Donation After Circulatory Death Cardiac Recovery Technique: Single-Center Observational Outcomes.

BACKGROUND: Recovery of hearts from donation after circulatory death donors has been performed either with direct procurement and perfusion (DPP) using the TransMedics Organ Care System or with normothermic regional perfusion (NRP) with subsequent cold storage. It remains unclear which of these 2 strategies yields optimal posttransplant outcomes. METHODS: All heart transplant recipients from donors after circulatory death donors at the Vanderbilt University Medical Center (Nashville, TN) were reviewed (February 2020 to January 2023). Recipients were stratified into an NRP or DPP cohort. All DPP recoveries were performed using the TransMedics Organ Care System. The key outcome was severe primary graft dysfunction at 24 hours, defined by the need for postoperative extracorporeal membrane oxygenation. RESULTS: A total of 118 hearts were transplanted (NRP, 87; DPP, 31). Donors recovered using NRP were younger (25 years [interquartile range {IQR}, 21-31 years] vs 31 years [IQR, 24-37 years]; P = .008) and had shorter distance traveled (292 miles [158-516 miles] vs 449 miles [IQR, 248-635 miles]; P = .02). Recipient preoperative risk factors were similar between the groups. There was no difference in the incidence of severe primary graft dysfunction at 24 hours (NRP, 5.8%; and DPP, 12.9%; P = .24). However, ejection fraction at 7 days after transplantation was higher in the NRP group (65% [IQR, 60%-65%] vs 60% [IQR, 60%-68%]; P = .005). There was no difference in inotrope scores at 24 hours (P = 1.00) or 72 hours (P = .87) or in 30-day (NRP, 95% vs DPP, 97%; P = .75) and 1-year (NRP, 94% vs DPP, 86%; P = .19) survival. CONCLUSIONS: NRP and DPP strategies for recovery of cardiac allografts yield comparable early allograft outcomes. Future studies are needed to confirm these findings in larger prospective cohorts.

Transcatheter Aortic Valve Replacement and Surgical Aortic Valve Replacement Outcomes in Left Ventricular Assist Device Patients with Aortic Insufficiency.

Background: Worsening aortic insufficiency (AI) is a known sequela of prolonged continuous-flow left ventricular assist device (LVAD) support with a significant impact on patient outcomes. While medical treatment may relieve symptoms, it is unlikely to halt progression. Surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) are among non-medical interventions available to address post-LVAD AI. Limited data are available on outcomes with either SAVR or TAVR for the management of post-LVAD AI. Methods: The National Inpatient Sample data collected for hospital admissions between the years 2015 and 2018 for patients with pre-existing continuous-flow LVAD undergoing TAVR or SAVR for AI were queried. The primary outcome of interest was a composite of in-hospital mortality, stroke, transient ischaemic attack, MI, pacemaker implantation, need for open aortic valve surgery, vascular complications and cardiac tamponade. Results: Patients undergoing TAVR were more likely to receive their procedure during an elective admission (57.1 versus 30%, p=0.002), and a significantly higher prevalence of comorbidities, as assessed by the Elixhauser Comorbidity Index, was observed in the SAVR group (29 versus 18; p=0.0001). We observed a significantly higher prevalence of the primary composite outcome in patients undergoing SAVR (30%) compared with TAVR (14.3%; p=0.001). Upon multivariable analysis adjusting for the type of admission and Elixhauser Comorbidity Index, TAVR was associated with significantly lower odds of the composite outcome (odds ratio 0.243; 95% CI [0.06-0.97]; p=0.045). Conclusion: In this nationally representative cohort of LVAD patients with post-implant AI, it was observed that TAVR was associated with a lower risk of adverse short-term outcomes compared with SAVR.

Impact of increased donor distances following adult heart allocation system changes: A single center review of 1-year outcomes.

BACKGROUND: On October 18, 2018, several changes to the donor heart allocation system were enacted. We hypothesize that patients undergoing orthotopic heart transplantation (OHT) under the new allocation system will see an increase in ischemic times, rates of primary graft dysfunction, and 1-year mortality due to these changes. METHODS: In this single-center retrospective study, we reviewed the charts of all OHT patients from October 2017 through October 2019. Pre- and postallocation recipient demographics were compared. Survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 184 patients underwent OHT. Recipient demographics were similar between cohorts. The average distance from donor increased by more than 150 km (p = .006). Patients in the postallocation change cohort demonstrated a significant increase in the rate of severe left ventricle primary graft dysfunction from 5.4% to 18.7% (p = .005). There were no statistically significant differences in 30-day mortality or 1-year survival. Time on the waitlist was reduced from 203.8 to 103.7 days (p = .006). CONCLUSIONS: Changes in heart allocation resulted in shorter waitlist times at the expense of longer donor distances and ischemic times, with an associated negative impact on early post-transplantation outcomes. No significant differences in 30-day or 1-year mortality were observed.

