Cohort Of Heart Transplant Recipients Research Articles

Association of early post-transplant hyperglycaemia and diabetes mellitus on outcomes following heart transplantation.

Early post-transplant hyperglycaemia (EPTH) and post-transplant diabetes mellitus (PTDM) are common following solid organ transplantation and may be associated with adverse outcomes. We studied the prevalence of EPTH and cumulative 5-year prevalence of PTDM in a modern cohort of heart transplant recipients who were free from diabetes at baseline as well as the association of EPTH, PTDM and pre-transplant T2DM with adverse transplant-related outcomes. Retrospective cohort study of heart transplant recipients followed for 5 years at a single centre in Sydney, Australia. A total of 141 patients were included, of whom 25 had pre-existing type 2 diabetes mellitus (T2DM) and 116 were free from diabetes at baseline. In patients without pre-existing T2DM, 88 of 116 (76%) experienced EPTH, which was associated with higher rates of acute rejection and hospitalizations, and lower 5-year survival. PTDM developed in 45 of 116 (39%) patients, all of whom had experienced EPTH. Both PTDM and pre-existing T2DM were associated with increased rates of graft rejection and hospitalization, and greater than three-fold increased likelihood of death compared to patients that remained free from diabetes. EPTH and PTDM are highly prevalent following cardiac transplantation. EPTH develops within days of transplant and is strongly associated with progression to PTDM. Pre-existing T2DM, PTDM and EPTH are associated with greater hospitalization, increased episodes of rejection and worse 5-year survival compared to patients who remained free from diabetes during follow-up.

Cytomegalovirus infection in heart transplant recipients: Epidemiology, risk factors, and long-term outcomes from a major transplant center in the United States

BackgroundDespite the use of antiviral prophylaxis, cytomegalovirus (CMV) remains a common opportunistic infection following heart transplantation. This study analyzes the rates, risk factors, and outcomes of CMV among heart transplant recipients. MethodsA retrospective cohort study was conducted of adults who underwent heart transplantation between January 1, 2011, and March 31, 2019. The primary outcome was clinically significant CMV infection (csCMVi), defined as CMV disease or asymptomatic infection requiring preemptive therapy. The secondary outcome was all-cause mortality. Patients received valganciclovir prophylaxis up to 6 months, depending on CMV donor/recipient serostatus. Kaplan-Meier curve and multivariable Cox regression were used for outcome analysis. ResultsAmong 553 heart transplant recipients, 101 (18.3%) experienced csCMVi, including 35 (6.3%) with CMV disease. csCMVi was uncommon during prophylaxis. In multivariable analysis, CMV D+/R- status (HR 12.88, 95% CI 6.76-24.56; p<0.001) and lower absolute lymphocyte counts in seropositive recipients (HR 1.48, 95% CI 1.23-1.79; p<0.001), but not CMV D+/R- patients (HR 1.18, 95% CI 0.94-1.47; p=0.162), were significantly associated with csCMVi. Sixty patients died during follow-up, and csCMVi was associated with increased mortality (HR 2.84, 95% CI 1.62-4.98; p<0.001). ConclusionsIn this large cohort of heart transplant recipients, csCMVi was linked to higher mortality. CMV D+/R- serostatus was associated with an increased risk of csCMVi, with lower absolute lymphocyte counts increasing risk only in CMV seropositive recipients. Strategies for optimizing CMV prevention in serodiscordant heart recipients are warranted.

Post-transplant survival with pre-transplant durable continuous-flow mechanical circulatory support in a Swiss cohort of heart transplant recipients.

Worldwide, almost half of all heart transplantation candidates arrive today at their transplant operation with durable continuous-flow mechanical circulatory support (CF-MCS). This evolution is due to a progressive increase of waiting list time and hence an increased risk of haemodynamic worsening. Longer duration of CF-MCS is associated with a higher risk of device-related complications with potential adverse impact on post-transplant outcome as suggested by recent results from the United Network of Organ Sharing of the United States. A 2-centre Swiss heart transplantation programme conducted a retrospective observational study of consecutive patients of theirs who underwent a transplant in the period 2008-2020. The primary aim was to determine whether post-transplant all-cause mortality is different between heart transplant recipients without or with pre-transplant CF-MCS. The secondary outcome was the acute cellular rejection score within the first year post-transplant. The study participants had a median age of 54 years; 38/158 (24%) were females. 53/158 study participants (34%) had pre-transplant CF-MCS with a median treatment duration of 280 days. In heart transplant recipients with pre-transplant CF-MCS, the prevalence of ischaemic cardiomyopathy was higher (51 vs 32%; p = 0.013), the left ventricular ejection fraction was lower (20 vs 25; p = 0.047) and pulmonary vascular resistance was higher (2.3 vs 2.1 Wood Units; p = 0.047). Over the study period, the proportion of heart transplant recipients with pre-transplant CF-MCS and the duration of pre-transplant CF-MCS treatment increased (2008-2014 vs 2015-2020: 22% vs 45%, p = 0.009; increase of treatment days per year: 34.4 ± 11.2 days, p = 0.003; respectively). The primary and secondary outcomes were not different between heart transplant recipients with pre-transplant CF-MCS or direct heart transplantation (log-rank p = 0.515; 0.16 vs 0.14, respectively; p = 0.81). This data indicates that the strategy of pre-transplant CF-MCS with subsequent orthotopic heart transplantation provides post-transplant outcomes not different to direct heart transplantation despite the fact that the duration of pre-transplant assist device treatment has progressively increased.

