Alterations in Sarcopenia Index are Associated with Inflammation, Gut and Oral Microbiota among Heart Failure, Left Ventricular Assist Device and Heart Transplant Patients.

BACKGROUND: Sarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and predicts poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate for skeletal muscle mass, in HF, left ventricular assist device (LVAD) and heart transplant (HT), and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota. METHODS: We enrolled 460 HF, LVAD and HT patients. Repeated measures pre/post procedures were obtained prospectively in a subset of LVAD and HT patients. SI (serum Creatinine/Cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S rRNA sequencing among 335 stool and 341 saliva samples. Multivariable regression assessed the relationship between SI and i) New York Heart Association class; ii) pre- vs. post-LVAD or HT; iii) biomarkers of inflammation and microbial diversity. RESULTS: Median (interquartile range) natural logarithm (ln)-SI was -0.13 (-0.32,0.05). Ln-SI decreased across worsening HF class, further declined at 1-month after LVAD and HT and rebounded over time. Ln-SI was correlated with inflammation (r=-0.28, p<0.01), and gut (r=0.28, p<0.01) and oral microbial diversity (r=0.24, p<0.01), these associations remained significant after multivariable adjustment in the combined cohort but not for all individual cohorts. Presence of the gut taxa Roseburia inulinivorans was associated with increased SI. CONCLUSIONS: SI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. In the combined cohort, SI levels covaried with inflammation in a similar fashion and significantly related to overall microbial (gut and oral) diversity, including specific taxa compositional changes.

Utility of a fusion protein T-cell co-stimulation blocker Belatacept in heart transplant recipients: Real world experience from a high volume center.

BACKGROUND: Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. METHODS: A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023. RESULTS: Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (± 12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p = .054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p = .24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%). CONCLUSION: In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.

Long-term outcomes for pediatric heart transplant recipients transitioning to adult care teams.

BACKGROUND: There are limited data evaluating the success of a structured transition plan specifically for pediatric heart transplant (HT) recipients following their transfer of care to an adult specialist. We sought to identify risk factors for poor adherence, graft failure, and mortality following the transfer of care to adult HT care teams. METHODS: We retrospectively reviewed all patients who underwent transition from the pediatric to adult HT program at our center between January 2011 and June 2021. Demographic characteristics, comorbid conditions, and psychosocial history were collected at the time of HT, the time of transition, and the most recent follow-up. Adverse events including mortality, graft rejection, infection, and renal function were also captured before and after the transition. RESULTS: Seventy-two patients were identified (54.1% male, 54.2% Caucasian). Mean age at the time of transition was 23 years after a median of 11.6 years in the pediatric program. The use of calcineurin inhibitors was associated with reduced mortality (HR .04, 95% CI .0-.6, p = .015), while prior psychiatric hospitalization (HR 45.3, 95% CI, 6.144-333.9, p = .0001) was associated with increased mortality following transition. Medication nonadherence and young age at the time of transition were markers for high-risk individuals prior to the transition of care. CONCLUSIONS: Transition of HT recipients from a pediatric program to an adult program occurs during a vulnerable time of emerging adulthood, and we have identified risk factors for mortality following transition. Development of a formalized transition plan with a large multidisciplinary team with focused attention on high-risk patients, including those with psychiatric comorbidities, may favorably influence outcomes.

Hemodynamic Optimization by Invasive Ramp Test in Patients Supported With HeartMate 3 Left Ventricular Assist Device.