Early Outcomes of Multivisceral Transplant Using Hepatitis C-Positive Donors.

BACKGROUND: In the era of direct-acting antiviral therapies, hepatitis C-positive organs offer a strategy to expand the donor pool. Heart failure patients with concomitant renal insufficiency benefit from combined heart/kidney transplant. In 2017, we began utilizing organs from hepatitis C donors for heart/kidney transplants. METHODS: Characteristics and outcomes of heart/kidney transplants were collected at our institution from 2012 through 2019. We determined patient cohorts by donor hepatitis C antibody status, antibody positive (HCV+) vs antibody negative (HCV-). Outcomes of interest include survival, postoperative allograft function, and waitlist time. Summary and descriptive statistics, as well as survival analyses, were performed. RESULTS: Thirty-nine patients underwent heart/kidney transplantation from 2012-2019. Twelve patients received HCV+ organs, and 27 patients received HCV- organs with minimal differences in donor and recipient cohort characteristics. Recipients who consented to receive HCV+ organs had a shorter median waitlist time. HCV+ and HCV- groups had similar perioperative and early postoperative cardiac function and similar rates of delayed renal graft function. HCV+ recipients demonstrated higher creatinine levels at 3 months posttransplant compared with HCV- recipients, but by 1-year post-transplant, creatinine levels in both groups were similar. The groups had similar 30-day and 1-year survival. CONCLUSIONS: This study is a single-center series of heart/kidney transplant using HCV+ donors. When the potential increased risk of early postoperative renal dysfunction is balanced against similar survival and decreased waitlist time, the results suggest that HCV+ donors are an important source of transplantable organs for heart/kidney transplantation.

Sizing heart transplant donors in adults with congenital heart disease.

OBJECTIVE: Optimal donor sizing for heart transplantation (HT) in adults with congenital heart disease (CHD) remains unclear, given the propensity for pulmonary hypertension related to shunting, staged repairs, and periods of pulmonary overcirculation. We studied HT outcomes related to donor size matching in the adult CHD population. METHODS: We conducted a retrospective cohort analysis of patients with CHD undergoing HT in the United States from January 1, 2000, to December 31, 2015. Patients were selected from the United Network for Organ Sharing database; 827 patients met inclusion criteria and were analyzed. RESULTS: At a median follow-up of 1462 days, 548 (66.3%) subjects were alive and 279 (33.7%) were deceased. All-cause mortality did not differ based on donor sizing (by predicted heart mass ratio: hazard ratio, 1.03; confidence interval, 0.86-1.23; P = .74). Pulmonary hypertension was not significantly associated with survival (by predicted heart mass ratio, χ2 = 2.01, P = .73). CONCLUSIONS: Our data demonstrate that donor oversizing, to the extent used in current practice, does not affect survival after HT in adults with CHD. Our findings from the United Network for Organ Sharing database demonstrate that donor oversizing in these patients is not associated with improved mortality.

Impact of implantation time on early function of cardiac transplant.

BACKGROUND: Data on out-of-ice implantation ischemia in heart transplant are scarce. We examined implantation time's impact on allograft dysfunction. METHODS: We conducted a single-site retrospective review of all primary adult heart transplants from June 2012 to August 2019 for implantation warm ischemic time (WIT), defined as first atrial stitch to aortic crossclamp removal. Univariate regression was used to assess the relationship of perioperative variables to primary graft dysfunction (PGD) and to pulmonary artery pulsatility index (PAPi) at postoperative hour 24. A threshold of p < .10 was set for the inclusion of covariates in multivariate regression. Secondary analyses evaluated for consistency among alternative criteria for allograft dysfunction. A post hoc subgroup analysis examined WIT effect in prolonged total ischemia of 240 min or longer. RESULTS: Complete data were available for 201 patients. Baseline characteristics were similar between patients who did and did not have WIT documented. In univariate analysis, female gender, longer total ischemic time (TIT), longer bypass time, greater blood transfusions, and pretransplant intensive care unit (ICU) care were associated with PGD, whereas longer bypass time was associated with worse PAPi and pretransplant ICU care was associated with better PAPi. In multivariate analysis, longer bypass time predicted PGD, and worse PAPi and preoperative ICU admission predicted PGD and better PAPi. Results did not differ in secondary or subgroup analyses. CONCLUSIONS: This study is one of few examining the functional impact of cardiac implantation ischemia. Results suggest allograft implantation time alone may not impact postoperative graft function, which was driven by intraoperative bypass duration and by preoperative ICU care, instead.

