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In addition to goal-directed therapies, advanced therapies for heart failure including left ventricular assist devices (LVADs) remain underutilized in women. Sex-specific data in the area of mechanical circulatory support remains sparse and women are often underrepresented in heart failure trials. Even less is known about sex differences in outcomes with the HeartMate 3 LVAD, an FDA approved centrifugal-flow device. Consecutive patients who received HeartMate 3 LVAD as bridge-to-transplant or destination therapy at a single institution were included in the study. Demographics, co-morbidities, device-related factors, and outcomes were comparatively examined between women and men. 175 patients (28 women, 16.0%) were identified. Women were significantly younger than men (53.9 vs. 60.1 years, p=0.023) with smaller body surface area (1.83 vs 2.08, p <0.001). Women were less likely to have hypertension (42.9% vs 64.6%, p=0.030), to use tobacco (35.7% vs 57.5%, p=0.034), and to have an ischemic etiology of HF (21.4% vs 52.4%, p=0.003). There were no differences in the use of temporary mechanical circulatory support and INTERMACS profiles. There were similar rates of RVAD use (35.7% vs. 30.6%, p=0.594) and continuous veno-venous hemofiltration (10.7% vs 8.2%, p=0.659) in women and men. There were no differences in in-hospital mortality (3.7% vs 6.3%, p=0.595) or 90-day mortality (8.7% vs 6.9%, p=0.762) between women and men. There was no difference in post-implant survival (82.8% vs 87.7%, log-rank p=0.944) [Figure], freedom from gastrointestinal bleeding (70.5% vs 69.1%, log-rank p =0.278) or freedom from stroke (96.4% vs 91.4%, log-rank p = 0.471) at 2-year follow-up between women and men. In our single-center experience with HeartMate 3 LVADs, there were no significant differences in early morbidity and mortality between women and men. [ABSTRACT FROM AUTHOR]

MOMENTUM 3 trial excluded patients with planned biventricular support prior to enrollment and 4.2% right ventricular failure requiring RVAD in Heartmate 3 (HM 3) patients. The aim of this study was to assess the use of RVAD in the real-world post-approval era. HM3 implantation at a major academic center were categorized into two era: HM 3 implanted 1) before FDA approval (8/23/2017) [N=67] and 2) after FDA approval [N=107]. Baseline patient characteristics, RVAD utilization patterns, and LVAD complications and mortality were analyzed in the pre- vs. post-approval era. In the post-approval era, HM3 patients were younger (57.5±14.1 vs 61.7±11.2 yrs, p=0.031), more likely to have ischemic etiology of heart failure (55.6% vs 34.3%, p=0.006), to be INTERMACS Class I (21.3% vs. 1.5%, p=0.002), and to have VA-ECMO or paracorporeal VAD support (12.0% vs 0.0%, p=0.012) prior to HM3 implant. 8 (11.9%) patients out of 67 required RVAD in the pre-approval era as opposed to 47 patients out of 108 (43.5%) in the post-approval era (p<0.001). All patients in the pre-approval era received unplanned RVAD (8, 100%) compared to 16 patients (34.0%) in the post-approval era (p<0.001). Despite increased utilization of RVADs, the risk of CVVHD (6.0% vs 10.2%, p=0.413), post-LVAD length of stay (34.3±32.9 vs 41.7±40.0 days), and in-hospital mortality (4.5% vs 6.9%, p=0.741) were comparable in pre- vs. post-approval era. There was no difference in post-implant survival (89.7% vs. 84.7%, log-rank p=0.357), freedom from gastrointestinal bleeding (70.0% vs. 70.4%, log-rank p =0.831) or freedom from stroke (93.2% vs. 92.2% log-rank p = 0.547) at 2-year follow-up in the pre- vs. post- approval period. Level of sickness at the time of device implantation as well as need for RVAD utilization increased substantially in HM3 patients following the FDA approval. However, the change in practice did not adversely affect post-LVAD morbidity or mortality. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Low muscle mass and sarcopenia: common and predictive of osteopenia in inflammatory bowel disease," by R. V. Bryant and colleagues in the 2015 issue.

