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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., (Copyright © 2023. Published by Elsevier Inc.)

Background: Extracorporeal membrane oxygenation (ECMO) has revolutionized the treatment of refractory cardiac and respiratory failure, and its use continues to increase, particularly in adults. However, ECMO-related morbidity and mortality remain high., Main Text: In this review, we investigate and expand upon the current state of the art in thoracic transplant and extracorporeal life support (ELS). In particular, we examine recent increase in incidence of heart transplant in patients supported by ECMO; the potential changes in patient care and selection for transplant in the years prior to updated United Network for Organ Sharing (UNOS) organ allocation guidelines versus those in the years following, particularly where these guidelines pertain to ECMO; and the newly revived practice of heart-lung block transplants (HLT) and the prevalence and utility of ECMO support in patients listed for HLT., Conclusions: Our findings highlight encouraging outcomes in patients bridged to transplant with ECMO, considerable changes in treatment surrounding the updated UNOS guidelines, and complex, diverse outcomes among different centers in their care for increasingly ill patients listed for thoracic transplant., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: We compared health-related quality of life (HRQOL), depressive symptoms, anxiety, and burden in caregivers of older patients with heart failure based on the intended therapy goal of the patient: awaiting heart transplantation (HT) with or without mechanical circulatory support (MCS) or prior to long-term MCS; and we identified factors associated with HRQOL., Methods: Caregivers (n = 281) recruited from 13 HT and MCS programs in the United States completed measures of HRQOL (EQ-5D-3L), depressive symptoms (PHQ-8), anxiety (STAI-state), and burden (Oberst Caregiving Burden Scale). Analyses included ANOVA, Kruskal-Wallis tests, χ 2 tests, and linear regression., Results: The majority of caregivers were female, white spouses with ≤ 2 comorbidities, median [Q1,Q3] age = 62 [57.8, 67.0] years. Caregivers (HT with MCS = 87, HT without MCS = 98, long-term MCS = 96) reported similarly high baseline HRQOL (EQ-5D-3L visual analog scale median score = 90; P = 0.67 for all groups) and low levels of depressive symptoms. STAI-state median scores were higher in the long-term MCS group vs the HT groups with and without MCS, (38 vs 32 vs 31; P < 0.001), respectively. Burden (task: time spent/difficulty) differed significantly among groups. Caregiver factors (number of comorbidities, diabetes and higher anxiety levels) were significantly associated with worse caregiver HRQOL, R 2  = 26%., Conclusions: Recognizing caregiver-specific factors, including comorbidities and anxiety, associated with the HRQOL of caregivers of these older patients with advanced HF may guide support strategies., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest related to this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cardiac allograft vasculopathy (CAV) constitutes a primary cause of death after heart transplantation. Balloon angioplasty and bare metal stents have been used for revascularization but they are associated with a high risk of re-stenosis. Limited data have shown favorable results with drug-eluting stents (DES). This study examines the rate of re-stenosis for DES in CAV as well as predictors for its occurrence., Methods: Cardiac transplant patients who received at least one DES for a previously untreated coronary lesion were included. These patients were retrospectively followed until February 2007. Re-stenosis was defined as >or=50% lumen diameter narrowing on coronary angiography at the site of the DES., Results: During the study period, 35 patients underwent percutaneous coronary intervention (PCI) on a total of 84 de novo lesions. The mean follow-up was 22 +/- 14 months. Twenty-six (31%) lesions developed re-stenosis during follow-up. Re-stenosis rates were 18%, 21% and 26% at 6, 9 and 12 months, respectively. Predictors of re-stenosis included non-white race, ischemic etiology, intervention precipitated by symptoms and severe stenosis (>/=90% stenosis) of the target lesion., Conclusions: Use of DES has a favorable outcome when used in heart transplant patients for the treatment of CAV. An aggressive strategy for the treatment of CAV using DES may provide good long-term outcome compared with other available therapies.

Objectives: The purpose of this study was to evaluate the incidence and prognostic implication of diastolic dysfunction (DD) occurring in the first year after transplant., Background: Diastolic dysfunction is a recognized complication in heart transplant recipients, but its true incidence and natural history has been poorly characterized. We studied the prognostic implication of DD, as defined by elevated filling pressures with normal systolic function, occurring in the first year after transplant., Methods: Between June 1992 and June 2002, all patients who underwent heart transplantation at a single institution were included in the study (231 at 6 weeks and 250 at 6 months and 1 year). Diastolic dysfunction was defined as right atrial pressure (RAP) >/=15 mm Hg (right ventricular [RV] DD) or pulmonary capillary wedge pressure >/=18 mm Hg (left ventricular [LV] DD) with normal systolic function by echocardiogram and without severe mitral or tricuspid insufficiency. In addition, RV DD was defined by a RAP/stroke volume (SV) ratio., Results: The incidence of DD was 22%, 8%, and 12% at 6 weeks, 6 months, and 1 year, respectively. The incidence of LV DD was more frequent than that of RV DD at any time point (p < 0.0001). By multivariable analysis RV DD, as manifested by an elevated RAP/SV, but not LV DD was a strong predictor of cardiac mortality at all time points., Conclusions: Diastolic dysfunction is common early after transplant, and its incidence decreases during the first year. Right ventricular DD, as measured by an elevated RAP/SV ratio, but not LV DD is a strong predictor of cardiac mortality. Further studies are needed to evaluate the functional status of patients with RV or LV DD and whether aggressive medical therapy for early DD could alter outcome.

