BackgroundProlonged ischemic times (IT) for transplant hearts transported under cold storage conditions are associated with an increased risk of mortality, however the impact of IT on functional outcomes, such as exercise capacity, is not fully understood. This prospective, observational cohort study aimed to determine the association between exercise capacity, a strong predictor for post-transplant survival, and relatively longer IT.MethodsThirty heart transplant recipients were grouped dichotomously according to relatively longer (>180 min) or shorter (≤180 min) IT. A cardiopulmonary exercise test (CPET) was performed post-transplant upon entry into cardiac rehabilitation, during which peak VO2 was measured using a metabolic cart. CPET variables, including exercise capacity and test duration, were compared between groups.ResultsThis cohort was predominantly male (n=22, 73%) with a median age of 57.5 years [Q1-Q3: 54.0 - 65.0]). Baseline demographics and characteristics were similar between groups aside from UNOS listing status, in which patients listed as Status 1 or 2 were more likely to have long IT. Twelve (40%) participants received a donor heart with long IT. Surprisingly, higher peak VO2 was observed in those with long (15.0±2.8) than short (13.1±3.7) IT (p=0.009). However, CPET duration was significantly shorter in recipients with a long IT (6.3 vs. 7.7 minutes, p=0.048) despite similar time since transplant, rate of perceived exertion, protocol performed, and exercise capacity.ConclusionsIn this modest-sized cohort, exercise capacity was higher in heart transplant recipients with donor IT >180 minutes compared to those with IT ≤180 minutes. However, exercise duration was significantly shorter in those with relatively longer IT.

BACKGROUND:Endomyocardial biopsy (EMBx) is considered the gold standard for rejection monitoring after heart transplantation; however, it is invasive and histologic interpretation has limitations. Sensitive blood biomarkers, including donor-derived cell-free DNA (dd-cfDNA), have emerged to decrease EMBx frequency. METHODS:We retrospectively reviewed data on 237 patients who underwent heart transplantation at our institution. Of these, 125 patients underwent monitoring using dd-cfDNA, combined with a fewer number of EMBx, and 112 patients underwent monitoring using EMBx only. We compared rates of rejection, graft dysfunction, and survival at 1 year. RESULTS:Median age at time of transplant was 59.8 years, and 77.6% were men. In the dd-cfDNA group, there were significantly fewer episodes of EMBx defined acute cellular rejection (ACR) (2.5% vs 18.8%, p < 0.001) and treated ACR (4.2% vs 19.6%, p = 0.001). Comparatively, there were more EMBx defined antibody-mediated rejection (AMR) (5% vs 0.9%) and treated AMR (5% vs 2.7%) in the dd-cfDNA group. No significant differences were observed in graft dysfunction, presence of donor-specific antibodies, or survival at 1 year. CONCLUSIONS:In conclusion, a modern rejection surveillance protocol utilizing noninvasive testing is safe, led to significantly fewer EMBx, fewer treated rejection episodes, and no difference in survival at 1 year. More AMR episodes identified via dd-cfDNA could lead the way for more accurate diagnostic and treatment decisions.

Little is known about the comparative differences between the Allosure (CareDx) and Prospera (Natera) donor derived cell-free DNA (dd-cfDNA) assays following heart transplantation. We retrospectively analyzed 248 consecutive samples that had both dd-cfDNA assays simultaneously performed. 26 biopsy specimens were available within 7 days from dd-cfDNA assays. Both dd-cfDNA assays were correctly suggestive of rejection when biopsy was available. However, discordant classifications were present in 23/248 samples when utilizing respective recommended cutoff values for each assay (0.12% for Allosure and 0.15% for Prospera). Discordance was due to increased classification as abnormal results with Allosure (McNemar’s p=0.004). However, there were no significant differences between assays when identical thresholds of 0.12% or 0.15% were implemented for both assays (McNemar’s, p=NS). We conclude that both dd-cfDNA assays can be utilized interchangeably for surveillance of rejection following heart transplantation.