1082-P: Safety of SGLT2 Inhibitors in Heart Transplant Recipients

Objective: The safety of SGLT2 inhibitor (SGLT2I) use in patients receiving heart transplants is unknown. We aimed to evaluate key measures of safety after initiation of SGLT2I in a cohort of heart transplant recipients. Methods: Patients in the University of Colorado Health system who received a heart transplant between 1991 and 2022 were included if an SGLT2I was prescribed post-transplant and continued for at least 1 month. Number of urinary tract infections (UTI), urogenital yeast infections (UGI), and ED visits and hospital admissions for skin and soft tissue infections (SSTI) and euglycemic DKA (eDKA) were collected by chart review for the duration of SGLT2I use. Vital signs and lab values were collected at baseline, 3 months, and 6 months after SGLT2I initiation. Least squared means and mean differences were extracted from a random intercept mixed model with an unstructured covariance matrix for each variable. Results: Forty-six (46) patients met criteria for analysis. Mean age was 56.1 years, 80.4% had DM, and 84.8% had CKD at the time of SGLT2I initiation. Mean time on SGLT2I was 15 months (range 1-91 months). Three patients (6.5%) developed UTI and one developed UGI. Three (6.5%) had ED visits and admissions for SSTI: 1 had a post-surgical scalp infection and 2 had lower extremity cellulitis (1 led to hallux gangrene and amputation). No patients developed eDKA. Seven patients (15.2%) discontinued their SGLT2I: 2 for UTI and 1 each for hypotension, cost, fatigue, dialysis, and unspecified. Thirty-six (36) patients with adequate data over time were included in the analysis to assess change in vital signs and labs. There were no statistically significant changes from baseline to 3 months or 6 months after SGTL2I initiation for weight, BMI, SBP, DBP, Cr, eGFR, serum Na or serum K. Conclusions: In this sample of heart transplant recipients on SGLT2I, there were few urogenital and SSTI infections, no eDKA, and no significant change in renal function or electrolytes, which adds support for the safety of SGLT2I in this population. Disclosure S.Zahalka: None. C.C.Low wang: Research Support; Dexcom, Inc., Virta Health Corp., CellResearch Corporation. P.Choksi: None. H.M.Lawler: None. L.Grau: None. T.Jensen: Other Relationship; Somalogic.

Blood, cellular, and tissular calcineurin inhibitors pharmacokinetic-pharmacodynamic relationship in heart transplant recipients: the INTRACAR study.

After heart transplantation, calcineurin inhibitors (CNI) (cyclosporin A and tacrolimus) are key immunosuppressive drugs to prevent graft rejection. Whole-blood concentration (Cblood)-guided therapeutic drug monitoring (TDM) is systematically performed to improve graft outcomes. However, some patients will still experience graft rejection and/or adverse events despite CNI Cblood within the therapeutic range. Other pharmacokinetic parameters, such as the intra-graft, or intracellular concentration at the CNI site of action could refine their TDM. Nonetheless, these remain to be explored. The objective of the INTRACAR study was to describe the relationship between whole blood, intra-graft, and intracellular CNI concentrations as well as their efficacy in heart transplant recipients (HTR). In a cohort of HTR, protocol endomyocardial biopsies (EMB) were collected to assess rejection by anatomopathological analysis. Part of the EMB was used to measure the intra-graft concentrations of CNI (CEMB). Cblood, and the concentration inside peripheral blood mononuclear cells (CPBMC), a cellular fraction enriched with lymphocytes, were also monitored. Concentrations in the three matrices were compared between patients with and without biopsy-proven acute rejection (BPAR). Thirty-four HTR were included, representing nearly 100 pharmacokinetic (PK) samples for each CNI. Cblood, CEMB and CPBMC correlated for both CNI. BPAR was observed in 74 biopsies (39.6 %) from 26 patients (76.5 %), all except one of low-grade. None of the PK parameters (Cblood, CEMB, CPBMC, CEMB/blood and CPBMC/blood) was associated with BPAR. In this cohort of well-immunosuppressed patients, no association was observed for any of the PK parameters including Cblood, with the occurrence of BPAR. However, a trend was noticed for the CEMB and CEMB/blood of cyclosporin A. Further studies in higher-risk patients may help optimize the use of CEMB and CPBMC for CNI TDM in HTR.

