Use of exception status listing and related outcomes during two heart allocation policy periods.

BACKGROUND: The October 2018 update to the heart allocation policy was intended to decrease exception status requests, whereby candidates are listed at a specific status due to perceived need despite not meeting prespecified criteria of illness severity. We assessed the use of exception status and waitlist outcomes before and after the 2018 policy. METHODS: We used data from the Scientific Registry of Transplant Recipients on adult heart transplant candidates listed from 2015 to 2021. We assessed (1) the use of exception status across patient characteristics between the two periods and (2) transplant rate and waitlist mortality or delisting due to deterioration in each period. Patients listed by exception versus standard criteria were compared with multivariable logistic regression, and waitlist outcomes were assessed using Cox proportional hazard models with medical urgency and exception status as time-dependent covariates. RESULTS: During the study period (n = 19,213), heart transplants under exception status increased postpolicy from 10.0% to 32.3%, with 20.6% of transplants performed for patients at status 2 exception. Exception status candidates postpolicy were more frequently Black or Hispanic/Latino and less likely to have hypertrophic or restrictive cardiomyopathy and had worse hemodynamics. Exception status listing was associated with higher transplant rates in both periods. Postpolicy, candidates listed status 1 exception had a lower likelihood for waitlist mortality or delisting (hazard ratio, 0.60; 95% CI, 0.37-0.99; and p = 0.05). CONCLUSIONS: Under the 2018 policy, exception status listings dramatically increased. The policy change shifted the population of patients listed by exception status and affected waitlist mortality, which suggests a need to further evaluate the policy's impact.

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 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.

Ending Gender Inequality in Cardiovascular Clinical Trial Leadership: JACC Review Topic of the Week.

Women are under-represented as leaders of cardiovascular randomized controlled trials, representing 1 in 10 lead authors of cardiovascular trials published in high-impact journals. Although the proportion of cardiovascular specialists who are women has increased in recent years, the proportion of cardiovascular clinical trialists who are women has not. This gap, underpinned by systemic sexism, has not been adequately addressed. The benefits of diverse randomized controlled trial leadership extend to patients and professionals. In this position statement, we present strategies adopted by some organizations to end gender inequality in research leadership. We offer an actionable roadmap for early-career researchers, scientists, academic institutions, professional societies, trial sponsors, and journals to follow, with the goal of harnessing the strength of women and under-represented groups as research leaders and facilitating a just culture in the cardiovascular clinical trial enterprise.

Varied Factors were Associated with Different Types of Self-Care in Heart Failure.

Poor self-care is prevalent in patients with heart failure and adversely affects heart failure symptoms, hospitalization, and mortality. Adherence rates to different types of self-care vary in patients with heart failure. The purpose of this study was to examine factors associated with medication adherence, dietary sodium adherence, and symptom management in patients with heart failure. Data were collected using questionnaires, Medication Electronic Monitoring System, and 24-hour urine sodium output (N = 94). In logistic regression analysis, social support, education level, and race were associated with medication adherence (p = .002). Gender, race, perceived control, and depressive symptoms were associated with dietary sodium adherence (p = .030). Gender, education level, and depressive symptoms were associated with symptom management (p = .006). Different factors were associated with each type of self-care. Thus, clinicians need to manage each type of self-care by considering factors associated with it.

Prediction of Heart Failure Symptoms and Health-Related Quality of Life at 12 Months From Baseline Modifiable Factors in Patients With Heart Failure.

BACKGROUND: In patients with heart failure (HF), good health-related quality of life (HRQOL) is as valuable as, or more valuable than, longer survival. However, HRQOL is remarkably poor, and HF symptoms are strongly associated with poor HRQOL. Yet, the multidimensional, modifiable predictors have been rarely examined. OBJECTIVE: The aim of this study was to examine the baseline psychosocial, behavioral, and physical predictors of HF symptoms and HRQOL at 12 months and the mediator effect of HF symptoms in the relationship between depressive symptoms and HRQOL. METHODS: We collected data from 94 patients with HF (mean ± SD age, 58 ± 14 years). Data included sample characteristics, depressive symptoms, perceived control, social support, New York Heart Association (NYHA) functional class, medication adherence, sodium intake, self-care management, and HF symptoms at baseline, as well as HF symptoms and HRQOL at 12 months. Multiple regression analyses were performed to address the purpose. RESULTS: Baseline depressive symptoms (P < .001), medication adherence (P = .010), sodium intake (P = .032), and NYHA functional class (P = .040) significantly predicted 12-month HF symptoms, controlling for covariates (F = 7.363, R = 47%, P < .001). Baseline medication adherence (P = .001), NYHA functional class (P < .001), and HF symptoms (P = .013) significantly predicted 12-month HRQOL (F = 10.701, R = 59%, P < .001). Baseline HF symptoms fully mediated the relationship between baseline depressive symptoms and 12-month HRQOL. CONCLUSION: Symptoms of HF and HRQOL could be improved by targeting multidimensional, modifiable predictors, such as self-care, depressive symptoms, and NYHA functional class.

