Longitudinal Effects of Left Ventricular Assist Device Implantation on Global and Domain-Specific Cognitive Function.

BACKGROUND: Left ventricular assist devices (LVADs) are a common treatment of advanced heart failure, but cognitive dysfunction, which is common in heart failure, could limit the ability to perform postimplantation LVAD care. Implantation of an LVAD has been associated with improved cerebral perfusion and may improve cognitive function post implantation. OBJECTIVE: The aim of this study was to quantify longitudinal change in cognitive function after LVAD implantation. METHODS: A secondary analysis of data on 101 adults was completed to evaluate cognitive function before implantation and again at 1, 3, and 6 months post implantation of an LVAD. Latent growth curve modeling was conducted to characterize change over time. Serial versions of the Montreal Cognitive Assessment were used to measure overall (total) cognitive function and function in 6 cognitive domains. RESULT: There was moderate, nonlinear improvement from preimplantation to 6 months post implantation in Montreal Cognitive Assessment total score (Hedges' g = 0.50) and in short-term memory (Hedges' g = 0.64). There also were small, nonlinear improvements in visuospatial ability, executive function, and attention from preimplantation to 6 months post implantation (Hedges' g = 0.20-0.28). The greatest improvements were observed in the first 3 months after implantation and were followed by smaller, sustained improvements or no additional significant change. CONCLUSIONS: Implantation of an LVAD is associated with significant, nonlinear improvement in short-term memory and global cognitive function, with the most significant improvements occurring in the first 3 months after implantation. Clinicians should anticipate improvements in cognitive function after LVAD implantation and modify postimplantation education to maximize effectiveness of LVAD self-care.

Heart Failure Symptom Biology in Response to Ventricular Assist Device Implantation.

BACKGROUND: We have a limited understanding of the biological underpinnings of symptoms in heart failure (HF), particularly in response to left ventricular assist device (LVAD) implantation. OBJECTIVE: The aim of this study was to quantify the degree to which symptoms and biomarkers change in parallel from before implantation through the first 6 months after LVAD implantation in advanced HF. METHODS: This was a prospective cohort study of 101 patients receiving an LVAD for the management of advanced HF. Data on symptoms (dyspnea, early and subtle symptoms [HF Somatic Perception Scale], pain severity [Brief Pain Inventory], wake disturbance [Epworth Sleepiness Scale], depression [Patient Health Questionnaire], and anxiety [Brief Symptom Inventory]) and peripheral biomarkers of myocardial stretch, systemic inflammation, and hypervolumetric mechanical stress were measured before implantation with a commercially available LVAD and again at 30, 90, and 180 days after LVAD implantation. Latent growth curve and parallel process modeling were used to describe changes in symptoms and biomarkers and the degree to which they change in parallel in response to LVAD implantation. RESULTS: In response to LVAD implantation, changes in myocardial stretch were closely associated with changes in early and subtle physical symptoms as well as depression, and changes in hypervolumetric stress were closely associated with changes in pain severity and wake disturbances. Changes in systemic inflammation were not closely associated with changes in physical or affective symptoms in response to LVAD implantation. CONCLUSIONS: These findings provide new insights into the many ways in which symptoms and biomarkers provide concordant or discordant information about LVAD response.

Depressive symptoms in couples living with heart failure: the role of congruent engagement in heart failure management.

OBJECTIVES: The life-threatening context of heart failure (HF), high variability of the illness and complexity of care place considerable demands on both the adult patient and his/her spouse. The current study examines the role of congruent engagement in HF management behaviors on the depressive symptoms of the couple living with HF. METHOD: A cross-sectional design was used to examine 60 couples living with HF. Multilevel modeling was used to examine partner and within-dyad effects of engagement in HF behaviors on depressive symptoms. RESULTS: Just over one quarter (27%) of couples had both members experiencing at least mild depressive symptoms. Controlling for stage of HF and one's own level of engagement, one's partner's level of engagement was significantly associated with one's level of depressive symptoms; higher levels of engagement by one's partner were associated with lower levels of depressive symptoms. Additionally, spouses had lower levels of depressive symptoms when they had similar levels of engagement to their partner with HF; spouses had higher levels of depressive symptoms when they had higher levels of engagement than their partner with HF. CONCLUSION: Findings confirm the importance of screening both members of the couple for depression and fostering collaboration within the couple.

