Extruded poly (glycerol sebacate) and polyglycolic acid vascular graft forms a neoartery.

In the ongoing search for the optimal biomaterial for tissue engineered vascular grafts (TEVGs), poly (glycerol sebacate) (PGS) has emerged as a new potential candidate. We have utilized a novel method to create unique, pore-free, extruded PGS grafts with and without a supportive exterior layer of polyglycolic acid (PGA). The 1 mm diameter by 5 mm length TEVGs were implanted in a rat model of infrarenal abdominal aorta interposition grafting. Three months after implantation, TEVGs comprised of extruded PGS with an external PGA braid demonstrated a patency rate of 9/10 (90%) with no signs of dilatation, dehiscence, or rupture. The PGS/PGA graft was remodeled into a neoartery with complete endothelialization of the neoartery lumen and formation of smooth muscle actinin multilayers as demonstrated via immunohistochemistry. Formation and maturation of extracellular matrix material were also observed, with amounts of elastin and collagen comparable to native rat aorta. No significant host inflammatory response was observed. These findings suggest the combination of an extruded PGS tube with an external reinforcing PGA braid is a promising material for small diameter TEVGs.

Recent Changes in Durable Left Ventricular Assist Device Bridging to Heart Transplantation.

This study evaluates the impact of the recent United Network for Organ Sharing (UNOS) allocation policy change on outcomes of patients bridged with durable left ventricular assist devices (LVADs) to orthotopic heart transplantation (OHT). Adults bridged to OHT with durable LVADs between 2010 and 2019 were included. Patients were stratified based on the temporal relationship of their OHT to the UNOS policy change on October 18, 2018. The primary outcome was early post-OHT survival. In total, 9,628 OHTs were bridged with durable LVADs, including 701 (7.3%) under the new policy. Of all OHTs performed during the study period, the proportion occurring following durable LVAD bridging decreased from 45% to 34% (p < 0.001). The more recent cohort was higher risk, including more extracorporeal membrane oxygenation bridging (2.6% vs. 0.3%, p < 0.001), more mechanical right ventricular support (9.7% vs. 1.4%, p < 0.001), greater pretransplant ICU admission (22.8% vs. 8.7%, p < 0.001) more need for total functional assistance (62.8% vs. 53.0%, p < 0.001), older donor age (33.3 vs. 31.7 years, p < 0.001), and longer ischemic times (3.38 vs. 3.13 hours, p < 0.001). Despite this, early post-OHT survival was comparable at 30 days (96.1% vs. 96.0%, p = 0.89), 90 days (93.7% vs. 94.0%, p = 0.76), and 6 months (91.0% vs. 93.0%, p = 0.96), findings that persisted after risk-adjustment. In this early analysis, OHT following bridging with durable LVADs is performed less frequently and in higher risk recipients under the new allocation policy. Despite this, short-term posttransplant outcomes appear to be unaffected in this patient cohort in the current era.

Diazoxide preserves myocardial function in a swine model of hypothermic cardioplegic arrest and prolonged global ischemia.

OBJECTIVE: Adenosine triphosphate potassium sensitive channels provide endogenous myocardial protection via coupling of cell membrane potential to myocardial metabolism. Adenosine triphosphate potassium sensitive channel openers, such as diazoxide, mimic ischemic preconditioning, prevent cardiomyocyte swelling, preserve myocyte contractility after stress, and provide diastolic protection. We hypothesize that diazoxide combined with hyperkalemic cardioplegia provides superior myocardial protection compared with cardioplegia alone during prolonged global ischemia in a large animal model. METHODS: Twelve pigs were randomized to global ischemia for 2 hours with a single dose of cold blood (4:1) hyperkalemic cardioplegia alone (n = 6) or with diazoxide (500 µmol/L) (n = 6) and reperfused for 1 hour. Cardiac output, myocardial oxygen consumption, left ventricular developed pressure, left ventricular ejection fraction, diastolic function, myocardial troponin, myoglobin, markers of apoptosis, and left ventricular infarct size were compared. RESULTS: Four pigs in the cardioplegia alone group could not be weaned from cardiopulmonary bypass. There were no differences in myoglobin, troponin, or apoptosis between groups. Diazoxide preserved cardiac output versus control (74.5 vs 18.4 mL/kg/min, P = .01). Linear mixed regression modeling demonstrated that the addition of diazoxide to cardioplegia preserved left ventricular developed pressure by 36% (95% confidence interval, 9.9-61.5; P < .01), dP/dt max by 41% (95% confidence interval, 14.5-67.5; P < .01), and dP/dt min by 33% (95% confidence interval, 8.9-57.5; P = .01). It was also associated with higher (but not significant) myocardial oxygen consumption (3.7 vs 1.4 mL O2/min, P = .12). CONCLUSIONS: Diazoxide preserves systolic and diastolic ventricular function in a large animal model of prolonged global myocardial ischemia. Diazoxide as an adjunct to hyperkalemic cardioplegia may allow safer prolonged ischemic times during increasingly complicated cardiac procedures.