A subset of HT recipients are considered for cardiac re-transplantation for various forms of graft dysfunction. Outcomes of individuals who undergo ≥2 re-transplant are not well-described. Patients in the United Network for Organ Sharing (UNOS) registry who received HT between January 1, 1990 and December 31, 2020 were included. Patient characteristics and post-transplant outcomes in HT recipients who received ≥2 re-transplants during the study period were evaluated. Between 1990 and 2020, there were 87 individuals who received 3 HT and 3 individuals who received 4 HT. Of the 68 individuals with initial HT within the study period, median age at the time of first HT was 24 years (IQR 14-44), with 49 (72%) individuals <18 years of age. Fifty-three percent were male; 62% identified as White. Dilated cardiopathy (47%) and congenital heart defects (34%) were the most common etiologies leading to initial HT. Median time from initial HT to first re-transplant was 5.8 years (IQR 3.0-10.1) and 5.5 years (IQR 2.9-10.8) from first re-transplant to second re-transplant. Twelve individuals (13%) received concomitant renal transplants with the first cardiac re-transplant, and 5 (6%) received concomitant renal transplants with the second cardiac re-transplant. The most common causes of graft failure necessitating a second cardiac re-transplant were CAV (62%) followed by chronic rejection (10%). Survival estimates at 1 year and 10 years following the second re-transplant were 85.2% (95% CI 75.7%-91.1%) and 56.8% (95% CI 44.8%-61.7%), respectively. A small subset of HT recipients go on to receive multiple cardiac re-transplants. Survival at 10-years following the second cardiac re-transplant is greater than 50%. Further examination of the ethical implications around cardiac re-transplantation is needed. [ABSTRACT FROM AUTHOR]

Heartmate II risk score (HMRS) and MELD-Xi score are validated mortality risk predictors in Heartmate II left ventricular assist device (LVAD) patients. Prognostic utility of these risk scores remains unknown in patients considered for Heartmate 3 (HM3) LVAD therapy. HMRS were calculated for 175 consecutive patients who underwent HM3 LVAD implantation at a single academic institution. Receiver operating characteristic (ROC) curve and logistic- and cox-regression models were developed to assess the impact of HMRS and MELD-Xi scores on short- and long-term outcomes in HM3 patients. Mean HMRS and MELD-Xi scores in HM3 population was 1.38±0.57 and 14.4±0.28, respectively. Pre-implant HMRS was not predictive of RVAD use (OR 1.25, p=0.392), CVVHD (OR 1.16, p=0.722), in-hospital mortality (OR 1.52, p=0.409), or 90-day mortality (OR 1.44, p=0.457). Pre-implant MELD-Xi score showed trend towards increased RVAD use (OR 1.09, p=0.056) and need for CVVH (OR 1.14, p=0.064), however was not predictive of in-hospital mortality (OR 1.02, p=0.836), or 90-day post-LVAD mortality (OR 0.958, p=0.636). Area under curve (AUC) for in-hospital mortality was 0.531 for HMRS and 0.525 for MELD-Xi score (Figure). There was no difference in post-implant survival (88.6% vs. 85.7%, log-rank p=0.569), freedom from GI bleeding (73.5% vs. 65.1%, log-rank p =0.257) or freedom from stroke (93.3% vs. 90.8% log-rank p = 0.478) at 2-year follow-up in patients with below average vs. above average HMRS. Similarly, There was no difference in post-implant survival (91.3% vs. 82.3%, log-rank p=0.121), freedom from gastrointestinal bleeding (72.2% vs. 65.2%, log-rank p =0.257) or freedom from stroke (92.0% vs. 92.4% log-rank p = 0.820) at 2-year follow-up in patients with below average vs. above average MELD-Xi score. HMRS and MELD-Xi scores do not predict mortality in patients undergoing HM3 implantation. New prediction models are required to optimize patient selection and outcomes in HM3 patients. [ABSTRACT FROM AUTHOR]