Self-care Moderates the Relationship Between Symptoms and Health-Related Quality of Life in Heart Failure.

BACKGROUND: Physical symptoms and depression in heart failure (HF) are key drivers of health-related quality of life (HRQOL). Heart failure self-care behaviors are believed to influence how symptoms affect HRQOL. OBJECTIVE: The goal of this study was to determine if HF self-care behaviors moderate the relationships between physical and depressive symptoms and HRQOL. METHODS: In a cohort of adults with moderate to advanced HF, multivariate linear regression was used to evaluate the interaction between self-care behaviors (Self-care of HF index maintenance and management scales) and physical HF symptoms (HF Somatic Perception Scale) on emotional HRQOL (emotional dimension of Minnesota Living With HF Questionnaire). The interaction between self-care behaviors and depression (9-item Patient Health Questionnaire) was evaluated on physical HRQOL (physical dimension of Minnesota Living With HF Questionnaire). RESULTS: The mean age of the sample (N = 202) was 57 ± 13 years, 50% were women, and 61% had New York Heart Association class III or IV HF. Controlling for age, Seattle HF score, functional ability, and comorbidities, self-care maintenance and management moderated the relationship between physical HF symptoms and emotional HRQOL. Only self-care maintenance moderated the relationship between depression and physical HRQOL. CONCLUSION: In HF, HRQOL is dependent on both the severity of physical and depressive symptoms and the level of engagement in HF self-care behaviors. Future research should consider both self-care behaviors and symptoms when examining patient HRQOL.

Implant Strategy-Specific Changes in Symptoms in Response to Left Ventricular Assist Devices.

BACKGROUND: Although we know that the quality of life generally improves after left ventricular assist device (LVAD) implantation, we know little about how symptoms change in response to LVAD. METHODS: The purpose of this study was to compare the changes in symptoms between bridge and destination therapy patients as part of a prospective cohort study. Physical (dyspnea and wake disturbances) and affective symptoms (depression and anxiety) were measured before LVAD and at 1, 3, and 6 months after LVAD. Multiphase growth modeling was used to capture the 2 major phases of change: initial improvements between preimplant and 1 month after LVAD and subsequent improvements between 1 and 6 months after LVAD. RESULTS: The sample included 64 bridge and 22 destination therapy patients as the preimplant strategy. Destination patients had worse preimplant dyspnea and wake disturbances, and they experienced greater initial improvements in these symptoms compared with bridge patients (all P < .05); subsequent change in both symptoms were similar between groups (both P > .05). Destination patients had worse preimplant depression (P = .042) but experienced similar initial and subsequent improvements in depression in response to LVAD compared with bridge patients (both P > .05). Destination patients had similar preimplant anxiety (P = .279) but experienced less initial and greater subsequent improvements in anxiety after LVAD compared with bridge patients (both P < .05). CONCLUSION: There are many differences in the magnitude and timing of change in symptom responses to LVAD between bridge and destination therapy patients. Detailed information on changes in specific symptoms may better inform shared decision-making regarding LVAD.

Quality of Life, Depression, and Anxiety in Ventricular Assist Device Therapy: Longitudinal Outcomes for Patients and Family Caregivers.

BACKGROUND: Patients who receive ventricular assist device (VAD) therapy typically rely on informal caregivers (family members or friends) to assist them in managing their device. OBJECTIVE: The purpose of this study is to characterize changes in person-oriented outcomes (quality of life [QOL], depression, and anxiety) for VAD patients and their caregivers together from pre-implantation to 3 months post-implantation. METHODS: This was a formal interim analysis from an ongoing prospective study of VAD patients and caregivers (n = 41 dyads). Data on person-oriented outcomes (QOL: EuroQol 5 Dimensions Visual Analog Scale; depression: Patient Health Questionnaire-8; anxiety: Brief Symptom Inventory) were collected at 3 time points (just prior to implantation and at 1 and 3 months post-implantation). Trajectories of change for patients and caregivers on each measure were estimated using latent growth modeling with parallel processes. RESULTS: Patients' QOL improved significantly over time, whereas caregiver QOL worsened. Depression and anxiety also improved significantly among patients but did not change among caregivers. There was substantial variability in change on all outcomes for both patients and their caregivers. CONCLUSIONS: This is the first quantitative study of VAD patient-caregiver dyads in modern devices that describes change in person-oriented outcomes from pre-implantation to post-implantation. This work supports the need for future studies that account for the inherent relationships between patient and caregiver outcomes and examine variability in patient and caregiver responses to VAD therapy.