A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report.

BACKGROUND: In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device. METHODS: We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years. RESULTS: This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).

Changes in Heart Failure Symptoms are Associated With Changes in Health-related Quality of Life Over 12 Months in Patients With Heart Failure.

PURPOSE: Patients with heart failure (HF) have notably poor health-related quality of life (HRQOL). A 5-point improvement in HRQOL is associated with reduction in hospitalization and mortality rates. Heart failure symptoms are associated with poor HRQOL, but little is known about whether changes in HF symptoms lead to changes in HRQOL over time. Therefore, we examined the association of changes in HF symptoms with changes in overall, physical, and emotional aspects of HRQOL over a 12-month period, controlling for typical covariates. METHODS: Data on HF symptoms and HRQOL (Minnesota Living Heart Failure questionnaire) were collected from 94 patients with HF (mean age, 58 years; 58.5% female) at baseline and 12-month follow-up. Psychosocial factors (depressive symptoms, perceived control, and social support), behavioral factors (medication adherence and sodium intake), sociodemographic and clinical factors (age, comorbidities, and body mass index), and a physical factor (functional status) were collected at baseline. Multiple and logistic regression analyses were used to analyze the data. RESULTS: In complete models, changes in HF symptoms were associated with changes in the total HRQOL (P < .001) and the physical (P < .001) and emotional (P < .001) aspects of HRQOL over 12 months, controlling for all the factors. Changes in HF symptoms were significantly associated with the likelihood of at least a 5-point improvement in HRQOL (P = .001), controlling for covariates. CONCLUSIONS: Improvement in HF symptoms was associated with improvement in HRQOL over 12 months. Thus, development and delivery of interventions that target improvement in HF symptoms may improve HRQOL.

Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure.

BACKGROUND: In an early analysis of this trial, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial continuous-flow pump, at 6 months in patients with advanced heart failure. METHODS: In a randomized noninferiority and superiority trial, we compared the centrifugal-flow pump with the axial-flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal-flow pump group minus axial-flow pump group) was -10 percentage points. RESULTS: Of 366 patients, 190 were assigned to the centrifugal-flow pump group and 176 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal-flow pump group, as compared with 106 (60.2%) in the axial-flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points [P<0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P<0.001 for superiority]). Reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (3 patients [1.6%] vs. 30 patients [17.0%]; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P<0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal-flow pump group than in the axial-flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02). CONCLUSIONS: In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was superior to a mechanical-bearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

A Fully Magnetically Levitated Circulatory Pump for Advanced Heart Failure.

BACKGROUND: Continuous-flow left ventricular assist systems increase the rate of survival among patients with advanced heart failure but are associated with the development of pump thrombosis. We investigated the effects of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis. METHODS: We randomly assigned patients with advanced heart failure to receive either the new centrifugal continuous-flow pump or a commercially available axial continuous-flow pump. Patients could be enrolled irrespective of the intended goal of pump support (bridge to transplantation or destination therapy). The primary end point was a composite of survival free of disabling stroke (with disabling stroke indicated by a modified Rankin score >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove the device at 6 months after implantation. The trial was powered for noninferiority testing of the primary end point (noninferiority margin, -10 percentage points). RESULTS: Of 294 patients, 152 were assigned to the centrifugal-flow pump group and 142 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 131 patients (86.2%) in the centrifugal-flow pump group and in 109 (76.8%) in the axial-flow pump group (absolute difference, 9.4 percentage points; 95% lower confidence boundary, -2.1 [P<0.001 for noninferiority]; hazard ratio, 0.55; 95% confidence interval [CI], 0.32 to 0.95 [two-tailed P=0.04 for superiority]). There were no significant between-group differences in the rates of death or disabling stroke, but reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (1 [0.7%] vs. 11 [7.7%]; hazard ratio, 0.08; 95% CI, 0.01 to 0.60; P=0.002). Suspected or confirmed pump thrombosis occurred in no patients in the centrifugal-flow pump group and in 14 patients (10.1%) in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, implantation of a fully magnetically levitated centrifugal-flow pump was associated with better outcomes at 6 months than was implantation of an axial-flow pump, primarily because of the lower rate of reoperation for pump malfunction. (Funded by St. Jude Medical; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

Variables Measured During Cardiopulmonary Exercise Testing as Predictors of Mortality in Chronic Systolic Heart Failure.

