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Introduction:There are a number of gender differences in heart failure (HF) care and outcomes; yet there remain gaps in our understanding of gender differences in HF symptoms. The aim of this study was to use propensity matching to examine gender differences in physical and depressive HF symptoms between women and men.Methods:Data from 6 studies of unique patients with NYHA Functional Class I-IV HF were combined. Across all studies, physical symptoms were measured with the HF Somatic Perception Scale (HFSPS; including two subscales - Early & Subtle and Dyspnea), and depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9). Using clinical and behavioral characteristics based on prior gender research in HF, a propensity score was derived for each participant. Then, nearest neighbor matching was performed to determine pairs of women and men with similar propensity scores and examined the average treatment effects (ATE) between genders on the symptom measures.Results:Nearest neighbor matching yielded 183 matched pairs (n = 366). The average age was 58 years. Common clinical characteristics were: non-ischemic etiology (66%), systolic HF (83%), hypertension (53%), Type II Diabetes (23%), and atrial fibrillation (43%). The average mean difference in symptom scores between women and men (ATE), is displayed in Table 1.Women reported lower scores on all symptom measures compared with men; however, this difference was not statistically significant.Conclusions:In this propensity matched sample of women and men with HF, there were no significant gender differences in physical and depressive symptom scores. Additional gender-balanced research is needed to elucidate nuances in symptom presentation among women with HF.

Introduction:Physical frailty is strongly related to adverse outcomes in heart failure (HF), including greater adverse clinical event risk and poor quality-of-life. In HF, women are more likely to be physically frail than men, but little is known about how this sex difference affects outcomes. The purpose of this study was to quantify sex differences in the associations between physical frailty and clinical and quality-of-life outcomes in HF.Methods:This was a prospective study of adults with NYHA Functional Class I-IV HF. A formal assessment of physical frailty was performed using the Frailty Phenotype Criteria; scores range from 0-5. Clinical characteristic data specific to the Seattle HF Model score (SHFM) were collected to account for the severity and treatment of HF. Clinical events (all-cause death, emergency room visit, or hospitalization for cardiovascular cause) over 12 months were adjudicated. Health-related quality-of-life was assessed using the Minnesota Living with HF Questionnaire (MLHFQ). Sex-stratified Cox regression analysis was used to examine associations between physical frailty and clinical events. Sex-stratified generalized linear modeling was used to examine associations between physical frailty and MLHFQ scores.Results:The sample (n = 115) was 63.5±15.7 years old, 49% women, and 29% had HF with preserved EF. After adjusting for SHFM scores, continuous physical frailty scores were significantly associated with time to first clinical event among men but not women. Specifically, for every one point increase in physical frailty score, there was a 46% higher risk of experiencing an event among men (HR = 1.46 [1.00, 2.11], p = 0.047) but not women (HR = 1.21 [0.81, 1.81], p = 0.36). After adjusting for SHFM scores, physical frailty was associated with 89% worse MLHFQ scores among women (p = 0.005) but was not significantly associated with MLHFQ scores among men (p = 0.14).Conclusions:This study demonstrates that physical frailty in HF may be predominantly associated with worse clinical event risk among men and worse quality-of-life among women.

Introduction:Physical frailty is highly prevalent and associated with worse outcomes among adults with heart failure (HF). However, the biological mechanisms underlying physical frailty in HF are poorly understood. The aim was to identify biomarkers associated with physical frailty in HF using a multimarker strategy to reflect multiple physiological processes.Hypothesis:We hypothesized that biomarkers of neurohormonal activation, inflammation, insulin resistance, and adipose and skeletal muscle dysfunction would differentiate physically frail from non-physically frail adults with HF.Methods:We collected data and plasma samples from adults with New York Heart Association Functional Class I-IV HF. Physical frailty was measured with the Frailty Phenotype Criteria. Plasma biomarkers assayed were: N-terminal pro-B-type natriuretic peptide, norepinephrine, dihydroxyphenolglycol, soluble tumor necrosis factor alpha receptor 1, adiponectin, insulin, glucose, insulin-like growth factor-1, and myostatin. Comparative statistics and multivariate linear regression were used.Results:The average age of the participants (n = 113) was 63.5±15.7 years, half (48%) were women, and most had a non-ischemic etiology of HF (73%). Physical frailty was identified in 42% of the sample and associated with female gender, higher body mass index, more comorbidities, and HF with preserved ejection fraction. After adjusting for Seattle HF Model projected survival scores, comorbidities, body mass index, and gender, those physically frail had significantly lower plasma adiponectin, lower insulin-like growth factor-1, and lower myostatin compared with those non-physically frail (all p< 0.05). There were no significant differences in other biomarkers between physical frailty groups.Conclusions:Biomarkers involved in adipose tissue and skeletal muscle development, maintenance, and function were significantly different between those physically frail and non-physically frail. Physical frailty in HF may be, in part, underpinned by dysfunctional peripheral processes involving the adipose tissue and skeletal muscle.

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