Caregiver burden before heart transplantation and long-term mechanical circulatory support: Findings from the sustaining quality of life of the aged: Transplant or mechanical support (SUSTAIN-IT) study.

BACKGROUND: Caregiving for heart failure (HF) patients is burdensome. We examined differences in caregiver burden for 3 groups of older advanced HF patients: (1) supported with mechanical circulatory support (MCS) before heart transplantation (HT MCS), (2) awaiting transplant without MCS (HT non-MCS), and (3) prior to long-term MCS and factors associated with burden. METHOD: From October 1, 2015 to December 31, 2018, we enrolled 276 caregivers for HF patients from 13 U.S. sites: 85 HT MCS, 96 HT non-MCS, and 95 prior to long-term MCS. At enrollment, caregivers completed the Oberst Caregiving Burden Scale (15 items, 2 subscales: time (range = 1-5; higher score = more time spent on task) and difficulty (range = 1-5; higher score = higher difficulty of task) and other measures. Statistical analyses included descriptive statistics, ANOVA, chi-square tests, and linear regression. RESULT: Overall, caregivers were aged 60.8 ± 9.8 years and predominantly white, female, spouses, well educated, and reported ≥1 comorbidities. Caregivers overall reported a moderate amount of time spent on tasks and slight task difficulty. Caregivers for HT non-MCS candidates reported significantly less perceived time spent on tasks than caregivers for HT MCS candidates and caregivers for patients prior to long-term MCS (2.2 ± 0.74 vs 2.4 ± 0.74 vs 2.5 ± 0.71, respectively, p = 0.02) and less perceived difficulty of tasks (1.2 ± 0.33 vs 1.4 ± 0.53 vs 1.4 ± 0.54, respectively, p = 0.01). Caregiver and patient factors were associated with caregiver burden. CONCLUSIONS: Prior to HT and long-term MCS, caregiver burden was low to moderate. Caregiver factors were predominantly associated with caregiver burden. Understanding caregiver burden and factors affecting caregiver burden may enhance preoperative advanced therapies discussions and guide caregiver support.

Hyponatremia Is a Powerful Predictor of Poor Prognosis in Left Ventricular Assist Device Patients.

Serum sodium is an established prognostic marker in heart failure (HF) patients and is associated with an increased risk of morbidity and mortality. We sought to study the prognostic value of serum sodium in left ventricular assist device (LVAD) patients and whether hyponatremia reflects worsening HF or an alternative mechanism. We identified HF patients that underwent LVAD implantation between 2008 and 2019. Hyponatremia was defined as Na ≤134 mEq/L at 3 months after implantation. We assessed for differences in hyponatremia before and after LVAD implantation. We also evaluated the association of hyponatremia with all-cause mortality and recurrent HF hospitalizations. There were 342 eligible LVAD patients with a sodium value at 3 months. Among them, there was a significant improvement in serum sodium after LVAD implantation compared to preoperatively (137.2 vs. 134.7 mEq/L, P < 0.0001). Patients with and without hyponatremia had no significant differences in echocardiographic and hemodynamic measurements. In a multivariate analysis, hyponatremia was associated with a markedly increased risk of all-cause mortality (HR 3.69, 95% CI, 1.93-7.05, P < 0.001) when accounting for age, gender, co-morbidities, use of loop diuretics, and B-type natriuretic peptide levels. Hyponatremia was also significantly associated with recurrent HF hospitalizations (HR 2.11, 95% CI, 1.02-4.37, P = 0.04). Hyponatremia in LVAD patients is associated with significantly higher risk of all-cause mortality and recurrent HF hospitalizations. Hyponatremia may be a marker of ongoing neurohormonal activation that is more sensitive than other lab values, echocardiography parameters, and hemodynamic measurements.

Innovations in Undergraduate Research Training Through Multisite Collaborative Programming: American Heart Association Summer Undergraduate Research Experience Syndicate.

Background To support diversity in biomedical science, the American Heart Association launched the Supporting Undergraduate Research Experiences for undergraduate students from underrepresented backgrounds to provide mentorship and high-level exposure at 5 leading medical institutions. Here we describe the initial formation of the partnership and the alteration made in response to the program to accommodate COVID-19 safety precautions. Methods and Results We outline how programming shifted from local, in-person programming in the summer of 2019 to a collaborative, mainly virtual curriculum in 2020 using students' self-reported before and after surveys from both 2019 (n=33) and 2020 (n=42). Students from both in-person (2019) and virtual programs (2020) self-reported significant gains in scientific proficiency. A qualitative-directed content analysis of student open-response questions was performed. Students reported extensive benefits from the 2020 virtual training, including Personal Gains, Research Skills, Thinking and Working Like a Scientist, and Attitudes and Behaviors. Notedly, we observed increases in the Attitudes and Behaviors category. We outline the pros and cons of in-person and virtual programming and make recommendations moving forward in a postpandemic world with hybrid work and learning systems. Conclusions Our effort informs the development of future undergraduate research training programs, significantly maximizing a hybrid training modality. The American Heart Association Supporting Undergraduate Research Experiences serves as a model for building multi-institutional partnerships and providing research experiences that overcome institutional barriers and support students' interests, commitment, and ability to persist in science, technology, engineering, and math fields.