Mechanical stimulation enhances development of scaffold-free, 3D-printed, engineered heart tissue grafts.

Current efforts to engineer a clinically relevant tissue graft from human-induced pluripotent stem cells (hiPSCs) have relied on the addition or utilization of external scaffolding material. However, any imbalance in the interactions between embedded cells and their surroundings may hinder the success of the resulting tissue graft. Therefore, the goal of our study was to create scaffold-free, 3D-printed cardiac tissue grafts from hiPSC-derived cardiomyocytes (CMs), and to evaluate whether or not mechanical stimulation would result in improved graft maturation. To explore this, we used a 3D bioprinter to produce scaffold-free cardiac tissue grafts from hiPSC-derived CM cell spheroids. Static mechanical stretching of these grafts significantly increased sarcomere length compared to unstimulated free-floating tissues, as determined by immunofluorescent image analysis. Stretched tissue was found to have decreased elastic modulus, increased maximal contractile force, and increased alignment of formed extracellular matrix, as expected in a functionally maturing tissue graft. Additionally, stretched tissues had upregulated expression of cardiac-specific gene transcripts, consistent with increased cardiac-like cellular identity. Finally, analysis of extracellular matrix organization in stretched grafts suggests improved remodeling by embedded cardiac fibroblasts. Taken together, our results suggest that mechanical stretching stimulates hiPSC-derived CMs in a 3D-printed, scaffold-free tissue graft to develop mature cardiac material structuring and cellular fates. Our work highlights the critical role of mechanical conditioning as an important engineering strategy toward developing clinically applicable, scaffold-free human cardiac tissue grafts.

NMDA Receptor Antagonism for Neuroprotection in a Canine Model of Hypothermic Circulatory Arrest.

BACKGROUND: Hypothermic circulatory arrest (HCA) is associated with neurologic morbidity, in part mediated by activation of the N-methyl-D-aspartate glutamate receptor causing excitotoxicity and neuronal apoptosis. Using a canine model, we hypothesized that the N-methyl-D-aspartate receptor antagonist MK801 would provide neuroprotection and that MK801 conjugation to dendrimer nanoparticles would improve efficacy. MATERIALS AND METHODS: Male hound dogs were placed on cardiopulmonary bypass, cooled to 18°C, and underwent 90 min of HCA. Dendrimer conjugates (d-MK801) were prepared by covalently linking dendrimer surface OH groups to MK801. Six experimental groups received either saline (control), medium- (0.15 mg/kg) or high-dose (1.56 mg/kg) MK801, or low- (0.05 mg/kg), medium-, or high-dose d-MK801. At 24, 48, and 72 h after HCA, animals were scored by a standardized neurobehavioral paradigm (higher scores indicate increasing deficits). Cerebrospinal fluid was obtained at baseline, eight, 24, 48, and 72 h after HCA. At 72 h, brains were examined for histopathologic injury in a blinded manner (higher scores indicate more injury). RESULTS: Neurobehavioral deficit scores were reduced by low-dose d-MK801 on postoperative day two (P < 0.05) and by medium-dose d-MK801 on postoperative day 3 (P = 0.05) compared with saline controls, but free drug had no effect. In contrast, high-dose free MK801 significantly improved histopathology scores compared with saline (P < 0.05) and altered biomarkers of injury in cerebrospinal fluid, with a significant reduction in phosphorylated neurofilament-H for high-dose MK801 versus saline (P < 0.05). CONCLUSIONS: Treatment with MK-801 demonstrated significant improvement in neurobehavioral and histopathology scores after HCA, although not consistently across doses and conjugates.