Donor hyperoxia is a novel risk factor for severe cardiac primary graft dysfunction

Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). Donor risk factors for the development of PGD are incompletely characterized. Donor management goals (DMG) are predefined critical care endpoints used to optimize donors. We evaluated the relationship between DMGs as well as non-DMG parameters, and the development of PGD after HT. A cohort of HT recipients from 2 transplant centers between 1/1/12 and 12/31/19 was linked to their respective donors in the United Network for Organ Sharing (UNOS) DMG Registry (n=1,079). PGD was defined according to modified ISHLT criteria. Variables were subject to univariate and multivariable multinomial modeling with development of mild/moderate or severe PGD as the outcome variable. A second multicenter cohort of 4,010 donors from the DMG Registry was used for validation. Mild/moderate and severe PGD occurred in 15% and 6% of the cohort. Multivariable modeling revealed 6 variables independently associated with mild/moderate and 6 associated with severe PGD, respectively. Recipient use of amiodarone plus beta-blocker, recipient mechanical circulatory support, donor age, donor fraction of inspired oxygen (FiO2), and donor creatinine increased risk whereas predicted heart mass ratio decreased risk of severe PGD. We found that donor age and FiO2 ≥ 40% were associated with an increased risk of death within 90 days post-transplant in a multicenter cohort. Donor hyperoxia at heart recovery is a novel risk factor for severe primary graft dysfunction and early recipient death. These results suggest that excessive oxygen supplementation should be minimized during donor management.

Role of Quantitative Flow Ratio in Predicting Future Cardiac Allograft Vasculopathy in Heart Transplant Recipients.

Coronary angiography is the gold standard for cardiac allograft vasculopathy (CAV) diagnosis, but it usually detects the disease at an advanced stage. We investigated the role of quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, in predicting CAV development in heart transplant recipients. Consecutive heart transplant recipients with no evidence of angiographic CAV at baseline coronary angiography were retrospectively included between January 2010 and December 2015, and QFR computation was performed. The relationship between vessel QFR and the occurrence of angiographic vessel-related CAV (≥50% stenosis) was assessed. One hundred forty-three patients were included and QFR computation was feasible in 241 vessels. The median value of QFR at baseline coronary angiography was 0.98 (interquartile range, 0.94-1.00). During a median follow-up of 6.0 years (interquartile range, 4.6-7.8 years), vessel-related CAV occurred in 25 (10.4%) vessels. Receiver-operating characteristic curve analysis identified a QFR best cutoff of ≤0.95 (area under the curve, 0.81 [95% CI, 0.71-0.90]; P<0.001). QFR≤0.95 was associated with an increased risk of vessel-related CAV (adjusted hazard ratio, 20.87 [95% CI, 5.35-81.43]; P<0.001). In an exploratory analysis, QFR≤0.95 in at least 2 vessels was associated with higher incidence of cardiovascular death or late graft dysfunction (71.4% in recipients with 2-3 vessels affected versus 5.1% in recipients with 0-1 vessels affected, P<0.001). In a cohort of heart transplant recipients, QFR computation at baseline coronary angiography may be a safe and reliable tool to predict vessel-related CAV and clinical outcomes at long-term follow-up.

Organ Care System Heart Perfusion Registry (OHP Registry) - Overview of a National Data Repository of Ex-Vivo Perfusion in DBD and DCD Heart Transplantation