Background: The role of cytokine gene polymorphism and its association with acute heart allograft rejection and cardiac allograft vasculopathy (CAV) is controversial. The role of growth factor gene polymorphism has never been investigated in heart allograft recipients., Methods: Seventy heart transplant recipients were studied. Mean age at transplant was 50.4 +/- 12.4 years (73% white, 91% male). Patients were followed for an average of 28 +/- 12 months. Cellular rejection episodes were determined based on criteria established by the International Society of Heart and Lung Transplantation. Angiography and intravascular ultrasound (IVUS) were performed annually. Cytokine and growth factor polymorphism data were analyzed using the single-nucleotide polymorphism polymerase chain reaction (SNP PCR) approach., Results: Patients who developed early CAV, documented by angiography, had increased frequency of the interferon-gamma high-producer phenotype, increased frequency of PDGF-286 AA, and decreased frequency of PDGF-1135 CC (p < 0.03, p < 0.03 and p = 0.01, respectively). Platelet-derived growth factor (PDGF) associations with early CAV were substantiated when vasculopathy was determined by IVUS. Additional associations were identified with vascular endothelial growth factor (VEGF) polymorphisms-1154 GG and -2578 AC (p < 0.03 and p = 0.01, respectively). Some of these associations translated to decreased patient survival, as indicated by Kaplan-Meier analysis. No significant association was identified between cytokine gene polymorphism (tumor necrosis factor-alpha, transforming growth factor-beta, interferon-gamma, interleukin-6 and interleukin-10) and acute cellular rejection episodes., Conclusions: These data suggest an association between PDGF and VEGF polymorphism and CAV. It is essential, however, due to the redundancy of the immune system and other confounding factors, that future studies be centrally conducted and include multiple programs, large cohorts of patients and properly chosen controls. Only then will we be able to identify the true association between cytokine and growth factor polymorphism and heart transplant outcome.

Background: Photopheresis therapy (photo) has been advocated as a therapy to improve outcome after recalcitrant or severe rejection, but objective evidence of a beneficial effect has been elusive. This study examined the hypothesis that photo provides protection against rejection, rejection with hemodynamic compromise (HC), and death from rejection after cardiac transplantation., Methods: Between 1990 and 2003, 36 adult patients (from 343 adult transplant recipients) received at least 3 months of photo (2-day treatment every 3 to 6 weeks for a target of 18 months) after HC rejection (n = 12), recurrent/recalcitrant rejection (n = 20), or as prophylaxis in the presence of anti-donor antibodies (n = 4). Survival and risk factors were examined by analysis using multivariate hazard function modulated renewal function., Results: Patients selected for photo were at greater risk for rejection (p < 0.0001) and HC rejection (p < 0.0001) than non-photo patients. After 3 months of photo therapy, rejection risk was decreased (p = 0.04). More importantly, the hazard for subsequent HC rejection or rejection death was significantly reduced toward the risk-adjusted level of lower-risk non-photo patients (p = 0.006)., Conclusions: This study provides objective evidence that photo reduces the risk of subsequent HC rejection and/or death from rejection when initiated for patients with high rejection risk. Photopheresis is recommended as an important therapeutic modality after rejection with hemodynamic compromise, although further studies are needed to define the precise mechanism of the effect and the potential for benefit in other patient sub-sets.

Management of anticoagulation in patients with heparin-induced thrombocytopenia (HIT) undergoing surgery requiring cardiopulmonary bypass (CPB), such as cardiac transplantation, represents a difficult clinical problem and no clear management strategy exists. The cases of 2 patients with HIT who underwent cardiac transplantation using differing anticoagulation strategies are presented with a discussion of potential advantages and pitfalls of each approach used.

