Donor Hearts Research Articles

CARD28: Prolonged Graft Preservation of Biostasis Induced Porcine Hearts using the VP.S ENCORE® Machine Perfusion Device

Purpose: Heart transplantation is the gold standard therapy for patients with end-stage heart failure. However, the supply of donor hearts does not meet the demand, and many patients die on the waitlist. The purpose of this study was to test the efficacy of a novel machine perfusion device, the VP.S ENCORE® cardiac preservation device, in preserving porcine hearts conditioned with a biostasis-inducing compound (WC1) during prolonged 6-8 hour perfusion. Methods: Isolated porcine hearts were recovered under anesthesia. Following cannulation, the hearts were placed in the VP.S ENCORE® cardiac preservation device for oxygenated perfusion at 23-25°C for either 6 (n = 3) or 8 (n = 4) hours. At hour 3, WC1 (n = 2) was administered through the arterial line and the hearts continued to be perfused for additional 5 hours. Hourly flow, pressure, temperature, blood gases, and various metabolites were recorded. After preservation, hearts were placed in a Langendorff model for reperfusion and evaluated for cardiac function. Biopsy samples were taken before and at the end of preservation for histological and gene expression analyses. Results: During perfusion, oxygen consumption was significantly reduced in WC1-treated hearts (p < 0.0001). However, during re-perfusion, WC1-treated hearts had an initial lower oxygen consumption that recovered to normal with time and temperature. Before defibrillating the hearts, oxygen consumption was 1.61 ± 0.59 (vehicle) & 1.05 ± 0.39 (WC1), while after defibrillation the oxygen consumption increased to 3.29 ± 0.63 & 2.66 ± 0.32 ml/min/100g, respectively. The contractility of the WC1-treated hearts was similar to a normal human heart in vivo. Furthermore, gene expression analysis showed a significant reduction (p < 0.0008) of inflammation (IL-6, TNFα), hypoxia (Hif1a), & cell death markers (p53) in WC1 treated hearts when compared to control hearts. Conclusions: Our preliminary results demonstrate that the portable, simple-to-use VP.S ENCORE® cardiac preservation machine perfusion device coupled with the torpor properties of compounds like WC1 may provide a new paradigm to prolonged organ preservation, and may offer many advantages over currently tested machine perfusion technologies. Further, this innovative work is a result of integrating science and engineering to target unmet patients’ needs in the field of organ preservation.Figure 1. Subnormothermic Perfusion of Porcine Hearts using VP.S ENCORE®

TOP1: Outcomes in Heart Transplant Recipients by Bridge-To-Transplant Strategy When Using the SherpaPak Cardiac Transport System

Background: The last several years have seen a rise in the use of mechanical circulatory support (MCS) to bridge heart transplant recipients. This may be due to expanding indications for devices such as extracorporeal membrane oxygenation (ECMO), but also to changes in the UNOS allocation policy in 2018. A controlled hypothermic organ preservation system, the SherpaPak Cardiac Transport System (CTS), was also introduced in 2018 and has grown in utilization with reports of improved post-transplant outcomes. We present here a subgroup analysis in recipients bridged with various MCS devices in the GUARDIAN-Heart Registry. Methods: The GUARDIAN-Heart registry is an international, multicenter registry assessing outcomes after transplant using CTS preservation. A retrospective review of clinical outcomes in transplant recipients with ventricular assist devices (VAD), intra-aortic balloon pumps (IABP) and ECMO prior to transplant were examined using summary statistics. Further analysis with ongoing enrollment will be available for presentation. Results: A total of 373 heart transplant recipients with donor hearts transported using the CTS system were included in this analysis. VADs were used in 171 recipients, IABP in 165, and ECMO in 37 recipients. Average ischemic times were over 3.5 hours for all cohorts. Mean IMPACT scores increased across groups (VAD = 6.8, IABP = 9.4, ECMO = 15.9), as did the rates of severe PGD post-transplant (VAD = 4.7%, IABP 7.9%, ECMO 18.9%). However, overall one-year survival was excellent (LVAD = 90.3%, IABP = 94.1%, ECMO = 93.3%). Median ICU length of stay was longer in the EMCO cohort (13.0 days) compared to the LVAD and IABP cohorts (each 7.0 days), as well as total hospital length of stay at 27.0 (ECMO) compared to 21.5 (LVAD) and 18.0 days (IABP). Conclusions: Despite average ischemic times in excess of 3.5 hours, use of the SherpaPak CTS for recipients with various bridging strategies results in excellent survival.

