treatment with an angiotensin-converting enzyme inhibitor or angiotensin-II receptor blocker, betablockers, statins or antiplatelet agents. The principal factor associated with cardiovascular death was an ischemic etiology. No factor studied clearly predicted sudden death. Conclusions. Even though mortality in patients treated at a specialist heart failure unit was not low, a quarter died from non-cardiovascular causes. The principal factor associated with cardiovascular death was an ischemic etiology. Only 5.8% of the study population experienced sudden death (AU)