The 2018 OPTN heart allocation policy was modified with a stated goal of improving access to individuals with the greatest medical need through improved stratification of risk. Criteria were created to identify patients with the highest risk (Status 1 and 2) to facilitate timely transplantation. This study sought to evaluate changes in wait times for the highest priority patients since implementation of the 2018 policy. All adult single-organ transplant recipients were identified in the UNOS registry from 10/18/18 through 7/8/22. Patients were identified from the date they were upgraded to Status 1 or 2 and separated to 4 periods: 10/2018-9/2019, 9/2019-8/2020, 8/2020-7/2021, & 7/2021-6/2022. Outcomes were compared by blood type and UNOS region. 897 patients were upgraded to Status 1 (n=197, 194, 231, & 290 in each period) and there was no clinically meaningful change in median waitlist time during the study period (4 days (IQR 2-7), 4 days (IQR 2-9), 4 days (IQR 2-7), 5 days (IQR 2-9)). There was also no difference by blood type or listing region (Figures 1A & B). 4,523 patients were upgraded to Status 2 (n=861, 1,076, 1,242, & 1,344 in each period), and the median waitlist time incrementally increased during each period: 7 days (IQR 4-13) to 8 (IQR 4-17) to 9 (IQR 5-20) to 12 (IQR 6-25), p<0.0001. Wait time was consistently longest for Blood Type O and shortest for Type AB & Type A (Figure 1C). Regional variations in wait time continue, however wait time increased in every region over time (Figure 1D). After adjusting for age, gender, race, cPRA>50%, UNOS region, recipient BMI, and blood type, time period continued to be significantly associated with longer wait time for Status 2 (p<0.0001). Status 1 wait time has been consistent since implementation of the 2018 heart allocation policy change. However, Status 2 wait time continues to increase with variation by region and blood type, limiting the ability to improve transplant access to individuals with the greatest medical need. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). CAV results in impaired blood flow in the epicardial coronaries and microvasculature. Reduction in myocardial blood flow reserve (MBFR) by cardiac PET has been associated with adverse post-HT events. This study sought to investigate the prognostic implication of isolated microvascular CAV. Consecutive adult HT recipients who underwent cardiac N13 ammonia PET for assessment of CAV from 2016-2019 were included. Primary outcome was death or retransplant. Patients were classified into 2 groups according to MBFR >2 or ≤2. Microvascular CAV was defined as an MBFR≤2 without epicardial CAV on PET (SDS<2) or angiography (ISHLT CAV 0). Mixed CAV had both ischemia on PET (SDS≥2) or angiography (ISHLT CAV 1+) and MBFR≤2. 465 patients were included, with median age of 61 years, median time from transplant of 7.8 years, and 26.2% were women. 139 (29.9 %) patients had MBFR≤2, which was associated with a 3-fold increased risk of death/retransplant (HR 3.0, 95% CI 2.0-4.4, p<0.0001). Patients with reduced MBFR were further divided into microvascular (n=114) and mixed CAV (n=25). Mixed CAV was associated with 3.7 times the risk of death/retransplant (95% CI 2.1-6.6, p<0.0001). Microvascular CAV (PET or angiography definition) more than doubled the risk of death/retransplant (HR 2.1, 95% CI 1.4-3.2, p<0.0001; HR 2.1, 95% CI 1.3-3.2, p=0.001, Figure 1A & B). In a multivariable model with significant univariate predictors including sex, time post-HT, PSI use, statin use, ISHLT CAV 2 or 3, DM, GFR<60, prior ACR, prior AMR, and DSA, Microvascular CAV (HR 1.8, 95% CI 1.2-2.7, p=0.006) remained independently associated with an increased risk of death/retransplant. Isolated Microvascular CAV is a harbinger of death/retransplant. This highlights the clinical utility of measuring MBFR to help risk stratify patients following HT. [ABSTRACT FROM AUTHOR]

Cardiac positron emission tomography (PET) has been used for surveillance of cardiac allograft vasculopathy (CAV) following heart transplant (HT). Visually estimated coronary artery calcium (VECAC) can be quantified during PET and has been associated with adverse cardiovascular outcomes in CAD. The utility of VECAC following HT has not been established, and given the differing pathophysiology of CAV and CAD, we investigated the prognostic value of VECAC following HT. We performed a retrospective analysis of all consecutive adult HT patients who underwent N-13 cardiac PET 2016-2019 with follow-up through June 30, 2022. VECAC categories were defined as: 0 (V0, n=319), 1-9 (V1, n=44), 10-99 (V2, n=34), and 100+ (V3, n=33). The association between baseline VECAC categories and various outcomes was assessed using univariate and multivariable Cox regression. The primary outcome was death or retransplantation. 