Time-Resolved Echo-Particle Image/Tracking Velocimetry Measurement of Interactions Between Native Cardiac Output and Veno-Arterial ECMO Flows.

Determination of optimal hemodynamic and pressure-volume loading conditions for patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) would benefit from understanding the impact of ECMO flow rates (QE) on the native cardiac output in the admixing zone, i.e., aortic root. This study characterizes the flow in the aortic root of a pig with severe myocardial ischemia using contrast-enhanced ultrasound particle image/tracking velocimetry (echo-PIV/PTV). New methods for data preprocessing are introduced, including autocontouring to remove surrounding tissues, followed by blind deconvolution to identify the centers of elongated bubble traces in images with low signal to noise ratio. Calibrations based on synthetic images show that this procedure increases the number of detected bubbles and reduces the error in their locations by 50%. Then, an optimized echo-PIV/PTV procedure, which integrates image enhancement with velocity measurements, is used for characterizing the time-resolved two-dimensional (2D) velocity distributions. Phase-averaged and instantaneous flow fields show that the ECMO flow rate influences the velocity and acceleration of the cardiac output during systole, and secondary flows during diastole. When QE is 3.0 L/min or higher, the cardiac ejection velocity, phase interval with open aortic valve, velocity-time integral (VTI), and mean arterial pressure (MAP) increase with decreasing QE, all indicating sufficient support. For lower QE, the MAP and VTI decrease as QE is reduced, and the deceleration during transition to diastole becomes milder. Hence, for this specific case, the optimal ECMO flow rate is 3.0 L/min.

Evaluation of Extracorporeal Membrane Oxygenation Therapy as a Bridging Method.

BACKGROUND: With the implementation of the new heart allocation system, heart transplantation teams are prompted to reevaluate management of patients requiring mechanical circulatory support. The purpose of our study is to compare the outcomes of patients supported with extracorporeal membrane oxygenation (ECMO) before transplantation. METHODS: The United Network for Organ Sharing database was queried for all adult patients (aged 18 years or more) who required support with ECMO before heart transplantation from 2001 to 2018. Patients were stratified into patients who did not require ECMO before transplantation, who were weaned off ECMO before transplantation, who were bridged immediately to transplantation from ECMO, and who were bridged to a left ventricular assist device (LVAD) before transplantation. Demographics and outcomes including 1-year survival, postoperative stroke, postoperative renal failure requiring dialysis, episodes of rejection, and graft failure were compared. RESULTS: Overall, 29,370 patients did not require ECMO before transplantation, 101 patients were weaned off ECMO before transplantation, 118 were bridged from ECMO directly to transplantation, and 55 patients were successfully bridged from ECMO to LVAD before transplantation. Kaplan-Meier survival estimates found a statistically significant decrease in 1-year survival for patients who were bridged from ECMO to transplantation compared with patients who were bridged to LVAD before subsequent transplantation (P < .001). CONCLUSIONS: Our study suggests bridging ECMO patients to an LVAD before transplantation will result in improved 1-year survival compared with patients bridged to immediate transplantation. With the new heart allocation system, continued evaluation of outcomes is required to inform management strategies.

Long-term Survival After Heart Transplantation: A Population-based Nested Case-Control Study.