Perioperative blood product use: a comparison between HeartWare and HeartMate II devices.

BACKGROUND: The HeartWare (HW) (Framingham, MA) and the HeartMate II (HM II) (Thoratec Inc, Pleasanton, CA) continuous-flow left ventricular assist devices (CF-LVADs) are commonly used to bridge patients to transplantation. We hypothesized that there are differences in perioperative blood product (BP) use and chest tube (CT) output between CF-LVAD types. METHODS: We retrospectively evaluated BP use in 71 patients who were implanted with a CF-LVAD (HM II = 38; HW = 33) by median sternotomy for bridge to transplantation (BTT) indications from 2009 to 2013. Detailed BP use data were collected during the intraoperative and postoperative periods and included packed red blood cells, platelets, fresh frozen plasma, and cryoprecipitate. RESULTS: Preoperative characteristics (age, left ventricular ejection fraction, previous sternotomy, ischemic cause), and risk stratification scores (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS]) profile, Leitz-Miller score, Kormos score) were comparable between groups (all p > 0.05). Total average intraoperative and postoperative BP use was different between device types: HW = 8.3 ± 13 versus HM II = 12.6 ± 14.0 units (p = 0.002) and HW = 6.1 ± 12.0 units compared with HM II = 13.5 ± 24.1 units (p = 0.022), respectively. Average postoperative CT output for HW (3,231 ± 3,648 mL) and HM II (3,463 ± 3,050) (p < 0.008) were different between device types. Multivariate analysis revealed that a higher preoperative Leitz-Miller score, implantation of an HM II CF-LVAD, previous sternotomy, and a longer duration of cardiopulmonary bypass (CPB) time were independently associated with increased need for BP use, whereas only use of the HM II device and a longer bypass time predicted a greater CT output. CONCLUSIONS: Compared with HM II, implantation of the HW CF-LVAD was associated with reduced intraoperative and postoperative BP use and decreased CT output. Increased awareness of device-related differences in bleeding and BP use may improve CF-LVAD patient outcomes.

Does renal dysfunction and method of bridging support influence heart transplant graft survival?

BACKGROUND: Renal insufficiency is common in status 1B patients supported with inotropes or a continuous flow left ventricular device (CF-LVAD) as a bridge to heart transplantation. We evaluated the association of renal function and inotrope versus CF-LVAD support on posttransplant graft survival in status 1B patients. METHODS: The Scientific Registry for Transplant Recipients database was analyzed for posttransplant survival in status 1B patients bridged with inotropes or CF-LVAD who underwent transplantation between 2003 and 2012. Pretransplant renal function was measured by estimating glomerular filtration rate (GFR) and was stratified as less than 45 mL · min(-1) · 1.73 m(-2), 45 to 59, and 60 or greater. Univariate Kaplan-Meier and multivariate Cox regression models were used to evaluate the main effects of GFR strata and inotropes versus CF-LVAD, and the interaction effect of GFR strata by CF-LVAD, on graft survival. RESULTS: This study included 4,158 status 1B patients (74% male, aged 53 ± 12 years). Of those, 659 patients had a CF-LVAD (HeartMate-II [Thoratec, Pleasanton, CA], n = 638; HVAD [HeartWare, Framingham, MA], n = 21), and 3,530 were receiving inotropes (31 CF-LVAD patients were also receiving inotropes). Kaplan-Meier analyses demonstrated reduced graft survival (p = 0.022) in patients with pretransplant GFR less than 45 versus GFR 45 to 59 (p = 0.062) and versus GFR 60 or greater (p = 0.007), and no effect of inotrope versus CF-LVAD support on graft survival (p = 0.402). Multivariate analysis demonstrated that, after adjusting for the main effects of GFR stratum, CF-LVAD, and inotropes, status 1B patients bridged with a CF-LVAD and GFR in the lowest stratum had reduced graft survival (interaction effect p = 0.040). CONCLUSIONS: Pretransplant renal insufficiency was associated with reduced posttransplant graft survival in status 1B patients. This risk is increased for patients bridged with a CF-LVAD (versus inotropes) who have GFR in the lowest stratum.

Mechanical circulatory support and heart transplantation: donor and recipient factors influencing graft survival.