Background:Conduction abnormality requiring the implantation of a permanent pacemaker (PPM) is a well-known and clinically important complication of transcatheter aortic valve replacement (TAVR). However, PPM implantation may result in lead-associated tricuspid valve regurgitation (TR). This study sought to determine the incidence and progression of TR following PPM implantation after TAVR.Methods:This was a retrospective review of all echocardiograms of patients who underwent PPM following TAVR at the Baylor Scott & White hospitals from 2012 to 2021. The primary endpoint was TR progression at 30 days and 1 year. A subanalysis comparing the change in TR progression between small and large TAVR devices was also conducted. Secondary outcomes included all-cause death at 30 days and 1 year.Results:Out of the 2744 patients who underwent TAVR between April 2012 and August 2021, 177 patients (6.5%) subsequently received a new PPM. There was a statistically significant progression of TR at 1-year follow-up (McNemar's P value = 0.02). TR progression rates were comparable between the small and large valve groups at 1-year follow-up (4% vs 11%, P = 0.09, respectively).Conclusion:In this single healthcare system study, we demonstrated a significant progression of TR in patients with PPM post TAVR at 1 year.

Background Little is known about the relationship between the use of the temporary mechanical support device, Impella 5.5, and it's impact on the mRNA expression measured by the molecular microscope (MMDx) following heart transplantation. Methods Data from 30 consecutive heart transplant recipients between January 2021 and June 2022 at a single institution was reviewed. 18 patients had MMDx analysis performed within 1 month after transplant. The average time from transplant to biopsy was 14.2 days. The remaining 12 patients (5 Impella and 7 control patients) without MMDx samples drawn within the first month following transplantation were excluded. We reviewed all injury-associated transcript levels for this cohort in patients without rejection and compiled a database to identify potential variations in expression profiles of clinical significance. Results A total of 18 heart transplant recipients, 10 controls and 8 with Impella 5.5 used as bridge to transplant, were included in the analysis. Baseline characteristics include median age of 57.4 years and 72% male. There was no significant variation in injury pattern between the control group and the Impella group (p value>0.05 on all transcripts, Figure). Furthermore, MMDx analysis revealed concurrent with native heart biopsy that none of the samples had diagnosis of t-cell mediated rejection or antibody mediated rejection. Conclusion The use of Impella 5.5 does not have a significant impact on mRNA expression profiles following transplant in this small cohort. Further studies are needed to validate these preliminary findings.

Introduction Advanced heart failure therapies, heart transplantation (HT) and left ventricular assist device (LVAD) are limited due to scarcity of donors, expenses, and expansive lifetime care. Psychosocial determinants are persistently emphasized, but subjectively considered during the selection process. Described is our center's proof of concept utilizing a new behavioral/palliative consult system. Hypothesis The delivery of validated psychosocial measures, yields an objective risk score potentiating patient stratification and improving clinical outcomes. Methods HT or LVAD patients were assessed by Patient Health Questionnaire 9-Item (PHQ-9), Generalized Anxiety Disorder 7-Item (GAD-7), and the Millon Behavioral Medicine Diagnostic (MBMD) prior to selection. Associations with post-HT/LVAD readmission-free 1-year survival were assessed using univariable analysis. Risk factors with p<0.20 were included in a cumulative risk score. The cumulative sum of dichotomous risk factors was used to categorize patients into 3 risk groups (G1:0, G2: 1-5, G3: 5+). Kaplan Meier curve was used to assess the readmission-free 1-year survival of each risk groups. The hazards ratio of the risk groups was evaluated using a log rank test. Results Twenty-four patients were included (median age of 59, 46% female). The readmission and death rate within 1-year was 54%. Demographic, socioeconomic factors, and substance use rates did not differ significantly. Risk G3 patients with moderate anxiety, moderate depression, underestimating HT/LVAD care, and higher MBMD scores (anxiety, depression, emotional lability, inhibited, dejected, oppositional, denigrated, isolation, interventional fragility, medication abuse, and psychological referral) had a higher risk of death and/or readmission. Readmission-free survival decreased with increasing risk scores (p=0.002). The figure. Conclusions An objective risk score utilizing psychosocial determinants is feasible,. Aiding in patient selection and identifying at-risk patients may provide opportunities to improve outcomes.

