Efficient measurement of multiple ventricular assist device patient-reported outcomes: Creation of a 20-item profile from the MCS A-QOL study.

BACKGROUND: Patient-reported outcome (PRO) measures of distinct concepts are often put together into patient profile assessments. When brief, profile assessments can decrease respondent burden and increase measure completion rates. In this report, we describe the creation of 5 self-reported 4-item short forms and the Mechanical Circulatory Support: Measures of Adjustment and Quality of Life (MCS A-QOL) 20-item profile to assess PROs specific to adjustment and health-related quality of life (HRQOL) among patients who undergo left ventricular assist device (LVAD) implantation. METHODS: Using a cross-sectional sample of patients (n = 620) who underwent LVAD implantation at 12 U.S. sites or participated in the MyLVAD.com support group, we created 5 4-item short forms: Satisfaction with Treatment, ventricular assist device (VAD) Team Communication, Being Bothered by VAD Self-care and Limitations, Self-efficacy Regarding VAD self-care, and Stigma, which we combined into a 20-item profile. Analyses included intercorrelations among measures, Cronbach's alpha (i.e., internal consistency reliability)/score-level-specific reliability, and construct validity. RESULTS: The 620 patients were mean age = 57 years, 78% male, 70% White, and 56% on destination therapy LVADs. Intercorrelations among the 5 4-item measures were low to moderate (≤0.50), indicating they are associated yet largely distinct, and correlations with calibrated measures and 6-item short forms were ≥0.76, indicating their ability to reflect full-item bank scores. Internal consistency reliability for the 5 4-item short forms ranged from acceptable (≥0.70) to good (≥0.80). Construct validity was demonstrated for these measures. CONCLUSIONS: Our 5 4-item short forms are reliable and valid and may be used individually or together as a 20-item profile to assess adjustment and HRQOL in patients who undergo LVAD implantation.

The Association of Unmet Palliative Care Needs and Physical Frailty With Clinical Outcomes: A Prospective Study of Adults With Heart Failure.

BACKGROUND: People with heart failure, particularly those who are physically frail, experience complex needs that can be addressed by palliative care (PC). However, we have a limited understanding of how the intersection of unmet PC needs and physical frailty contributes to health-related quality of life (HRQOL) and risk for hospitalization or mortality. OBJECTIVE: In this study, we sought to examine the association of unmet PC needs and physical frailty with clinical outcomes (baseline HRQOL and hospitalizations or mortality at 6 months). METHODS: We recruited a convenience sample of community-dwelling persons with heart failure from an urban hospital system who were older than 50 years and hospitalized in the last year. We measured physical frailty using the FRAIL scale (nonfrail, 0-2; frail, 3-5), PC needs using the Integrated Palliative Outcome Scale (range, 0-58; higher scores indicating higher needs), and HRQOL using the Kansas City Cardiomyopathy Questionnaire (range, 0-100; higher scores indicate higher HRQOL). We performed multivariable linear regression to test the relationships between physical frailty, PC needs, and HRQOL, and multivariable logistic regression for associations with all-cause 6-month hospitalization or mortality. We also performed an exploratory analysis of 4 PC needs/frailty groups (high PC needs/frail, high PC needs/nonfrail, low PC needs/frail, low PC needs/nonfrail) with outcomes. RESULTS: In our overall sample (n = 298), mean (SD) age was 68 (9.8) years, 37% were women (n = 108), 28% identified as Black/African American (n = 84), and 65% had heart failure with preserved ejection fraction (n = 194). Mean PC needs score was 19.7, and frail participants (n = 130, 44%) had a significantly higher mean PC needs score than nonfrail participants (P < .001). Those with higher PC needs (Integrated Palliative Care Outcome Scale ≥ 20) had significantly worse HRQOL (P < .001) and increased odds of hospitalization or mortality (odds ratio, 2.5; P < .01) compared with those with lower PC needs, adjusting for covariates. Physically frail participants had significantly worse HRQOL (P < .001) and higher odds of hospitalization or mortality at 6 months (odds ratio, 2.6; P < .01) than nonfrail participants, adjusting for covariates. In an exploratory analysis, physically frail participants with high PC needs had the lowest HRQOL score, with an average score of 28.6 points lower (P < .001) and 4.6 times higher odds of hospitalization or mortality (95% confidence interval, 2.03-10.43; P < .001) than low-needs/nonfrail participants. CONCLUSION: Higher unmet PC needs and physical frailty, separately and in combination, were associated with lower HRQOL and higher odds of hospitalization or mortality. Self-reported PC needs and physical frailty assessment in clinical settings may improve identification of patients at the highest risk for poor HRQOL and hospitalization or mortality amenable to PC intervention.

