Gene expression profiling to study racial differences after heart transplantation.

BackgroundThe basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores.MethodsWe determined the event rate of the primary outcome, comparing racial groups, stratified by time after transplant. Logistic regression was used to compute the relative risk across racial groups, and linear modeling was used to measure the dependence of CNI levels and GEP score on race.ResultsIn 580 patients monitored for a median of 19 months, the incidence of the primary end point was 18.3% in African Americans, 22.2% in other non-Caucasians, and 8.5% in Caucasians (p < 0.001). There were small but significant correlations of race and tacrolimus trough levels to the GEP score. Tacrolimus levels were similar among the races. Of patients receiving tacrolimus, other non-Caucasians had higher GEP scores than the other racial groups. African American recipients demonstrated a unique decrease in expression of the FLT3 gene in response to higher tacrolimus levels.ConclusionsAfrican Americans and other non-Caucasian heart transplant recipients were 2.5-times to 3-times more likely than Caucasians to experience outcome events in the Invasive Monitoring Attenuation through Gene Expression study. The increased risk of adverse outcomes may be partly due to the biology of the alloimmune response, which is less effectively inhibited at similar tacrolimus levels in minority racial groups

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 three 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. Methods: From 10/1/15-12/31/18, 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. Results: 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

Cost-effectiveness of left ventricular assist devices as destination therapy in the United Kingdom

AIMS: Continuous-flow left ventricular assist devices (LVADs) as destination therapy (DT) are a recommended treatment by National Institute for Health and Care Excellence England for end-stage heart failure patients ineligible for cardiac transplantation. Despite the fact that DT is frequently used as an LVAD indication across other major European countries and the United States, with consistent improvements in quality-of-life and longevity, National Health Service (NHS) England does not currently fund DT, mainly due to concerns over cost-effectiveness. On the basis of the recently published ENDURANCE Supplemental Trial studying DT patients, we assessed for the first time the cost-effectiveness of DT LVADs compared with medical management (MM) in the NHS England. METHODS AND RESULTS: We developed a Markov multiple-state economic model using NHS cost data. LVAD survival and adverse event rates were derived from the ENDURANCE Supplemental Trial. MM survival was based on Seattle Heart Failure Model estimates in the absence of contemporary clinical trials for this population. Incremental cost-effectiveness ratios (ICERs) were calculated over a lifetime horizon. A discount rate of 3.5% per year was applied to costs and benefits. Deterministic ICER was £46 207 per quality-adjusted life year (QALY). Costs and utilities were £204 022 and 3.27 QALYs for the LVAD arm vs. £77 790 and 0.54 QALYs for the MM arm. Sensitivity analyses confirmed robustness of the primary analysis. CONCLUSIONS: The implantation of the HeartWare™ HVAD™ System in patients ineligible for cardiac transplantation as DT is a cost-effective therapy in the NHS England healthcare system under the end-of-life willingness-to-pay threshold of £50 000/QALY, which applies for VAD patients

Cost‐effectiveness of left ventricular assist devices as destination therapy in the United Kingdom

AIMS: Continuous-flow left ventricular assist devices (LVADs) as destination therapy (DT) are a recommended treatment by National Institute for Health and Care Excellence England for end-stage heart failure patients ineligible for cardiac transplantation. Despite the fact that DT is frequently used as an LVAD indication across other major European countries and the United States, with consistent improvements in quality-of-life and longevity, National Health Service (NHS) England does not currently fund DT, mainly due to concerns over cost-effectiveness. On the basis of the recently published ENDURANCE Supplemental Trial studying DT patients, we assessed for the first time the cost-effectiveness of DT LVADs compared with medical management (MM) in the NHS England. METHODS AND RESULTS: We developed a Markov multiple-state economic model using NHS cost data. LVAD survival and adverse event rates were derived from the ENDURANCE Supplemental Trial. MM survival was based on Seattle Heart Failure Model estimates in the absence of contemporary clinical trials for this population. Incremental cost-effectiveness ratios (ICERs) were calculated over a lifetime horizon. A discount rate of 3.5% per year was applied to costs and benefits. Deterministic ICER was £46 207 per quality-adjusted life year (QALY). Costs and utilities were £204 022 and 3.27 QALYs for the LVAD arm vs. £77 790 and 0.54 QALYs for the MM arm. Sensitivity analyses confirmed robustness of the primary analysis. CONCLUSIONS: The implantation of the HeartWare™ HVAD™ System in patients ineligible for cardiac transplantation as DT is a cost-effective therapy in the NHS England healthcare system under the end-of-life willingness-to-pay threshold of £50 000/QALY, which applies for VAD patients

Management of pulmonary mucormycosis after orthotopic heart transplant: A case series

Invasive pulmonary mucormycosis is a potentially fatal infection that can occur in immunosuppressed patients such as those who have undergone orthotopic heart transplant (OHT). High-dose intravenous antifungal agents, including amphotericin B, are generally accepted as the first-line medical treatment, with prompt surgical resection of lesions if feasible. The body of evidence guiding treatment decisions, however, is sparse, particularly regarding adjustment of immunosuppression during acute infection and long-term recovery. We present 2 cases of patients with pulmonary mucormycosis occurring within the first 6 months after OHT, both of whom successfully recovered after appropriate medical and surgical treatment, and we highlight differences in immunosuppression management strategies for this life-threatening condition

Impact of pre-existing heart failure on 60-day outcomes in patients hospitalized with COVID-19

Background: In the coronavirus disease 2019 (COVID-19) global pandemic, patients with cardiovascular disease represent a vulnerable population with higher risk for contracting COVID-19 and worse prognosis with higher case fatality rates. However, the relationship between COVID-19 and heart failure (HF) is unclear, specifically whether HF is an independent risk factor for severe infection or if other accompanying comorbidities are responsible for the increased risk. Methods: This is a retrospective analysis of 1331 adult patients diagnosed with COVID-19 infection between March and June 2020 admitted at Rush University System for Health (RUSH) in metropolitan Chicago, Illinois, USA. Patients with history of HF were identified by International Classification of Disease, Tenth Revision (ICD-10) code assignments extracted from the electronic medical record. Propensity score matching was utilized to control for the numerous confounders, and univariable logistic regression was performed to assess the relationship between HF and 60-day morbidity and mortality outcomes. Results: The propensity score matched cohort consisted of 188 patients in both the HF and no HF groups. HF patients did not have lower 60-day mortality (OR 0.81; Conclusions: This study highlights the complex network of confounders present between HF and COVID-19. When balanced for these numerous factors, those with HF appear to be at no higher risk of 60-day mortality from COVID-19 but are at increased risk for morbidity