Background and Design of the Biological and Physiological Mechanisms of Symptom Clusters in Heart Failure (BIOMES-HF) Study.

BACKGROUND: Symptoms, which often cluster together, are a significant problem in heart failure (HF). There is considerable heterogeneity in symptom burden, particularly in the vulnerable transition period after a hospitalization for HF, and the biological underpinnings of symptoms during transitions are unclear. The purpose of this article is to describe the background and design of a study that addresses these knowledge gaps, entitled Biological and Physiological Mechanisms of Symptom Clusters in Heart Failure (BIOMES-HF). METHODS AND RESULTS: BIOMES-HF is a prospective gender- and age-balanced longitudinal study of 240 adults during the 6-month transition period after a HF hospitalization. The aims are to (1) identify clusters of change in physical symptoms, (2) quantify longitudinal associations between biomarkers and physical symptoms, and (3) quantify longitudinal associations between physical frailty and physical symptoms among adults with HF. We will measure multiple symptoms, biomarkers, and physical frailty at discharge and then at 1 week and 1, 3, and 6 months after hospitalization. We will use growth mixture modeling and longitudinal mediation modeling to examine changes in symptoms, biomarkers, and physical frailty after HF hospitalization and associations therein. CONCLUSIONS: This innovative study will advance HF symptom science by using a multibiomarker panel and the physical frailty phenotype to capture the multifaceted nature of HF. Using advanced quantitative modeling, we will characterize heterogeneity and identify potential mechanisms of symptoms in HF. As a result, this research will pinpoint amenable targets for intervention to provide better, individualized treatment to improve symptom burden in HF. LAY SUMMARY: Adults with heart failure may have significant symptom burden. This study is designed to shed light on our understanding of the role of biological and physiological mechanisms in explaining heart failure symptoms, particularly groups of co-occurring symptoms, over time. We explore how symptoms, biomarkers, and physical frailty change after a heart failure hospitalization. The knowledge generated from this study will be used to guide the management and self-care for adults with heart failure.

Candidate biomarkers of physical frailty in heart failure: an exploratory cross-sectional study.

AIMS: Physical frailty is highly prevalent and predictive of worse outcomes in heart failure (HF). Candidate biomarker analysis may help in understanding the mechanisms underlying physical frailty in HF. We aimed to identify candidate biomarkers associated with physical frailty in HF using a multimarker strategy of distinct pathophysiological processes. METHODS AND RESULTS: We collected data and plasma samples from 113 adults with New York Heart Association Functional Class I-IV HF. Physical frailty was measured with the Frailty Phenotype Criteria. Plasma biomarkers included: N-terminal pro-B-type natriuretic peptide, norepinephrine, dihydroxyphenylglycol, soluble tumour necrosis factor alpha receptor-1, adiponectin, insulin, glucose, insulin-like growth factor-1 (IGF-1), and myostatin. Comparative statistics and multivariate linear regression were used to test group differences and associations. The average age was 63.5 ± 15.7 years, half were women (48%), and most had a non-ischaemic aetiology of HF (73%). Physical frailty was identified in 42% and associated with female sex, higher body mass index and percent body fat, more comorbidities, and HF with preserved ejection fraction. Adjusting for Seattle HF Model projected survival score, comorbidities, body composition, and sex, physical frailty was associated with significantly lower plasma adiponectin [ß ± standard error (SE) -0.28 ± 0.14, P = 0.047], IGF-1 (ß ± SE -0.21 ± 0.10, P = 0.032), and myostatin (ß ± SE -0.22 ± 0.09, P = 0.011). In sex-stratified analyses, IGF-1 and myostatin were significantly associated with physical frailty in men but not women. CONCLUSION: We identified biomarkers involved in adipose tissue and skeletal muscle development, maintenance, and function that were associated with physical frailty in HF.

Characterizing Sex Differences in Physical Frailty Phenotypes in Heart Failure.

BACKGROUND: Although women with heart failure (HF) are potentially more likely to be physically frail compared with men with HF, the underlying contributors to this sex difference are poorly understood. The purpose of this study was to characterize sex differences in physical frailty phenotypes in HF. METHODS: We prospectively enrolled adults with class I-IV HF. Physical frailty was measured with the frailty phenotype criteria. Symptoms of dyspnea, sleep-related impairment, pain interference, depression, and anxiety were assessed. Body composition was measured using dual-energy x-ray absorptiometry. Simple comparative statistics and stepwise regression modeling were used. RESULTS: The average age of the sample (n=115) was 63.6±15.7 years, 49% were women, and 73% had nonischemic cause. Forty-three percent of the sample was physically frail. Women had a 4.6 times greater odds of being physically frail compared with men, adjusting for covariates (odds ratio=4.63 [95% CI, 1.81-11.84], P=0.001). Both physically frail men and women were characterized by more type 2 diabetes, higher comorbidity burden, and worse dyspnea symptoms. Physically frail women had significantly worse symptoms compared with non-physically frail women but no difference in body composition characteristics. Physically frail men had significantly lower appendicular muscle mass, higher percent fat, lower hemoglobin, and more depressive symptoms compared with non-physically frail men. CONCLUSIONS: Women are significantly more likely to be physically frail compared with men in HF. Physical frailty in both women and men is characterized by comorbidities and worse symptoms; physical frailty in men is characterized by worse physiological characteristics.

Palliative care and decision making in advanced heart failure.

OPINION STATEMENT: The diagnosis of advanced heart failure (HF) is established in patients for whom symptoms are refractory to guideline-directed therapies. Palliative care (PC) is based on symptom management and support of the patient and family, making its integration into the care of those with advanced HF essential. Comorbidities including frailty, cognitive dysfunction, and depression are often under-recognized in patients with advanced HF and may correlate with outcomes. Decisions should be based on the patient's values, goals agreed upon by the clinician with the patient, and what is medically reasonable. Palliative Care should be integrated to help with both palliation of symptoms and support for families and patients.