Background: Little is known about the relationship between cytomegalovirus (CMV) infections and donor-derived cell-free DNA (dd-cfDNA) in heart transplant recipients. Methods: In our study, CMV and dd-cfDNA results were prospectively collected on single-organ heart transplant recipients. If the CMV study was positive, a CMV study with dd-cfDNA was repeated 1-3 months later. The primary aim was to compare dd-cfDNA between patients with positive and negative CMV results. Results: Of 44 patients enrolled between August 2022 and April 2023, 12 tested positive for CMV infections, 25 were included as controls, and seven patients with a viral infection without CMV were excluded. Baseline characteristics did not differ significantly between CMV-positive and CMV-negative patients with the exception of a later median time post-transplant in the CMV-positive group (253 days vs. 120 days, p = .03). Dd-cfDNA levels were significantly higher in patients with CMV infections compared to those without (p < .001) with more patients in the CMV positive group showing dd-cfDNA results >=.12% (75% vs. 8%, p < .001) and >= 20% (58% vs. 8%, p = .002). Each 1 log10 copy/ml reduction in CMV viral load from visit 1 to visit 2 was associated with a.23% reduction in log10 dd-cfDNA (p = .002). Conclusion: Our findings suggest that active CMV infections may raise dd-cfDNA levels in patients following heart transplantation. Larger studies are needed to validate these preliminary findings.

PRA access for cardiac catheterization is safe but can jeopardize subsequent use of the artery due to occlusion. DRA access in the anatomical snuffbox preserves the RA but safety and potential detrimental effects on hand function are unknown. We aimed to assess hand function and complications post Distal radial artery (DRA) and Proximal radial artery (PRA).In this single center trial, 300 patients were randomized 1:1 to cardiac catheterization through DRA or PRA. The primary endpoint of change in hand function from baseline to 1 year was a composite of the QuickDASH questionnaire, hand-grip test, and thumb forefinger pinch test. Secondary endpoints included access feasibility and complications. Of 216 patients with 1-year completed follow-up, 112 were randomized to DRA and 104 to PRA with balanced demographics and procedural characteristics. Both groups had similar access site bleeding rates (DRA 0% vs PRA 1.4%; p=0.25). RA occlusion occurred in 1 PRA patient vs 2 in DRA. There was no significant difference in change of hand function, in median [IQR] hand grip (DRA 0.7 [-3, 4.5] vs PRA 1.3 [-2, 4.3] kg; P=0.57), pinch grip (DRA -0.1 [-1.1, 1] vs PRA -0.3 [-1, 0.7] kg; P=0.66), and QuickDASH (DRA 0 [-6.6, 2.3] vs PRA 0 [-4.6, 2.9] points, P= 0.58). The composite of hand function was comparable between PRA and DRA. In conclusion, DRA is a safe strategy for cardiac catheterization with a low complication rate. Compared to PRA, there is no increased risk of hand dysfunction or RA occlusion at 1 year.

Purpose Little is known about the safety and impact of the pulmonary artery remote monitoring system, CardioMEMS, in reducing heart failure hospitalizations in patients following lung transplantation who developed heart failure with preserved ejection fraction (HFpEF). Methods A retrospective review of all patients who had cardioMEMS implanted after lung transplantation at our single center were reviewed. The total number of heart failure hospitalizations per patient month pre and post six months and one year of cardioMEMS were compared. Results A total of three patients with HFpEF following lung transplantation were included. Average mean pulmonary artery pressures at time of implantation were 33 ± 12 mmHG and reduced to 24 ± 2mmHg at 6 months. Overall, the total number of heart failure hospitalizations per patient month reduced from 0.28 to 0.17 at 6 months and from 0.19 to 0.14 at 1-year follow up. (Table) There was one procedure related complication with hemoptysis at time of CardioMEMS implantation, which was conservatively managed. Two patients have expired from pneumonia and respiratory failure. Conclusion CardioMEMS remote monitoring system may be promising to help decrease heart failure hospitalizations in patients following lung transplantation. The device can be successfully implanted in the transplanted lung. Further studies are needed to validate these preliminary findings.

BACKGROUND:Extended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. METHODS:25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. RESULTS:LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, -37%, -1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. CONCLUSION:LCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients.