BACKGROUND: Heart transplantation is the mainstay of treatment for patients in end-stage heart failure. This study sought to contrast survival after transplantation with that of the general population to quantify standardized mortality rates using a nested case-control study design. METHODS: Control subjects were noninstitutionalized inhabitants of the United States identified through the National Longitudinal Mortality study. Case subjects were adults who underwent heart transplantation between 1990 and 2007 and identified through the Organ Procurement and Transplantation Network. Propensity-matching (5:1, nearest neighbor, caliper = 0.1) was utilized to identify suitable control subjects based on age, sex, race, and state of permanent residency. The primary study endpoint was 10-year survival. RESULTS: In all, 31,883 heart transplant recipients were matched to 159,415 noninstitutionalized residents of the United States. The 10-year survival of heart transplant recipients was 53%. The population expected mortality rate was 15.9 deaths per 100 person-years with an observed rate of 45.1 deaths per 100 person-years (standardized mortality rate [SMR] 2.84; 95% confidence interval, 2.82 to 2.87). The broadest gaps between observed and expected survival were evident in female (SMR 3.63), black (SMR 3.67), and Hispanic (SMR 4.12) recipients. Standardized mortality ratios declined over time (1990 to 1995, 3.09; 1996 to 2000, 2.90; 2001 to 2007, 2.58). The long-term standardized survival of older recipients was closest to that expected for their age. CONCLUSIONS: Heart transplant recipients have considerable long-term survival and have a threefold higher standardized long-term mortality rate than that of the noninstitutionalized population. Long-term mortality rates have consistently declined over time and will likely continue to decrease.

Left Ventricular Assist Device Exchange Increases Heart Transplant Wait-List Mortality.

BACKGROUND: The new heart transplant allocation criteria prioritize inpatients who require temporary mechanical circulatory support and give lower urgency to candidates on a durable left ventricular assist device (LVAD) who require a device exchange. This study explores whether the latter group should warrant higher priority to reduce wait-list mortality. METHODS: This is a retrospective observational study of 13,113 adult heart transplant candidates in the Organ Procurement and Transplantation Network database who underwent LVAD implantation between 2007 and 2017. It evaluates the impact of LVAD exchange on the composite endpoint of death or removal from the wait list owing to worsening medical condition 1 y after device implantation. RESULTS: There were 1085 pump exchanges in 954 patients (7% of candidates), of which 22% were women. The pump exchange rate was 5.92 events per 100 patient-years. One-year survival was lower for those who required a pump exchange (76.3% versus 88.5%, logrank P < 0.001). This was congruent with the risk-adjusted mortality 1-y after implantation (hazards ratio: 2.56, 95% confidence interval: 2.18-3.00, P < 0.001). CONCLUSIONS: These findings indicate that among candidates awaiting heart transplantation with a durable LVAD, undergoing pump exchange doubles the risk of 1-y mortality. Giving priority to these candidates may reduce wait-list mortality.

Impact of cytomegalovirus serologic status on heart transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection has been associated with increased risk of mortality, cardiac allograft vasculopathy, and de novo malignancy following heart transplantation in prior institutional reports. This study examines the impact of the recipient and donor CMV status on heart recipients in the United States. METHODS: Adult heart transplant recipients were identified in the OPTN registry between 2005-2016. Recipients were stratified based on the recipient (R) and donor (D) CMV serologic status (+/-). The primary endpoint was survival 5-years after transplantation. The secondary endpoint was cardiac allograft vasculopathy 5-years after transplantation. Separate Cox proportional hazards regression models were developed to evaluate independent associations between CMV status and each of the study endpoints. RESULTS: A total of 21 878 recipients met the inclusion criteria. The breakdown of study arms by CMV serologic status was R-/D- = 3412, R+/D- = 4939; R-/D+ = 5230, and R+/D+ = 8,297. Five-year survival estimates were similar across groups (77-79%). CMV status was associated with increased mortality at 5-years (23%-41% increased risk) which was most evident in the first 3 months. The use of valganciclovir was associated with decreased risk of mortality (HR 0.56; 95% CI, 0.52-0.60). The cumulative incidence of cardiac allograft vasculopathy (R-/D- = 31%, R+/D- = 30%, R-/D+ = 31%, and R+/D+ = 30%) was similar across groups. CONCLUSIONS: CMV seropositivity at the time of transplantation is associated with increased long-term risk of mortality. Chemoprophylaxis with antivirals seems to mitigate this risk. There was no association with an increased risk of allograft vasculopathy.