In patients supported by the HeartMate 3 left ventricular assist device (HM3 LVAD), pump speed adjustments may improve hemodynamics. We investigated the hemodynamic implications of speed adjustments in HM3 recipients undergoing hemodynamic ramp tests. Clinically stable HM3 recipients who underwent routine invasive hemodynamic ramp tests between 2015 and 2022 at our center were included. Filling pressure optimization, defined as central venous pressure (CVP) <12 mm Hg and pulmonary capillary wedge pressure (PCWP) <18 mm Hg, was assessed at baseline and final pump speeds. Patients with optimized pressures were compared to nonoptimized patients. Overall 60 HM3 recipients with a median age of 62 years (56, 71) and time from LVAD implantation of 187 days (124, 476) were included. Optimized filling pressures were found in 35 patients (58%) at baseline speed. Speed was adjusted in 84% of the nonoptimized patients. Consequently, 39 patients (65%) had optimized pressures at final speed. There were no significant differences in hemodynamic findings between baseline and final speeds (p > 0.05 for all). Six and 12 month readmission-free rates were higher in optimized compared with nonoptimized patients (p = 0.03 for both), predominantly due to lower cardiac readmission-free rates (p = 0.052). In stable outpatients supported with HM3 who underwent routine ramp tests, optimized hemodynamics were achieved in only 2 of 3 of the patients. Patients with optimized pressures had lower all-cause readmission rates, primarily driven by fewer cardiac-related hospitalizations.

A change of heart: Characteristics and outcomes of multiple cardiac retransplant recipients.

BACKGROUND: Among heart transplant (HT) recipients who develop advanced graft dysfunction, cardiac re-transplantation may be considered. A smaller subset of patients will experience failure of their second allograft and undergo repeat re-transplantation. Outcomes among these individuals are not well-described. METHODS: Adult and pediatric patients in the United Network for Organ Sharing (UNOS) registry who received HT between January 1, 1990 and December 31, 2020 were included. RESULTS: Between 1990 and 2020, 90 individuals received a third HT and three underwent a fourth HT. Recipients were younger than those undergoing primary HT (mean age 32 years). Third HT was associated with significantly higher unadjusted rates of 1-year mortality (18% for third HT vs. 13% for second HT vs. 9% for primary HT, p < .001) and 10-year mortality (59% for third HT vs. 42% for second HT vs. 37% for primary HT, p < .001). Mortality was highest amongst recipients aged >60 years and those re-transplanted for acute graft failure. Long-term rates of CAV, rejection, chronic dialysis, and hospitalization for infection were also higher. CONCLUSIONS: Third HT is associated with higher morbidity and mortality than primary HT. Further consensus is needed regarding appropriate organ stewardship for this unique subgroup.

Pumping for Two: Pregnancy in Patients Supported With a Left Ventricular Assist Device.

This review discusses the challenges and outcomes associated with pregnancy during left ventricular assist device (LVAD) support. Women account for a third of the heart failure population in the United States. Left ventricular assist devices have emerged as a safe and effective treatment option for patients with advanced heart failure. Pregnancy during LVAD support can occur, and it presents significant risks to both mother and fetus, including hemodynamic stress, thrombotic events, medication-associated teratogenicity, and uterine impingement. This literature review identified 10 cases of confirmed pregnancy during LVAD support, of which eight resulted in successful births. Maternal and fetal mortality occurred in one case, and there was a spontaneous abortion in one case. The review highlights the importance of a multidisciplinary approach, promotion of shared decision-making, thoughtful anticoagulation, adjustment of LVAD speed, and medication optimization to maintain hemodynamic support during pregnancy. Hemodynamic changes during pregnancy include increased cardiac output, heart rate, and plasma volume, as well as decreased systemic vascular resistance, which can impact LVAD support. Despite reduced pulsatility in LVAD-supported patients, ovulation and reproductive capacity might be preserved, and viable pregnancies may be achieved with appropriate management. The review provides insights into the risks and considerations for a viable pregnancy during LVAD support, including the need for ongoing research to inform joined decision-making.

The utilization of molecular microscope in management of heart transplant recipients in the era of noninvasive monitoring.

INTRODUCTION: Monitoring for graft rejection is a fundamental tenet of post-transplant follow-up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor-derived cell-free DNA (dd-cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB. METHODS: This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection. CONCLUSIONS: We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies.

Do age and functional dependence affect outcomes of simultaneous heart-kidney transplantation?