BACKGROUND: Data from a cardiopulmonary exercise (CPX) test are used to determine prognosis in patients with chronic heart failure (HF). However, few published studies have simultaneously compared the relative prognostic strength of multiple CPX variables. OBJECTIVES: The study sought to describe the strength of the association among variables measured during a CPX test and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF), including the influence of sex and patient effort, as measured by respiratory exchange ratio (RER). METHODS: Among patients (n = 2,100, 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial, 10 CPX test variables measured at baseline (e.g., peak oxygen uptake [Vo2], exercise duration, percent predicted peak Vo2 [%ppVo2], ventilatory efficiency) were examined. RESULTS: Over a median follow-up of 32 months, there were 357 deaths. All CPX variables, except RER, were related to all-cause mortality (all p < 0.0001). Both %ppVo2 and exercise duration were equally able to predict (Wald chi-square: ∼141) and discriminate (c-index: 0.69) mortality. Peak Vo2 (ml·kg(-1)·min(-1)) was the strongest predictor of mortality among men (Wald chi-square: 129) and exercise duration among women (Wald chi-square: 41). Multivariable analyses showed that %ppVo2, exercise duration, and peak Vo2 (ml·kg(-1)·min(-1)) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak Vo2 of 10.9 ml·kg(-1)·min(-1) versus 5.3 ml·kg(-1)·min(-1) in women. CONCLUSIONS: Peak Vo2, exercise duration, and % ppVo2 carried the strongest ability to predict and discriminate the likelihood of death in patients with HFrEF. The prognosis associated with a given peak Vo2 differed by sex. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).

Work Activities and Compensation of Male and Female Cardiologists.

BACKGROUND: Much remains unknown about experiences, including working activities and pay, of women in cardiology, which is a predominantly male specialty. OBJECTIVES: The goal of this study was to describe the working activities and pay of female cardiologists compared with their male colleagues and to determine whether sex differences in compensation exist after accounting for differences in work activities and other characteristics. METHODS: The personal, job, and practice characteristics of a national sample of practicing cardiologists were described according to sex. We applied the Peters-Belson technique and multivariate regression analysis to evaluate whether gender differences in compensation existed after accounting for differences in other measured characteristics. The study used 2013 data reported by practice administrators to MedAxiom, a subscription-based service provider to cardiology practices. Data regarding cardiologists from 161 U.S. practices were included, and the study sample included 2,679 subjects (229 women and 2,450 men). RESULTS: Women were more likely to be specialized in general/noninvasive cardiology (53.1% vs. 28.2%), and a lower proportion (11.4% vs. 39.3%) reported an interventional subspecialty compared with men. Job characteristics that differed according to sex included the proportion working full-time (79.9% vs. 90.9%; p < 0.001), the mean number of half-days worked (387 vs. 406 days; p = 0.001), and mean work relative value units generated (7,404 vs. 9,497; p < 0.001) for women and men, respectively. Peters-Belson analysis revealed that based on measured job and productivity characteristics, the women in this sample would have been expected to have a mean salary that was $31,749 (95% confidence interval: $16,303 to $48,028) higher than that actually observed. Multivariate analysis confirmed the direction and magnitude of the independent association between sex and salary. CONCLUSIONS: Men and women practicing cardiology in this national sample had different job activities and salaries. Substantial sex-based salary differences existed even after adjusting for measures of personal, job, and practice characteristics.

Advanced (stage D) heart failure: a statement from the Heart Failure Society of America Guidelines Committee.

We propose that stage D advanced heart failure be defined as the presence of progressive and/or persistent severe signs and symptoms of heart failure despite optimized medical, surgical, and device therapy. Importantly, the progressive decline should be primarily driven by the heart failure syndrome. Formally defining advanced heart failure and specifying when medical and device therapies have failed is challenging, but signs and symptoms, hemodynamics, exercise testing, biomarkers, and risk prediction models are useful in this process. Identification of patients in stage D is a clinically important task because treatments are inherently limited, morbidity is typically progressive, and survival is often short. Age, frailty, and psychosocial issues affect both outcomes and selection of therapy for stage D patients. Heart transplant and mechanical circulatory support devices are potential treatment options in select patients. In addition to considering indications, contraindications, clinical status, and comorbidities, treatment selection for stage D patients involves incorporating the patient's wishes for survival versus quality of life, and palliative and hospice care should be integrated into care plans. More research is needed to determine optimal strategies for patient selection and medical decision making, with the ultimate goal of improving clinical and patient centered outcomes in patients with stage D heart failure.