Cardiohepatic Interactions: Implications for Management in Advanced Heart Failure.

Liver disease is a common sequela of heart failure and can range from mild reversible liver injury to hepatic fibrosis and, in its most severe form, cardiac cirrhosis. Hepatic fibrosis and cirrhosis due to chronic heart failure have important implications for prognosis, medication management, mechanical circulatory support, and heart transplantation. This article reviews the current understanding of liver disease in heart failure and provides a framework for approaching liver disease in the advanced heart failure population.

Physical and psychological symptom biomechanics in moderate to advanced heart failure.

BACKGROUND: There is a common dissociation between objective measures and patient symptomatology in heart failure (HF). OBJECTIVE: The aim of this study was to explore the relationship between cardiac biomechanics and physical and psychological symptoms in adults with moderate to advanced HF. METHODS: We performed a secondary analysis of data from 2 studies of symptoms among adults with HF. Stepwise regression modeling was performed to examine the influence of cardiac biomechanics (left ventricular internal diastolic diameter, right atrial pressure [RAP], and cardiac index) on symptoms. RESULTS: The average age of the sample (n = 273) was 57 ± 16 years, 61% were men, and 61% had class III or IV HF. Left ventricular internal diastolic diameter (ß = 4.22 ± 1.63, P = .011), RAP (ß = 0.71 ± 0.28, P = .013), and cardiac index (ß = 7.11 ± 3.19, P = .028) were significantly associated with physical symptoms. Left ventricular internal diastolic diameter (ß = 0.10 ± 0.05, P = .038) and RAP (ß = 0.03 ± 0.01, P = .039) were significantly associated with anxiety. There were no significant biomechanical determinants of depression. CONCLUSION: Cardiac biomechanics were related to physical symptoms and anxiety, providing preliminary evidence of the biological underpinnings of symptomatology among adults with HF.

Symptom-Hemodynamic Mismatch and Heart Failure Event Risk.

BACKGROUND: Heart failure (HF) is a heterogeneous condition of both symptoms and hemodynamics. OBJECTIVE: The goals of this study were to identify distinct profiles among integrated data on physical and psychological symptoms and hemodynamics and quantify differences in 180-day event risk among observed profiles. METHODS: A secondary analysis of data collected during 2 prospective cohort studies by a single group of investigators was performed. Latent class mixture modeling was used to identify distinct symptom-hemodynamic profiles. Cox proportional hazards modeling was used to quantify difference in event risk (HF emergency visit, hospitalization, or death) among profiles. RESULTS: The mean age (n = 291) was 57 ± 13 years, 38% were female, and 61% had class III/IV HF. Three distinct symptom-hemodynamic profiles were identified: 17.9% of patients had concordant symptoms and hemodynamics (ie, moderate physical and psychological symptoms matched the comparatively good hemodynamic profile), 17.9% had severe symptoms and average hemodynamics, and 64.2% had poor hemodynamics and mild symptoms. Compared with those in the concordant profile, both profiles of symptom-hemodynamic mismatch were associated with a markedly increased event risk (severe symptoms hazards ratio, 3.38; P = .033; poor hemodynamics hazards ratio, 3.48; P = .016). CONCLUSIONS: A minority of adults with HF have concordant symptoms and hemodynamics. Either profile of symptom-hemodynamic mismatch in HF is associated with a greater risk of healthcare utilization for HF or death.

Gender-Specific Physical Symptom Biology in Heart Failure.