<h3>Purpose</h3> Organ Care System (OCS, Transmedics Inc) is the first clinically available system for ex-vivo normothermic heart perfusion. OHP Registry is a prospective real-world registry of Donation after Brain Death (DBD) or Donation after Circulatory Death (DCD) heart transplantation in hearts perfused and assessed on OCS Heart. OHP Registry will collect OCS ex-vivo perfusion & assessment parameters and post-transplant short & long-term clinical outcomes of heart transplant recipients in the U.S. <h3>Methods</h3> All adult heart transplant recipients of DBD or DCD heart allografts perfused and assessed on OCS Heart technology will be included, along with data on hearts perfused and assessed on OCS Heart but not transplanted. OCS Heart perfusion and assessment parameters will be prospectively collected. All recipients will be followed up to 5 years post-transplant. Patient and graft survival will be compared to a UNOS/SRTR cohort of heart transplant recipients of cold stored donor hearts transplanted at the same OHP Registry centers over the same period of time. <h3>Results</h3> Endpoints: Patient and graft survival at 1, 2, 3, 4, 5 years post-transplantation. Incidence of moderate or severe heart primary graft dysfunction (left or right ventricle) defined according to ISHLT 2014 consensus definitions. OCS Heart utilization rate defined as the number of hearts transplanted by OCS perfusion and assessment, divided by the total number of hearts perfused and assessed on the OCS Heart System. <h3>Conclusion</h3> We anticipate analyses of OHP Registry will provide important data that will inform clinical care. We plan to present regular updates at future ISHLT Annual Meetings.

Impact of COVID-19 Infection Among Heart Transplant Recipients: A Southern Brazilian Experience.

PurposeThe coronavirus-2019 (COVID-19) infection is associated with a high risk of complications and death among heart transplant recipients. However, most cohorts are from high-income countries, while data from Latin America are sparse.MethodsThis is a retrospective cohort of heart transplant recipients followed at a hospital in Rio Grande do Sul, Brazil, between March 1st 2020 and October 1st 2021.ResultsOf the 62 heart transplant recipients on follow-up, 21 (34%) were infected by COVID-19, 58 (36–63) years of age, 67% male, body mass index of 26 (23-29) kg/m2, 48% with hypertension, 43% with chronic kidney disease, 5% with diabetes, within 2 (1–4) years of post-transplant follow-up. At presentation, the main symptoms were fever (62%), myalgia (33%), cough (33%), headache (33%), and dyspnea (19%). Hospitalization was required for 13 (62%) patients, with a time from first symptoms to the admission of 5 (1–12) days. In 38%, supplementary oxygen was needed, 19% required intensive care, and 10% mechanical ventilation. Three (14%) were infected after at least a first dose of COVID-19 vaccine. The main complications were bacterial pneumonia (38%), renal replacement therapy (19%), sepsis (10%) and venous thromboembolism (10%). Immunosuppression therapy was modified in 48%, with a reduction in the majority (89%). Two (10%) patients died in the hospital due to refractory hypoxemia and multiple organ dysfunction. The incidence of COVID-19 among transplant patients was comparable to the general population in the State of Rio Grande do Sul with a peak in December 2020.ConclusionHeart transplant recipients shown a high rate of COVID-19 infection in Southern Brazil, with typical symptom presentation in most cases. There was an elevated rate of hospitalization, supplementary oxygen support, and complications. In-hospital lethality among infected heart transplanted recipients was similar to previously reported data worldwide despite the high rates of infection in Latin America.

Impacto de la variabilidad intrapaciente en la concentración sanguínea de anticalcineurínicos en los resultados del trasplante cardiaco

Introduction and objectivesIntrapatient blood level variability (IPV) of calcineurin inhibitors has been associated with poor outcomes in solid-organ transplant, but data for heart transplant are scarce. Our purpose was to ascertain the clinical impact of IPV in a multi-institutional cohort of heart transplant recipients. MethodsWe retrospectively studied patients aged ≥18 years, with a first heart transplant performed between 2000 and 2014 and surviving≥ 1 year. IPV was assessed by the coefficient of variation of trough levels from posttransplant months 4 to 12. A composite of rejection or mortality/graft loss or rejection and all-cause mortality/graft loss between years 1 to 5 posttransplant were analyzed by Cox regression analysis. ResultsThe study group consisted of 1581 recipients (median age, 56 years; women, 21%). Cyclosporine immediate-release tacrolimus and prolonged-release tacrolimus were used in 790, 527 and 264 patients, respectively. On multivariable analysis, coefficient of variation> 27.8% showed a nonsignificant trend to association with 5-year rejection-free survival (HR, 1.298; 95%CI, 0.993-1.695; P=.056) and with 5-year mortality (HR, 1.387; 95%CI, 0.979-1.963; P=.065). Association with rejection became significant on analysis of only those patients without rejection episodes during the first year posttransplant (HR, 1.609; 95%CI, 1.129-2.295; P=.011). The tacrolimus-based formulation had less IPV than cyclosporine and better results with less influence of IPV. ConclusionsIPV of calcineurin inhibitors is only marginally associated with mid-term outcomes after heart transplant, particularly with the tacrolimus-based immunosuppression, although it could play a role in the most stable recipients.Full English text available from:www.revespcardiol.org/en

