This retrospective observational study aimed to determine whether echocardiographic markers of restrictive physiology can identify early cardiac allograft vasculopathy (CAV). There were 136 heart transplant (HT) recipients evaluated between January 2018 and December 2023. The echocardiographic parameters assessed were E/A ratio, isovolumetric relaxation time (IVRT), deceleration time (DT), E/e', and tissue Doppler indices. The primary outcome was angiographic CAV (ISHLT grade ≥1) at 1 year, which was observed in 15% of recipients. Only DT <150 ms was significantly associated with CAV (OR 2.73, 95% CI 1.03-7.21). A multivariable model incorporating age, sex, and DT <150 ms demonstrated good discrimination for CAV (AUC 0.78). These findings suggest that DT may be a non-invasive marker of early CAV and merit further studies to determine long-term risk prediction.
Cardiac allograft vasculopathy (CAV) is a leading cause of late graft failure with limited revascularization options and high rates of in-stent restenosis (ISR). This report details a 33-year-old heart transplant recipient with progressive CAV that underwent multiple prior revascularizations, including drug-eluting stents and coronary artery bypass grafting. He developed ISR of the right coronary artery stent, treated with paclitaxel drug-coated balloon (DCB) without further stenting. Follow-up at 3 and 9 months showed patent vessels without recurrent restenosis and preserved graft function. DCB may be a viable option for ISR in advanced CAV when additional stenting is undesirable. Larger studies are needed to define its long-term role.
Ex-vivo lung perfusion (EVLP) has expanded donor lung utilization, with over 1000 cases performed at our center since 2008. A next-generation Toronto EVLP system (TorEx EVLP) was introduced in December 2022, enabling simplified circuit setup by loading an organ chamber into an all‑in‑one device, potentially facilitating EVLP use at less experienced centers. This study reports the initial experience with TorEx EVLP and compares outcomes with (1) first‑generation EVLP and (2) conventional lung transplantation without EVLP. In this single-center retrospective cohort study, 1067 EVLP procedures were performed from September 2008 to September 2024 (first-generation EVLP [G1], n=874; TorEx EVLP [G2], n=193). Post-transplant short- and long-term outcomes were compared among G1, G2, and contemporaneous direct transplants without EVLP (direct, n=1575). Of 1067 EVLP cases, 684 were accepted for transplant (utilization: G1 64.4%, G2 62.7%), and 700 transplants were performed (including 16 split singles). G1 and G2 had significantly higher DCD donor use (direct vs G1 vs G2: 17% vs 48% vs 60%, p<0.001) and lower donor P/F ratios (422 vs 368 vs 368 mmHg, p<0.001). Recipients in G1 and G2 were older than direct recipients (59 vs 61 vs 65 years, p<0.05). Post‑transplant outcomes were similar across groups, including PGD3 at 72 h (15% vs 16% vs 10%, p=0.21), extubation within 72 h (65% vs 64% vs 68%, p=0.67), overall survival, and CLAD‑free survival. Despite higher-risk donor use, outcomes with both first- and next-generation Toronto EVLP systems were comparable to direct transplantation.
Evidence guiding optimal size-matching in lung transplantation is limited, and no consensus exists. Most current approaches fail to account for the recipient's underlying pathology. A recently proposed "adjusted" total lung capacity (TLC) ratio, incorporating actual (aTLC) and predicted TLC (pTLC), may offer a physiologically relevant size-matching strategy. However, its clinical performance has not been reported. We retrospectively reviewed 376 double lung transplants at our center between January 2017 and March 2023, excluding lobar transplants. We calculated the adjusted TLC ratio as the donor pTLC divided by the mean of the recipient pTLC and aTLC. Patients were categorized into 3 groups as follows: all recipients (Cohort A, n = 376), restrictive lung disease (Cohort B, n = 204), and restrictive disease without volume-reduction procedures (Cohort C, n = 150). The primary outcome was peak posttransplant forced expiratory volume in 1 s (FEV1). Secondary outcomes included baseline lung allograft dysfunction (BLAD), chronic lung allograft dysfunction (CLAD), survival, and time to normalization of lung function. Based on posttransplant peak FEV1, we identified an adjusted TLC ratio of 0.9 to 1.0 as the optimal range for lung-size matching. Optimally sized (0.9-1.0) and undersized (0.79-0.89) grafts showed the highest FEV1 posttransplant. Oversized grafts (>1.0) were associated with lower FEV1 across all cohorts and higher BLAD incidence in Cohort A. The adjusted TLC ratio did not influence survival. Size-matching using an adjusted TLC ratio of 0.79 to 1.0 correlates with improved long-term outcomes in lung transplantation, whereas oversizing may impair lung function. The effect on survival remains inconclusive due to study limitations.