CARD17: 24 hr Normothermic Ex Vivo Heart Perfusion in Adult Porcine Hearts with Hemofiltration

Introduction: Currently, to successfully transplant a heart, cardiac preservation relies on cold static storage at 5C for up to 6 hours. If hearts are stored at this temperature for a longer duration, their function after transplantation is compromised, increasing post-transplant morbidity and mortality. This time restriction negatively impacts the availability of donor hearts and limits distance and transportation options, optimal cross-matching, and organ assessment, all of which facilitate successful transplantation. Previous studies from our group have demonstrated that: 1) Plasma cross circulation at 1 L/hr from a living paracorporeal sheep allowed for safe normothermic ex vivo heart perfusion (NEVHP) for 3 days, 2) NEVHP for 24 hours is feasible with plasma exchange without a paracorporeal animal, 3) 24-hour NEVHP is also feasible with the addition of hemofiltration (22 kDa filter) and filtration replacement. All studies with up to 24hr of NEVHP were performed using piglet hearts (60±8.8 g) The experiments described in this study were designed to evaluate the efficacy of hemofiltration and filtrate replacement in adult porcine hearts. Methods: We performed 24-hour NEVHP on 5 consecutive hearts (mean weight 263±15.5 g). Following anesthetic induction, sternotomy, cardioplegia administration, explantation, and back-table instrumentation, NEVHP was initiated in beating, resting mode. After 1 hour plasma exchange was performed and hemofiltration was initiated. Heart function parameters and arterial blood gasses were obtained hourly and at termination of prep all hearts were removed from circuit and stored in formalin. Results: All hearts (n=5) were viable at the 24-hour mark. Aortic blood flow was adjusted to maintain coronary artery blood flow at 0.7 mL/min/g. Average LV systolic pressure at the beginning of the prep was 36.6±7.9 mmHg compared to 27±5.5 mmHg at the end. Coronary resistance at the beginning of prep was 0.79±0.10 mmHg/L/min and at the end of prep was 0.93±0.28 mmHg/L/min. Glucose levels averaged 223±13.9 mg/dL and the lactate average at the termination of prep was 2.6±0.3 mmol/L. Conclusions: We successfully perfused adult porcine hearts at normothermic temperatures for 24 hours with results comparable to our pediatric porcine heart model. The next steps in our research are NEVHP evaluation in a working mode using left atrial perfusion, extension of NEVHP preservation beyond 24 hours, and verification of functional status of the ex vivo heart by transplantation after 24 hours on our circuit.

Impact of bench repair for donor mitral valve before orthotopic heart transplantation: a case report

BackgroundThe use of donor hearts with valvular disease has been considered debatable in heart transplantation for many years. However, few reports indicate successful heart transplantation using donor hearts with mitral regurgitation that underwent mitral valve repair on the back bench.Case presentationWe report two cases of a 38-year-old and a 48-year-old woman with implantable left ventricular assist devices who underwent heart transplantation at our institution. Transthoracic echocardiography of donor hearts just before the explant revealed that each donor heart had preserved cardiac function and significant mitral regurgitation due to mitral posterior leaflet prolapse and annular dilatation, respectively. Bench mitral valve repair was accomplished using triangular resection for one patient and annuloplasty for the other. This was followed by confirmation of excellent mitral leaflet coaptation without residual mitral regurgitation. Transthoracic echocardiography and right heart catheterization performed 6 months after transplantation clarified the favorable cardiac function of each transplanted heart without mitral regurgitation recurrence.ConclusionsEfficient utilization of donor hearts with mitral regurgitation may be acceptable when the cardiac function of donor hearts with mitral regurgitation is preserved and heart transplantation, including bench mitral valve repair, is feasible within an acceptable ischemic time.

