Comparative Effectiveness of Psychotherapy vs Antidepressants for Depression in Heart Failure: A Randomized Clinical Trial.

Importance: Heart failure (HF) affects more than 6 million adults in the US and more than 64 million adults worldwide, with 50% prevalence of depression. Patients and clinicians lack information on which interventions are more effective for depression in HF. Objective: To compare the effectiveness of behavioral activation psychotherapy (BA) vs antidepressant medication management (MEDS) on patient-centered outcomes inpatients with HF and depression. Design, Setting, and Participants: This pragmatic randomized comparative effectiveness trial was conducted from 2018 to 2022, including 1-year follow-up, at a not-for-profit academic health system serving more than 2 million people from diverse demographic, socioeconomic, cultural, and geographic backgrounds. Participant included inpatients and outpatients diagnosed with HF and depression, and data were analyzed as intention-to-treat. Data were analyzed from 2022 to 2023. Interventions: BA is an evidence-based manualized treatment for depression, promoting engagement in personalized pleasurable activities selected by patients. MEDS involves the use of an evidence-based collaborative care model with care managers providing coordination with patients, psychiatrists, and primary care physicians to only administer medications. Main Outcomes and Measures: The primary outcome was depressive symptom severity at 6 months, measured using the Patient Health Questionnaire 9-Item (PHQ-9). Secondary outcomes included physical and mental health-related quality of life (HRQOL), measured using the Short-Form 12-Item version 2 (SF-12); heart failure-specific HRQOL, measured using the Kansas City Cardiomyopathy Questionnaire; caregiver burden, measured with the Caregiver Burden Questionnaire for Heart Failure; emergency department visits; readmissions; days hospitalized; and mortality at 3, 6, and 12 months. Results: A total of 416 patients (mean [SD] age, 60.71 [15.61] years; 243 [58.41%] male) were enrolled, with 208 patients randomized to BA and 208 patients randomized to MEDS. At baseline, mean (SD) PHQ-9 scores were 14.54 (3.45) in the BA group and 14.31 (3.60) in the MEDS group; both BA and MEDS recipients experienced nearly 50% reduction in depressive symptoms at 3, 6, and 12 months (eg, mean [SD] score at 12 months: BA, 7.62 (5.73); P < .001; MEDS, 7.98 (6.06); P < .001; between-group P = .55). There was no statistically significant difference between BA and MEDS in the primary outcome of PHQ-9 at 6 months (mean [SD] score, 7.53 [5.74] vs 8.09 [6.06]; P = .88). BA recipients, compared with MEDS recipients, experienced small improvement in physical HRQOL at 6 months (mean [SD] SF-12 physical score: 38.82 [11.09] vs 37.12 [10.99]; P = .04), had fewer ED visits (3 months: 38% [95% CI, 14%-55%] reduction; P = .005; 6 months: 30% [95% CI, 14%-40%] reduction; P = .008; 12 months: 27% [95% CI, 15%-38%] reduction; P = .001), and spent fewer days hospitalized (3 months: 17% [95% CI, 8%-25%] reduction; P = .002; 6 months: 19% [95% CI, 13%-25%] reduction; P = .005; 12 months: 36% [95% CI, 32%-40%] reduction; P = .001). Conclusions and Relevance: In this comparative effectiveness trial of BA and MEDS in patients with HF experiencing depression, both treatments significantly reduced depressive symptoms by nearly 50% with no statistically significant differences between treatments. BA recipients experienced better physical HRQOL, fewer ED visits, and fewer days hospitalized. The study findings suggested that patients with HF could be given the choice between BA or MEDS to ameliorate depression. Trial Registration: ClinicalTrials.gov Identifier: NCT03688100.

The impact of the United Network of Organ Sharing allocation change on waitlist trajectories of inpatients listed with inotropic support: A single-center analysis.