The heart transplant allocation change attenuates but does not eliminate blood group O waitlist outcome disadvantage.

BACKGROUND: Patients with blood group O have historically been disadvantaged in the United Network for Organ Sharing (UNOS) heart transplant allocation system. We sought to determine whether the new UNOS allocation system implemented in 2018 had an impact on waitlist and post-transplant outcomes among blood groups. METHODS: Using the UNOS database we included all adult patients listed and transplanted with first-time single-organ heart transplant between 10/17/15 and 10/1/21. For post-transplant outcomes, we separately evaluated all adult patients transplanted with the same time-frame. We used exclusion criteria and censoring to limit biases from changing clinical practices around the allocation change (10/18/2018), and from unequal or inadequate follow-up. We compared clinical characteristics and outcomes before and after the allocation change among each blood group. Fine-Gray and Cox regression models were used to estimate the effect of the new allocation system on competing waitlist outcomes- transplantation, death-or-removal from waitlist- and post-transplant survival, respectively. RESULTS: Of the 21,565 patients listed for transplantation 14,000 met criteria for waitlist analysis (7,035 in the old system vs. 6,965 in the new), and 7,657 met criteria for post-transplant analysis (3,519 in the old system vs. 4,138 in the new). Among each blood group, new allocation change was associated with higher transplantation rates lower waitlist days and lower waitlist mortality (except Group AB). However, despite improvements, Group O was still associated with worse waitlist outcomes for each metric compared to non-O Groups. The new allocation system did not have a significant impact on post-transplant survival among any blood groups. CONCLUSION: Changes in heart transplant allocation have attenuated but not eliminated blood group O disadvantage in access to donor hearts.

Thirty-Year Trends in Graft Survival After Heart Transplant: Modeled Analyses of a Transplant Registry.

BACKGROUND: Heart failure is an epidemic in the United States, and transplantation remains the most definitive therapy. We describe multidecade trends in posttransplant graft survival, adjusted for concurrent changes in the population, over the 30 years antecedent to the most recent heart allocation policy change. METHODS: Scientific Registry of Transplant Recipients data were used to identify all primary adult heart recipients from 1989 to 2017. We described temporal changes in population characteristics (recipient and donor demographics and comorbidities, pretransplant interventions, clinical transplant measures, and providers). The primary outcome was graft survival, defined as freedom from all-cause death and graft failure, within 6 months posttransplant. Modified Poisson logistic regression estimated relative changes in risk of outcomes compared with 1989, with and without adjustment for changing population characteristics. We identified risk factors, quantified by associated risk ratios. RESULTS: Among 56,488 primary adult heart recipients, we observed 5529 (9.8%) all-cause deaths and 1933 (3.4%) graft failure events within 6 months posttransplant. Prevalence of known recipient risk factors increased over time. Unadjusted modeling demonstrated a significant 30-year improvement in graft survival, averaging 2.6% per year (95% confidence interval, 2.4-2.9; P for trend < .001). After adjusting for population changes the 30-year trend remained significant and graft survival improved on average 3.0% per year (95% confidence interval, 2.6-3.3). Regression modeling identified multiple predictors of graft survival. Modeling 2 additional outcomes of 6-month mortality and 6-month graft failure produced similar results. CONCLUSIONS: Short-term graft survival after heart transplantation has improved significantly leading up to the 2018 heart allocation policy change, despite concurrent increase in prevalence of higher risk population characteristics.

Heart transplantation outcomes in cardiac sarcoidosis.