Monitoring of myocardial microcirculation during machine perfusion of donor hearts for prediction of contractility

Monitoring of myocardial microcirculation during machine perfusion of donor hearts for prediction of contractility

Impact of Donor Hemodynamics on Recipient Survival in Heart Transplantation

Heart transplantation is the gold-standard therapy for end-stage heart failure, but rates of donor-heart use remain low due to various factors that are often not evidence based. The impact of donor hemodynamics obtained via right-heart catheterization on recipient survival remains unclear. The United Network for Organ Sharing registry was used to identify donors and recipients from September 1999-December 2019. Donor hemodynamics data were obtained and analyzed using univariate and multivariable logistical regression, with the primary endpoints being 1- and 5-year post-transplant survival. Of the 85,333 donors who consented to heart transplantation during the study period, 6573 (7.7%) underwent right-heart catheterization, of whom 5531 eventually underwent procurement and transplantation. Donors were more likely to undergo right-heart catheterization if they had high-risk criteria. Recipients who had donor hemodynamic assessment had 1- and 5-year survival rates similar to those without donor hemodynamic assessment (87% vs 86%, 1 year). Abnormal hemodynamics were common in donor hearts but did not impact recipient survival rates, even when risk-adjusted in multivariable analysis. Donors with abnormal hemodynamics may represent an opportunity to expand the pool of viable donor hearts.

Intravascular imaging of angioplasty balloon under-expansion during pre-dilation predicts hyperelastic behavior of coronary artery lesions.

Introduction: Stent-induced mechanical stimuli cause pathophysiological responses in the coronary artery post-treatment. These stimuli can be minimized through choice of stent, size, and deployment strategy. However, the lack of target lesion material characterization is a barrier to further personalizing treatment. A novel ex-vivo angioplasty-based intravascular imaging technique using optical coherence tomography (OCT) was developed to characterize local stiffness of the target lesion. Methods: After proper institutional oversight, atherosclerotic coronary arteries (n = 9) were dissected from human donor hearts for ex vivo material characterization <48h post-mortem. Morphology was imaged at the diastolic blood pressure using common intravascular OCT protocols and at subsequent pressures using a specially fabricated perfusion balloon that accommodates the OCT imaging wire. Balloon under-expansion was quantified relative to the nominal balloon size at 8 ATM. Correlation to a constitutive hyperelastic model was empirically investigated (n = 13 plaques) using biaxial extension results fit to a mixed Neo-Hookean and Exponential constitutive model. Results and discussion: The average circumferential Cauchy stress was 66.5, 130.2, and 300.4kPa for regions with <15, 15-30, and >30% balloon under-expansion at a 1.15 stretch ratio. Similarly, the average longitudinal Cauchy stress was 68.1, 172.6, and 412.7kPa, respectively. Consequently, strong correlation coefficients >0.89 were observed between balloon under-expansion and stress-like constitutive parameters. These parameters allowed for visualization of stiffness and material heterogeneity for a range of atherosclerotic plaques. Balloon under-expansion is a strong predictor of target lesion stiffness. These findings are promising as stent deployment could now be further personalized via target lesion material characterization obtained pre-operatively.

Mitochondrial transplantation preserves myocardial function and viability in pediatric and neonatal pig hearts donated after circulatory death

ObjectiveMitochondrial transplantation has been shown to preserve myocardial function and viability in adult porcine hearts donated after circulatory death (DCD) . Herein, we investigate the efficacy of mitochondrial transplantation for the preservation of myocardial function and viability in neonatal and pediatric porcine DCD heart donation. MethodsCirculatory death was induced in neonatal and pediatric Yorkshire pigs by cessation of mechanical ventilation. Hearts underwent 20 or 36 minutes of warm ischemia time (WIT), 10 minutes of cold cardioplegic arrest, and then were harvested for ex situ heart perfusion (ESHP). Following 15 minutes of ESHP, hearts received either vehicle (VEH) or vehicle containing isolated autologous mitochondria (MITO). A sham nonischemic group (SHAM) did not undergo WIT, mimicking donation after brain death heart procurement. Hearts underwent 2 hours each of unloaded and loaded ESHP perfusion. ResultsFollowing 4 hours of ESHP perfusion, left ventricle developed pressure, dP/dt max, and fractional shortening were significantly decreased (P < .001) in DCD hearts receiving VEH compared with SHAM hearts. In contrast, DCD hearts receiving MITO exhibited significantly preserved left ventricle developed pressure, dP/dt max, and fractional shortening (P < .001 each vs VEH, not significant vs SHAM). Infarct size was significantly decreased in DCD hearts receiving MITO as compared with VEH (P < .001). Pediatric DCD hearts subjected to extended WIT demonstrated significantly preserved fractional shortening and significantly decreased infarct size with MITO (P < .01 each vs VEH). ConclusionsMitochondrial transplantation in neonatal and pediatric pig DCD heart donation significantly enhances the preservation of myocardial function and viability and mitigates against damage secondary to extended WIT.