IntroductionLiving with a left ventricular assist device (LVAD) comes with potentially burdensome aspects posed by e.g. battery packs and device drivelines. We aim to describe the impact of living with a durable LVAD on sexual quality of life (QOL), depression, and anxiety in patients and their partners.MethodsIn this single-center, prospective, observational study, patients ≥4 months post-LVAD implantation and their partners completed the Sexual Activities in Left Ventricular Assist Device Patients or Partners (SALVADOR) questionnaire to assess their sexual QOL, the 8-item Patient Health Questionnaire (PHQ-8) to assess symptoms of depression and the 7-item Generalized Anxiety Disorder (GAD-7) to assess symptoms of anxiety.Results60 patients and 60 partners completed the questionnaires 2.3 ± 1.9 years post-implantation. 87% patients and 13% partners were male. The mean age of patients was 57.4 ± 13.3 years with 90% living with their partner. 10% of patients and 18% of partners had a current diagnosis of a psychological condition, most frequently depression and/or anxiety. Overall, 49% of participants indicated the LVAD influenced their sexual activity (patients 53% vs. partners 45%, p=0.33). Disturbances from the driveline were the most common problem indicated. 24% of participants had scored in the mild to moderate depression range on the PHQ-8 and 28% scored in the mild to severe anxiety range on the GAD-7. The median total GAD-7 (1 [0, 4.25] vs. 2.5 [0, 5], p=0.06) were comparable between patients and partners; whereas patients had a higher total PHQ-8 score (3 [0, 5.25] vs. 1 [0, 3.25], p=0.02). A preference to receive information regarding sexuality while on LVAD support was indicated by 54% of participants and did not differ between patients and partners (p>0.99). Written resources were the most commonly preferred source of information.ConclusionLVADs severely affect the sexual QOL for patients and their partners. The presence of a driveline is a major cause for concern. Patients prefer receiving written information on how to improve their sexual QOL.

Little is known about de novo human leukocyte antigen (HLA) antibody development with Impella 5.5 temporary mechanical circulatory assist support and downstream effects following heart transplantation in the new heart allocation system. 13 Impella and 17 control patients without device support were prospectively enrolled between December 2020 and June 2022. HLA antibodies with calculated panel reactive antibodies (cPRA) were assessed pre- and post-device implantation and within 1-year post-heart transplantation. Baseline prevalence of HLA antibodies and median cPRA were similar between groups. Patients in the study arm were on Impella support for a median of 7 days. No significant differences in HLA antibodies were observed post-device or post-heart transplant. One patient in the Impella arm developed rejection and required treatment. One Impella patient died due to infection and one control patient died due to primary graft dysfunction. Short-term use of Impella 5.5 in the new heart allocation system does not appear to increase risk of de novo HLA antibody development. Further studies are needed to validate these preliminary findings.

BACKGROUND:Bioimpedance spectroscopy yields measurements of fat-free mass, fat mass, phase angle, and other measures. Bioimpedance spectroscopy has been validated as a preoperative assessment tool in cardiac surgical studies, in which low phase angle predicted morbidity and mortality. No studies have evaluated bioimpedance spectroscopy following heart transplantation. METHODS:We evaluated body composition, nutrition status (Subjective Global Assessment, body mass index, midarm muscle circumference, and triceps skinfolds), and functional status (handgrip strength and 6-min walk test) in 60 adults. Body composition measurements via a 256-frequency bioimpedance spectroscopy device included fat and fat-free mass as well as phase angle calculated at 50 kHz. Testing was completed at baseline and 1, 3, 6, and 12 mo following heart transplantation. Mortality and hospital readmissions were analyzed. RESULTS:Phase angle and fat mass increased while fat-free mass decreased; grip strength and 6-min walk test improved after transplantation (all P <  0.001). Improvement in phase angle in the first month postoperatively was associated with reduced risk of readmission. Low perioperative and 1-mo phase angles were associated with prolonged posttransplant length of stay (median: 13 versus 10 d, P =  0.03), increased infection-related readmissions (40% versus 5%, P =  0.001), and increased 4-y mortality (30% versus 5%, P =  0.01). CONCLUSIONS:Phase angle, grip strength, and 6-min walk test distance improved after heart transplantation. Low phase angle appears to be associated with suboptimal outcomes and may be a feasible and affordable method to predict outcomes. Further research should ascertain whether preoperative phase angle can predict outcomes.