BACKGROUND: There are several gender differences that may help explain the link between biology and symptoms in heart failure (HF). OBJECTIVE: The aim of this study was to examine gender-specific relationships between objective measures of HF severity and physical symptoms. METHODS: Detailed clinical data, including left ventricular ejection fraction and left ventricular internal end-diastolic diameter, and HF-specific physical symptoms were collected as part of a prospective cohort study. Gender interaction terms were tested in linear regression models of physical symptoms. RESULTS: The sample (101 women and 101 men) averaged 57 years of age and most participants (60%) had class III/IV HF. Larger left ventricle size was associated with better physical symptoms for women and worse physical symptoms for men. CONCLUSION: Decreased ventricular compliance may result in worse physical HF symptoms for women and dilation of the ventricle may be a greater progenitor of symptoms for men with HF.

Comorbidity profiles and inpatient outcomes during hospitalization for heart failure: an analysis of the U.S. Nationwide inpatient sample.

BACKGROUND: Treatment of heart failure (HF) is particularly complex in the presence of comorbidities. We sought to identify and associate comorbidity profiles with inpatient outcomes during HF hospitalizations. METHODS: Latent mixture modeling was used to identify common profiles of comorbidities during adult hospitalizations for HF from the 2009 Nationwide Inpatient Sample (n = 192,327). RESULTS: Most discharges were characterized by "common" comorbidities. A "lifestyle" profile was characterized by a high prevalence of uncomplicated diabetes, hypertension, chronic pulmonary disorders and obesity. A "renal" profile had the highest prevalence of renal disease, complicated diabetes, and fluid and electrolyte imbalances. A "neurovascular" profile represented the highest prevalence of cerebrovascular disease, paralysis, myocardial infarction and peripheral vascular disease. Relative to the common profile, the lifestyle profile was associated with a 15% longer length of stay (LOS) and 12% greater cost, the renal profile was associated with a 30% higher risk of death, 27% longer LOS and 24% greater cost, and the neurovascular profile was associated with a 45% higher risk of death, 34% longer LOS and 37% greater cost (all p < 0.001). CONCLUSIONS: Comorbidity profiles are helpful in identifying adults at higher risk of death, longer length of stay, and accumulating greater costs during hospitalizations for HF.

Physical and psychological symptom profiling and event-free survival in adults with moderate to advanced heart failure.

UNLABELLED: : Heart failure (HF) is a heterogeneous symptomatic disorder. The goal of this study was to identify and link common profiles of physical and psychological symptoms to 1-year event-free survival in adults with moderate to advanced HF. METHODS: Multiple valid, reliable, and domain-specific measures were used to assess physical and psychological symptoms. Latent class mixture modeling was used to identify distinct symptom profiles. Associations between observed symptom profiles and 1-year event-free survival were quantified using Cox proportional hazards modeling. RESULTS: The mean age of the participants (n = 202) was 57 ± 13 years, 50% were men, and 60% had class III/IV HF. Three distinct profiles, mild (41.7%), moderate (30.2%), and severe (28.1%), that captured a gradient of both physical and psychological symptom burden were identified (P < .001 for all comparisons). Controlling for the Seattle HF Score, adults with the moderate symptom profile were 82% more likely (hazard ratio, 1.82; 95% confidence interval, 1.07-3.11; P = .028) and adults with the severe symptom profile were more than twice as likely (hazard ratio, 2.06; 95% confidence interval, 1.21-3.52; P = .001) to have a clinical event within 1 year than patients with the mild symptom profile. CONCLUSIONS: Profiling patterns among physical and psychological symptoms identifies HF patient subgroups with significantly worse 1-year event-free survival independent of prognostication based on objective clinical HF data.

Background and design of the profiling biobehavioral responses to mechanical support in advanced heart failure study.