Substance Use-Associated Mortality among Heart Donors after the COVID-19 National Emergency Increased but Did Not Affect Peri-Transplant Outcomes

The COVID-19 pandemic and consequent social isolation prompted a surge in mental health disorders and substance use in the general population and, therefore, in potential organ donors. We aimed to evaluate if this led to a change in donor characteristics, including the mechanism and circumstance of death, and how this may have affected clinical outcomes following heart transplantation. We identified all heart donors from the SRTR database between 18 October 2018 and 31 December 2021, excluding those who donated immediately after the US national emergency declaration. Donors were stratified into pre-COVID-19 (Pre-Cov; through 12 March 2020) and post-COVID-19 national emergency declaration cohorts (Post-Cov; 1 August 2020 through 31 December 2021) based on the heart procurement date. Relevant demographics, cause of death, and substance use history were collected in addition to graft cold ischemic time, the incidence of primary graft dysfunction (PGD), and recipient survival at 30 days post-transplant. A total of 10,314 heart donors were identified; 4941 were stratified into the Pre-Cov and 5373 into the Post-Cov cohorts. There was no difference in demographics, but illicit drug use was significantly higher in the Post-Cov group, leading to an increased incidence of death from drug intoxication. Fatal gunshot wounds were also more common. Despite these changes, the incidence of PGD remained similar (p = 0.371), and there was no difference in 30 days recipient survival (p = 0.545). Our findings confirm that COVID-19 had a major impact on mental health and psychosocial life with an associated increase in illicit substance use and fatal intoxication rates in heart transplant donors. These changes did not alter peri-operative mortality following heart transplantation. Future studies are needed to ensure that long-term outcomes remain unaffected.

C61 RAREFACTION OF MYOCARDIAL LYMPHATIC VESSELS IN PATIENTS WITH CARDIAC AMYLOIDOSIS

Abstract Introduction In cardiac amyloidosis (CA), amyloid fibers accumulate in the extracellular spaces of the heart, causing a compression and obliteration of lymphatic vessels, and possibly their disappearance. As lympathic drainage removes proteins from the interstitial spaces, including amyloid precursors, an impairment of lympathic vessels could exacerbate amyloid accumulation, triggering a vicious circle. Methods Lymphatic vessels were visualized by immunohistochemistry using a monoclonal antibody against podoplanin (D2–40, a marker of lymphatic endothelial cells) and the immunopreroxidase technique. We investigated 3 groups of cases: 1) as a reference standard, endomyocardial specimens from the left ventricular (LV) endomyocardium of 10 heart valve donors, deceased for trauma and/or cerebral hemorrhage, with no evidence of cardiac disease on gross and microscopic examination; 2) 15 consecutive LV endomyocardial biopsies (EMBs) from patients with CA, where cardiac amyloid was detected and typed by Congo red staining, immunohistochemistry and proteomics, and 3) 13 surgical endomyocardial biopsies from patients with septal LV hypertrophy, undergoing aortic valve surgery and with CA excluded by histology. Results In donor hearts (n=10), lymphatic vessels were mostly distributed in the subendocardial and subepicardial layers, with some intra–myocardial lymphatic vessels near larger blood vessels. We then examined 15 patients with CA (amyloid transthyretin [ATTR]–CA, n=10; amyloid light–chain [AL]–CA, n=5; 50% men, median age 75 years [interquartile range 71–78]), and 13 patients with CA excluded (55% men, median age 68 years [59–71]). The density of lymphatic vessels in patients with CA was 0.52 vessels/mm2 (0–3.32), vs. 10.90 vessels/mm2 (3.10–26.25) in those without CA (p=0.001). No significant differences were found in LV mass index (p=0.170) or LV ejection fraction (p=0.262). Three patients with ATTR–CA and 2 patients with AL–CA showed no lymphatic vessels on EMB. The density of lymphatic vessels did not differ significantly in patients with ATTR– or AL–CA. Conclusions Patients with CA have significantly decreased endo–myocardial lymphatic vessels as compared to patients without CA, despite no significant difference in the degree of LV wall thickening or LV ejection fraction. These results support the hypothesis that the lymphatic drainage is deranged in patients with CA, possibly promoting further amyloid deposition.