Objective: This study assessed characteristics and outcomes of younger (18-65) versus older (>65) recipients of simultaneous heart-kidney (SHK) transplantation with varying functional dependence. Methods: This study retrospectively analyzed 1398 patients from the United Network for Organ Sharing database who received SHK between 2010 and 2021. Patients who were <18 year old, underwent transplant of additional organs simultaneously, or had previous heart transplant were excluded. The primary end point was all-cause mortality, and secondary end points included adverse events and cause of death. Outcomes were also evaluated by propensity score-matched comparison. Results: The number of annual SHK transplantation in the United States has significantly increased among both age groups over the past 2 decades (P < .0001). After propensity score matching of recipients aged 18 to 65 years (n = 1162) versus age >65 years (n = 236), baseline characteristics were similar and well-balanced between the 2 cohorts. Between matched cohorts, older recipients did not have increased posttransplant mortality compared with younger recipients (90-day survival, P = .85; 7-year survival, P = .61). Multivariable Cox regression analysis found that age (hazard ratio [HR], 1.039 [0.975-1.106], P = .2415) and pretransplant functional status with interaction term for age (some assistance, HR, 0.965 [0.902-1.033], P = .3079; total assistance, HR, 0.976 [0.914-1.041], P = .4610) were not significant risk factors for 7-year post-SHK transplantation mortality. Conclusions: Older and more functionally dependent recipients in this study did not have increased post-SHK transplantation mortality. These findings have important implications for organ allocation among elderly patients, as they support the need for thorough assessment of SHK candidates in terms of comorbidities, rather than exclusion solely based on age and functional dependence.

New system, old problem: Increased wait time for high-priority transplant candidates.

The 2018 heart allocation policy sought to improve risk stratification and reduce waitlist mortality for the sickest patients. This study sought to evaluate changes in wait times for the highest priority patients since policy implementation. All adult single-organ transplant recipients were identified in the United Network for Organ Sharing registry from October 18, 2018, to July 8, 2022, and separated into 4 periods. Outcomes were compared by blood type and UNOS region. Over the study period, 897 of 9,143 patients were listed as status 1 with no significant change in median wait time by blood type or region. More patients were listed as status 2 (4,523/9,143), and each subsequent period postpolicy change was associated with a 4.2-day increase in mean status 2 waitlist time (95% confidence interval 3.0-5.5, p < 0.0001). Wait times were longest for candidates with blood type O and shortest for AB & A. Regional variations continued, however, wait time increased in every region over time.

Impact of preheart transplant spirometry and DCLO measurement on post-transplant pulmonary outcomes.

BACKGROUND: Pulmonary function tests (PFT) are a frequent component of heart transplant evaluation. In cardiac surgery abnormal PFTs, especially reduced DLCO, have been associated with poor outcomes. We sought to evaluate the impact of pretransplant PFTs on post-transplant pulmonary outcomes and patient survival. METHODS: Among the 652 adult heart transplant recipients between January 1, 2010 and July 31, 2021, 462 had PFTs and constituted the patient cohort. Obstructive ventilatory defects (OVD), restrictive ventilatory defects (RVD), and reduced DLCO were defined according to established criteria. The primary outcome was the combined endpoint of a post-transplant pulmonary complication defined as reintubation, postoperative pneumonia, prolonged intubation, or tracheostomy. Secondary outcomes included 90-day all-cause mortality, length of stay, and the odds of individual pulmonary complications. Kaplan-Meier survival analysis, multivariable Cox proportional-hazards regression, and multivariable logistic regression were performed to compare outcomes between the groups. RESULTS: Patients with severe OVD (OR 1.48, 95% CI 1.18-5.23, p = 0.02) or severely reduced DLCO (OR 1.95, 95% CI 1.19-3.20, p = 0.008) had increased odds of post-transplant pulmonary complications. Following multivariable adjustment, severe OVD (aOR 2.67, 95% CI 1.15-6.19, p = 0.02) and severely reduced DLCO (aOR 1.79, 95% CI 1.05-3.04) remained strongly associated with post-transplant pulmonary complications. Patients with any degree of extrinsic RVD, moderate or less OVD, or moderately reduced DLCO or less did not have increased odds of post-transplant pulmonary complications. Ninety-day post-transplant survival was significantly reduced for both severe OVD (97.2% vs 86.5%, p = 0.04) and severely reduced DLCO (97.3% vs 90.4%, p = 0.004). Post-transplant ICU and hospital length of stay were nominally longer for both groups as well. CONCLUSIONS: Severe OVD or severely reduced DLCO on preheart transplant PFTs were associated with increased odds of post-transplant pulmonary complications and early mortality.