Introduction Little is known about the use of the newer generation's temporary mechanical circulatory (tMCS) device, the Impella 5.5, in patients with restrictive cardiomyopathies. Case Report 55-year old African-American male with non-ischemic cardiomyopathy secondary to hereditary transthyretin amyloidosis and listed for heart transplantation, presented for a right heart catheterization that showed increased biventricular filling pressures with a cardiac index (CI) of 0.93 L/min/m2 despite home milrinone use. Even after attempts to optimize hemodynamics with dual inotropes, the patient continued to decline. While there were concerns with his restrictive physiology, relatively small left ventricular cavity size of 4.9 cm, and concentric hypertrophy, the team placed an axillary Impella 5.5 for further hemodynamic support (Image 1). At P7 support, the patient's hemodynamics improved to a CI of 2.9 L/min/m2, reducing his inotropic needs. The patient tolerated the Impella 5.5 until a suitable donor heart became available 3 days later. Despite the proximity of the Impella inflow cannula to the hypertrophied septum, the patient did not have any device related alarms or complications. Additionally, he also had no tMCS related complications peri and post-transplant. Summary The Impella 5.5 can safely support patients with restrictive physiology and small ventricular cavities as a bridge to transplantation.

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) has gained traction as a viable salvage option for cardiac arrest patients, with most programs led by cardiothoracic surgeons. Critical care surgeons possess the unique combination of the necessary surgical and resuscitation skills, and comfort with urgent interventions. Additionally, they maintain a continuous physical presence in the hospital that other specialties often lack. We hypothesized that an ECPR program led by a surgical intensivists would increase access to care and volume while also improving quality. Methods: A retrospective review was performed of a prospectively maintained database at a single center that has provided ECPR since 2012, with the surgical critical care division assuming leadership of the program in 2018. Volume and survival to discharge pre- and post-2018 were compared. Patient demographics and clinical parameters were assessed for risk factors associated with survival to discharge neurologically intact (cerebral performance score 1-2) using logistic regression in the post-2018 cohort. Statistically significant variables from univariable analysis were included in a stepwise selection process to construct a multivariable model. Results: From 2018-June 2022, 133 patients were supported with ECPR with 38% survival to discharge improving from 28% (7/25) during 2012-2017. Patients were 59 years old (interquartile range, 44-65 yr), 68% male, and presenting most frequently with cardiogenic shock (37%). Survival to discharge neurologically intact (SNI) was 29% (38/133). Male sex, subsequent catheterization lab and/or advanced heart failure therapies, increased hospital length of stay (LOS), and STEMI/NSTEMI were associated with increased SNI. Left sided arterial cannulation, same side A&V cannulation, increased lactate, anoxic brain injury (ABI), and cardiogenic shock were associated with decreased SNI. Multivariable analysis identified same side A&V cannulation (Odds Ratio (OR): 3.1, 95%CI: 1.2-8.3), left arterial cannulation (OR: 3.2, 95%CI: 1.14-8.7), ABI (OR: 34.7, 95%CI: 3.4-359), and shorter LOS (OR per 7-day increase: 0.75, 95%CI: 0.63-0.88) as risk factors for not achieving SNI. Conclusions: An ECPR program led by a surgical critical care team can increase access to extracorporeal support and improve outcomes.

Untreated sleep disorders form a risk of coronary artery disease, hypertension, obesity, and diabetes mellitus. Access to polysomnography is limited, especially during the COVID-19 pandemic, with home sleep apnea testing (HSAT) being a potentially viable alternative. We describe an HSAT protocol in patients with advanced heart failure (HF). In a single-center, observational analysis between 2019 and 2021 in patients with advanced HF and heart transplant (HT), 135 screened positive on the STOP-Bang sleep survey and underwent a validated HSAT (WatchPAT, ZOLL-Itamar). HSAT was successful in 123 patients (97.6%), of whom 112 (91.1%; 84 HF and 28 HT) tested positive for sleep apnea. A total of 91% of sleep apnea cases were obstructive, and 63% were moderate to severe. Multivariable linear regression showed that the apnea hypopnea index was 34% lower in the HT group than in the HF group (p = 0.046) after adjusting for gender, and that this effect persisted in White patients but not among African-Americans. Patient characteristics were similar between groups, with coronary artery disease, diabetes mellitus, and hypertension as the most prevalent co-morbidities. In conclusion, sleep apnea remains prevalent in patients with HF with a high co-morbidity burden. HSAT is a feasible and effective tool for screening and diagnosis in this population.