BACKGROUND: In the United Network of Organ Sharing (UNOS) allocation scheme prior to October 18, 2018, heart transplant (HTx) candidates with extracorporeal membrane oxygenation (ECMO), temporary mechanical circulatory support (MCS), or pulmonary artery (PA) catheter inotropic support all received Status 1A priority. In revised scheme, patients with PA catheter and inotropic support are Status 3 after those on ECMO (Status 1) or temporary MCS (Status 2). We examined the impact of the allocation change on HTx candidates listed Status 1A versus Status 3 at a high-volume transplant center. METHODS: Between January 2017 and January 2021, 75 patients were listed with a PA catheter and inotropic support prior to the allocation change (Era 1) and 48 were listed after (Era 2). Clinical characteristics and outcomes were compared for these 123 patients. RESULTS: Heart transplant (HTx) candidates in Era 2 had higher median inotrope doses at listing. There was no significant difference in inpatient wait list days (12 vs. 20 days, P = .15), transition to temporary MCS (33.3% vs. 22.7%, P = .15), or wait list mortality (6.3% vs. 4.0%, P = .68). There was also no significant difference in survival to transplantation (91.7% vs. 94.7%, P = .71). There were no differences in post-transplant outcomes including 1-year survival (88.6% vs. 93.0%, P = .38). CONCLUSION: At a high-volume transplant center, the UNOS allocation change did not result in increased wait list time, use of temporary MCS, or mortality on the waitlist or post-transplant for candidates on inotropic support with continuous hemodynamic monitoring.

Mediating a host cell signaling pathway linked to overwinter mortality offers a promising therapeutic approach for improving bee health.

INTRODUCTION: Honey bees provides valuable pollination services for world food crops and wild flowering plants which are habitats of many animal species and remove carbon dioxide from the atmosphere, a powerful tool in the fight against climate change. Nevertheless, the honey bee population has been declining and the majority of colony losses occur during the winter. OBJECTIVES: The goal of this study was to understand the mechanisms underlying overwinter colony losses and develop novel therapeutic strategies for improving bee health. METHODS: First, pathogen prevalence in overwintering bees were screened between 2015 and 2018. Second, RNA sequencing (RNA-Seq) for transcriptional profiling of overwintering honey bees was conducted and qRT-PCR was performed to confirm the results of the differential expression of selected genes. Lastly, laboratory bioassays were conducted to measure the effects of cold challenges on bee survivorship and stress responses and to assess the effect of a novel medication for alleviating cold stress in honey bees. RESULTS: We identified that sirtuin signaling pathway is the most significantly enriched pathway among the down-regulated differentially expressed genes (DEGs) in overwintering diseased bees. Moreover, we showed that the expression of SIRT1 gene, a major sirtuin that regulates energy and immune metabolism, was significantly downregulated in bees merely exposed to cold challenges, linking cold stress with altered gene expression of SIRT1. Furthermore, we demonstrated that activation of SIRT1 gene expression by SRT1720, an activator of SIRT1 expression, could improve the physiology and extend the lifespan of cold-stressed bees. CONCLUSION: Our study suggests that increased energy consumption of overwintering bees for maintaining hive temperature reduces the allocation of energy toward immune functions, thus making the overwintering bees more susceptible to disease infections and leading to high winter colony losses. The novel information gained from this study provides a promising avenue for the development of therapeutic strategies for mitigating colony losses, both overwinter and annually.

Outcomes After Transcatheter Edge-to-Edge Mitral Valve Repair According to Mitral Regurgitation Etiology and Cardiac Remodeling.

BACKGROUND: Transcatheter edge-to-edge repair (TEER) has been increasingly used for selected patients with mitral regurgitation (MR), but limited data are available regarding clinical outcomes in patients with varied etiology and mechanism of MR. OBJECTIVES: The aim of this study was to evaluate the outcomes of TEER according to etiology and left ventricular (LV) and left atrial remodeling. METHODS: Consecutive patients who underwent TEER between 2007 and 2020 were included in the analysis. Among patients with functional MR (FMR), those with predominant LV remodeling were classified as having ventricular FMR (v-FMR), whereas those without LV remodeling but predominant left atrial remodeling were classified as having atrial FMR (a-FMR). The primary outcome was a composite of all-cause mortality and heart failure hospitalization at 2 years and was compared among patients with degenerative MR (DMR), a-FMR, and v-FMR. RESULTS: A total of 1,044 patients (11% with a-FMR, 48% with v-FMR, and 41% with DMR) with a mean Society of Thoracic Surgeons score of 8.6 ± 7.8 underwent TEER. Patients with a-FMR had higher rates of atrial fibrillation and severe tricuspid regurgitation with larger left and right atria, whereas patients with v-FMR had lower LV ejection fractions with larger LV dimensions. Residual MR more than moderate at discharge was not significantly different among the 3 groups (5.2% vs 3.2% vs 2.6%; P = 0.37). Compared with patients with DMR, 2-year event rates of the primary outcome were significantly higher in patients with a-FMR and v-FMR (21.6% vs 31.5% vs 42.3%; log-rank P < 0.001). CONCLUSIONS: Despite excellent procedural outcomes, patients with a-FMR and v-FMR had worse clinical outcomes compared with those with DMR.