Thrombotic microangiopathy (TMA) represents a heterogeneous group of disorders characterized by endothelial injury, complement activation, and platelet aggregation, and may occur in association with systemic diseases, infections, or drug exposure. In solid organ transplant recipients, TMA is most commonly linked to immunosuppressive therapy, particularly calcineurin inhibitors and mammalian target of rapamycin inhibitors, with increased risk during combined use. Drug-induced TMA is rare but potentially life-threatening, and management relies primarily on prompt withdrawal of the offending agent and modification of immunosuppression. We report the successful use of belatacept-based immunosuppression in a heart transplant recipient with tacrolimus-associated TMA. Belatacept, a selective T-cell costimulation blocker, represents a promising alternative immunosuppressive strategy in this setting, particularly in patients with drug-related vascular toxicity.
The use of amiodarone prior to cardiac transplant in adults is associated with worse post-transplant outcomes. Data are scarce in pediatrics regarding the association of pre-amiodarone use with post-transplant outcomes. We aim to describe and compare pediatric post-transplant outcomes based on use of pre-transplant amiodarone at a large pediatric cardiac transplant center. We performed a retrospective cohort study of pediatric patients 18 years or younger who underwent cardiac transplant between 2015 - 2021. Pre-transplant amiodarone use was defined as use/administration of amiodarone within two weeks pre-transplant. Pre-transplant characteristics and post-transplant outcomes including mortality and markers of morbidity were compared between the two groups. Six percent (10/156) of the study population were on amiodarone pre-transplant. There were no differences in mortality between the two groups. Severe primary graft dysfunction (PGD) incidence was higher in the pre-transplant amiodarone group (p = 0.04). The use of post-transplant isoproterenol (p = 0.01) and temporary pacing (p = 0.01) were higher in the pre-transplant amiodarone group. There was no association between either amiodarone dose or length therapy with post-transplant outcomes. Higher rates of PGD, increased use of isoproterenol, and need for temporary pacing post-transplant among patients receiving pre-transplant amiodarone suggests that amiodarone may contribute to inadequate chronotropy in the acute post-operative period. The need for chronotropic support occurred irrespective of amiodarone dose or length of therapy.
Cardiac allograft vasculopathy (CAV) is one of the major long-term complications in patients after heart transplantation (HTx) limiting allograft function and longevity. CAV can be studied non-invasively by evaluating myocardial perfusion (MP). Aspirin is re--ed after Htx, but it is unclear whether it affects the development of CAV. The aim of this study was to investigate the association between aspirin therapy and MP, as a marker of CAV, using cardiovascular magnetic resonance (CMR). We consecutively included HTx patients from 2 centers in Sweden who were examined with CMR and coronary angiography. Patients were categorized by the presence or absence of aspirin therapy. As a part of routine surveillance, quantitative short-axis perfusion maps were acquired at rest and during stress hyperemia. A global average MP was calculated at rest and stress and myocardial perfusion reserve (MPR) was defined as the ratio between stress and rest MP. Cine images and T1 maps were also acquired. A total of 137 patients (n = 107 aspirin) were included in the study. Resting myocardial perfusion was lower in HTx recipients receiving aspirin therapy compared with those not receiving aspirin (1.0 ± 0.3 vs 1.2 ± 0.4 ml/min/g; p = 0.003); stress myocardial perfusion was higher in patients treated with aspirin (2.6 ± 0.8 vs 2.2 ± 1.0 ml/min/g; p = 0.037). Consequently, myocardial perfusion reserve (MPR) was significantly greater in patients receiving aspirin compared with those not on aspirin therapy (2.5 ± 0.7 vs 1.9 ± 0.8; p < 0.001). In both univariable and multivariable linear regression analyses, aspirin therapy remained independently associated with higher MPR after adjustment for sex, CAV grade, time from transplantation to CMR, diabetes, statin therapy, and everolimus use. In this retrospective study, aspirin therapy in heart transplant patients was independently associated with higher myocardial perfusion reserve.