Modifiable correlates of physical symptoms and health-related quality of life in patients with heart failure: a cross-sectional study.

BACKGROUND: Heart failure is associated with high rates of hospitalization and mortality. The majority of patients with heart failure suffer from physical symptoms, and these symptoms are strongly associated with poor health-related quality of life. To improve physical symptoms and health-related quality of life, the modifiable factors associated with physical symptoms need to be examined. PURPOSE: To examine modifiable psychosocial and behavioral factors associated with physical symptoms and health-related quality of life, and the mediator effects of physical symptoms on the relationships between the modifiable factors and health-related quality of life in patients with heart failure. METHODS: Data on potential correlates of physical symptoms (i.e., depressive symptoms, perceived control, social support, medication adherence, sodium intake, and self-care management) were collected from 109 patients with heart failure (mean age 58 ± 14 years, 46% male, 89% New York Heart Association class II/III). Data on physical symptoms (Symptom Status Questionnaire-Heart Failure) and health-related quality of life (Minnesota Living with Heart Failure) also were collected. Simple and multiple regression analyses were used to analyze the data. RESULTS: Among the potential correlates, depressive symptoms and sodium intake were associated with physical symptoms (F=11.63, p<.001), and depressive symptoms and perceived control were associated with health-related quality of life (F=9.917, p<.001). Physical symptoms mediated the relationship between depressive symptoms and health-related quality of life. CONCLUSION: Improving depressive symptoms and eating the appropriate amount of sodium may be primary intervention targets to improve physical symptoms. To improve health-related quality of life, depressive symptoms as well as physical symptoms need to be managed appropriately.

Effects of exercise training on outcomes in women with heart failure: analysis of HF-ACTION (Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing) by sex.

OBJECTIVES: The authors hypothesized that the women enrolled in the HF-ACTION (Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing) trial and randomly assigned to exercise training (ET) would improve functional capacity as measured by peak oxygen uptake (VO2) compared with those in the usual care group. Furthermore, they hypothesized that the improvement in peak VO2 would correlate with prognosis. They explored whether exercise had a differential effect on outcomes in women versus men. BACKGROUND: There is less evidence for the benefit of ET in women with heart failure (HF) compared with men because of the small numbers of women studied. METHODS: HF-ACTION was a randomized trial of ET versus usual care in 2,331 patients with class II-IV HF and a left ventricular ejection fraction of ≤35%. Sex differences in the effects of randomized treatment on clinical outcomes were assessed through the use of a series of Cox proportional hazards models, controlling for covariates known to affect prognosis in HF-ACTION. RESULTS: Women had lower baseline peak VO2 and 6-min walk distance than did men (median, 13.4 vs. 14.9 ml/min/kg and 353 vs. 378 m, respectively). An increase in peak VO2 at 3 months was present in women and men in the ET group (mean ± SD; median, 0.88 ± 2.2, 0.80 and 0.77 ± 2.7, 0.60, respectively, women vs. men; p = 0.42). Women randomly assigned to ET had a significant reduction in the primary endpoint, (hazard ratio: 0.74) compared with men (hazard ratio: 0.99) randomly assigned to ET, with a significant treatment-by-sex interaction (p = 0.027). CONCLUSIONS: Although there is no significant difference between men and women in the effect of ET on peak VO2 change at 3 months, ET in women with HF is associated with a larger reduction in rate of the combined endpoint of all-cause mortality and hospital stay than in men.

Acute decompensated heart failure: update on new and emerging evidence and directions for future research.

Acute decompensated heart failure (ADHF) is a complex clinical event associated with excess morbidity and mortality. Managing ADHF patients is challenging because of the lack of effective treatments that both reduce symptoms and improve clinical outcomes. Existing guideline recommendations are largely based on expert opinion, but several recently published trials have yielded important data to inform both current clinical practice and future research directions. New insight has been gained regarding volume management, including dosing strategies for intravenous loop diuretics and the role of ultrafiltration in patients with heart failure and renal dysfunction. Although the largest ADHF trial to date (ASCEND-HF, using nesiritide) was neutral, promising results with other investigational agents have been reported. If these findings are confirmed in phase III trials, novel compounds, such as relaxin, omecamtiv mecarbil, and ularitide, among others, may become therapeutic options. Translation of research findings into quality clinical care can not be overemphasized. Although many gaps in knowledge exist, ongoing studies will address issues around delivery of evidence-based care to achieve the goal of improving the health status and clinical outcomes of patients with ADHF.