Impact of intrapatient blood level variability of calcineurin inhibitors on heart transplant outcomes

Introduction and objectivesIntrapatient blood level variability (IPV) of calcineurin inhibitors has been associated with poor outcomes in solid-organ transplant, but data for heart transplant are scarce. Our purpose was to ascertain the clinical impact of IPV in a multi-institutional cohort of heart transplant recipients. MethodsWe retrospectively studied patients aged ≥18 years, with a first heart transplant performed between 2000 and 2014 and surviving≥ 1 year. IPV was assessed by the coefficient of variation of trough levels from posttransplant months 4 to 12. A composite of rejection or mortality/graft loss or rejection and all-cause mortality/graft loss between years 1 to 5 posttransplant were analyzed by Cox regression analysis. ResultsThe study group consisted of 1581 recipients (median age, 56 years; women, 21%). Cyclosporine immediate-release tacrolimus and prolonged-release tacrolimus were used in 790, 527 and 264 patients, respectively. On multivariable analysis, coefficient of variation> 27.8% showed a nonsignificant trend to association with 5-year rejection-free survival (HR, 1.298; 95%CI, 0.993-1.695; P=.056) and with 5-year mortality (HR, 1.387; 95%CI, 0.979-1.963; P=.065). Association with rejection became significant on analysis of only those patients without rejection episodes during the first year posttransplant (HR, 1.609; 95%CI, 1.129-2.295; P=.011). The tacrolimus-based formulation had less IPV than cyclosporine and better results with less influence of IPV. ConclusionsIPV of calcineurin inhibitors is only marginally associated with mid-term outcomes after heart transplant, particularly with the tacrolimus-based immunosuppression, although it could play a role in the most stable recipients.

Association between cytomegalovirus infection and allograft rejection in a large contemporary cohort of heart transplant recipients

AbstractBackgroundCytomegalovirus (CMV) infection remains a common complication after heart transplantation (HTx). The association between CMV infection and allograft rejection is debated in the era of efficient prophylactic antiviral therapies.MethodsThis single‐center cohort study utilized a highly phenotyped database of HTx recipients (2012‐2016). The primary endpoint was the analysis of the association between CMV infection (CMV load ≥ 500 IU/mL whole blood) and the risk of allograft rejection (cellular rejection ≥ 1R1B, antibody‐mediated rejection ≥ pAMR1). Secondary endpoints included the analysis of a higher CMV load threshold (≥10 000 IU/mL) and different risk periods after PCR positivity. A mixed‐effect logistic regression model with a random intercept was applied. Results were adjusted for important risk factors of rejection.ResultsOverall, 384 patients were included and 6388 CMV loads and 3,494 endomyocardial biopsies were analyzed. CMV infections ≥ 500 IU/mL were diagnosed on 1223 (19.2%) blood samples from 284 (72.1%) patients and allograft rejections on 246 biopsies (7%) from 149 patients (38.8%). We did not find any association between CMV infection ≥ 500 IU/mL and rejection (univariable: OR 0.94, 95% CI [0.61, 1.45], P = .78, multivariable: OR 0.86, 95% CI [0.55, 1.33], P = .85). These results were consistent when analyzing a higher CMV load threshold and different periods of risk, reinforced by internal validation procedures and a posteriori calculation of the power (primary endpoint: power = 0.82, 95% CI [0.79‐0.84]) and reproducible across different clinical scenarios.ConclusionsCMV infection was not associated with an increased risk of rejection in a contemporary cohort of HTx recipients.

Determinants of sudden cardiac death after heart transplantation

Heart transplant recipients are at high-risk of sudden cardiac death (SCD). However, risk factors of SCD in heart recipients remained poorly described. To assess the predictors of SCD beyond the first-year post-transplant. We enrolled consecutive patients transplanted between 2004 and 2017 in two French referral centres. We excluded patients deceased during the first year. Patients underwent an evaluation at the day of transplantation and during the first year, comprising clinical, biological, histological, immunological (circulating anti-HLA DSA) and interventional (cardiac allograft vasculopathy assessment) parameters. According to the last consensus, SCD was defined as an unexpected out-of-hospital cardiac arrest without obvious non-cardiac cause, in the first hour after initiation of symptoms. A total of 913 patients were included. The median follow-up post-HT was 5.9 years (IQR = 2.9–8.5). Among the 60 parameters tested in univariate analysis, we identified 4 independent factors independently associated with sudden death after 1 year post-HT: donor age (HR = 1.55; 95% CI: 1.14–2.11; P = 0.005), recipient age (HR = 0.74; 95% CI: 0.59–0.93; P = 0.011), ventricular ejection fraction (LVEF) < 55% any time after transplantation (HR: 3.95; 95% CI: 1.95–8.02; P < 0.001), the presence of circulating anti-HLA DSA at the time of transplantation (HR: 2.18; 95% CI: 1.15–4.11; P = 0.017). The incidence rate of SCD was 2.17 per 100 person-year (95% CI: 1.42–4.60) and 1.21 per 100 person-year (95% CI: 0.80–2.58) in patients with FEVG < 55% ( n = 73) and in patients with pre-formed DSA ( n = 260), respectively ( Table 1 ). In a large multicentric and highly phenotyped cohort of heart transplant recipients, we identified four independent factors associated with SCD beyond the first year. This study provides fresh evidence of SCD assessment for improving risk stratification of HT recipients.