Conditional Survival in Heart Transplantation: An Organ Procurement and Transplantation Network Database Analysis.

BACKGROUND: Survival after heart transplantation is typically reported only in terms of overall survival. Conditional survival may provide prognostic information for patients after surviving a given period. This study sought to provide an analysis of conditional survival in heart transplantation. METHODS: Data from 29,000 patients who underwent heart transplantation between 2002 and 2016 were analyzed from the Organ Procurement and Transplantation Network database, and 5-year conditional survival rates were calculated according to age, sex, race, renal function, and hepatic function at transplantation. RESULTS: As time from transplantation increased from 0 to 5 years, the 5-year observed conditional survival changed from 74% to 82% for ages younger than 40 years, 79% to 82% for ages 40 to 49, 79% to 78% for ages 50 to 60, and 75% to 70% for ages older than 60 at transplantation. Conditional survival peaked at 1 and 2 years after transplantation for most subgroups. In recipients younger than 40 years, men had slightly higher conditional survival than women (absolute difference, 3%-4%). In recipients older than 60 years, women had slightly higher conditional survival (absolute difference, 1%-4%). Black recipients had lower survival than white and Hispanic recipients for nearly all time points. Recipients younger than 40 years with the worst renal (65% to 88%) and hepatic function (66% to 83%) at transplantation experienced the largest increase in conditional survival. CONCLUSIONS: The conditional survival of patients who undergo heart transplantation changes substantially over time. The largest increases in conditional survival are in young patients with impaired renal and hepatic function. Conditional survival can provide more accurate prognostic information for heart recipients who survive a given period after transplantation.

Increased Use of Multiorgan Transplantation in Heart Transplantation: Only Time Will Tell.

BACKGROUND: The utilization of multiorgan transplantation in cardiac transplantation has steadily increased over the past several years. We sought to characterize the trends and outcomes in simultaneous heart and other organ transplantation compared with heart transplantation alone. METHODS: The United Network for Organ Sharing database was queried for all adult patients (age ≥ 18 y) who underwent isolated heart transplantation or simultaneous heart-lung or heart-kidney transplantation from 1987-2016. Patients were stratified into 3 equal time intervals. Demographics and postoperative outcomes were compared. RESULTS: A total of 58,060 patients were identified with a distribution based on era. Dual organ recipients had more factors associated with increased operative risk including higher rates of diabetes, pulmonary hypertension, intensive care unit admissions, and dialysis prior to transplantation. Heart-lung and heart-kidney recipients had decreased 1-year survival compared with isolated heart recipients from 2007-2016. However, heart-kidney recipients had significantly increased 5-year post-transplantation survival compared with isolated heart recipients with impaired renal function. For isolated heart transplants and heart-lung transplants, 5-year survival rates improved over time, whereas 5-year survival for heart-kidney recipients did not improve with time. CONCLUSIONS: We found a significantly increased 5-year survival rate for heart-kidney transplant recipients compared with isolated heart transplant recipients with renal impairment. Lack of improvement in 5-year postoperative outcomes for heart-kidney recipients in the setting of higher-risk pretransplant clinical characteristics suggests decreased selectivity regarding heart-kidney recipients. Continued scrutiny and evaluation of postoperative outcomes are required to ensure just and appropriate utilization of organs.

Corrugated nanofiber tissue-engineered vascular graft to prevent kinking for arteriovenous shunts in an ovine model.