Sympathetic dysfunction is associated with worse fatigue and early and subtle symptoms in heart failure: an exploratory sex-stratified analysis.

AIMS: Physical symptoms impact patients with heart failure (HF) despite treatment advancements; however, our understanding of the pathogenic mechanisms underlying HF symptoms remains limited, including sex differences therein. The objective of this study was to quantify associations between sympathetic markers [norepinephrine (NE) and 3,4-dihydroxyphenylglycol (DHPG)] and physical symptoms in patients with HF and to explore sex differences in these associations. METHODS AND RESULTS: We performed a secondary analysis of combined data from two studies: outpatients with HF (n = 111), and patients prior to left ventricular assist device implantation (n = 38). Physical symptoms were measured with the Heart Failure Somatic Perception Scale (HFSPS) dyspnoea and early/subtle symptom subscales and the Functional Assessment in Chronic Illness Therapy Fatigue Scale (FACIT-F) to capture dyspnoea, early symptoms of decompensation, and fatigue. Norepinephrine and DHPG were measured with high-performance liquid chromatography with electrochemical detection. Multivariate linear regression was used to quantify associations between symptoms and sympathetic markers. The sample (n = 149) was 60.8 ± 15.7 years, 41% women, and 71% non-ischaemic aetiology. Increased plasma NE and NE:DHPG ratio were associated with worse FACIT-F scores (P = 0.043 and P = 0.013, respectively). Increased plasma NE:DHPG ratio was associated with worse HFSPS early/subtle symptoms (P = 0.025). In sex-stratified analyses, increased NE:DHPG ratio was associated with worse FACIT-F scores (P = 0.011) and HFSPS early/subtle scores (P = 0.022) among women but not men. CONCLUSION: In patients with HF, sympathetic dysfunction is associated with worse fatigue and early/subtle physical symptoms with associations stronger in women than men.

Incorporating reproductive system history data into cardiovascular nursing research to advance women's health.

The lack of sex-specific variables, such as reproductive system history (RSH), in cardiovascular research studies is a missed opportunity to address the cardiovascular disease (CVD) burden, especially among women who face sex-specific risks of developing CVD. Collecting RSH data from women enrolled in research studies is an important step towards improving women's cardiovascular health. In this paper, we describe two approaches to collecting RSH in CVD research: extracting RSH from the medical record and participant self-report of RSH. We provide specific examples from our own research and address common data management and statistical analysis problems when dealing with RSH data in research.

Novel measures to assess ventricular assist device patient-reported outcomes: Findings from the MCS A-QOL study.

BACKGROUND: Generic and heart failure-specific measures do not capture unique aspects of living with a ventricular assist device (VAD). Using state-of-the-science psychometric measurement methods, we developed a measurement system to assess post-ventricular assist device adjustment and health-related quality of life (HRQOL). METHODS: Patients were recruited from 10/26/16-2/29/20 from 12 U.S. VAD programs. We created a dataset of participants (n = 620) enrolled before left (L)VAD implantation, with data at 3- or 6- months post-implantation (group1 [n = 154]), and participants enrolled after LVAD implantation, with data at one timepoint (group 2 [n = 466]). We constructed 5 item banks: 3 modified from existing measures and 2 new measures. Analyses included item response theory (IRT) modeling, differential item functioning tests for systematic measurement bias, and indicators of reliability and validity. RESULTS: Of 620 participants, 56% (n = 345) were implanted as destination therapy, 51% (n = 316) were <12 months post-implantation, mean age = 57.3 years, 78% (n = 485) male, 70% (n = 433) White, 58% (n = 353) married/partnered, and 58% (n = 357) with >high school education. We developed 5 new VAD item banks/measures: 6-item VAD Team Communication; 12-item Self-efficacy Regarding VAD Self-care; 11-item Being Bothered by VAD Self-care and Limitations; 7-item Satisfaction with Treatment; and 11-item Stigma. Cronbach's alpha reliability ranged from good (≥0.80) to excellent (≥0.90) for item banks/measures. All measures, except VAD Team Communication, demonstrated at least moderate correlations (≥0.30) with construct validity indicators. CONCLUSIONS: These measures meet IRT modeling assumptions and requirements; scores demonstrate reliability and validity. Use of these measures may assist VAD clinicians to inform patients about VADs as a treatment option and guide post-VAD interventions.

Guidelines on the use of sex and gender in cardiovascular research.