BACKGROUND: Unexplained heterogeneity in response to ventricular assist device (VAD) implantation for the management of advanced heart failure impedes our ability to predict favorable outcomes, provide adequate patient and family education, and personalize monitoring and symptom management strategies. The purpose of this article was to describe the background and the design of a study entitled "Profiling Biobehavioral Responses to Mechanical Support in Advanced Heart Failure" (PREMISE). STUDY DESIGN AND METHODS: PREMISE is a prospective cohort study designed to (1) identify common and distinct trajectories of change in physical and psychological symptom burden; (2) characterize common trajectories of change in serum biomarkers of myocardial stress, systemic inflammation, and endothelial dysfunction; and (3) quantify associations between symptoms and biomarkers of pathogenesis in adults undergoing VAD implantation. Latent growth mixture modeling, including parallel process and cross-classification modeling, will be used to address the study aims and will entail identifying trajectories, quantifying associations between trajectories and both clinical and quality-of-life outcomes, and identifying predictors of favorable symptom and biomarker responses to VAD implantation. CONCLUSIONS: Research findings from the PREMISE study will be used to enhance shared patient and provider decision making and to shape a much-needed new breed of interventions and clinical management strategies that are tailored to differential symptom and pathogenic responses to VAD implantation.

Blunted responses to heart failure symptoms in adults with mild cognitive dysfunction.

INTRODUCTION: Mild cognitive dysfunction is common among adults with heart failure (HF). We hypothesized that mild cognitive dysfunction would be associated with poor HF self-care behaviors, particularly patients' ability to respond to symptoms. METHODS: We analyzed data on 148 participants in an observational study of symptoms in adults with moderate-to-advanced HF. Mild cognitive dysfunction was measured with the Montreal Cognitive Assessment (MoCA; range, 0-30), using cutoff scores for the general population (26) and for adults with cardiovascular disease (24). Heart failure self-care management (evaluation and response to HF symptoms) was measured with the Self-care of HF Index, and consulting behaviors (calling a provider when symptoms occur) were measured using the European HF Self-care Behavior Scale-9. Generalized linear modeling and hierarchical linear modeling were used to quantify the relationship between MoCA cutoff scores and indices of HF self-care. RESULTS: The mean age of the sample was 57 ± 12 years, 61.5% were men, and 58.8% had class III/IV HF; the mean left ventricular ejection fraction was 28% ± 12%. Using MoCA scores of 26 and 24, respectively, 33.1% and 14.2% of the sample had mild cognitive dysfunction. Controlling for common confounders, participants with MoCA scores lower than 26 reported self-care comparable with that of participants with MoCA scores of 26 or higher. Participants with MoCA scores lower than 24, however, reported 21.5% worse self-care management (P = 0.014) and 51% worse consulting behaviors (P < 0.001) compared with participants with MoCA scores of 24 or higher. CONCLUSIONS: A disease-specific cutoff for mild cognitive dysfunction reveals marked differences patients' ability to recognize and respond to HF symptoms when they occur. Adults with HF and mild cognitive dysfunction are a vulnerable patient group in great need of interventions that complement HF self-care.

Patterns and predictors of dyspnoea following left ventricular assist device implantation.

AIMS: Dyspnoea is a common symptom of heart failure (HF) that often prompts patients to seek treatment. Implantation of a left ventricular assist device (LVAD) has been associated with reduced dyspnoea but it is unclear if all patients experience similar improvements in dyspnoea over time following LVAD implantation. Our aim was to identify distinct trajectories of dyspnoea symptoms over time following LVAD implantation and predictors of dyspnoea trajectory. We hypothesized that at least two, distinct trajectories of dyspnoea would be observed following LVAD implantation. METHODS AND RESULTS: This was a secondary analysis of data from the Profiling Biobehavioral Responses to Mechanical Support in Advanced Heart Failure study. In the parent study, sociodemographic and clinical data were collected prior to LVAD implantation and at 1, 3, and 6 months following LVAD implantation from a sample (n = 101) of patients with advanced HF. Latent growth mixture modelling was performed to identify distinct trajectories of dyspnoea symptoms. Backwards stepwise logistic regression was used to identify predictors of dyspnoea trajectory. Two, distinct trajectories of dyspnoea symptoms were identified: sustained improvement and unsustained improvement. Participants who experienced sustained improvement (86.7% of sample) demonstrated large, significant improvement in dyspnoea from pre-implantation to 3 months post-implant followed by smaller, non-significant improvement from 3 to 6 months. Participants who experienced unsustained improvement (13.3% of sample) demonstrated initial improvement from pre-implantation to 3 months post-implantation followed by worsening of dyspnoea from 3 to 6 months. Greater depressive symptoms at baseline and living alone were significant predictors of unsustained improvement. CONCLUSION: Patients experience different patterns of dyspnoea over time following LVAD implantation. Clinicians should inquire about living arrangements and depressive symptoms at each visit to determine risk of unsustained improvement in dyspnoea.