OBJECTIVE: Prosthetic grafts are often needed in open vascular procedures. However, the smaller diameter prosthetic grafts (<6 mm) have low patency and often result in complications from infection. Tissue-engineered vascular grafts (TEVGs) are a promising replacement for small diameter prosthetic grafts. TEVGs start as a biodegradable scaffold to promote autologous cell proliferation and functional neotissue regeneration. Owing to the limitations of graft materials; however, most TEVGs are rigid and easily kinked when implanted in limited spaces, which precludes clinical application. We have developed a novel corrugated nanofiber graft to prevent kinking. METHODS: TEVGs with corrugated walls (5-mm internal diameter by 10 cm length) were created by electrospinning a blend of poly-ε-caprolactone and poly(L-lactide-co-caprolactone). The biodegradable grafts were then implanted between the carotid artery and the external jugular vein in a U-shape using an ovine model. TEVGs were implanted on both the left and right side of a sheep (n = 4, grafts = 8). The grafts were explanted 1 month after implantation and inspected with mechanical and histologic analyses. Graft patency was confirmed by measuring graft diameter and blood flow velocity using ultrasound, which was performed on day 4 and every following week after implantation. RESULTS: All sheep survived postoperatively except for one sheep that died of acute heart failure 2 weeks after implantation. The graft patency rate was 87.5% (seven grafts out of eight) with one graft becoming occluded in the early phase after implantation. There was no significant kinking of the grafts. Overall, endothelial cells were observed in the grafts 1 month after the surgeries without graft rupture, calcification, or aneurysmal change. CONCLUSIONS: Our novel corrugated nanofiber vascular graft displayed neotissue formation without kinking in large animal model.

Impact of Left Ventricular Assist Device Exchange on Outcomes After Heart Transplantation.

BACKGROUND: Left ventricular assist devices (LVADs) are the most common mode of circulatory support for patients awaiting heart transplantation. Unfortunately, a fraction of these patients require pump exchange during their course for pump-related adverse events. This study examined whether LVAD exchanges affect posttransplantation outcomes. METHODS: This study focused on adult patients in the Organ Procurement and Transplantation Network database who were bridged to transplant with a LVAD implanted between 2007 and 2017. Patients who underwent LVAD exchange were compared with those supported with a single device. The primary end point was all-cause mortality at 1, 2, and 5 years after transplantation. The impact of device exchange on risk-adjusted outcomes was examined using Cox proportional hazards models. RESULTS: Among 8239 patients who met the inclusion criteria, there were 611 pump exchanges in 560 patients (7% of recipients). The pump exchange rate was 6.24 events per 100 patient-years. Survival at 5 years was lower for those who underwent LVAD exchange (69.4% vs 77.5%, log-rank P = .027). This finding was similar for risk-adjusted 5-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.11 to 1.67; P = .003). Subgroup analysis revealed lower 5-year survival for female recipients who underwent LVAD exchange (55.4% vs 79.7%, log-rank P < .001). The interaction between female sex and LVAD exchange was associated with increased risk-adjusted 5-year mortality (hazard ratio, 1.65; 95% confidence interval, 1.05 to 2.59; P = .030). CONCLUSIONS: Recipients who underwent pump exchange while awaiting heart transplantation had a higher mortality compared with those on a primary device. Subgroup analysis revealed a marked increase in mortality of female recipients who experienced LVAD exchange.

Matchmaking Just Got Easier: Impact of Phenotypic Donor-Recipient Likeness in Heart Transplantation.

BACKGROUND: Phenotypic matching in heart transplantation, where donors and recipients are matched based on physical characteristics, has been previously limited to only analyzing individual variables such as sex and age. This study examines the effects of phenotypic matching utilizing multiple factors simultaneously. METHODS: Adult patients undergoing heart transplantation between 2006 and 2016 were identified from the Organ Procurement and Transplantation Network database. Phenotypic matching was defined based on six factors: body mass index difference >30%, age difference >30%, height difference >7%, non-identical ABO blood grouping, race, and sex. A value between 0 and 1 mismatched characteristics was considered phenotypically like matching, whereas 2-6 mismatches was considered phenotypically unlike matching. The primary study endpoint was 1-year survival. Risk-adjusted mortality was examined with multivariable Cox regression models. RESULTS: During the study period, 20,052 adult patients underwent heart transplantation, of whom 9595 (47.9%) were phenotypically like and 10,457 (52.1%) were phenotypically unlike matched. No differences in 1-year survival were seen between like and unlike matched patients (risk-adjusted odds ratio 1.05, 95% confidence interval 0.96-1.15, P = .305) after controlling for clinically relevant covariates. Subgroup analyses did not demonstrate survival differences after stratification based on hospital transplant volume and initial waitlist status. Phenotypically like matched patients had longer waiting times compared with unlike matched patients overall (225 days vs 192 days, P < .001). CONCLUSIONS: Waiting for a phenotypically matched heart provides no survival benefit and exposes patients to prolonged waitlist times. These findings challenge the notion that a perfect donor heart exists, when in fact this concept may be a misnomer.