BACKGROUND: Cardiac sarcoidosis (CS) is a progressive inflammatory cardiomyopathy that can lead to heart failure, arrhythmia, and death. There is limited data on Orthotopic Heart Transplantation (OHT) outcomes in patients with CS. Here we examine outcomes in patients with CS who have undergone OHT at centers throughout the United States from 1987 to 2019. METHODS: This was an analysis of 63,947 adult patients undergoing OHT captured in the United Network for Organ Sharing (UNOS) registry. Patients were characterized as cardiac sarcoidosis (CS) or Non-CS. Baseline characteristics were compared using chi-square and Kruskal-Wallis Tests. Outcomes of interest included primary graft failure, patient survival, treated graft rejection, hospitalization for infection, and post-transplant malignancy. RESULTS: During the study period 227 patients with CS underwent OHT. Patients with CS were younger, had higher proportion of non-white patients, and received transplants at more urgent statuses. After multivariable modeling there was no difference in survival (HR 0.86, CI 0.59-1.3, p = 0.446) or graft failure (HR 0.849, CI 0.58-1.23, p = 0.394) between patients with CS and Non-CS. Patients with CS had lower odds of rejection (OR 0.558, CI 0.315- 0.985, p = 0.0444). Patients with CS had similar odds of hospitalization for infection and post-transplant malignancy, as Non-CS patients. CONCLUSIONS: Patients with CS and Non-CS had similar post OHT survival, odds of graft failure, hospitalizations for infection, and post-transplant malignancy. Results of this study confirm the role of heart transplantation as a viable option for patients with CS.

Cardiac transplantation outcomes in patients with amyloid cardiomyopathy.

OBJECTIVE: Amyloid cardiomyopathy (ACM) is a progressive and life-threatening disease caused by abnormal protein deposits within cardiac tissue. The most common forms of ACM are caused by immunoglobulin derived light chains (AL) and transthyretin (TTR). Orthotopic heart transplantation (OHT) remains the definitive treatment for patients with end stage heart failure. In this study, we perform a contemporary multicenter analysis evaluating post OHT survival in patients with ACM. METHODS: We conducted a multicenter analysis of 40,044 adult OHT recipients captured in the United Network for Organ Sharing (UNOS) registry from 1987-2018. Patients were characterized as ACM or non-ACM. Baseline characteristics were obtained, and summary characteristics were calculated. Outcomes of interest included post-transplant survival, infection, treated rejection, and the ability to return to work. Racial differences in OHT survival were also analyzed. Unadjusted associations between ACM and non-ACM survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models. RESULTS: Three hundred ninety-eight patients with a diagnosis of ACM were identified of which 313 underwent heart only OHT. ACM patients were older (61 vs 53; P < .0001) and had a higher proportion of African Americans (30.7% vs 17.6%; P < .0001). Median survival for ACM was 10.2 years vs 12.5 years in non-ACM (P = .01). After adjusting for confounding, ACM patients had a higher likelihood of death post-OHT (HR 1.39 CI: 1.14, 1.70; P = .001). African American ACM patients had a higher likelihood of survival compared to White ACM patients (HR 0.51 CI 0.31-0.85; P = .01). No difference was observed in episodes of treated rejection (OR 0.63 CI 0.23, 1.78; P = .39), hospitalizations for infections (OR 1.24 CI: 0.85, 1.81; P = .26), or likelihood of returning to work for income (OR 1.23 CI: 0.84, 1.80; P = .30). CONCLUSIONS: In this analysis of OHT in ACM, ACM was associated with a higher likelihood of post-OHT mortality. Racial differences in post-OHT were observed with African American patients with ACM having higher likelihood of survival compared to White patients with ACM. No differences were observed in episodes of treated rejection, hospitalization for infection, or likelihood to return to work for income.

Association of cigarette smoking and adverse events in left ventricular assist device patients.

INTRODUCTION: Adverse events (AEs) associated with left ventricular assist devices (LVADs) cause significant morbidity and mortality. Little is known about patient-specific factors that contribute to rates of AEs. The purpose of this study was to assess the association of cigarette smoking history and AEs following LVAD implantation. METHODS: This study was a single-center, observational examination of 355 consecutive patients who underwent continuous-flow LVAD implantation from May 1, 2008 to July 1, 2018. Based on self-report, 348 patients with available data were categorized as never, former, or current smokers. Pre-LVAD implantation baseline characteristics were obtained, and summary characteristics were calculated. Hospitalizations for gastrointestinal bleeds, driveline infections, strokes, pump thromboses, and acute heart failure were evaluated. The Cox proportional hazard model was used to estimate the association of smoking and AE-related hospital admissions. The cumulative incidence competing risk method was used for survival analysis. RESULTS: Current (8.22%, p 0.006) and former (4.75%, p 0.026) smokers had a greater proportion of admissions for pump thrombosis compared to never smokers (2.22%). Former smoking was associated with admission for driveline infection (HR 2.43, CI 1.08-5.46, p 0.03) on multivariate analysis. There were no significant associations between smoking and the other AEs of interest. There was no difference in survival among the three groups. CONCLUSIONS: Smokers had a higher proportion of admissions for pump thrombosis compared to never smokers, and former smoking was associated with admission for driveline infections in patients with LVADs.

Disparities in cardiovascular care: Past, present, and solutions.