Early post-transplant leukopenia in heart transplant recipients and its impact on outcomes.

BACKGROUND: Leukopenia in the early period following heart transplantation (HT) is not well-studied. The aim of this study was to evaluate risk factors for the development of post-transplant leukopenia and its consequences for HT recipients. METHODS: Adult patients at a large-volume transplant center who received HT between January 1, 2010 and December 31, 2020 were included. The incidence of leukopenia (WBC ≤3 × 103 /µL) in the first 90-days following HT, individual risk factors, and its effect on 1-year outcomes were evaluated. RESULTS: Of 506 HT recipients, 184 (36%) developed leukopenia within 90-days. Median duration of the first leukopenia episode was 15.5 days (IQR 8-42.5 days). Individuals who developed leukopenia had lower pre-transplant WBC counts compared to those who did not (6.1 × 103 /µL vs. 6.9 × 103 /µL, p = .02). Initial immunosuppressive and infectious chemoprophylactic regimens were not significantly different between groups. Early leukopenia was associated with a higher mortality at 1-year (6.6% vs. 2.1%, p = .008; adjusted HR 3.0) and an increased risk of recurrent episodes. Rates of infection and rejection were not significantly different between the two groups. CONCLUSIONS: Leukopenia in the early period following HT is common and associated with an increased risk of mortality. Further study is needed to identify individuals at highest risk for leukopenia prior to transplant and optimize immunosuppressive and infectious chemoprophylactic regimens for this subgroup.

Combined heart and liver transplantation in a patient supported by left ventricular assist device (LVAD) with propionic acidemia.

Propionic acidemia (PA) is a rare inherited metabolic disease due to inborn errors of metabolism. PA results in the accumulation of abnormal organic acid metabolites in multiple systems, mainly the central nervous system and the heart. Cardiac complications include dilated cardiomyopathy (DCM) and carry a 40-50% increased mortality risk. Liver transplantation (LT) is required in PA patients when medical treatment fails and may prevent or slow down the cardiomyopathy progression. However, severe heart disease may be a serious contraindication to LT. We present a complicated case of a PA patient, supported with a Left Ventricular Assist Device, who underwent a heart and Liver transplant. PA patients are at increased risk for metabolic acidosis during surgery, with increased anion gap and hyperammonemia. A strict multi-disciplinary approach is needed to prevent and treat metabolic decompensation. The patient had a successful heart and liver transplant after a strict treatment protocol in the pre, intra, and post-operative periods. His case highlights the complexity of PA patients and the increased risk for metabolic decompensation during surgery and provides an insight into how to manage such complicated patients.

PCSK9 inhibitors safely and effectively lower LDL after heart transplantation: a systematic review and meta-analysis.