Early Vascular Cells Improve Microvascularization Within 3D Cardiac Spheroids.

Introduction: A key obstacle in the creation of engineered cardiac tissues of clinically relevant sizes is limited diffusion of oxygen and nutrients. Thus, there is a need for organized vascularization within a three-dimensional (3D) tissue environment. Human induced pluripotent stem cell (hiPSC)-derived early vascular cells (EVCs) have shown to improve organization of vascular networks within hydrogels. We hypothesize that introduction of EVCs into 3D microtissue spheroids will lead to increased microvascular formation and improve spheroid formation. Methods: HiPSC-derived cardiomyocytes (CMs) were cocultured with human adult ventricular cardiac fibroblasts (FB) and either human umbilical vein endothelial cells (HUVECs) or hiPSC-derived EVCs for 72 h to form mixed cell spheroids. Three different groups of cell ratios were tested: Group 1 (control) consisted of CM:FB:HUVEC 70:15:15, Group 2 consisted of CM:FB:EVC 70:15:15, and Group 3 consisted of CM:FB:EVC 40:15:45. Vascularization, cell distribution, and cardiac function were investigated. Results: Improved microvasculature was found in EVC spheroids with new morphologies of endothelial organization not found in Group 1 spheroids. CMs were found in a core-shell type distribution in Group 1 spheroids, but more uniformly distributed in EVC spheroids. Contraction rate increased into Group 2 spheroids compared to Group 1 spheroids. Conclusion: The triculture of CM, FB, and EVC within a multicellular cardiac spheroid promotes microvascular formation and cardiac spheroid contraction.

Effects of Systemic and Device-Related Complications in Patients Bridged to Transplantation With Left Ventricular Assist Devices.

BACKGROUND: The use of left ventricular assist devices (LVADs) as a bridge to heart transplantation has increased rapidly over the last 2 decades. We aim to explore the effect of pretransplant systemic and device-related complications on posttransplant survival for patients bridged with LVADs. MATERIALS AND METHODS: The United Network of Organ Sharing (Organ Procurement and Transplantation Network) database was queried for all adult heart transplant recipients (aged ≥ 18 y) transplanted from April 1, 2015, to June 31, 2018. Device-related complications included thrombosis, device infection, device malfunction, life-threatening arrhythmia, and other device complications. Systemic complications included a new dialysis need or ventilator dependence between the time of listing and transplantation, transfusion, or systemic infection requiring treatment with intravenous antibiotics within 2 wk of transplantation. RESULTS: A total of 2131 patients were identified as requiring LVAD support before transplantation. LVAD patients had high rates of preoperative systemic complications (53%) and high rates of device-related complications (42.7% experienced at least one device-related complication). Kaplan-Meier analysis revealed a significantly decreased 1-y survival for LVAD patients bridged to transplantation who experienced a pretransplant systemic complication (P = 0.041). Interestingly, preoperative device-related complications had no effect on 1-y posttransplantation survival (P = 0.93). Multivariate Cox modeling revealed that systemic complications were associated with a significantly increased risk of posttransplant mortality for LVAD patients (hazard ratio 1.45; P = 0.033). CONCLUSIONS: Recipients who suffered a systemic complication while awaiting heart transplantation experienced higher short-term mortality rates. Device-related complications do not appear to impact posttransplantation outcomes.

Discrepancies in access and institutional risk tolerance in heart transplantation: A national open cohort study.