ADONHERS (Aged DONor HEart Rescue by Stress Echo) National Protocol: Recipient's Survival after 10-Year Follow-Up.

Background: The gold-standard treatment for end-stage heart failure is heart transplantation, but the lack of organ donors remains an important limitation in this field. An accurate selection of marginal hearts is fundamental to increase organ availability. Purpose: In our study we analyzed if recipients receiving marginal donor (MD) hearts, selected by dipyridamole stress echocardiography according to the ADOHERS national protocol, had different outcomes compared to recipients with acceptable donor (AD) hearts. Methods: Data were collected and retrospectively analyzed from patients who received an orthotopic heart transplant at our institution between 2006 and 2014. Dipyridamole stress echo was performed on identified marginal donors and selected hearts were eventually transplanted. Clinical, laboratory and instrumental features of the recipients were evaluated and patients with homogenous baseline characteristics were selected. Results: Eleven recipients transplanted with a selected marginal heart and eleven recipients transplanted with an acceptable heart were included. Mean donor age was 41 ± 23. The median follow-up was 113 months (IQR 86-146 months). Age, cardiovascular risk and morpho-functional characteristics of the left ventricle were comparable between the two populations (p > 0.05). Left atrial size was significantly higher in patients with marginal hearts (acceptable atrial volume: 23 ± 5 mL; marginal atrial volume: 38 ± 5 mL; p = 0.003). Acceptable donor recipients showed a higher impact of Cardiac Allograph Vasculopathy (p = 0.019). No rejection differences were found between the two groups. Four patients deceased, three were standard donor recipients and one was from the marginal donor group. Conclusions: Our study shows how cardiac transplant (Htx) from selected marginal donor hearts through a non-invasive bedside technique can alleviate the shortage of organs without a difference in survival compared to acceptable donor hearts.

The 2-year postoperative left heart function in marginal donor heart recipients assessing by speckle tracking echocardiography.

This study analyzed the differences and explored the donor/recipient factors between marginal and standard donor heart recipients after heart transplantation (HT) by speckle tracking echocardiography (STE). Seventy-two HT patients were enrolled: 25 standard and 47 marginal donor heart recipients. Thirty HT patients completed 2-year continuous follow-up (1, 6, 12, 24months). Thirty healthy volunteers were controls. STE was used to track the strain characteristics of the left ventricle and atrium for detecting early changes in marginal donor heart recipients, including left ventricular global longitudinal, circumferential and radial strain (LVGLS, LVGCS, LVGRS) and left atrial strain in systole (LAS-S) and late diastole (LAS-A). The perioperative parameters were similar between the standard and marginal groups. No significant differences were found in left heart size, systolic and diastolic function parameters. Left ventricular systolic strain (LVGLS, LVGCS, LVGRS) and systolic and late diastolic left atrial strain (LAS-S, LAS-A) were lower in the HT recipients than the control group (P < 0.05), but there was no difference between the marginal and standard groups (P > 0.05). LVGLS, LVGCS, and LAS-S were low in the marginal group 1month after surgery but recovered gradually at 6months. The patients with donor/recipient body weight ratio < 0.8 group had lower LVGLS and LAS-S. STE showed no significant difference between marginal and standard donor recipients. The LVGLS and LAS-S were lower in those with a smaller donor/recipient body weight ratio. The cardiac function of HT patients was lower in the early postoperative period but gradually recovered over time.