Coronary allograft vasculopathy (CAV) continues to afflict a high number of heart transplant (HT) recipients, and elevated LDL is a key risk factor. Many patients cannot tolerate statin medications after HT; however, data for alternative agents remains scarce. To address this key evidence gap, we evaluated the safety and efficacy of the PCSK9i after HT through systematic review and meta-analysis. We searched Medline, Cochrane Central, and Scopus from the earliest date through July 15th, 2021. Citations were included if they were a report of PCSK9i use in adults after HT and reported an outcome of interest. Outcomes included change in LDL cholesterol from baseline, incidence of adverse events, and evidence of CAV. Changes from baseline and outcome incidences were pooled using contemporary random-effects model methodologies. A total of six studies including 97 patients were included. Over a mean follow-up of 13 months (range 3-21), PCSK9i use lowered LDL by 82.61 mg/dL (95% CI - 119.15 to - 46.07; I2 = 82%) from baseline. Serious adverse drug reactions were rarely reported, and none was attributable to the PCSK9i therapy. Four studies reported stable calcineurin inhibitor levels during PCSK9i initiation. One study reported outcomes in 33 patients with serial coronary angiography and intravascular ultrasound, and PCSK9i were associated with stable coronary plaque thickness and lumen area. One study reported on immunologic safety, showing no DSA development within 1 month of therapy. Preliminary data suggest that long-term PCSK9i therapy is safe, significantly lowers LDL, and may attenuate CAV after HT. Additional study on larger cohorts is warranted to confirm these findings.

The impact of pre-transplant weight loss on survival following cardiac transplantation.

BACKGROUND: Significant weight loss due to cardiac cachexia is an independent predictor of mortality in many heart failure (HF) clinical trials. The impact of significant weight loss while on the waitlist for heart transplant (HT) has yet to be studied with respect to post-transplant survival. METHODS: Adult HT recipients from 2010 to 2021 were identified in the UNOS registry. Patients who experienced an absolute weight change from the time of listing to transplant were included and classified into two groups by percent weight loss from time of listing to time of transplant using a cut-off of 10%. The primary endpoint was 1-year survival following HT. RESULTS: 5951 patients were included in the analysis, of whom 763 (13%) experienced ≥10% weight loss from the time of listing to transplant. Weight loss ≥ 10% was associated with reduced 1-year post-transplant survival (86.9% vs. 91.0%, long-rank p = .0003). Additionally, weight loss ≥ 10% was an independent predictor of 1-year mortality in a multivariable model adjusting for significant risk factors (adjusted HR 1.23, 95% CI 1.04-1.46). In secondary analyses, weight loss ≥ 10% was associated with reduced 1-year survival independent of hospitalized status at time of transplant as well as obesity status at listing (i.e., body mass index [BMI] < 30 kg/m2 and BMI ≥ 30 kg/m2 ). CONCLUSIONS: Preoperative weight loss ≥ 10% is associated with reduced survival in patients listed for HT. Nutrition interventions prior to transplant may prove beneficial in this population.

Noninvasive Physiologic Assessment of Cardiac Allograft Vasculopathy Is Prognostic for Post-Transplant Events.

BACKGROUND: Cardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial coronary arteries and the microvasculature. A leading cause of post-transplant mortality, CAV affects 50% of heart transplant recipients within 10 years of heart transplant. OBJECTIVES: This analysis examined the outcomes of heart transplant recipients with reduced myocardial blood flow reserve (MBFR) and microvascular CAV detected by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging. METHODS: A total of 181 heart transplant recipients who underwent PET to assess for CAV were included with a median follow-up of 4.7 years. Patients were classified into 2 groups according to the total MBFR: >2.0 and ≤2.0. Microvascular CAV was defined as no epicardial CAV detected by PET and/or coronary angiography, but with an MBFR ≤2.0 by PET. RESULTS: In total, 71 (39%) patients had an MBFR ≤2.0. Patients with an MBFR ≤2.0 experienced an increased risk for all outcomes: 7-fold increase in death or retransplantation (HR: 7.05; 95% CI: 3.2-15.6; P < 0.0001), 12-fold increase in cardiovascular death (HR: 12.0; 95% CI: 2.64-54.12; P = 0.001), and 10-fold increase in cardiovascular hospitalization (HR: 10.1; 95% CI: 3.43-29.9; P < 0.0001). The 5-year mean survival was 302 days less than those with an MBFR >2.0 (95% CI: 260.2-345.4 days; P < 0.0001). Microvascular CAV (adjusted HR: 3.86; 95% CI: 1.58-9.40; P = 0.003) was independently associated with an increased risk of death or retransplantation. CONCLUSIONS: Abnormal myocardial blood flow reserve, even in the absence of epicardial CAV, identifies patients at a high risk of death or retransplantation. Measures of myocardial blood flow provide prognostic information in addition to traditional CAV assessment.