Impact of Left Ventricular Global Longitudinal Strain on Outcomes After Transcatheter Edge-to-Edge Repair in Secondary Mitral Regurgitation.

Assessment of left ventricular (LV) systolic function is essential in patient selection for transcatheter edge-to-edge repair (TEER) in secondary mitral regurgitation (MR). Although LV ejection fraction (EF) is mostly used for assessing LV function, it represents the change of LV chamber size, but not myocardial contractility. LV global longitudinal strain (GLS) provides an alternative to assess LV systolic function in patients with secondary MR. This study included 380 patients with secondary MR (mean age 71.0 ± 13.0 years; 61.1% male) who underwent TEER. Patients were dichotomized based on baseline LV GLS (more impaired GLS [<7.0%] vs less impaired GLS [≥7%]) based on existing literature. The primary outcome was all-cause mortality, whereas the secondary outcome was the composite end point of all-cause mortality and heart failure hospitalization. The mean LV GLS was 8.1 ± 3.8%, and 162 patients had GLS <7%. Patients with more impaired GLS (<7%) were more likely to be male (68.5% vs 55.5%; p = 0.01) and have larger LV end-diastolic volume (110.5 ± 36.5 ml/m2 vs 92.9 ± 34.3 ml/m2; p <0.001) and lower LVEF (22.2 ± 8.9% vs 36.4 ± 14.5%; p <0.001) than those with less impaired GLS (≥7%). The number of clips used and residual MR were similar between the 2 groups. Patients with more impaired LV GLS (<7%) had significantly higher 2-year event rates of the primary outcome (38.2% vs 25.9%; log-rank p = 0.003) and the secondary outcome (52.5% vs 36.3%; log-rank p <0.001). Multivariate analysis showed that LV GLS (<7%) was independently associated with the primary outcome (hazard ratio 1.65, 95% confidence interval 1.16 to 2.34, p = 0.005) and the secondary outcome (hazard ratio 1.54, 95% confidence interval 1.08 to 2.20, p = 0.016) whereas such associations were not observed with LVEF. In conclusion, LV GLS (<7%) was independently associated with a higher risk of adverse events in patients with secondary MR who underwent TEER.

Prognostic Value of Increased Mitral Valve Gradient After Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation.

OBJECTIVES: This study sought to evaluate the prognostic value of an increased mean mitral valve pressure gradient (MVG) in patients with primary mitral regurgitation (MR) after transcatheter edge-to-edge repair (TEER). BACKGROUND: Conflicting data exist regarding impact of increased mean MVG on outcomes after TEER. METHODS: This study included 419 patients with primary MR (mean age 80.6 ± 10.4 years; 40.6% female) who underwent TEER. Patients were divided into quartiles (Qs) based on discharge echocardiographic mean MVG. Primary outcome was the composite endpoint of all-cause mortality and heart failure hospitalization. Secondary outcomes included all-cause mortality and the secondary composite endpoint of all-cause mortality, heart failure hospitalization, and mitral valve reintervention. RESULTS: The median number of MitraClips used was 2 per patient. MR reduction ≤moderate was achieved in 407 (97.1%) patients. Mean MVG was 1.9 ± 0.3 mm Hg, 3.0 ± 0.1 mm Hg, 4.0 ± 0.1 mm Hg, and 6.0 ± 1.2 mm Hg in Q1, Q2, Q3, and Q4, respectively. There was no significant differences across quartiles in the primary outcome (15.4%, 19.6%, 22.0%, and 21.9% in Q1-Q4, respectively; P = 0.63), all-cause mortality (15.9% vs 18.6% vs 19.4% vs 17.1%, respectively; P = 0.91), and the secondary composite endpoint at 2 years (33.3% vs 29.5% vs 22.0% vs 31.6%, respectively; P = 0.37). After multivariate adjustment for baseline clinical and procedural variables, the mean MVG in Q4 compared with Q1 to Q3 was not independently associated with the primary outcome (HR: 1.22; 95% CI: 0.82-1.83; P = 0.33), all-cause mortality, and the secondary composite endpoint. CONCLUSIONS: Increased mean MVG was not independently associated with adverse events after TEER in patients with primary MR.