Exploring gender differences in trajectories of clinical markers and symptoms after left ventricular assist device implantation.

AIMS: Despite well-known gender differences in heart failure, it is unknown if clinical markers and symptoms differ between women and men after left ventricular assist device (LVAD) implantation. Our aim was to examine gender differences in trajectories of clinical markers (echocardiographic markers and plasma biomarkers) and symptoms from pre- to post-LVAD implantation. METHODS AND RESULTS: This was a secondary analysis of data collected from a study of patients from pre- to 1, 3, and 6 months post-LVAD implantation. Data were collected on left ventricular internal end-diastolic diameter (LVIDd) and ejection fraction (LVEF), plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP), and soluble suppressor of tumorigenicity (sST2). Physical and depressive symptoms were measured using the Heart Failure Somatic Perception Scale and Patient Health Questionnaire-9, respectively. Latent growth curve modelling was used to compare trajectories between women and men. The average age of the sample (n = 98) was 53.3 ± 13.8 years, and most were male (80.6%) and had non-ischaemic aetiology (65.3%). Pre-implantation, women had significantly narrower LVIDd (P < 0.001) and worse physical symptoms (P = 0.041) compared with men. Between pre- and 6 months post-implantation, women had an increase in plasma sST2 followed by a decrease, whereas men had an overall decrease (slope: P = 0.014; quadratic: P = 0.011). Between 1 and 6 months post-implantation, women had a significantly greater increase in LVEF (P = 0.045) but lesser decline in plasmoa NT-proBNP compared with men (P = 0.025). CONCLUSION: Trajectories of clinical markers differed somewhat between women and men, but trajectories of symptoms were similar, indicating some physiologic but not symptomatic gender differences in response to LVAD.

Cross-classification of physical and affective symptom clusters and 180-day event-free survival in moderate to advanced heart failure.

BACKGROUND: The relationship between physical and affective symptom clusters in heart failure (HF) is unclear. OBJECTIVES: To identify associations between physical and affective symptom clusters in HF and to quantify outcomes and determinants of symptom subgroups. METHODS: This was a secondary analysis of data from two cohort studies among adults with HF. Physical and affective symptom clusters were compared using cross-classification modeling. Cox proportional hazards modeling and multinomial logistic regression were used to identify outcomes and determinants of symptom subgroups, respectively. RESULTS: In this young, mostly male sample (n = 274), physical and affective symptom clusters were cross-classified in a model with acceptable fit. Three symptom subgroups were identified: congruent-mild (69.3%), incongruent (13.9%), and congruent-severe (16.8%). Compared to the congruent-mild symptom group, the incongruent symptom group had significantly worse 180-day event-free survival. CONCLUSION: Congruence between physical and affective symptom clusters should be considered when identifying patients at higher risk for poor outcomes.

Device-detected congestion is associated with worse patient-reported outcomes in heart failure.