Letermovir for cytomegalovirus prophylaxis in high-risk heart transplant recipients.

Letermovir is a novel agent for the prevention of cytomegalovirus (CMV) infection and disease that, unlike traditional CMV DNA polymerase inhibitors, does not carry the risk of myelosuppression. The purpose of this study was to evaluate the safety, efficacy, and clinical application of letermovir for CMV prophylaxis in heart transplant (HT) recipients. Between November 1, 2019, and October 1, 2021, at a single, tertiary care hospital, 17 HT recipients were initiated on letermovir due to leukopenia while on valganciclovir. Fifteen (88%) had high-risk mismatch (CMV D+/R-). Median time on letermovir was 5 months (interquartile range, 2-8 months.) At the end of the study period, nine of 17 patients (52.9%) were still on letermovir and four of the 17 (23.5%) had successfully completed the prophylaxis window on letermovir and been switched to the pre-emptive strategy. One patient developed clinically significant CMV viremia in the setting of being unable to obtain medication due to insurance barriers but was later successfully restarted on letermovir. One patient was unable to tolerate letermovir due to symptoms of headache and myalgias. Two patients developed low-level non-clinically significant CMV viremia and were switched back to valacyclovir. All patients had tacrolimus dosages reduced at time of letermovir initiation to minimize the risk of supratherapeutic tacrolimus concentration. One patient required hospitalization due to symptomatic tacrolimus toxicity. For HT recipients who cannot tolerate valganciclovir, letermovir presents an alternative for CMV prophylaxis. Close monitoring for breakthrough CMV and calcineurin inhibitor levels is necessary. Larger studies are required to further delineate its use and help provide further evidence of its safety and efficacy.

Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation.

STUDY OBJECTIVE: Mycophenolate mofetil (MMF) is the gold-standard immunosuppressive agent in heart transplantation (HT), but dose-dependent toxicities (e.g., neutropenia) are frequent. Gut bacteria ß-d-glucuronidases (GUS) modulate MMF bioavailability, and changes in the intestinal flora may influence the pharmacokinetics of MMF. The objective of this study was to evaluate the safety and efficacy of MMF 1.5 g every 12 h (q12) [high-dose, HD] versus 1 g q12 [low-dose, LD] and explore the association between neutropenia and GUS. MEASUREMENTS: We compared the incidence of acute cellular rejection (ACR) and neutropenia during the first 6 months post-HT. The association between neutropenia and GUS was investigated in an exploratory analysis on a subset of patients with prospectively collected stool data. Stool samples were analyzed using 16S rRNA sequencing. MAIN RESULTS: A total of 168 patients (120 MMF-HD, 48 MMF-LD; mean age 55.7 years, 79% male) were studied. Neutropenia occurred in 38.6% of patients at a median of 106 [64-143] days. Freedom from neutropenia was lower in MMF-HD compared with MMF-LD (57% vs. 73%, p = 0.03). ACR (≥1R/1B) occurred in 37.5% of patients at a median of 20 [10-96] days, while high-grade ACR (≥2R/3A) occurred in 11.3% at a median of 14 [9-89] days. Freedom from ACR was similar between groups. MMF-LD was associated with more high-grade ACR (hazard ratio [HR] 3.47, 95% confidence interval [CI] 1.09-11.08, p = 0.03) during the first month, but less neutropenia (HR 0.54, 95% CI 0.29-1.00, p = 0.05) between 1 and 6 months. GUS-producing bacteria were more abundant in neutropenic patients. CONCLUSIONS: MMF-LD was associated with higher rates of early high-grade ACR and lower rates of later neutropenia. Further studies are warranted to test whether temporal MMF dose adjustments and gut microbial composition could improve clinical outcomes post-HT.