In cardiovascular research, sex and gender have not typically been considered in research design and reporting until recently. This has resulted in clinical research findings from which not only all women, but also gender-diverse individuals have been excluded. The resulting dearth of data has led to a lack of sex- and gender-specific clinical guidelines and raises serious questions about evidence-based care. Basic research has also excluded considerations of sex. Including sex and/or gender as research variables not only has the potential to improve the health of society overall now, but it also provides a foundation of knowledge on which to build future advances. The goal of this guidelines article is to provide advice on best practices to include sex and gender considerations in study design, as well as data collection, analysis, and interpretation to optimally establish rigor and reproducibility needed to inform clinical decision-making and improve outcomes. In cardiovascular physiology, incorporating sex and gender is a necessary component when optimally designing and executing research plans. The guidelines serve as the first guidance on how to include sex and gender in cardiovascular research. We provide here a beginning path toward achieving this goal and improve the ability of the research community to interpret results through a sex and gender lens to enable comparison across studies and laboratories, resulting in better health for all.

Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement.

Frailty is increasingly recognized as a salient condition in patients with heart failure (HF) as previous studies have determined that frailty is highly prevalent and prognostically significant, particularly in those with advanced HF. Definitions of frailty have included a variety of domains, including physical performance, sarcopenia, disability, comorbidity, and cognitive and psychological impairments, many of which are common in advanced HF. Multiple groups have recently recommended incorporating frailty assessments into clinical practice and research studies, indicating the need to standardize the definition and measurement of frailty in advanced HF. Therefore, the purpose of this consensus statement is to provide an integrated perspective on the definition of frailty in advanced HF and to generate a consensus on how to assess and manage frailty. We convened a group of HF clinicians and researchers who have expertise in frailty and related geriatric conditions in HF, and we focused on the patient with advanced HF. Herein, we provide an overview of frailty and how it has been applied in advanced HF (including potential mechanisms), present a definition of frailty, generate suggested assessments of frailty, provide guidance to differentiate frailty and related terms, and describe the assessment and management in advanced HF, including with surgical and nonsurgical interventions. We conclude by outlining critical evidence gaps, areas for future research, and clinical implementation.

Are Physical and Depressive Symptoms Different Between Women and Men With Heart Failure?: An Exploration Using Two Analytic Techniques.

BACKGROUND: Adults with heart failure (HF) experience a constellation of symptoms; however, understanding of gender differences in HF symptoms remain elusive. The aim of this study was to determine whether there are gender differences in physical and depressive symptoms and symptom patterns in HF using 2 different analytic techniques. METHODS: We performed a secondary analysis of combined data from 6 studies of adults with HF. Physical symptoms were measured with the HF Somatic Perception Scale, and depressive symptoms were measured with the Patient Health Questionnaire-9. First, we performed propensity matching with the nearest neighbor to examine the average treatment effect for HF Somatic Perception Scale and Patient Health Questionnaire-9 in the matched sample of women and men. Next, we used the entire data set in a latent class mixture model to determine patterns of symptoms. Finally, we calculated predictors of class membership with multinomial logistic regression. RESULTS: The sample (n = 524, 86.5% systolic HF) was 37% women with a mean age of 58.3 ± 13.9 years and mean number of years with HF of 6.9 ± 6.9. Three hundred sixty-six participants were matched on propensity scores; there were no significant gender differences in symptom scores between matched women (n = 183) and men (n = 183). Among all 524 participants, 4 distinct latent classes of symptom patterns indicate that many patients with HF are fatigued, some have more depressive symptoms, and others have significantly more edema or cough. Gender did not predict membership to any symptom pattern. CONCLUSIONS: There were significant gender differences in sociodemographics, health behaviors, and clinical characteristics, but not HF symptoms or symptom patterns, using either analytic technique.

Sex differences in the impact of physical frailty on outcomes in heart failure.

BACKGROUND: Physical frailty is strongly related to adverse outcomes in heart failure (HF), and women are more likely to be physically frail than men; however, it is unknown if this sex difference affects outcomes. OBJECTIVES: To determine if there are sex differences in the associations between physical frailty and health-related quality of life (HRQOL) and clinical outcomes in HF. METHODS: We conducted a prospective study of adults with HF. Physical frailty was assessed using the Frailty Phenotype Criteria. HRQOL was assessed using the Minnesota Living with HF Questionnaire. One-year clinical events (all-cause death or cardiovascular hospitalization or emergency department visit) were ascertained. We used generalized linear modeling to quantify associations between physical frailty and HRQOL, and Cox proportional hazards modeling to quantify associations between physical frailty and clinical events, adjusting for Seattle HF Model scores. RESULTS: The sample (n = 115) was 63.5 ± 15.7 years old and 49% women. Physical frailty was associated with significantly worse total HRQOL among women (p = 0.005) but not men (p = 0.141). Physical frailty was associated with worse physical HRQOL among both women (p < 0.001) and men (p = 0.043). There was a 46% higher clinical event risk for every one-point increase in physical frailty score among men (p = 0.047) but not women (p = 0.361). CONCLUSIONS: Physical frailty is associated with worse overall HRQOL among women and higher clinical event risk among men, indicating a need to better understand contributors to sex-specific health differences associated with physical frailty in HF.