Use of Donor Hearts ≥50 Years Old for Septuagenarians in Heart Transplantation

BackgroundThe impact of using donors ≥50 years old on heart transplantation outcomes of septuagenarians is unknown, which may have a potential to expand the donor pool. MethodsFrom January 2011 to December 2021, 817 septuagenarians received donor hearts <50 years old (DON<50) and 172 septuagenarians received donor hearts ≥50 years old (DON≥50) in the United Network for Organ Sharing database. Propensity score matching was performed using recipient characteristics (167 pairs). The Kaplan-Meier method and Cox proportional hazards model were used to analyze death and graft failure. ResultsThe number of heart transplants in septuagenarians has been increasing (54 per year in 2011 to 137 per year in 2021). In a matched cohort, the donor age was 30 years in DON<50 and 54 years in DON≥50. In DON≥50, cerebrovascular disease was the main cause of death (43%), whereas head trauma (38%) and anoxia (37%) were the causes in DON<50 (P < .001). The median heart ischemia time was comparable (DON<50, 3.3 hours; DON≥50, 3.2 hours; P = .54). In matched patients, 1- and 5-year survival rates were 88.0% (DON<50) vs 87.2% (DON≥50) and 79.2% (DON<50) vs 72.3% (DON≥50), respectively (log-rank, P = .41). In the multivariable Cox proportional hazards models, donors ≥50 years old were not associated with death in matched (hazard ratio, 1.05; 95% CI, 0.67-1.65; P = .83) and nonmatched groups (hazard ratio, 1.11; 95% CI, 0.82-1.50; P = .49). ConclusionsThe use of donor hearts older than 50 years can be an effective option for septuagenarians, thereby potentially increasing organ availability without compromising outcomes.

Rethinking Donor and Recipient Risk Matching in Europe and North America: Using Heart Transplant Predictors of Donor and Recipient Risk.

In Europe, there is greater acceptance of hearts from higher-risk donors for transplantation, whereas in North America, the donor heart discard rate is significantly higher. A Donor Utilization Score (DUS) was used to compare European and North American donor characteristics for recipients included in the International Society for Heart and Lung Transplantation registry from 2000 to 2018. DUS was further evaluated as an independent predictor for 1-year freedom from graft failure, after adjusting for recipient risk. Lastly, we assessed donor-recipient risk matching with the outcome of 1-year graft failure. DUS was applied to the International Society for Heart and Lung Transplantation cohort using meta-modeling. Posttransplant freedom from graft failure was summarized by Kaplan-Meier survival. Multivariable Cox proportional hazard regression was applied to quantify the effects of DUS and Index for Mortality Prediction After Cardiac Transplantation score on the 1-year risk of graft failure. We present 4 donor/recipient risk groups using the Kaplan-Meier method. European centers accept significantly higher-risk donor hearts compared to North America. DUS 0.45 versus 0.54, P<0.005). DUS was an independent predictor for graft failure with an inverse linear relationship when adjusted for covariates (P<0.001). The Index for Mortality Prediction After Cardiac Transplantation score, a validated tool to assess recipient risk, was also independently associated with 1-year graft failure (P<0.001). In North America, 1-year graft failure was significantly associated with donor-recipient risk matching (log-rank P<0.001). One-year graft failure was highest with pairing of high-risk recipients and donors (13.1% [95% CI, 10.7%-13.9%]) and lowest among low-risk recipients and donors (7.4% [95% CI, 6.8%-8.0%]). Matching of low-risk recipients with high-risk donors was associated with significantly less graft failure (9.0% [95% CI, 8.3%-9.7%]) than high-risk recipients with low-risk donors (11.4% [95% CI, 10.7%-12.2%]) Conclusions: European heart transplantation centers are more likely to accept higher-risk donor hearts than North American centers. Acceptance of borderline-quality donor hearts for lower-risk recipients could improve donor heart utilization without compromising recipient survival.

Indexed donor cardiac output for improved size matching in heart transplantation: A United Network for Organ Sharing database analysis

ObjectiveImplantation of an appropriately sized donor heart is critical for optimal outcomes after heart transplantation. Although predicted heart mass has recently gained consideration, there remains a need for improved granularity in size matching, particularly among small donor hearts. We sought to determine if indexed donor cardiac output is a sensitive metric to assess the adequacy of a donor heart for a given recipient. MethodsA retrospective analysis was performed (2003-2021) in isolated orthotopic heart transplant recipients from the United Network for Organ Sharing database. Donor cardiac output was divided by recipient body surface area to compute cardiac index (donor cardiac index). Predicted heart mass ratio was computed as donor/recipient predicted heart mass. The primary outcome was mortality 1 year after transplant. ResultsAmong transplant recipients, median donor cardiac output was 7.3 (5.8-9.0) liters per minute and donor cardiac index was 3.7 (3.0-4.6) liters per minute/m2. Predicted heart mass ratio was 1.01 (0.91-1.13). After multivariable adjustment, higher donor cardiac index was associated with lower 1-year mortality risk (odds ratio, 0.92, P = .042). Recipients with predicted heart mass ratio less than 0.80 (n = 255) had a lower median donor cardiac index than those with a predicted heart mass ratio of 0.80 or greater (3.2 vs 3.7, P < .001). As predicted, heart mass ratio became smaller and the association between donor cardiac index and 1-year mortality became progressively stronger. ConclusionsHigher donor cardiac index was associated with a lower probability of 1-year mortality among patients undergoing heart transplantation and served to further quantify mortality risk among those with a small predicted heart mass ratio. Donor cardiac index appears to be an effective tool for size matching and may serve as an adjunctive strategy among small donor hearts with a low predicted heart mass ratio.