Heart transplantation in muscular dystrophy: Single-center analysis.

INTRODUCTION: Cardiac involvement may occur in many forms of muscular dystrophy (MD). While cardiac disease may progress to warrant heart transplantation (HTx), there may be contraindications related to extra-cardiac disease including pulmonary and skeletal muscle involvement that limit overall survival and impairs post-transplant rehabilitation efforts. This study describes the MD HTx experience at a single high-volume center. METHODS: We examined the clinical characteristics and outcomes of patients with MD with heart failure (HF) (n = 28), patients with MD status post HTx (n = 20) and non-MD HTx control group (n = 40) matched 2:1 for age at transplant, sex, listing status, and antibody sensitization. RESULTS: Patients with MD who underwent HTx had increased ventilator days (2 vs. 1 days, p = .013), increased hospital length of stay (20 vs. 12 days, p = .022), and increased discharge to inpatient rehab (60% vs. 8%, p < .001). By 1 year post HTx, patients with MD more often required assistive devices for walking (55% vs. 10%, p = .01). Nonetheless, post-HTx survival was similar at 1 year (100% vs. 97.5%, p = .48) and 5 years (95.0% vs. 87.5%, p = .36). Of the HTx recipients with MD, 95% were followed by a neurologist, 60% by a neuromuscular specialist as part of the Muscular Dystrophy Association Clinic at our center. CONCLUSION: Transplantation is a feasible option for patients with MD and advanced HF. MD patients who undergo transplantation may benefit from multidisciplinary specialized care to optimize MD-related morbidity.

Quantitative Assessment of Cardiac Hypermetabolism and Perfusion for Diagnosis of Cardiac Sarcoidosis.

BACKGROUND: Quantitative assessment of cardiac hypermetabolism from 18Flourodeoxy glucose (FDG) positron emission tomography (PET) may improve diagnosis of cardiac sarcoidosis (CS). We assessed different approaches for quantification of cardiac hypermetabolism and perfusion in patients with suspected CS. METHODS AND RESULTS: Consecutive patients undergoing 18FDG PET assessment for possible CS between January 2014 and March 2019 were included. Cardiac hypermetabolism was quantified using maximal standardized uptake value (SUVMAX), cardiometabolic activity (CMA) and volume of inflammation, using relative thresholds (1.3× and 1.5× left ventricular blood pool [LVBP] activity), and absolute thresholds (SUVMAX > 2.7 and 4.1). Diagnosis of CS was established using the Japanese Ministry of Health and Wellness criteria. In total, 69 patients were studied, with definite or possible CS in 29(42.0%) patients. CMA above 1.5× LVBP SUVMAX had the highest area under the receiver operating characteristic curve (AUC 0.92). Quantitative parameters using relative thresholds had higher AUC compared to absolute thresholds (p < 0.01). Interobserver variability was low for CMA, with excellent agreement regarding absence of activity (Kappa 0.970). CONCLUSIONS: Quantitation with scan-specific thresholds has superior diagnostic accuracy compared to absolute thresholds. Based on the potential clinical benefit, programs should consider quantification of cardiac hypermetabolism when interpreting 18F-FDG PET studies for CS.

A novel method for the detection and diagnosis of virus infections in honey bees.