Cardiovascular disease has been the leading cause of death in the United States since the early 20th century. With advances in prevention and treatment, cardiovascular mortality rates are on the decline. Nevertheless, disparities in care persist, with devastating impact in select populations in the United States. This paper reviews the impact of disparate care on risk-factor burden, coronary artery disease, heart failure, and cardiovascular research.

Efficacy of Intravenous Furosemide Versus a Novel, pH-Neutral Furosemide Formulation Administered Subcutaneously in Outpatients With Worsening Heart Failure.

OBJECTIVES: This study sought to determine the efficacy and safety of a novel, pH-neutral formulation of furosemide administered subcutaneously (SC) for treatment of acute decompensated heart failure (HF). BACKGROUND: Congestion requiring intravenous (IV) administration of a diuretic agent is the main reason patients with HF present for acute medical care. METHODS: Outpatients presenting with decompensated HF were randomized to receive a single SC or IV dose of furosemide. Primary outcome was 6-h urine output, and secondary outcomes were weight change, natriuresis, and adverse events. RESULTS: Forty-one patients were randomized: 19 were treated with IV (mean dose: 123 ± 47 mg) and 21 with SC furosemide (fixed dose of 80 mg over 5 h). The 6-h urine output in the IV group was not significantly different from that in the SC furosemide group (median IV: 1,425 ml; interquartile range [IQR]: 1,075 to 1,950 ml; vs. median SC: 1,350 ml; IQR: 900 to 1,900 ml; p = 0.84). Additionally, mean weight loss was not significantly different (-1.5 ± 1.1 kg in the IV group vs. -1.5 ± 1.2 kg in the SC group; p = 0.95). Hourly urine output was significantly higher in the IV group at hour 2 (425 ml in the IV group vs. 250 ml in the SC group; p = 0.02) and higher in the SC group at hour 6 (125 ml, IV group vs. 325 ml, SC group; p = 0.005). Natriuresis was higher in the SC group (IV: 7.3 ± 35.3 mEq/l vs. SC: 32.8 ± 43.6 mEq/l; p = 0.05). There was no worsening renal function, ototoxicity, or skin irritation with either formulation. Thirty-day hospitalization rates were similar. CONCLUSIONS: In this phase II trial, we did not identify significant differences between urine output obtained with pH-neutral furosemide administered SC and that obtained by IV. This method of decongestion may allow treatment at home and reduced HF resources and warrants further investigation. (Sub-Q Versus IV Furosemide in Acute Heart Failure; NCT02579057).

Patients Commonly Believe Their Heart Failure Hospitalizations Are Preventable and Identify Worsening Heart Failure, Nonadherence, and a Knowledge Gap as Reasons for Admission.

BACKGROUND: There are few data describing patient-identified precipitants of heart failure (HF) hospitalization. We hypothesized a patient's perception of reason for or preventability of an admission may be related to 30-day readmission rates. METHODS AND RESULTS: Ninety-four patients admitted with decompensated HF from July 2014 to March 2015 completed a brief questionnaire regarding circumstances leading to admission. Thirty-day outcomes were assessed via telephone call and chart review. Mean age was 58 ± 14 years, with 60% blacks (n = 56) and 41% females (n = 39). Median left ventricular ejection fraction was 30%; 27 had preserved ejection fraction. Seventy-two patients identified their hospitalization to be due to HF (± another condition). Most common patient-identified precipitants of admission were worsening HF (n = 37) and dietary nonadherence (n = 11). Readmitted patients tended to have longer time until first follow-up appointment (21 vs 8 days). Seven of the 42 patients who identified their hospitalization as preventable were readmitted compared with 21/49 who believed their hospitalization was unpreventable (P = .012). On multivariate regression analysis, patients who thought their hospitalization was preventable were less likely to be readmitted (odds ratio 0.31; 95% confidence interval 0.10-0.91; P = .04). CONCLUSION: Almost 50% of patients believe their HF hospitalization is preventable, and these patients appear to be less likely to be readmitted within 30 days. Notably, patients cite nonadherence and lack of knowledge as reasons hospitalizations are preventable. These results lend insight into possible interventions to reduce HF readmissions.

Worldwide disparities in cardiovascular disease: Challenges and solutions.

The 20th century saw cardiovascular disease ascend as the leading cause of death in the world. In response to the new challenge that heart disease imposed, the cardiovascular community responded with ground breaking innovations in the form of evidence based medications that have improved survival, imaging modalities that allow for precise diagnosis and guide treatment; revascularization strategies that have not only reduced morbidity, but also improved survival following an acute myocardial infarction. However the benefits have not been distributed equitably and as a result disparities have arisen in cardiovascular care. There is tremendous data from the United States demonstrating the many phenotypical forms of disparities. This paper takes a global view of disparities and highlights that disparate care is not limited to the United States and it is another challenge that the medical community should rise and face head on.