Socioeconomic and partner status in chronic heart failure: Relationship to exercise capacity, quality of life, and clinical outcomes.

BACKGROUND: Prognosis in patients with heart failure (HF) is commonly assessed based on clinical characteristics. The association between partner status and socioeconomic status (SES) and outcomes in chronic HF requires further study. METHODS: We performed a post hoc analysis of HF-ACTION, which randomized 2,331 HF patients with ejection fraction ≤35% to usual care ± aerobic exercise training. We examined baseline quality of life and functional capacity and outcomes (all-cause mortality/hospitalization) by partner status and SES using adjusted Cox models and explored an interaction with exercise training. Outcomes were examined based on partner status, education level, annual income, and employment. RESULTS: Having a partner, education beyond high school, an income >$25,000, and being employed were associated with better baseline functional capacity and quality of life. Over a median follow-up of 2.5 years, higher education, higher income, being employed, and having a partner were associated with lower all-cause mortality/hospitalization. After multivariable adjustment, lower mortality was seen associated with having a partner (hazard ratio 0.91, 95% CI 0.81-1.03, P=.15) and more than a high school education (hazard ratio 0.91, CI 0.80-1.02, P=.12), although these associations were not statistically significant. There was no interaction between any of these variables and exercise training on outcomes (all P>.5). CONCLUSIONS: Having a partner and higher SES were associated with greater functional capacity and quality of life at baseline but were not independent predictors of long-term clinical outcomes in patients with chronic HF. These findings provide information that may be considered as potential variables impacting outcomes.

Blocking of targeted microRNAs from next-generation sequencing libraries.

Highly abundant microRNAs (miRNAs) in small RNA sequencing libraries make it difficult to obtain efficient measurements of more lowly expressed species. We present a new method that allows for the selective blocking of specific, abundant miRNAs during preparation of sequencing libraries. This technique is specific with little off-target effects and has no impact on the reproducibility of the measurement of non-targeted species. In human plasma samples, we demonstrate that blocking of highly abundant hsa-miR-16-5p leads to improved detection of lowly expressed miRNAs and more precise measurement of differential expression overall. Furthermore, we establish the ability to target a second abundant miRNA and to multiplex the blocking of two miRNAs simultaneously. For small RNA sequencing, this technique could fill a similar role as do ribosomal or globin removal technologies in messenger RNA sequencing.

Race, exercise training, and outcomes in chronic heart failure: findings from Heart Failure - a Controlled Trial Investigating Outcomes in Exercise TraiNing (HF-ACTION).

BACKGROUND: The strength of race as an independent predictor of long-term outcomes in a contemporary chronic heart failure (HF) population and its association with exercise training response have not been well established. We aimed to investigate the association between race and outcomes and to explore interactions with exercise training in patients with ambulatory HF. METHODS: We performed an analysis of HF-ACTION, which randomized 2331 patients with HF having an ejection fraction ≤35% to usual care with or without exercise training. We examined characteristics and outcomes (mortality/hospitalization, mortality, and cardiovascular mortality/HF hospitalization) by race using adjusted Cox models and explored an interaction with exercise training. RESULTS: There were 749 self-identified black patients (33%). Blacks were younger with significantly more hypertension and diabetes, less ischemic etiology, and lower socioeconomic status versus whites. Blacks had shorter 6-minute walk distance and lower peak VO2 at baseline. Over a median follow-up of 2.5 years, black race was associated with increased risk for all outcomes except mortality. After multivariable adjustment, black race was associated with increased mortality/hospitalization (hazard ratio [HR] 1.16, 95% CI 1.01-1.33) and cardiovascular mortality/HF hospitalization (HR 1.46, 95% CI 1.20-1.77). The hazard associated with black race was largely caused by increased HF hospitalization (HR 1.58, 95% CI 1.27-1.96), given similar cardiovascular mortality. There was no interaction between race and exercise training on outcomes (P > .5). CONCLUSIONS: Black race in patients with chronic HF was associated with increased prevalence of modifiable risk factors, lower exercise performance, and increased HF hospitalization, but not increased mortality or a differential response to exercise training.

Issues for recruitment and retention of clinical research professionals at academic medical centers: Part 1 - collaborative conversations Un-Meeting findings.

Background: Identification of evidence-based factors related to status of the clinical research professional (CRP) workforce at academic medical centers (AMCs) will provide context for National Center for Advancing Translational Science (NCATS) policy considerations and guidance. The objective of this study is to explore barriers and opportunities related to the recruitment and retention of the CRP workforce. Materials and Methods: Qualitative data from a series of Un-Meeting breakout sessions and open-text survey questions were analyzed to explore barriers and recommendations for improving AMC CRP recruitment, retention and diversity. Results: While certain institutions have established competency-based frameworks for job descriptions, standardization remains generally lacking across CTSAs. AMCs report substantial increases in unfilled CRP positions leading to operational instability. Data confirmed an urgent need for closing gaps in CRP workforce at AMCs, especially for attracting, training, retaining, and diversifying qualified personnel. Improved collaboration with human resource departments, engagement with principal investigators, and overcoming both organizational and resource challenges were suggested strategies, as well as development of outreach to universities, community colleges, and high schools raising awareness of CRP career pathways. Discussion: Based on input from 130 CRP leaders at 35 CTSAs, four National Institute of General Medical Sciences' Institutional Development Award (IDeA) program sites, along with industry and government representatives, we identified several barriers to successful recruitment and retention of a highly trained and diverse CRP workforce. Results, including securing institutional support, champions, standardizing and adopting proven national models, improving local institutional policies to facilitate CRP hiring and job progression point to potential solutions.