Delaminating Intramyocardial Hematoma in Patients with Heart Failure with Reduced Ejection Fraction: а Series of Clinical Cases

Delaminating intramyocardial hematoma (DIMH) is a rare and potentially life-threatening complication of acute myocardial infarction. Currently, only isolated reports of cases of myocardial dissection have been published, and until recently, the diagnosis of DIMH was carried out during autopsy or surgery. The article describes echocardiographic criteria and discusses some aspects of the therapy of this pathology. The description of clinical cases of noninvasive diagnosis of DIMH in men aged 60 and 62 years hospitalized with the clinic of decompensation of chronic heart failure is given. This complication in the presented patients was diagnosed using transthoracic echocardiography, thanks to which it was possible to identify the dissection of the myocardium, as well as to trace the dynamics of the organization of an intramyocardial hematoma into a parietal thrombus. Various approaches to patient management are demonstrated: conservative tactics allowed to successfully stabilize the course of chronic heart failure in the first patient, while the condition of the other required the transplantation of a donor heart a few months after discharge from the hospital.

Research Highlights.

Research Highlights.

Expanding Heart Donor Pool With a Broken Heart: Cardiac Transplant From Donor Following Circulatory Death With Takotsubo Syndrome.

Owing to the growth of patients with advanced heart failure and limited potential for donation after brain death, expanding donor source with hearts from controlled donation after circulatory death (cDCD) and meeting extended criteria are essential strategies. We present the first case of a patient who successfully underwent cardiac transplant (CT) from cDCD with Takotsubo syndrome (TTS). The donor was a 49-y-old man without risk factors for coronary artery disease (CAD) and terminal amyotrophic lateral sclerosis with respiratory failure and mechanical ventilation support. A decision was made with patient’s family to withdraw life-sustaining therapies (WLSTs). Organ donation option was presented and consented, and cDCD Maastricht Classification III1 was considered suitable. He presented normal blood tests, electrocardiogram, and echocardiogram. The cDCD process was performed using an extracorporeal membrane oxygenation circuit to perform thoracoabdominal normothermic regional perfusion.2 During intraoperative evaluation, transesophageal echocardiography revealed normal left ventricular ejection fraction (LVEF). However, after WLST, moderate dysfunction (LVEF 37%) and apical ballooning suggestive of TTS were observed (Figure 1A), continuing present after thoracoabdominal normothermic regional perfusion withdrawal and organ extraction. Epicardial coronary arteries palpation did not reveal pathology.FIGURE 1.: A, Intraoperative transesophageal echocardiography evaluation that shows the left ventricle in diastole and systole with apical akinesia and preserved contractility of basal segments. B, The 12-lead electrocardiogram reveals T wave inversion and prolonged QT interval. C, A graph of heart recovery timeline based on the high-sensitivity troponin T levels, left ventricular ejection fraction, and inotrope support, correlated with the d after cardiac transplant. D, Normal right and left coronary arteries in the post cardiac transplant protocol–based coronary angiography. LVEF, left ventricular ejection fraction.The heart recipient was a 52-y-old man with severe, irreversible ischemic cardiomyopathy and 10 d with a ventricular assist device, listed for CT after excluding severe comorbidities and a multidisciplinary team discussion. An orthotopic transplant was performed using the bicaval technique, with spontaneous heartbeat and cold ischemia time of 86 min. He required minimal vasoactive support, withdrawn 48 h after CT. The electrocardiogram showed diffuse negative T waves and prolonged QTc interval (Figure 1B), and peak level of high-sensitivity troponin T was 2115 ng/L. Six days after CT, LVEF normalized. The timeline of heart recovery is represented in Figure 1C. The coronary angiography ruled out donor CAD (Figure 1D). The patient was discharged 30 d after CT and is doing well 43 wk after. Serial echocardiograms reveal normal wall motion and function. DISCUSSION Although TTS and CT have been indirectly associated, few cases have been published on donor hearts with TTS, these with no compromised survival3; none in cDCD. Similar pathophysiological aspects, present in TTS and cDCD, could be responsible for the phenomenon that occurred during CT. In the cDCD, the heart experiences a warm ischemia period during the WLST, cardiac arrest, and CT. This implies ischemia–reperfusion injury: activation of inflammatory and coagulation cascades and release of catecholamines.4 The mechanisms behind TTS, clinical condition characterized by acute transient left ventricular dysfunction, remain unknown. The most widely accepted theory is catecholamine-induced cardiotoxicity, and growing evidence is arising for myocardial inflammation, endothelial and microcirculation dysfunction, and neurohormonal alterations.5 Because of donor’s age, low-risk profile of CAD, and echocardiographic abnormalities, TTS was suspected. The post-CT protocol–based coronary angiography ruled out obstructive CAD or atherosclerotic plaque rupture. There was a rapid normalization of LVEF, negative T waves in the electrocardiogram, and elevated cardiac enzymes. This fulfilled the most widely used TTS diagnostic criteria.5 A pre-CT coronary angiography in patients >40 y or at risk of CAD could avoid ruling out hearts with left ventricular dysfunction. CONCLUSION The pathophysiological knowledge of cDCD and TTS could increase CT rates. This first experience in cDCD should be cautiously interpreted and analyzed individually in future cases.