430 patients were identified with median age of 61 years and time post HT of 4.3 years. 73% were male, 33% had diabetes, 67% had GFR<60, and median BMI was 26. Compared with V0, VECAC categories V2 (HR 2.2, 95% CI 1.2-4.1, p=0.009) and V3 (HR 3.4, 95% CI 2.0-6.0, p<0.001) were associated with an increased risk of death/retransplantation (Figure 1). While V2 was not statistically associated with CV death (HR 2.0, 95% CI 0.83-5.0, p=0.1), V3 was (HR 2.6, 95% CI 1.1-6.1, p=0.03). Adjusting for risk factors including angiographic CAV, myocardial blood flow reserve (MBFR), GFR<60, DM, age, and time post HT, V2 (HF 1.9, 95% CI 1.0-3.6, p=0.05) and V3 (HR 2.9, 95% CI 1.5-5.7, p=0.001) remained associated with death/retransplantation. Interaction testing with MBFR demonstrated that V3 was consistently associated with death/retransplantation (MBFR<2: HR 3.1, p=0.01; MBFR>2: HR 2.8, p=0.007), while V2 was only associated with death/retransplantation when MBFR>2 (HR 2.3, p=0.04). VECAC is an independent prognostic marker of death or retransplantation following HT. [ABSTRACT FROM AUTHOR]

Adult congenital heart disease (ACHD) patients have the potential for increased sensitization and complications deriving from repeated interventions. Donor-derived cell-free-DNA (dd-cfDNA) test is a non-invasive method for surveillance of allograft injury. We sought to characterize dd-cfDNA in ACHD recipients and its impact on post-heart transplant (HT) outcomes. We performed a retrospective analysis of patients who underwent HT in our institution between January 2005 and January 2021, and who had at least one dd-cfDNA result. Multiorgan recipients were excluded. Patients with a history of ACHD were compared to adult HT recipients with no history of ACHD (control group). Dd-cfDNA was considered positive if >0.12%. Samples reported as <0.12% were analyzed as 0.11%. A total of 418 patients were identified; 23 ACHD patients and 395 control patients were included. ACHD patients were younger (38 years vs. 56 years, p <0.001) and the majority (73%) were male. The median dd-cfDNA did not differ between the groups (p=0.49). Endomyocardial biopsy proven allograft rejection, graft dysfunction, formation of donor specific antibody, and cardiac allograft vasculopathy did not differ between the groups during the follow-up period (2100 days in the ACHD group vs 1430 days in the control group, p=0.09). In this retrospective single center study, HT recipients with a history of ACHD did not demonstrate significantly elevated dd-cfDNA levels as compared to control. ACHD patients similarly did not have a higher incidence of endomyocardial biopsy proven allograft rejection or graft dysfunction. [ABSTRACT FROM AUTHOR]

Improvements in cancer therapies have led to a growing population of cancer survivors (CS) who are recipients of heart transplantation (HT). CS have been shown to have long-term alterations in immune function from prior cancer treatments leading to challenges in management of immunosuppression. Post-HT donor-derived cell-free-DNA (dd-cfDNA) testing is a noninvasive method used to detect allograft rejection. We sought to evaluate the effect of pre-HT malignancy on dd-cfDNA and post-HT outcomes. All consecutive patients who underwent HT at our institution between 1990 to 2022 with at least one dd-cfDNA result were included in the analysis. Dd-cfDNA results in the CS group were compared to patients free from malignancy (FFM). Dd-cfDNA was considered positive if >0.12%. For the purpose of this analysis, samples reported as <0.12% were analyzed as 0.11%. A total of 588 patients were identified. There were 47 (8%) patients in the CS group and 541 (92%) patients in the FFM group. CS were older at the time of transplant (60 vs 54 years, p = 0.03) with a median time from active malignancy to HT of 8 [3.5, 16.5] years. Leukemia/lymphoma was the most common cancer type (27.7%) followed by breast, prostate, and