BACKGROUND: Congestion is a common cause of symptoms in heart failure (HF). Yet, intrathoracic impedance, an objective marker of cardiopulmonary congestion, has not been examined in relation to HF symptoms. OBJECTIVE: To determine whether device-detected cardiopulmonary congestion is a predictor of physical and psychological symptoms and health-related quality of life (HRQOL) in adults with HF over 3 months. METHODS: Multivariate generalized linear modeling was used to quantify the association of cardiopulmonary congestion (Optivol® Index exceeding 60 Ω threshold) with HRQOL (12-item Kansas City Cardiomyopathy Questionnaire) and both physical symptoms (Functional Assessment of Chronic Illness Therapy-Fatigue Scale; HF Somatic Perception Scale Dyspnea and Early & Subtle Symptoms subscales) and affective symptoms (9-item Patient Health Questionnaire; 6-item Patient-Reported Outcomes Measurement Information System Anxiety Scale). RESULTS: The mean age of the sample (n = 49) was 62years old, 39% were women, and 63% had NYHA class III/IV HF. Participants who experienced threshold crossings in the previous 90days reported on average, 130% higher dyspnea (p = 0.017; confidence interval (CI) 10.2%, 437%), 40% higher early & subtle symptoms (p = 0.029; CI 3.4%, 89.7%), 106% higher depressive symptoms (p = 0.003; CI 19.1%, 257%) and 40% higher anxiety (p = 0.028; CI 3.7%, 89.1%). Threshold crossings in the previous 90days were also significantly associated with a clinically meaningful decrease in HRQOL (ß = -16.16 ±â€¯6.32; p = 0.01). CONCLUSIONS: Intrathoracic impedance measured with the Optivol Index can provide additional information regarding the patient experience of hallmark physical and psychological HF symptoms and HRQOL over 3months.

The role of estrogen, immune function and aging in heart transplant outcomes.

BACKGROUND: Aging and loss of estrogen suppress immune function, potentially improving survival after orthotopic heart transplant (OHT). The effect of female aging on OHT outcomes is unknown. METHODS: Between 1995 and 2015, 41,299 adult OHT recipients (24.3% women) were studied using a retrospective multi-institutional cohort. Patients were stratified by age and gender into premenopausal (18-39 years), perimenopausal (40-49 years), and postmenopausal (≥50 years) groups. Kaplan-Meier survival analyses and risk-adjusted models examined gender differences across groups at one, five, and ten years. RESULTS: Kaplan-Meier survival was equivalent for postmenopausal women and men, and lower for premenopausal women than men at all time points (p ≤ 0.05). Postmenopausal women had higher risk-adjusted five-year survival than premenopausal women (AOR 1.61, 95% CI 1.15-2.25, p = 0.006). CONCLUSIONS: Premenopausal women have lower unadjusted survival than men after OHT. Post-menopausal women have significantly better five-year survival than pre-menopausal women. Menopause may contribute to improved survival after OHT.

Development and Initial Validation of the PROMIS®-Plus-HF Profile Measure.

Background Bringing together generic and heart failure (HF)-specific items in a publicly available, patient-reported outcome measure may facilitate routine health status assessment for improving clinical care and shared decision-making, assessing quality of care, evaluating new interventions, and comparing groups with different conditions. Methods and Results We performed a mixed-methods study to develop and validate the PROMIS®-Plus-HF (Patient-Reported Outcomes Measurement Information System®-Plus-Heart Failure) profile measure-a HF-specific instrument based on the generic PROMIS. We conducted 8 focus groups with 61 patients with HF and phone interviews with 10 HF clinicians. The measure was developed via an iterative process of reviewing existing PROMIS items and developing and testing new HF items. In a 600-patient sample, we estimated reliability (internal consistency; test-retest, with n=100 participants). We conducted validity analyses using Pearson r and Spearman ρ correlations with Kansas City Cardiomyopathy Questionnaire subscores. In a longitudinal sample, we performed responsiveness testing (paired t tests) with 75 patients with HF receiving interventions with expected health status improvement. The PROMIS-Plus-HF measure comprises 86 items (64 existing; 22 new) across 18 domains. Internal consistency reliability (Cronbach α) coefficients ranged from 0.52 to 0.96, with α≥0.70 in 12 of 17 domains. Test-retest intraclass correlation coefficients were ≥0.90. Correlations with Kansas City Cardiomyopathy Questionnaire subscores supported expected convergent ( r/ρ>0.60) and divergent validity ( r/ρ<0.30). In the longitudinal sample, 10 of 18 domains had improved ( P<0.05) scores from baseline to follow-up. Conclusions The PROMIS-Plus-HF profile measure-a complete assessment of physical, mental, and social health-exhibited good psychometric characteristics and may facilitate patient-centered care and research. Subsets of domains and items can be used depending on the clinical or research purpose.