Incidence of sudden cardiac death after heart transplantation

Sudden cardiac death (SCD) is a major contributor to the rate of mortality after heart transplantation. However, little is known about the incidence of SCD in heart recipients. To assess the incidence of SCD after heart transplantation. We enrolled consecutive patients transplanted between 2004 and 2017 in two French referral centers. We defined 7 main groups of causes of deaths: SCD, cardiovascular (including Cardiac allograft vasculopathy), infection, primary graft dysfunction, graft failure (including late graft dysfunction, rejection), malignancy and others. Causes of deaths were independently adjudicated by two senior cardiologists based on the analysis of death certificates and medical records. Discrepancies were resolved by discussion until a consensus was made. SCD was defined as an unexpected out-of-hospital cardiac arrest without obvious non-cardiac cause, in the first hour after initiation of symptoms. A total of 1,363 patients were included. The median follow-up post-transplant was 3.99 years (IQR = 0.49–7.49). A total of 450 patients (33%) deceased during the first year. The leading cumulative causes of death in the first year after transplantation were infection, primary graft failure, multiple organ failure during the period in intensive car unit. Beyond the post-operative high-risk period of the first year, the leading cumulative cause of death was SCD: among the 213 deaths that occurred beyond the first year, 44 patients (21%) died from SCD. In this period, the incidence rate of SCD reached 0,82 per 100 person-year (95% CI: 0.51–2.05) ( Fig. 1 ). In a large multicentric and highly phenotyped cohort of heart transplant recipients, the leading cumulative cause of death beyond the first-year post transplant was sudden cardiac death. Our results open discussion on management of heart recipient, such as the implementation of cardioverter-defibrillators.

Statistical performance of sixteen post-transplant risk scores in a contemporary cohort of 9396 heart transplant recipients

Multiple pre-transplant scores aimed at stratifying the risk of death or allograft loss after heart transplantation have been developed over time but their use in clinical practice remains limited. We aimed to evaluate the statistical performance of all existing pre-transplant risk scores in a contemporary United Network for Organ Sharing (UNOS) cohort. We applied 16 different scoring systems developed between 1999 and 2019 to a contemporary UNOS cohort of heart transplant recipients. We selected first non-combined adult heart transplantations performed between January 1st, 2014 to December 31st, 2017. The primary endpoint was all-cause mortality or retransplantation during the first-year post-transplant. We analyzed the association between scores and outcomes, sensitivity, specificity, likelihood ratios (LR) and discrimination (c-statistics and overlap of individual scores according to the occurrence of the primary endpoint). The cohort included 9396 patients. Recipients were mostly males (74%) and mean age was 52.9 ± 13.5. All scores were significantly associated with the primary outcome (P < 0.001 for all scores). The LR of the scores were poor (positive LR < 2, negative LR > 0.5). The discriminative performance of all scores was limited, with c-statistics ranging from 0.548 to 0.652 (median 0.600, Fig. 1A) and an important overlap of individual scores between patients with or without the primary endpoint (Fig. 1B). Subgroup analyses revealed that discrimination may vary greatly according to donor age, recipient age and the type of assist device used at transplant. In a contemporary cohort, none of the 16 post-transplant risk scores were shown to accurately stratify the risk of early death or retransplantation after heart transplantation. our findings raise concerns concerning the use of the currently available prognosis scores in the clinical files and emphasize the need for a robust and reliable score.

Donor-recipient predicted heart mass ratio and right ventricular-pulmonary arterial coupling in heart transplant.