Severe obesity is a relative exclusion criterion for heart transplantation. This study assessed glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight loss as a bridge to heart transplantation candidacy. A retrospective study of end-stage heart failure (ESHF) outpatients commenced on semaglutide compared demographic, metabolic, and transplant listing data pre- and post-treatment. Nine patients (median pre-GLP-1 RA body mass index [BMI]: 35.9 kg/m2 [IQR 1.3]) received semaglutide for a median of 4 months (IQR 9). Seven patients (78%) had an initial BMI >35 kg/m2; an exclusion criterion for transplantation. Post-treatment, median BMI decreased to 32.2 kg/m2 (IQR 4.1), representing a 5.0 kg (IQR 6.3) median weight loss. All patients were subsequently transplant-listed, and 7 (78%) patients underwent transplantation. No significant adverse effects were reported. These preliminary findings suggest semaglutide may facilitate heart transplantation eligibility in ESHF patients with severe obesity, warranting larger studies to guide GLP-1 RA use in transplant protocols.
Baseline lung allograft dysfunction (BLAD) is a phenotype of early graft dysfunction associated with impaired survival after lung transplantation. Although prior work links BLAD with several pre- and post-transplant factors, a robust set of donor and recipient predictors remains unclear. What are important donor and recipient predictors of BLAD? We retrospectively reviewed 124 adults who underwent bilateral lung transplantation at a single center. Donor and recipient variables were evaluated using machine learning (gradient boosting and classification tree models), with high-importance predictors incorporated into logistic regression. Survival was assessed using Kaplan-Meier and Cox proportional hazards models. BLAD occurred in 58 of 124 patients (46.7%). Our analysis identified 7 key factors associated with BLAD: Increased cold ischemia time (p = 0.04) and extremes of Body Mass Index (BMI) (p = 0.04) were associated with BLAD in a non-linear manner. Increased post-transplant Intensive Care Unit (ICU) length of stay (Odds Ratio [OR]: 1.08, 95% Confidence Interval [CI]: 1.00-1.17, p = 0.04) and donor tobacco use > 20 pack years (OR: 16.83, 95% CI: 2.34-121.2, p = 0.005) were also associated with higher odds of BLAD. Female sex (OR: 0.08, 95% CI: 0.02-0.39, p = 0.002), older age (OR: 0.93, 95% CI: 0.88-0.97, p = 0.003), and higher pre-operative Forced Expiratory Volume in 1 second (FEV₁) (OR: 0.19, 95% CI: 0.07-0.55, p = 0.002) were associated with lower odds of BLAD. The model demonstrated strong predictive performance (C-index 0.79, cross-validated). Patients with moderate to severe BLAD (Grade 2 and 3) had a significantly increased risk of death over a median follow-up period of 815 days (Hazard Ratio [HR] 3.53, 95% CI: 1.07-11.71, p = 0.04). BLAD is common after bilateral lung transplantation. Moderate to severe BLAD is associated with worse survival. Machine learning identified biological variables associated with BLAD and modifiable peri-operative variables, highlighting opportunities for pre-transplant and intra-operative optimization.
Combined en-bloc heart-lung transplantation (HLT) remains the optimal treatment for selected patients with end-stage cardiopulmonary disease. The indications for and utilization of HLT have changed significantly over time. We report the changing landscape of HLT in the UK over recent decades, identifying factors that may inform future organization of services. Data were extracted from the UK Transplant Registry spanning 1984 to December 2023. All patients who were registered for and/or underwent HLT were included in our analysis. Baseline characteristics and outcomes from listing and transplantation were compared between 2 eras: pre-2000 and post-2000. Pre-2000, 1,199 patients were registered for HLT, and 915 received HLT, post-2000, there were 473 registrations and 200 transplantations, reflecting a significant decline in the use of this procedure. Those listed post-2000 were older, more symptomatic, and with more prior cardiac surgeries. Cystic fibrosis, the leading indication pre-2000, declined substantially in the later era. For patients requiring HLT in the later era, the risk of dying on the waiting list exceeded the chance of receiving a transplant. Median post-transplant survival improved from 4.07 (IQR 0.2, 12.3) to 7.9 (IQR 0.8, 21.6) years. Although HLT activity has declined, a considerable need remains, particularly among patients with congenital heart disease and pulmonary hypertension. The changes in patient demographics and high waiting list mortality highlight systemic inefficiencies in organ allocation and underscore the need for a revised system to ensure timely and equitable access for this high-risk population.