Referral Order Placement Decreases Time to Transfer to Adult Congenital Heart Disease Care.

Pediatric patients with moderate and great complexity congenital heart disease (CHD) may benefit from coordinated transfer to adult congenital heart disease (ACHD) centers to reduce the risk of complications; however, there are a variety of transfer practices. We examined the impact of referral order placement at the last pediatric cardiology visit on time to transfer to an ACHD center. We analyzed data collected from pediatric patients with moderate and great complexity CHD who were eligible to transfer to our tertiary center's accredited ACHD center. We examined transfer outcomes and time-to-transfer between those with a referral order placed at the last pediatric cardiology visit and those without using Cox proportional hazards modeling. The sample (n = 65) was 44.6% female and mean age at study start was 19.5 years (± 2.2). Referral orders were placed for 32.3% of patients at the last pediatric cardiology visit. Those who had a referral order placed at the last visit had significantly higher number of successful transfers to the ACHD center compared to those who did not (95% vs 25%, p < 0.001). In a Cox regression model, placement of a referral order at the last pediatric cardiology visit was associated significantly with a sooner time to transfer (HR 6.0; 95% CI 2.2-16.2, p > 0.001), adjusting for age, sex, complexity, living location, and pediatric cardiology visit location. Placement of a referral order at the last pediatric cardiology visit may improve transfer occurrence and time to transfer to accredited ACHD centers.

PROMIS: Physical, Mental and Social Health Outcomes Improve From Before to Early After LVAD Implant: Findings From the Mechanical Circulatory Support: Measures of Adjustment and Quality of Life (MCS A-QOL) Study.

Study participants (n = 272) completed 12 Patient-Reported Outcomes Measurement Information System (PROMIS) physical, mental and social health measures (questionnaires) prior to implantation of a left ventricular assist device (LVAD) and again at 3 and 6 months postimplant. All but 1 PROMIS measure demonstrated significant improvement from pre-implant to 3 months; there was little change between 3 and 6 months. Because PROMIS measures were developed in the general population, patients with an LVAD, their caregivers and their clinicians can interpret the meaning of PROMIS scores in relation to the general population, helping them to monitor a return to normalcy in everyday life.

Validity and reliability of the left ventricular assist device self-care behaviour scale.

BACKGROUND: Adequate self-care behaviour is essential for patients with a left ventricular assist device (LVAD) to prevent complications, prolong life, and optimise quality of life. However, there were no valid and reliable measurements available to assess self-care behaviour among patients with LVAD. We have previously developed the 33-item LVAD self-care behaviour scale. OBJECTIVES: To evaluate psychometric properties of the 33-item LVAD self-care behaviour scale. METHODS AND RESULTS: Data on 127 patients with a LVAD in Israel, Japan, and the USA were analysed (mean age 51±14.3, 81% male). Exploratory factor analysis extracted three factors, and 13 items were excluded from the scale. Internal consistency assessed by Cronbach's alpha was acceptable for the total scale (α = 0.80) and the three subscales: Factor 1: Monitoring (α = 0.81), Factor 2: Heart failure self-care (α = 0.67), and Factor 3: LVAD self-care (α = 0.63). The 20-item version of the LVAD self-care behaviour scale had sufficient convergent validity with another scale that assessed self-care related to the driveline of LVAD (r = 0.47, p<0.001). Test-retest reliability was adequate (intraclass correlation coefficient = 0.58). CONCLUSIONS: The 20-item version of the LVAD self-care behaviour scale showed adequate validity and reliability. The scale is ready for use in clinical practice and research. Additional testing might further optimise the scale.

Validity of Patient-Reported Outcomes Measurement Information System Physical, Mental, and Social Health Measures After Left Ventricular Assist Device Implantation and Implications for Patient Care.