In terms of infectious diseases caused by a variety of microorganisms, the ability to promptly and accurately identify the causative agents is the first step on the path to all types of effective management of such infections. Among the various factors that are affecting global bee health, viruses have often been linked to honey bee colony losses and they pose a serious threat to the fraction of agriculture that depends on the service of pollinators. Over the past few decades, PCR-based molecular methods have provided powerful tools for rapid, specific, and sensitive detection and the quantification of difficult-to-grow pathogenic microorganisms such as viruses in honey bees. However, PCR-based methods require nucleic acid extraction and purification, which can be quite laborious and time-consuming and they involve the use of organic solvents and chaotropic agents like phenol and chloroform which are volatile and highly toxic. In response, we developed a novel and non-sacrificial method for detecting viral infections in honey bees. As little as 1 µl of hemolymph was collected from adult workers, larvae, and queens of bee colonies by puncturing the soft inter-tergal integument between the second and third dorsal tergum with a fine glass capillary. The hemolymph was then diluted and subjected to RT-PCR analysis directly. The puncture wound caused by the glass capillary was found to heal automatically and rapidly without any trouble and the lifespan of the experimental workers remained unaffected. Using this method, we detected multiple viruses including Deformed wing virus (DWV), Black queen cell virus (BQCV), and Sacbrood virus (SBV) in infected bees. Furthermore, expressed transcripts that indicate the induction of innate immune response to the virus infections were also detected in the hemolymph of infected bees. The simplicity and cost-effectiveness of this innovative approach will allow it to be a valuable, time-saving, safer, and more environmentally friendly contribution to bee disease management programs.

Transferrin-mediated iron sequestration suggests a novel therapeutic strategy for controlling Nosema disease in the honey bee, Apis mellifera.

Nosemosis C, a Nosema disease caused by microsporidia parasite Nosema ceranae, is a significant disease burden of the European honey bee Apis mellifera which is one of the most economically important insect pollinators. Nevertheless, there is no effective treatment currently available for Nosema disease and the disease mechanisms underlying the pathological effects of N. ceranae infection in honey bees are poorly understood. Iron is an essential nutrient for growth and survival of hosts and pathogens alike. The iron tug-of-war between host and pathogen is a central battlefield at the host-pathogen interface which determines the outcome of an infection, however, has not been explored in honey bees. To fill the gap, we conducted a study to investigate the impact of N. ceranae infection on iron homeostasis in honey bees. The expression of transferrin, an iron binding and transporting protein that is one of the key players of iron homeostasis, in response to N. ceranae infection was analysed. Furthermore, the functional roles of transferrin in iron homeostasis and honey bee host immunity were characterized using an RNA interference (RNAi)-based method. The results showed that N. ceranae infection causes iron deficiency and upregulation of the A. mellifera transferrin (AmTsf) mRNA in honey bees, implying that higher expression of AmTsf allows N. ceranae to scavenge more iron from the host for its proliferation and survival. The suppressed expression levels of AmTsf via RNAi could lead to reduced N. ceranae transcription activity, alleviated iron loss, enhanced immunity, and improved survival of the infected bees. The intriguing multifunctionality of transferrin illustrated in this study is a significant contribution to the existing body of literature concerning iron homeostasis in insects. The uncovered functional role of transferrin on iron homeostasis, pathogen growth and honey bee's ability to mount immune responses may hold the key for the development of novel strategies to treat or prevent diseases in honey bees.

Personalized treatments for depressive symptoms in patients with advanced heart failure: A pragmatic randomized controlled trial.