Post-transplant diabetes mellitus (PTDM) is common after orthotopic heart transplantation (OHT), but its long-term impact on myocardial function is unclear. We aimed to evaluate the effects of PTDM on left ventricular (LV) systolic function. We prospectively studied 102 OHT recipients with echocardiographic follow-up at 1-, 3-, and 5-year post-transplant. Patients were classified according to PTDM status at 1 year. LV systolic function was assessed using ejection fraction (EF) and global longitudinal strain (GLS). Linear mixed-effects models were used to evaluate longitudinal associations, adjusting for age, sex, systolic blood pressure, and cardiac allograft vasculopathy (CAV). PTDM was present in 36% of patients. At 1-year, EF and GLS were similar between groups. At 3 years, patients with PTDM exhibited significantly lower systolic function as assessed by GLS (-14.9±2.8 vs. -16.0±3.0%, p=0.022), and at 5 years, EF was also significantly lower (52±4 vs. 57±7%, p=0.002). In longitudinal analyses, PTDM was associated with persistently impaired GLS without a significant interaction with time (p=0.192). In contrast, EF demonstrated a significant PTDM×time interaction (p=0.039), reflecting a greater decline over time in patients with PTDM. These associations remained significant after adjustment for CAV, which was not independently associated with GLS or EF. PTDM after OHT is associated with early and persistent impairment in myocardial deformation, followed by a progressive decline in systolic function. These findings suggest a metabolically mediated myocardial effect independent of chronic graft failure and highlight the importance of early detection and management of PTDM in heart transplant recipients.
Patients undergoing lung transplantation (LTx) are at risk of clinical deterioration during hospital ward care. The epidemiology of Medical Emergency Team (MET) calls in LTx patients and their association with patient outcomes are poorly described. We aimed to (1) measure the frequency, timing, and characteristics of MET activations in patients undergoing LTx, (2) evaluate differences in demographics and outcomes between those who had a MET call vs those who didn't. A retrospective cohort study of patients who received MET calls during their index admission for LTx at the Alfred Hospital between January 2016 and December 2021. Amongst 535 patients undergoing LTx, MET activation occurred in 265 (49.5%), with 738 MET activations in total. The MET group had a median (IQR) of 2 (1-4) MET calls. Pre-LTx period accounted for 15% of the calls, with hypoxia being the most common trigger (49.5%). During the post-LTx period, tachycardia (28.5%) and hypotension (33.1%) were the most common triggers. Hospital length-of stay (LOS) was longer in the MET group (26 [19-41] vs 19 days [15-27], p < 0.001), and ICU readmission occurred more frequently (27.5 vs 2.2%, p < 0.001). Post LTx MET activation had no impact on 90-day mortality [Adj HR (95% CI): 1.41 (0.19-10.60); p = 0.74] or on long-term survival [Adj HR (95% CI): 1.09 (0.80-1.49); p = 0.59]. MET activation is common in patients undergoing LTx. Admissions with MET are associated with higher rates of ICU readmission and longer hospital LOS compared to the no MET group, without affecting survival outcomes.
Perioperative bleeding is a frequent high-risk complication, especially during Left Ventricular Assist Device (LVAD) implantation, and frequently necessitates reoperation. Bleeding control required many therapeutic options, and in refractory cases, recombinant activated Factor VII (rFVIIa) was considered one of the additional off-label options used. We report our experience with rFVIIa administration during LVAD implantation, particularly with the HeartMate III device, to assess safety outcomes, including pump thrombosis, stroke, and thromboembolic events. This is a retrospective single-center study for patients who developed refractory perioperative bleeding during LVAD, HeartMate III, implantation, and received rFVIIa due to the failure of other therapeutic options. The study was conducted from the first of December 2022-31 July 2025. The primary endpoint was a composite of pump thrombosis, stroke and thromboembolic events. Among all HeartMate III LVAD implantations during the study period, eight patients received rFVIIa. There was no single recorded case of mortality, major stroke causing disability or device pump thrombosis. One patient (12.5%) experienced a minor stroke. There were a total of three patients (37.5%) identified to have a surgical source of bleeding, and two patients (25%) required operation re-exploration due to continued bleeding. This is a retrospective trial of a single cardiac center experience. rFVIIa use in refractory bleeding during HeartMate III LVAD implantation is safe with no significant additional risk of pump thrombosis or major stroke. A further large-scale investigation is needed to determine its safety and effectiveness.