Right ventricular-pulmonary arterial (RV-PA) coupling interactions are largely unexplored in heart transplant patients. The outcome of this study was RV-PA coupling at 7 and 30 days after heart transplant and its association with donor-recipient size matching. Clinical, echocardiographic and haemodynamic data from a retrospective cohort of heart transplant recipients and respective donors were reviewed. Coupling between RV-PA was examined by assessing the RV fractional area change and pulmonary artery systolic pressure ratio. Donor-recipient size matching was assessed by the predicted heart mass (PHM) ratio, and groups with a PHM ratio <1 and ≥1 were compared. Forty-four heart transplant recipients were included in this study (50 years, 57% male sex). Postoperative RV-PA coupling improved from 7 to 30 days (RV fractional area change/pulmonary artery systolic pressure 0.9 ± 0.3 vs 1.2 ± 0.3; P < 0.001). A positive association was found between an adequate PHM ratio and improvement of RV fractional area change/pulmonary artery systolic pressure at 30 days, independent of graft ischaemic time and pre-existent pulmonary hypertension (B coefficient 0.54; 95% confidence interval 0.11-0.97; P = 0.016; adjusted R2 = 0.24). These findings highlight the role of PHM as a metric to help donor selection and suggest its impact in RV-PA coupling interactions post-heart transplant.

Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation and association with mortality: a population-based study

Abstract Background Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. However, the associations between CAV trajectories and mortality remains poorly described. Purpose We aimed to identify the different evolutive profiles of CAV and to determine the respective association with all-cause mortality. Methods Heart transplant recipients receiving care at 4 academic centers were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The mainoutcome was a prediction for CAV trajectories using unsupervised latent class mixed models. We then identified their association with all-cause mortality (NCT04117152). Results Overall, 1,301 patients were included (815 and 486 in the development and validation cohorts, respectively). The median follow-up post-transplant was 6.6 years (IQR=4.7) with 4,710 coronary angiographies analyzed (3.6±1.6 CAV assessments per patient). We identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i)Patients without CAV at baseline and non-progression (n=823, 63.3%), ii) patients without CAV at baseline and late onset CAV progression (n=79, 6.1%), iii) patients with mild baseline CAV and mild progression (n=261, 20.1), iv) patients with mild baseline CAV and accelerated CAV progression (n=138, 10.6%, discrimination 0.95). The 4 CAV trajectories showed gradient for all-cause mortality (p&amp;lt;0.001). Trajectories #3 and #4 were associated with higher mortality rates (10-year patient survival of 73.43% [95% CI 65.18–80.02] and 51.89% [95% CI 38.76–63.51], respectively) as compared with trajectories #1, and #2 that were characterized by 10-year patient survival of 80.01 [95% CI 76.38–84.82] and 83.49% [95% CI 71.34–90.80], respectively (p&amp;lt;0.001). Conclusion In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 robust CAV trajectories. These different profiles were associated with distinct prognosis. Our results provide the basis for a trajectory-based assessment of heart transplant patients for early patient risk stratification and patient monitoring. Figure 1. Overall 10-year survival probability according to the CAV trajectory in the overall cohort (n=1,301). The left part represents the main profiles CAV grades identified with latent class mixed models. Thick lines represent latent class trajectory; thin lines represent CAV individual patient trajectory. The right part represent the Kaplan Meier curves of the different trajectories. Funding Acknowledgement Type of funding source: None

Shear wave elastography by high frame rate echocardiography can detect diffuse myocardial fibrosis after heart transplantation

Abstract Background Myocardial fibrosis is fundamental in the development of cardiac failure, regardless of ethiology. In both animal models and humans it has been shown that diffuse myocardial fibrosis (DMF) contributes to functional impairment, especially to increased passive myocardial stiffness, which is an important pathophysiological determinant of left ventricular diastolic dysfunction. Histological examination is the gold standard for myocardial fibrosis quantification, however, it requires endomyocardial biopsies which are invasive and not without risk. Echocardiographic shear wave (SW) elastography, based on high frame rate imaging, is an emerging approach for measuring myocardial stiffness in vivo. Natural SWs occur after mechanical excitation of the myocardium, e.g. after mitral valve closure (MVC) and their propagation velocity is directly related to myocardial stiffness, thus providing an opportunity to assess myocardial stiffness at end-diastole. Purpose The aim was to investigate if propagation velocities of natural SWs can be used to detect diffuse myocardial fibrosis in a cohort of heart transplant recipients. Methods We prospectively enrolled 22 patients (10.3±6.3 years after HTx) that underwent CMR during their annual check-up. We performed SW elastography in parasternal long axis views of the left ventricle using a fully programmable experimental scanner (HD-PULSE) equipped with a clinical phased array transducer (Samsung Medison P2–5AC) at 1100±250 frames per second. The SW propagation velocities at MVC were measured in the basal LV septum. Native T1 and extracellular volume (ECV) were measured at the same segment to evaluate DMF. A cut-off value for native T1 of 1040 ms and for ECV of 29% was used to define DMF in our cohort. Results We found good correlations between SW velocities and both myocardial T1 (r=0.80, p&amp;lt;0.0001, Figure A) and ECV (r=0.64, p=0.003, Figure B) measured with CMR. Further, we derived reference thresholds of natural SW velocities to identify DMF in HTx patients. The optimal cut-off value of SW velocity to identify patients with nativT1&amp;gt;1040 ms was 4.84 m/s (AUC 0.81, sensitivity 82%, specificity 82%, Figure C). To identify patients with ECV&amp;gt;0.29 the cut-off value of SW velocity was 4.74 m/s (AUC 0.74, sensitivity 73%, specificity 78%, Figure D). Conclusions End-diastolic shear wave propagation velocities, as measure of myocardial stiffness, showed a good correlation with CMR defined diffuse myocardial injury. Values higher than 4.74 m/s could identify diffuse myocardial injury in HTX patients with a good sensitivity and good specificity. These findings thus suggest that shear wave elastography has the potential to become a valuable non-invasive method for the detection of diffuse myocardial fibrosis. Funding Acknowledgement Type of funding source: None