OBJECTIVES: Heart Failure is a chronic syndrome affecting over 5.7 million in the US and 26 million adults worldwide with nearly 50% experiencing depressive symptoms. The objective of the study is to compare the effects of two evidence-based treatment options for adult patients with depression and advanced heart failure, on depressive symptom severity, physical and mental health related quality of life (HRQoL), heart-failure specific quality of life, caregiver burden, morbidity, and mortality at 3, 6 and 12-months. METHODS: Trial design. Pragmatic, randomized, comparative effectiveness trial. Interventions. The treatment interventions are: (1) Behavioral Activation (BA), a patient-centered psychotherapy which emphasizes engagement in enjoyable and valued personalized activities as selected by the patient; or (2) Antidepressant Medication Management administered using the collaborative care model (MEDS). Participants. Adults aged 18 and over with advanced heart failure (defined as New York Heart Association (NYHA) Class II, III, and IV) and depression (defined as a score of 10 or above on the PHQ-9 and confirmed by the MINI International Neuropsychiatric Interview for the DSM-5) selected from all patients at Cedars-Sinai Medical Center who are admitted with heart failure and all patients presenting to the outpatient programs of the Smidt Heart Institute at Cedars-Sinai Medical Center. We plan to randomize 416 patients to BA or MEDS, with an estimated 28% loss to follow-up/inability to collect follow-up data. Thus, we plan to include 150 in each group for a total of 300 participants from which data after randomization will be collected and analyzed. CONCLUSIONS: The current trial is the first to compare the impact of BA and MEDS on depressive symptoms, quality of life, caregiver burden, morbidity, and mortality in patients with depression and advanced heart failure. The trial will provide novel results that will be disseminated and implemented into a wide range of current practice settings. REGISTRATION: ClinicalTrials.Gov Identifier: NCT03688100.

Heart Transplantation for Giant Cell Myocarditis: A Case Series.

BACKGROUND: Giant cell myocarditis (GCM) has a poor prognosis without heart transplant, but post-transplant survival is unknown. PURPOSE: To describe the post-transplant survival of patients with GCM at a large transplant center. METHODS: Seven patients underwent heart transplant for histologically confirmed GCM of the explanted heart. The median age was 59 years, and 43% (3 of 7) were female. All patients had cardiogenic shock, multiorgan failure, elevated troponin, and recurrent ventricular tachycardia, and some required mechanical circulatory support. All patients received rabbit antithymocyte globulin (rATG) in the perioperative period at a dose of 1.5 mg/kg daily for 1 to 5 days and 4 received intravenous immunoglobulin 1 g/kg daily for 2 days after rATG. All patients had early initiation of tacrolimus by first to third postoperative day depending on renal function, early mycophenolate, and high dose steroid. All were maintained using tacrolimus, mycophenolate, and prednisone. RESULTS: One patient had asymptomatic recurrence of GCM at 3 months, managed by up-titration of tacrolimus, and had asymptomatic 2R cellular rejection at 4 months, managed with steroid bolus. No patient had high-grade rejection. One patient died at 267 days, possibly of GCM. Six of 7 (86%) remain alive at a median of 842 days (2.3 years) post transplant. CONCLUSIONS: Patients with GCM have excellent post-transplant survival with use of rATG and triple drug immunosuppressive therapy; however, some patients remain at risk for GCM recurrence after transplant, which may respond to augmented immunosuppression.

High-protein vs. standard-protein diets in overweight and obese patients with heart failure and diabetes mellitus: findings of the Pro-HEART trial.

AIMS: The intermediate-term effects of dietary protein on cardiometabolic risk factors in overweight and obese patients with heart failure and diabetes mellitus are unknown. We compared the effect of two calorie-restricted diets on cardiometabolic risk factors in this population. METHODS AND RESULTS: In this randomized controlled study, 76 overweight and obese (mean weight, 107.8 ± 20.8 kg) patients aged 57.7 ± 9.7 years, 72.4% male, were randomized to a high-protein (30% protein, 40% carbohydrates, and 30% fat) or standard-protein diet (15% protein, 55% carbohydrates, and 30% fat) for 3 months. Reductions in weight and cardiometabolic risks were evaluated at 3 months. Both diets were equally effective in reducing weight (3.6 vs. 2.9 kg) and waist circumference (1.9 vs. 1.3 cm), but the high-protein diet decreased to a greater extent glycosylated haemoglobin levels (0.7% vs. 0.1%, P = 0.002), cholesterol (16.8 vs. 0.9 mg/dL, P = 0.031), and triglyceride (25.7 vs. 5.7 mg/dL, P = 0.032), when compared with the standard-protein diet. The high-protein diet also significantly improved both systolic and diastolic blood pressure than the standard-protein diet (P < 0.001 and P = 0.040, respectively). CONCLUSIONS: Both energy-restricted diets reduced weight and visceral fat. However, the high-protein diet resulted in greater reductions in cardiometabolic risks relative to a standard-protein diet. These results suggest that a high-protein diet may be more effective in reducing cardiometabolic risk in this population, but further trials of longer duration are needed.