BACKGROUND: The impact of center volume on heart transplantation is widely recognized and serves as a benchmark for certification and reimbursement. STUDY AIMS: Study sociodemographic variables associated with access to high-volume centers and substantiate the importance of extending access to underserved populations. METHODS: This study focused on adults undergoing heart transplantation between 2006 and 2015. Centers were clustered into terciles (>25, 14-25, or <14 transplants per year) and factors associated with receiving care in different terciles were identified through multinomial regression. RESULTS: During the study period, 18 725 patients were transplanted at 145 centers. Younger age (<30 years) (P = .005), lower educational level (P < .001), and government-based insurance (P < .001) were associated to lower odds of receiving care at a high-volume center. These centers had higher risk recipients and accepted organs from higher risk donors, when compared to intermediate- and low-volume centers. Receiving care at high (odds ratio [OR], 1.212; P = .017) and intermediate-volume centers (OR, 1.304; P = .001) was associated with greater odds of 1-year survival when compared with low-volume centers. CONCLUSION: Social, demographic, and geographic factors affect access to high- and intermediate-volume centers. High-volume centers tolerate more risk while providing excellent survival. Awareness of this impact should prompt an extension of access to care for underserved patient populations.

Cardiac regeneration using human-induced pluripotent stem cell-derived biomaterial-free 3D-bioprinted cardiac patch in vivo.

One of the leading causes of death worldwide is heart failure. Despite advances in the treatment and prevention of heart failure, the number of affected patients continues to increase. We have recently developed 3D-bioprinted biomaterial-free cardiac tissue that has the potential to improve cardiac function. This study aims to evaluate the in vivo regenerative potential of these 3D-bioprinted cardiac patches. The cardiac patches were generated using 3D-bioprinting technology in conjunction with cellular spheroids created from a coculture of human-induced pluripotent stem cell-derived cardiomyocytes, fibroblasts, and endothelial cells. Once printed and cultured, the cardiac patches were implanted into a rat myocardial infarction model (n = 6). A control group (n = 6) without the implantation of cardiac tissue patches was used for comparison. The potential for regeneration was measured 4 weeks after the surgery with histology and echocardiography. 4 weeks after surgery, the survival rates were 100% and 83% in the experimental and the control group, respectively. In the cardiac patch group, the average vessel counts within the infarcted area were higher than those within the control group. The scar area in the cardiac patch group was significantly smaller than that in the control group. (Figure S1) Echocardiography showed a trend of improvement of cardiac function for the experimental group, and this trend correlated with increased patch production of extracellular vesicles. 3D-bioprinted cardiac patches have the potential to improve the regeneration of cardiac tissue and promote angiogenesis in the infarcted tissues and reduce the scar tissue formation.

Nutritional Support in Postcardiotomy Shock Extracorporeal Membrane Oxygenation Patients: A Prospective, Observational Study.

BACKGROUND: Despite the 6000 patients treated with extracorporeal membrane oxygenation (ECMO) annually, there is a paucity of data regarding the nutritional management of these patients. MATERIALS AND METHODS: We performed a prospective, observational study of nutrition in postcardiotomy shock patients at our institution. Over a 3.5-year study period, we identified 50 ECMO patients and 225 non-ECMO patients. We identified type, amount, duration, and disruption of nutritional delivery by cohort. The primary outcome was percent of caloric goal met, and secondary outcome was gastrointestinal complications. RESULTS: ECMO patients met less of their caloric (29% versus 40%, P = 0.017) and protein goals (34% versus 55%, P < 0.001) compared with non-ECMO patients. Tube feeds were administered more slowly (26 versus 37 mL/h, P < 0.001) and held for longer (8.3 versus 4.5 h/d, P < 0.001) in ECMO patients because of procedures (60%) and high-dose pressors (20% versus 7%, P < 0.001). Multivariate analysis demonstrated that ECMO decreased caloric intake by 14%, with no detected increased risk of gastrointestinal complications. CONCLUSIONS: -ECMO patients received significantly less nutrition support compared with a non-ECMO population. Tube feed hold deficits could potentially be avoided by utilizing postpyloric tubes to feed through procedures, by eliminating holds for vasopressors/inotropes in hemodynamically stable patients, or by establishing volume-based feeding protocols. Further clinical studies are needed to establish efficacy of these interventions and to understand the impact of nutrition on outcomes in ECMO patients.