Predictors of 1-year outcome after cardiac re-transplantation: Machine learning analysis.

BACKGROUND: As cardiac re-transplantation is associated with inferior outcomes compared with primary transplantation, allocating scarce resources to appropriate re-transplant candidates is important. The aim of this study is to elucidate the factors associated with 1-year mortality in cardiac re-transplantation using the random forests algorithm for survival analysis. METHODS: We retrospectively reviewed the United Network for Organ Sharing registry and identified all adult (> 17 years old) recipients who underwent cardiac re-transplantation between January 2000 and March 2020. The random forest algorithm on Cox modeling was used to calculate the variable importance (VIMP) of independent variables for contributing to 1-year mortality. RESULTS: A total of 1294 patients underwent cardiac re-transplantation. Of these, 137 patients were re-transplanted within 1 year of their first transplant, while 1157 patients were re-transplanted more than 1 year after their first transplant. One-year mortality was significantly higher for patients receiving early transplantation compared with those receiving late transplantation (Early 40.6% vs. Late 13.6%, log-rank P < .001). Machine learning analysis showed that total bilirubin (> 2 mg/dl) (VIMP, 2.99%) was an independent predictor of 1-year mortality after early re-transplant. High BMI (> 30.0 kg/m2 ) (VIMP, 1.43%) and ventilator dependence (VIMP, 1.47%) were independent predictors of 1-year mortality for the late re-transplantation group. CONCLUSION: Machine learning showed that optimal 1-year survival following cardiac re-transplantation was significantly related to liver function in early re-transplantation, and to obesity and preoperative ventilator dependence in late re-transplantation.

Deep vein thrombosis and pulmonary embolism after heart transplantation.

INTRODUCTION: Venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important and serious postoperative complication after heart transplantation. We sought to characterize in-hospital VTE after heart transplantation and its association with clinical outcomes. METHOD: Adult (≧18 years) patients undergoing heart transplantation from 2015 to 2019 at our center were retrospectively reviewed. Post-transplant VTE was defined as newly diagnosed venous system thrombus by imaging studies. RESULTS: There were 254 patients. The cohort's median age was 55 years. A total of 61 patients were diagnosed with VTE, including one with right atrial thrombus, 54 with upper extremity DVT in which one patient subsequently developed PE, four with lower extremity DVT, and two with upper and lower extremity DVT. The cumulative incidence of VTE was 42% at 60-days of post heart transplant. Patients with VTE had longer hospital stay (P < .001), higher in-hospital mortality (P = .010), and worse 5-year survival (P = .009). On the multivariable Cox analysis, history of DVT/PE and intubation for more than 3 days were associated with an increased risk of in hospital VTE. CONCLUSION: The incidence of VTE in heart transplant recipients is high. Post-transplant surveillance, and appropriate preventive measures and treatment strategies after diagnosis are warranted.

The use of telemedicine in cardiogenetics clinical practice during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has necessitated the rapid and widespread adoption of novel mechanisms of service delivery, including the use of telemedicine. The aim of this study was to examine the impact of COVID-19 on cardiogenetics practices. METHODS: We retrospectively analyzed the clinical characteristics of patients who were seen for cardiogenetics visits pre-pandemic (1 April-23 December 2019) and during the pandemic (1 April-23 December 2020) at Columbia University Irving Medical Center. RESULTS: Six percent (n = 6) of visits in 2019 were remote telemedicine encounters, whereas 80% (n = 106) of visits in 2020 were telemedicine encounters. In 2019, only 18% (n = 19) of the patients seen for genetic counseling were family members of probands; this percentage increased to 34% in 2020 (n = 45; p = .01). In 2020, the geographic reach of genetic counseling also extended far beyond New York State, reaching a total of 11 states as well as one patient in Puerto Rico. Genetic testing results were similar in 2019 and 2020. CONCLUSION: Despite the health-care delivery barriers created by the COVID-19 pandemic, the use of telemedicine allowed us to expand the reach of cardiovascular genetic counseling and testing.