BACKGROUND: Mechanical circulatory support is an accepted strategy to bridge patients to heart transplantation (HTx). Among mechanical circulatory support patients who go on to HTx, factors associated with improved graft survival have not been fully elucidated. METHODS: Using the Scientific Registry for Transplant Recipients, we identified adults who were treated with a left ventricular assist device (LVAD) or total artificial heart (TAH) before HTx. Kaplan-Meier and multivariate Cox regression models were used to identify patient, donor, and device characteristics associated with graft survival. RESULTS: Between January 1997 and February 2012, 2,785 adults underwent HTx. Before HTx, 2,674 patients were treated with a LVAD (HeartMate XVE, 724; HeartMate II, 1,882; HeartWare, 68), and 111 were treated with a TAH. Follow-up averaged 25 ± 24 months. Gender mismatch occurred in 23%. Graft survival did not differ between LVAD groups (all p > 0.168), but TAH was associated with reduced graft survival compared with LVADs (p < 0.001). After controlling for device type (LVAD vs TAH), lower recipient pulmonary vascular resistance, shorter ischemic time, younger donor age, donor-to-recipient gender match, and higher donor-to-recipient body mass index ratio were independent predictors of longer graft survival (all p < 0.05). CONCLUSIONS: TAH was associated with reduced graft survival after transplant, and survival did not differ between the LVAD device groups. Additional variables that were independently associated with graft survival were donor age, recipient peripheral vascular resistance, ischemic time, gender match, and donor-to-recipient body mass index ratio. Recognition of these factors may inform decisions regarding device support and donor suitability.

Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography.

BACKGROUND: Macrophage degradation of fibrous cap matrix is an important contributor to atherosclerotic plaque instability. An imaging technology capable of identifying macrophages in patients could provide valuable information for assessing plaque vulnerability. Optical coherence tomography (OCT) is a new intravascular imaging modality that allows cross-sectional imaging of tissue with a resolution of approximately 10 micro m. The aim of this study was to investigate the use of OCT for identifying macrophages in fibrous caps. METHODS AND RESULTS: OCT images of 26 lipid-rich atherosclerotic arterial segments obtained at autopsy were correlated with histology. Cap macrophage density was quantified morphometrically by immunoperoxidase staining with CD68 and smooth muscle actin and compared with the standard deviation of the OCT signal intensity at corresponding locations. There was a high degree of positive correlation between OCT and histological measurements of fibrous cap macrophage density (r=0.84, P<0.0001) and a negative correlation between OCT and histological measurements of smooth muscle actin density (r=-0.56, P<0.005). A range of OCT signal standard deviation thresholds (6.15% to 6.35%) yielded 100% sensitivity and specificity for identifying caps containing >10% CD68 staining. CONCLUSIONS: The high contrast and resolution of OCT enables the quantification of macrophages within fibrous caps. The unique capabilities of OCT for fibrous cap characterization suggest that this technology may be well suited for identifying vulnerable plaques in patients.

Characterization of human atherosclerosis by optical coherence tomography.

BACKGROUND: High-resolution visualization of atherosclerotic plaque morphology may be essential for identifying coronary plaques that cause acute coronary events. Optical coherence tomography (OCT) is an intravascular imaging modality capable of providing cross-sectional images of tissue with a resolution of 10 micro m. To date, OCT imaging has not been investigated in sufficient detail to assess its accuracy for characterizing atherosclerotic plaques. The aim of this study was to establish objective OCT image criteria for atherosclerotic plaque characterization in vitro. METHODS AND RESULTS: OCT images of 357 (diseased) atherosclerotic arterial segments obtained at autopsy were correlated with histology. OCT image criteria for 3 types of plaque were formulated by analysis of a subset (n=50) of arterial segments. OCT images of fibrous plaques were characterized by homogeneous, signal-rich regions; fibrocalcific plaques by well-delineated, signal-poor regions with sharp borders; and lipid-rich plaques by signal-poor regions with diffuse borders. Independent validation of these criteria by 2 OCT readers for the remaining segments (n=307) demonstrated a sensitivity and specificity ranging from 71% to 79% and 97% to 98% for fibrous plaques, 95% to 96% and 97% for fibrocalcific plaques, and 90% to 94% and 90% to 92% for lipid-rich plaques, respectively (overall agreement, kappa=0.83 to 0.84). The interobserver and intraobserver reliabilities of OCT assessment were high (kappa values of 0.88 and 0.91, respectively). CONCLUSIONS: Objective OCT criteria are highly sensitive and specific for characterizing different types of atherosclerotic plaques. These results represent an important step in validating this new intravascular imaging modality and will provide a basis for the interpretation of intracoronary OCT images obtained from patients.