Intra-aortic balloon pumps (IABPs) and percutaneous left ventricular assist devices (pLVADs; Impella) are used to stabilize patients with cardiogenic shock (CS). While recent evidence supports their usefulness in myocardial infarction (MI)-related CS, data on non-MI CS, particularly regarding newer Impella models, remain limited. We compared outcomes associated with IABP versus various Impella devices in non-MI CS. We retrospectively analyzed National Inpatient Sample (NIS) data from 2016 to 2022 to identify patients with non-MI CS who received IABP, Impella 2.5/CP, or Impella 5.0/LD/5.5. Outcomes explored were in-hospital mortality, rates of orthotopic heart transplant (OHT) and durable left ventricular assist device (LVAD) implantation, blood transfusion requirements, length of stay, and total hospital charges. Among patients with non-MI CS, Impella 5.0/LD/5.5 use was associated with lower in-hospital mortality (8.2% vs 14.9%, P=0.006), higher rates of OHT (27.6% vs 11.7%, P<0.001) and LVAD implantation (45.1% vs 15.6%, P<0.001), longer hospital stays (40.4 vs 23.5 d, P<0.001), greater transfusion requirements (21.8% vs 13.5%, P=0.004), and higher total charges ($1350,236 vs $653,962, P<0.001) than IABP. In contrast, Impella 2.5/CP use was associated with greater in-hospital mortality (39.6% vs 23.6%, P<0.001), lower rates of OHT and LVAD implantation, shorter hospital stays (11.2 vs 17.5d, P<0.001), and lower total charges ($416,416 vs $486,318, P<0.001) than IABP. In non-MI CS, the high-flow Impella 5.0/LD/5.5, but not the low-flow Impella 2.5/CP, was associated with better survival and higher rates of advanced therapies than IABP, albeit at the expense of greater transfusion requirements, longer hospitalization, and greater resource utilization.
Malignancy usually requires a cancer-free interval before lung transplantation, although individualized exceptions are allowed based on tumor biology and recurrence risk. We report a case of urgent bilateral lung transplantation performed 30 days after curative-intent therapy for hepatocellular carcinoma (HCC) in a 66-year-old man with rapidly progressive idiopathic pulmonary fibrosis. Over 52 months of MRI surveillance, there was no evidence of HCC recurrence. The patient ultimately died 4 years after transplantation from advanced chronic lung allograft dysfunction. This case illustrates that, in exceptionally selected patients with localized HCC and documented response to locoregional therapy, expedited lung transplant listing may be clinically and ethically justified when near-term respiratory mortality outweighs the anticipated risk of cancer recurrence. Such decisions should remain individualized and multidisciplinary rather than broadly generalizable.
Donation after circulatory death (DCD) has re-emerged as a means of expanding the donor heart pool. Current clinical practice relies mainly on direct procurement followed by normothermic machine perfusion or on thoraco-abdominal normothermic regional perfusion. This paper details the practical aspects with an alternative strategy: direct procurement followed by hypothermic oxygenated perfusion (HOPE). Key technical considerations include prevention of bubble formation in albumin-containing solutions and early machine priming to avoid ischemic delays. The final acceptance of grafts is based on a functional warm ischemic time <30 min, satisfactory cardioplegic flush and anatomy, and stable, uneventful machine perfusion. Though this approach does not permit functional assessment of the graft, early results suggest that when strict donor and procedural criteria are observed, outcomes are favorable. Direct procurement of the DCD heart with HOPE offers a simplified, logistically efficient preservation method that avoids donor blood recirculation. Further studies are warranted to refine candidate selection and assess long-term results.