Purpose: Limited options are available to improve the functional class of patients awaiting cardiac transplantation. We assessed the effect of carvedilol on New York Heart Association (NYHA) class, heart rate (HR), blood pressure (BP), jugular venous pressure (JVP), electrolytes and renal function in patients with markedly decreased left ventricular (LV) function referred for cardiac transplantation assessment., Methods: Sixty-one patients (age = 52 +/- 12 yr, EF = 23 +/- 7%, VO2 max = 16 +/- 5 mL/kg/min) referred to the cardiac transplant clinic were reviewed before and after the addition of carvedilol (starting dose 3.125 mg twice daily to target dose of 25 mg twice daily) to usual heart-failure therapy. Over a 1-yr period, at each visit prior to initiation, at baseline initiation visit and at each follow-up visit, NYHA class, BP, HR, JVP, electrolytes, and renal function were obtained. Statistical analysis was performed using random effects regression approach. A multiple logistic regression analysis was performed on 52/61 patients to determine possible associations between NYHA improvement and the following patient characteristics: sex, etiology of cardiomyopathy, initial NYHA class, and dose of carvedilol., Results: Three patients died (2 after stopping carvedilol) and 3 were transplanted. Median follow-up was 100 d. Sixteen patients reached the target dose after a mean of 137 d (2.75 visits). Estimated time-to-target dose is 8 months (5.6 visits). BP tended to increase (p = 0.07 for change in trend) with no change in JVP, electrolytes or renal function. HR decreased 6 +/- 3 b.p.m. (p = 0.03). Of 14 patients NYHA class I/II at baseline, none were class III/IV at last follow-up visit. Of 47 patients NYHA class III/IV at baseline, 25 were class I/II, and 22 were class III/IV at last follow-up (p < 0.001). Multiple logistic regression analysis did not demonstrate any factor predictive of subsequent NYHA class improvement., Conclusions: Despite less than target doses in most patients, a favorable effect of carvedilol on functional class in patients with severe congestive heart failure (CHF) referred for transplant was observed. Those with good functional status remained stable and those with poor functional status improved or remained stable. No baseline patient characteristic predicted improvement. The shortage of donor organ requires optimal use of medical regimens which may improve functional class while awaiting transplantation and which may delay the necessity for heart transplantation. Therefore, addition of carvedilol to usual medical therapy may be beneficial even in patients with severe LV dysfunction and poor NYHA classification.

Heart transplantation (HT) and mechanical circulatory support (MCS) has improved heart failure (HF) patient (PT) outcomes; it has also led to increased caregiver (CG) responsibility pre and post-surgery. We assessed whether PT and CG factors were related to baseline CG perceived burden in 3 groups of CGs of HF PTs (60-80 years): (1) PT supported with MCS as a bridge to HT (HT BTT), (2) PT awaiting HT without MCS (HT non BTT), and (3) PT prior to MCS for destination therapy (DT MCS). Between 10/1/15-12/31/18, we enrolled 302 CGs from 13 U.S. sites: 92 HT BTT, 101 HT non BTT, and 109 DT MCS. CG burden was measured with the Oberst Caregiving Burden Scale (OCBS: [1] time: higher score=more time spent on task and [2] difficulty: higher score=more difficulty of task). CGs also completed the EQ-5D-3L (Visual Analog Scale [VAS]: 0 [worst] to 100 [best] imaginable health state and 5 dimensions); STAI-State (higher score=more anxiety); PHQ-8 (score ≥10=significant depressive symptoms), and demographic/health history/impact of caregiving on own health questions. PTs completed the KCCQ-12, MoCA (measure of cognitive dysfunction) and all above measures except the OCBS. Analyses included multivariable logistic regression models in which the binary outcomes were whether individual OCBS difficulty and time scores were higher than the cohort median values of 1.20 and 2.26, respectively. CGs were 61.1±9.7 years, 85% spouses, 85% female, and 85% white. Overall CG difficulty was low and CG time spent was moderate. CGs who reported more difficulty on tasks perceived more impact on their own health and had more anxiety, with no differences by PT implant strategy (table). CGs with < a high school education and with more anxiety were likely to spend more time on CG tasks, with no differences by PT implant strategy (table). Only CG factors, and not PT factors, were related to CG perceived burden. Understanding factors that affect CG burden may aid in preoperative advanced therapies discussions. [ABSTRACT FROM AUTHOR]

Women are under-represented in heart failure (HF) trials and the reason remains unknown. To evaluate sex differences among patients who do not participate, we analyzed non-enrollment in SUSTAIN-IT, a multi-center study comparing health-related quality of life outcomes in 60-80 year old patients implanted with left ventricular assist devices as destination therapy (DT) or who awaited heart transplantation (HT). 238 patients were approached and not enrolled in SUSTAIN-IT. Reasons for not enrolling and for refusing were documented. Sex differences were evaluated for the cohort and then stratified by DT vs HT 50 women (29 DT, 21 HT) and 187 men (81 DT, 106 HT) approached did not enroll in SUSTAIN-IT. Women were more likely than men to refuse (92% vs 76%, P=0.015) and the reasons varied by sex. Women were more likely too tired, stressed, anxious, depressed, or unable to concentrate while men were mostly not interested (Table 1). When stratified by HF therapy, women were more likely to refuse when approached for HT (100% HT vs 86% DT, P=0.13), while refusal for men did not differ with HF therapy (76% HT and 77% DT). Refusal also varied by therapy with the majority of HT non-enrollers not interested (38% women, 52% men) and DT non-enrollers refusing for different reasons (women 56% symptoms; men 31% symptoms, 32% not interested). Women approached who did not enroll in SUSTAIN-IT were more likely than men to refuse to participate. Reasons for refusal varied for both women and men based on type of advanced HF therapy. Our novel findings may provide tailored guidance when recruiting men and women in clinical trials. [ABSTRACT FROM AUTHOR]