The impact of depression on heart transplant outcomes: A retrospective single-center cohort study.

BACKGROUND: Depression is prevalent in patients with heart failure and after heart transplant. We identified the prevalence of pre- and post-transplant depression and its association with clinical characteristics and post-transplant outcomes. METHODS: We reviewed 114 adults transplanted 1/1/2015 to 12/31/2015 and identified patients with pre- and post-transplant depression. Clinical characteristics and outcomes were compared. RESULTS: Of 114 patients, 35.1% had pre-transplant depression and 26.3% had post-transplant depression. Patients with post-transplant depression within the first year were significantly more likely to have acute rejection (10% vs 0%), longer intensive care unit (11.7 days vs 7.8 days) and hospital stay (31.7 days vs 16.3 days), and discharge to inpatient rehabilitation (26.7% vs 8.3%). Patients with post-transplant depression within the first year had significantly higher 5-year mortality (30% vs 9.5%, p = .009). However, after adjustment for total artificial heart/biventricular assist device, acute rejection, intensive care unit, and hospital length of stay, this relationship was no longer significant (HR 2.11; 95% CI 0.18-25.27; p = .556). CONCLUSIONS: Depression is common among heart transplant candidates and recipients. While pre-transplant depression did not impact outcomes, patients with post-transplant depression were more likely to have had a complicated course, suggesting the need for increased vigilance regarding depression in such patients.

Complement inhibition for prevention of antibody-mediated rejection in immunologically high-risk heart allograft recipients.

Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre-formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%-97%) and 6250 (5000-10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14-0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037.

Impact of the United Network for organ sharing 2018 donor heart allocation system on transplant morbidity and mortality.

BACKGROUND: While the revised UNOS HTx donor allocation system aimed to minimize waitlist mortality by prioritizing more critically ill transplant candidates, there is concern for increased post-transplant morbidity and mortality. We examined the impact of the revised allocation system on waitlist and post-transplant outcomes at a high-volume transplant center. METHODS: One hundred and sixty nine adult patients underwent first-time single-organ HTx one year before (Era 1:79 patients) and after (Era 2:90 patients) implementation of the new allocation system (10/18/2018). Clinical characteristics, waitlist outcomes, and post-transplant morbidity and mortality were compared. RESULTS: Era 2 patients were twice as likely to be transplanted on temporary mechanical circulatory support (43% vs. 19%, p < .0001). While Era 2 waitlist time was shorter (10 vs. 43 days, p < .001), exception status requests (21.1% vs. 17.9%) and waitlist mortality (3.3% vs. 2.2%) were similar. There was no difference in primary graft dysfunction, intensive care unit or hospital length of stay, readmissions, rejection, allograft vasculopathy, or 1-year survival (91.1% vs. 93.7%). CONCLUSIONS: In a high-volume center, the revised HTx allocation system shortened waitlist time with no significant change in waitlist mortality or observed impact on post-transplant outcomes. With careful patient selection, the revised allocation system may optimize waitlist and post-transplant outcomes.

Depression in Heart Failure: A Systematic Review.

Objective: This paper sought to identify the instruments used to measure depression in heart failure (HF) and elucidate the impact of treatment interventions on depression in HF. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Studies published from 1988 to 2018 covering depression and HF were identified through the review of the PubMed and PsycINFO databases using the keywords: "depres*" AND "heart failure." Two authors independently conducted a focused analysis, identifying 27 studies that met the specific selection criteria and passed the study quality checks. Results: Patient-reported questionnaires were more commonly adopted than clinician-rated questionnaires, including the Beck Depression Inventory, the Patient Health Questionnaire (PHQ-9), and the Hospital Anxiety and Depression Scale. Six common interventions were observed: antidepressant medications, collaborative care, psychotherapy, exercise, education, and other nonpharmacological interventions. Except for paroxetine, selective serotonin reuptake inhibitors failed to show a significant difference from placebo. However, the collaborative care model including the use of antidepressants showed a significant decrease in PHQ-9 score after one year. All of the psychotherapy studies included a variation of cognitive behavioral therapy and patients showed significant improvements. The evidence was mixed for exercise, education, and other nonpharmacological interventions. Conclusion: This study suggests which types of interventions are more effective in addressing depression in heart failure patients.