Incidence of sudden cardiac death after heart transplantation

Abstract Background Sudden cardiac death (SCD) is a major contributor to the rate of mortality after heart transplantation. However, little is known about the incidence of SCD in heart recipients. Objective To assess the incidence of SCD after heart transplantation. Methods We enrolled consecutive patients transplanted between 2004 and 2017 in two French referral centers. We defined 7 main groups of causes of deaths: SCD, cardiovascular (including Cardiac allograft vasculopathy), infection, primary graft dysfunction, graft failure (including late graft dysfunction, rejection), malignancy and others. Causes of deaths were independently adjudicated by two senior cardiologists based on the analysis of death certificates and medical records. Discrepancies were resolved by discussion until a consensus was made. SCD was defined as an unexpected out-of-hospital cardiac arrest without obvious non-cardiac cause, in the first hour after initiation of symptoms. Results A total of 1,363 patients were included. The median follow-up post-transplant was 3.99 years (IQR=0.49–7.49). 450 patients (33%) deceased during the first year. The leading cumulative causes of death in the first year after transplantation were infection, primary graft failure, multiple organ failure during the period in intensiv car unit. Beyond the post-operativ high-risk period of the first year, the leading cumulative cause of death was SCD: among the 213 deaths that occurred beyond the first year, 44 patients (21%) died from SCD. In this period, the incidence rate of SCD reached 0,82 per 100 person-year (95% CI: 0.51–2.05). Conclusion In a large multicentric and highly phenotyped cohort of heart transplant recipients, the leading cumulative cause of death beyond the first-year post transplant was sudden cardiac death. Our results open discussion on management of heart recipient, such as the implementation of cardioverter-defibrillators. Figure 1. Cumulative incidence of causes of death in heart transplant recipients beyond the first year (n=913). Funding Acknowledgement Type of funding source: None

Identification of trajectories of cardiac allograft vasculopathy after heart transplantation: a nationwide comparison

Abstract Background Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. However, little is known about CAV trajectories at a population level. Purpose We aimed to identify the different profiles of CAV trajectories. Methods Heart transplant recipients receiving care at 4 academic centers (2004 to 2016) were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The mainoutcome was the CAV trajectories, identified with unsupervised latent class mixed models. Results Overall, 1,301 patients were included (609 in France, 206 in Belgium and 486 in the US). The median follow-up post-transplant was 6.6 years (IQR=4.7) with 4,710 coronary angiographies analyzed (3.6±1.6 CAV assessments per patient). In the French development cohort, we identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i) Patients without CAV at baseline and non-progression (n=317, 52.1%), ii) patients without CAV at baseline and late onset CAV progression (n=52, 8.5%), iii) patients with mild baseline CAV and mild progression (n=151, 24.8%), iv) patients with mild baseline CAV and accelerated CAV progression (n=89, 14.6%, discrimination 0.92). The 4 CAV trajectories were independently validated in the external validation cohorts from Belgium (discrimination=0.92) and the US (discrimination=0.97). Conclusion In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified and validated 4 distinct CAV trajectories corresponding to specific initial CAV grades and subsequent evolutions. Our results provide the basis for a trajectory-based assessment for risk stratification at early-stage post heart transplantation. Figure 1. Cardiac allograft vasculopathy trajectories in France (n=609), in Belgium (n=206), in USA (n=486). Thick lines represent latent class trajectory; thin lines represent CAV individual patient trajectory. Funding Acknowledgement Type of funding source: None