gastrointestinal (13% each). In the CS group, 38.3% of the dd-cfdNA samples were positive compared to 29.4% in the FFM group (p=0.004). The prevalence of donor-specific antibodies (DSA) was similar in the CS and FFM groups, 23.7% and 23.4%, respectively (p=0.86). There was no difference in biopsy-proven cellular and antibody-mediated rejection or graft failure during the follow-up period (1450 and 1830 days in CS vs. FFM groups, respectively; p=0.62). In our cohort, the CS group had higher rates of positive donor-derived cell-free-DNA results compared to patients without preexisting malignancy. Future studies are needed to assess the immunosuppression protocols of both groups and assess if this can be the cause of the differences we found. [ABSTRACT FROM AUTHOR]

Left Ventricular Assist Devices (LVAD) improve the survival and quality of patients with advanced heart failure. LVAD implant centers are frequently located remotely from patients' homes, which can be challenging when frequent follow-up is required. Shared care is a system where care these patients are managed by a collaboration between the implanting center and local, shared-care sites. This study aimed to assess the outcome of patients treated in a shared care model Retrospective analysis of all patients implanted with a LVAD at a large academic center between 1/2015-9/2021 and were treated in a shared care model. 30 LVAD patients were identified for the analysis. The mean age was 61±10 years, 24 (80%) were men, and the median time of follow-up was 741 (IQR 398, 1381) days. Most patients were implanted as destination therapy (21, 70%), and 16 (53%) received a HeartMate III LVAD. During follow-up, 6 (20%) patients died at a median follow-up of 743 (IQR 403,1371) days, 7 (23%) were transplanted at a median follow-up of 739 (IQR 398,1338) days, and 17 (56%) are alive (Figure). 9 (30%) patients had major bleeding events, 6 (20%) had driveline infections, and 3 (10%) had device malfunction and 3 (10%) had device thrombosis. A shared care model is a feasible and effective way to care for LVAD patients who live far from their implanting center. In this study, adverse outcomes occurred in this population at an expected rate. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) emerged as a biomarker of inflammation in heart failure patients and associated with increased morbidity and mortality. We hypothesized that higher serum CRP level prior to Heartmate 3 LVAD implantation is associated with increased risk of post-implant adverse events and mortality. 123 patients who underwent Heartmate 3 LVAD implantation at a tertiary care center and had a CRP level measured prior to device implant were included in the analysis. Optimal CRP cut-off was determined used ROC curve and patients were categorized into high vs. low CRP groups accordingly. Study end-points included RVAD use, need for CVVH, in-hospital mortality, and 2-year survival. Mean and median pre-implant CRP levels in HM3 patients were 35.5±43.6 mg/L and 15.0 mg/L respectively. Patients with an elevated pre-implant CRP (≥12 mg/L) were more likely to be in INTERMACS Class I or II (78.4% vs. 46.6%), to have temporary MCS (49.2% vs. 27.5%), and elevated WBC count (9.1 vs. 7.5) compared to those with a pre-implant CRP less than 12 mg/L (all p <0.05). High CRP group had significantly higher RVAD use (32.3% vs. 15.5%, p=0.030), need for CVVHD (13.8% vs. 3.4%), and in-hospital mortality (14.0% vs. 1.8%, p=0.028). Patients with elevated pre-implant CRP had significantly lower survival compared to those with lower pre-implant CRP (74.2% vs. %96.1, log-rank p =0.020) and a trend-towards lower freedom from post-implant stroke (%89.2 vs. %98.3, log-rank p =0.072) at 2-year follow-up (Figure). After adjustment for age, ischemic etiology, creatinine, bilirubin, albumin, and INTERMACS Class, high CRP (≥ 12 mg/L) remained as an independent predictor of survival on LVAD support (HR 3.81 [1.35 - 10.75], p=0.011). Pre-implant CRP is a strong predictor of morbidity and mortality in patients undergoing HM3 implantation. Routine assessment of CRP prior to implant may improve patient selection and outcomes in this population. [ABSTRACT FROM AUTHOR]