Children supported with paracorporeal ventricular assist devices (VADs) are at increased risk of thrombotic complications despite anticoagulation advances. Bivalirudin, a direct thrombin inhibitor, has emerged as an alternative to heparin through initiatives led by ACTION. At our institution, a burst dosing protocol was implemented, consisting of a 20% to 50% dose increase per hour for 2 hours, to manage fibrin or pin-point thrombus deposition. In this case series, 9 patients received a total of 132 bivalirudin bursts across the duration of support. No bleeding events occurred within 12 hours of a burst, and no thromboembolic events occurred within 48 hours. These preliminary findings suggest that bivalirudin burst dosing is feasible and not temporally related to adverse events in our pediatric population requiring paracorporeal support. Further prospective investigation is necessary to validate safety, establish optimal dosing parameters, and develop standardized burst initiation criteria.
Left ventricular assist device (LVAD) driveline infections (DLIs) are common complications (1) and frequently recur despite definite treatment due to bacterial entry and biofilm formation. We report the first case of recurrent, extensively drug-resistant Pseudomonas aeruginosa LVAD infection successfully cured using systemic antimicrobials, continuous in-situ targeted antibiotics (CITA), and repeated surgical interventions, highlighting CITA's therapeutic potential.
Minimal data exists to predict the need for mechanical circulatory support (MCS) for patients with secondary pulmonary hypertension (SPH) undergoing single lung transplant (SLT). We aim to identify preoperative hemodynamic and echocardiographic variables that could predict MCS use and compare clinical outcomes for SLT with and without intraoperative MCS use. An institutional registry of SLT recipients with SPH between 2017 and 2021 were analyzed. Cohorts were separated by the use of intra-operative MCS and analyzed. Odds ratios and multivariable logistic regression were utilized to evaluate the likelihood of requiring intraoperative MCS during SLT. We identified 293 patients, of which 44 (15.1%) required intraoperative MCS use, while 249 (84.9%) did not. Preoperative RV-PA coupling ratio or TAPSE/PASP ratio <0.3 was highly associated with intraoperative MCS use during SLT (OR4.09 (95% 2.06 - 8.14, p=<0.0001). PCWP, pre-operative PVR, transplant laterality, LAS and intraoperative PA Systolic Pressure were also independently associated with intraoperative MCS use. Length of stay was longer in the MCS-use group (29.8 vs 18.5 days, p= 0.007) whereas survival was similar at 30 (100% MCS vs 99.6% non-MCS, p=1) and 60 days (100% MCS vs 98% non-MCS, p=0.75). A Kaplan-Meier analysis showed no survival difference to 3 years (p=0.92). Assessment of preoperative RV-PA uncoupling using TAPSE/PASP ratio can help predict intraoperative MCS use during SLT. A preoperative TAPSE/PASP <0.3 confers a 4-fold increase in the likelihood of MCS use. The use of MCS during SLT does increase the length of stay, however, does not significantly change survival.
Lung transplant (LTx) recipients are at high risk for severe COVID-19. Few data on morbidity and mortality in LTx recipients admitted to the intensive care unit (ICU) for COVID-19 are available. We conducted a multicenter retrospective study in the nine accredited adult LTx centers in France from March 2020 to December 2022. The primary objective was to identify risk factors for mortality in LTx recipients admitted to the ICU for severe COVID-19. We also described treatment strategies before and during the ICU stay, ventilation strategies, and medium-term changes in lung function tests in survivors. Of the 84 included patients, 39 (46.4%) died in the ICU. Factors independently associated with ICU mortality were time >30 months since LTx (OR, 5.52; 95%CI, 1.66-20.30; P=0.007) and intubation (OR, 4.90; 95%CI, 1.39-19.73; P=0.017). Among the 54 intubated patients, mortality was 59% both in those with first-line intubation (n=22) and in those with intubation after failure of non-invasive strategies (n=32). Mortality was 80% with intubation after ≥5 days of non-invasive strategies. The use of specific anti-SARS-CoV-2 treatments was not different between survivors and non-survivors. Lung function tests worsened significantly after the infection. The ICU mortality rate among LTx recipients with severe COVID-19 pneumonia was high. Although intubation was associated with mortality, the very high mortality when intubation was delayed by ≥5 days indicates a need for rapidly identifying those patients who will not recover with non-invasive strategies. Specific anti-SARS-CoV-2 treatments were not associated with decreased mortality.