BACKGROUND: A better understanding is needed of the burdens and benefits of left ventricular assist device (LVAD) implantation on patients' physical, mental, and social well-being. The purpose of this report was to evaluate the validity of Patient-Reported Outcomes Measurement Information System (PROMIS) measures for LVAD patients and to estimate clinically important score differences likely to have implications for patient treatment or care. METHODS: Adults from 12 sites across all US geographic regions completed PROMIS measures ≥3 months post-LVAD implantation. Other patient-reported outcomes (eg, Kansas City Cardiomyopathy Questionnaire-12 item), clinician ratings, performance tests, and clinical adverse events were used as validity indicators. Criterion and construct validity and clinically important differences were estimated with Pearson correlations, ANOVA methods, and Cohen d effect sizes. RESULTS: Participants' (n=648) mean age was 58 years, and the majority were men (78%), non-Hispanic White people (68%), with dilated cardiomyopathy (55%), long-term implantation strategy (57%), and New York Heart Association classes I and II (54%). Most correlations between validity indicators and PROMIS measures were medium to large (≥0.3; p<0.01). Most validity analyses demonstrated medium-to-large effect sizes (≥0.5) and clinically important differences in mean PROMIS scores (up to 14.8 points). Ranges of minimally important differences for 4 PROMIS measures were as follows: fatigue (3-5 points), physical function (2-3), ability to participate in social roles and activities (3), and satisfaction with social roles and activities (3-5). CONCLUSIONS: The findings provide convincing evidence for the relevance and validity of PROMIS physical, mental, and social health measures in patients from early-to-late post-LVAD implantation. Findings may inform shared decision-making when patients consider treatment options. Patients with an LVAD, their caregivers, and their clinicians should find it useful to interpret the meaning of their PROMIS scores in relation to the general population, that is, PROMIS may help to monitor a return to normalcy in everyday life.

Survival analysis 101: an easy start guide to analysing time-to-event data.

Survival analysis, also called time-to-event analysis, is a common approach to handling event data in cardiovascular nursing and health-related research. Survival analysis is used to describe, explain, and/or predict the occurrence and timing of events. There is a specific language used and methods designed to handle the unique nature of event data. In this methods paper, we provide an 'easy start guide' to using survival analysis by (i) providing a step-by-step guide and (ii) applying the steps with example data. Specifically, we analyse cardiovascular event data over 6 months in a sample of patients 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.

Frequency and Predictors of Falls Among Adults With Heart Failure: A Prospective Study.

OBJECTIVE: Adults with heart failure (HF) may be at high risk for falling due to age, comorbidities and frailty; however, few studies have examined falls in HF. The purpose of this study was to quantify the frequency and predictors of falls over 1 year among adults with HF. METHODS: We conducted a prospective study of adults with New York Heart Association (NYHA) functional class I-IV HF. After baseline assessment of physical frailty and clinical characteristics, participants self-reported falls every 3 months during 1 year. Comparative statistics were used to identify baseline differences between those who fell vs those who did not. A stepwise negative binomial regression model was used to identify predictors of fall rate over 1 year. RESULTS: The sample (n = 111) was 63.4 ± 15.7 years old, 48% were women, 28% had HF with preserved ejection fraction, and 41% were frail. Over 1 year, 43 (39%) of participants reported at least 1 fall and 28 (25%) of participants reported 2+ falls. Among those who fell, 29 (67%) reported injurious falls. Those who fell had significantly higher body mass indexes and were more likely to have NYHA class III/IV, type 2 diabetes and HF with preserved ejection fraction and to meet slowness and physical exhaustion criteria than those who did not fall. The fall rate was elevated among those with type 2 diabetes and those meeting the slowness and physical exhaustion criteria for physical frailty. CONCLUSIONS: Nearly 40% of adults with HF experienced a fall within 1 year. Screening for comorbidities, slowness and exhaustion may help to identify those at risk for a fall.

State of the Science: The Relevance of Symptoms in Cardiovascular Disease and Research: A Scientific Statement From the American Heart Association.

Symptoms of cardiovascular disease drive health care use and are a major contributor to quality of life. Symptoms are of fundamental significance not only to the diagnosis of cardiovascular disease and appraisal of response to medical therapy but also directly to patients' daily lives. The primary purpose of this scientific statement is to present the state of the science and relevance of symptoms associated with cardiovascular disease. Symptoms as patient-reported outcomes are reviewed in terms of the genesis, manifestation, and similarities or differences between diagnoses. Specifically, symptoms associated with acute coronary syndrome, heart failure, valvular disorders, stroke, rhythm disorders, and peripheral vascular disease are reviewed. Secondary aims include (1) describing symptom measurement methods in research and application in clinical practice and (2) describing the importance of cardiovascular disease symptoms in terms of clinical events and other patient-reported outcomes as applicable.