The relationship between body mass index and cardiopulmonary exercise testing in chronic systolic heart failure.

BACKGROUND: Cardiopulmonary exercise testing (CPX) in patients with systolic heart failure (HF) is important for determining HF prognosis and helping guide timing of heart transplantation. Although approximately 20% to 30% of patients with HF are obese (body mass index [BMI] >30 kg/m(2)), the impact of BMI on CPX results is not well established. The objective of this study was to assess the relationship between BMI and CPX variables, including peak oxygen uptake (VO(2)) at ventilatory threshold, oxygen pulse, and ventilation-carbon dioxide production ratio. METHODS: Consecutive patients with systolic HF (n = 2,324) enrolled in the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training trial who had baseline BMI recorded were included in this study. Subjects were divided into strata based on BMI: underweight (BMI <18.5 kg/m(2)), normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9 kg/m(2)), obese I (BMI 30-34.9 kg/m(2)), obese II (BMI 35-39.9 kg/m(2)), and obese III (BMI > or = 40 kg/m(2)). RESULTS: Obese III, but not overweight; obese I; or obese II was associated with decreased peak VO(2) (mL kg(-1) min(-1)) compared to normal weight status. Increasing BMI category was inversely related to ventilation/carbon dioxide production (V(E)/V(CO2)) ratio (P < .0001). On multivariable analysis, BMI was a significant independent predictor of peak VO(2) (partial R(2) = 0.07, P < .0001) and V(E)/V(CO2) slope (partial R(2) = 0.03, P < .0001) in patients with chronic systolic HF. CONCLUSIONS: Body mass index is significantly associated with key CPX fitness variables in patients with HF. The influence of BMI on the prognostic value of CPX in HF requires further evaluation in longitudinal studies.

Baseline differences in the HF-ACTION trial by sex.

BACKGROUND: In patients with heart failure (HF), assessment of functional capacity plays an important prognostic role. Both 6-minute walk and cardiopulmonary exercise testing have been used to determine physical function and to determine prognosis and even listing for transplantation. However, as in HF trials, the number of women reported has been small, and the cutoffs for transplantation have been representative of male populations and extrapolated to women. It is also well known that peak VO(2) as a determinant of fitness is inherently lower in women than in men and potentially much lower in the presence of HF. Values for a female population from which to draw for this important determination are lacking. METHODS: The HF-ACTION trial randomized 2,331 patients (28% women) with New York Heart Association class II-IV HF due to systolic dysfunction to either a formal exercise program in addition to optimal medical therapy or to optimal medical therapy alone without any formal exercise training. To characterize differences between men and women in the interpretation of final cardiopulmonary exercise testing models, the interaction of individual covariates with sex was investigated in the models of (1) VE/VCO(2), (2) VO(2) at ventilatory threshold (VT), (3) distance on the 6-minute walk, and (4) peak VO(2). RESULTS: The women were younger than the men and more likely to have a nonischemic etiology and a higher ejection fraction. Dose of angiotensin converting enzyme inhibitor (ACEI) was lower in the women, on average. The lower ACEI dose may reflect the higher use of angiotensin II receptor blocker (ARB) in women. Both the peak VO(2) and the 6-minute walk distance were significantly lower in the women than in the men. Perhaps the most significant finding in this dataset of baseline characteristics is that the peak VO(2) for women was significantly lower than that for men with similar ventricular function and health status. CONCLUSION: Therefore, in a well-medicated, stable, class II-IV HF cohort of patients who are able to exercise, women have statistically significantly lower peak VO(2) and 6-minute walk distance than men with similar health status and ventricular function. These data should prompt careful thought when considering prognostic markers for women and listing for cardiac transplant.

Discovery and Validation of Circulating Biomarkers of Colorectal Adenoma by High-Depth Small RNA Sequencing.

Purpose: Colorectal cancer is the third most common cancer worldwide, causing approximately 700,000 deaths each year. The majority of colorectal cancers begin as adenomas. Definitive screening for colorectal adenomas is currently accomplished through colonoscopy but, owing largely to costs and invasiveness, is typically limited to patient groups at higher risk by virtue of age or family history. We sought to determine if blood-based small RNA markers could detect colorectal adenoma.Experimental Design: We applied high-depth small RNA sequencing to plasma from a large (n = 189) cohort of patients, balanced for age, sex, and ancestry. Our analytical methodology allowed for the detection of both microRNAs and other small RNA species. We replicated sequencing results by qPCR on plasma samples from an independent cohort (n = 140).Results: We found several small RNA species with significant associations to colorectal adenoma, including both microRNAs and non-microRNA small RNAs. These associations were robust to correction for patient covariates, including age. Among the adenoma-associated small RNAs, two, a miR-335-5p isoform and an un-annotated small RNA, were validated by qPCR in an independent cohort. A classifier trained on measures of these two RNAs in the discovery cohort yields an AUC of 0.755 (0.775 with age) for adenoma detection in the independent cohort. This classifier accurately detects adenomas in patients under 50 and is robust to sex or ancestry.Conclusions: Circulating small RNAs (including but not limited to miRNAs) discovered by sequencing and validated by qPCR identify patients with colorectal adenomas effectively. Clin Cancer Res; 24(9); 2092-9. ©2018 AACR.