The impact of antidepressants on depressive symptom severity, quality of life, morbidity, and mortality in heart failure: a systematic review.

OBJECTIVE: The purpose of this paper is to review the literature on the impact of antidepressants on depressive symptom severity, quality of life (QoL), morbidity, and mortality in patients with heart failure (HF). METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies published from December 1969 to December 2019 that pertain to depression and HF were identified through the use of the PubMed and PsycINFO databases, using the keywords: 'antidepressant*' and 'heart failure.' Two authors independently conducted a focused analysis and reached a final consensus on 17 studies that met the specific selection criteria and passed the study quality checks. RESULTS: Studies varied in types of antidepressants used as well as in study designs. Ten studies were analyzed for the impact of antidepressant medications on depressive symptom severity. Five of these were randomized controlled trials (RCTs), out of which sertraline and paroxetine showed a significant reduction in depressive symptoms despite the small samples utilized. Four of the 17 studies addressed QoL as part of their outcomes showing no difference for escitalopram (RCT), significantly greater improvements for paroxetine controlled release (RCT), statistical significance for sertraline compared to control (pilot study), and showing significant improvement before and after treatment (open-label trial) for nefazodone. Thirteen of the 17 studies included measures of morbidity and mortality. Although early analyses have pointed to an association of antidepressant use and mortality particularly with fluoxetine, the reviewed studies showed no increase in mortality for antidepressants, and secondary analyses showed improved mortality in patients who achieved remission of depressive symptoms. CONCLUSION: Out of the various antidepressants studied, which included sertraline, paroxetine, escitalopram, citalopram, bupropion, nefazodone, and nortriptyline, selective serotonin reuptake inhibitors seem to be a safe treatment option for patients with depression and HF. However, due to the variety of study designs as well as the mixed results for each antidepressant, more information for reducing depression severity, morbidity, and mortality and improving quality of life in patients with HF should be examined using robust large sample RCTs.

cBIN1 Score (CS) Identifies Ambulatory HFrEF Patients and Predicts Cardiovascular Events.

BACKGROUND: Cardiac Bridging Integrator 1 (cBIN1) is a membrane deformation protein that generates calcium microdomains at cardiomyocyte t-tubules, whose transcription is reduced in heart failure, and is released into blood. cBIN1 score (CS), an inverse index of plasma cBIN1, measures cellular myocardial remodeling. In patients with heart failure with preserved ejection fraction (HFpEF), CS diagnoses ambulatory heart failure and prognosticates hospitalization. The performance of CS has not been tested in patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: CS was determined from plasma of patients recruited in a prospective study. Two comparative cohorts consisted of 158 ambulatory HFrEF patients (left ventricular ejection fraction (LVEF) ≤ 40%, 57 ± 10 years, 80% men) and 115 age and sex matched volunteers with no known history of HF. N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were also analyzed for comparison. CS follows a normal distribution with a median of 0 in the controls, which increases to a median of 1.9 (p < 0.0001) in HFrEF patients. CS correlates with clinically assessed New York Heart Association Class (p = 0.007). During 1-year follow-up, a high CS (≥ 1.9) in patients predicts increased cardiovascular events (43% vs. 26%, p = 0.01, hazard ratio 1.9). Compared to a model with demographics, clinical risk factors, and NT-proBNP, adding CS to the model improved the overall continuous net reclassification improvement (NRI 0.64; 95% CI 0.18-1.10; p = 0.006). Although performance for diagnosis and prognosis was similar to CS, NT-proBNP did not prognosticate between patients whose NT-proBNP values were > 400 pg/ml. CONCLUSION: CS, which is mechanistically distinct from NT-proBNP, successfully differentiates myocardial health between patients with HFrEF and matched controls. A high CS reflects advanced NYHA stage, pathologic cardiac muscle remodeling, and predicts 1-year risk of cardiovascular events in ambulatory HFrEF patients. CS is a marker of myocardial remodeling in HFrEF patients, independent of volume status.