Organ Donation and Transplantation among Non-US Citizens: Opportunities to Improve Global Equity in Heart Transplantation

BackgroundNon-US citizens/non-US residents (NCNR) are a unique and growing population. Patterns of heart donation and heart transplantation (HT) within this subgroup have not been described fully. The purpose of this study was to evaluate the use of organs from NCNR donors and the characteristics and outcomes of NCNR HT recipients. MethodsAll adult donors whose hearts were recovered for HT and all primary adult HT recipients from 2013 to 2020 were identified using the United Network for Organ Sharing. Donors and recipients were categorized as citizens, residents, or NCNR. NCNR were further categorized by reason for travel to the United States. Outcomes included mortality, infection, and rejection at 1-year after transplantation. ResultsNCNR accounted for 0.4% (n = 77) of heart donors. Most NCNR donors identified as Hispanic (61%), were predominately recovered from the South and Southwest United States, and were less likely to express written documentation to be a donor compared with citizens and residents. NCNR accounted for 0.7% (n = 147) of all HT recipients. The majority identified as non-Hispanic White individuals (57.1%). Compared with citizens and residents, NCNR recipients seemed to be sicker, as evidenced by higher intra-aortic balloon pump use before HT and higher priority United Network for Organ Sharing status. Of NCNR recipients, 63% traveled to the United States for HT, predominately from Kuwait (29.9%) and Saudi Arabia (20%). At 1-year after transplant, there were no differences in mortality, infection, or rejection between the groups. ConclusionsA growing subgroup of NCNR travel from countries with low HT rates to the United States for HT. This finding highlights the need for strategies to improve equitable access to HT domestically and abroad.

Rat Model of Normothermic Ex-Situ Perfused Heterotopic Heart Transplantation.

Heart transplantation is the most effective therapy for end-stage heart failure. Despite the improvements in therapeutic approaches and interventions, the number of heart failure patients waiting for transplantation is still increasing. The normothermic ex situ preservation technique has been established as a comparable method to the conventional static cold storage technique. The main advantage of this technique is that donor hearts can be preserved for up to 12 h in a physiologic condition. Moreover, this technique allows resuscitation of the donor hearts after circulatory death and applies required pharmacologic interventions to improve donor function after implantation. Numerous animal models have been established to improve normothermic ex situ preservation techniques and eliminate preservation-related complications. Although large animal models are easy to handle compared to small animal models, it is costly and challenging. We present a rat model of normothermic ex situ donor heart preservation followed by heterotopic abdominal transplantation. This model is relatively cheap and can be accomplished by a single experimenter.