Late Graft Dysfunction Research Articles

(904) - Are Highly Sensitized Recipients at Increased Risk for Early or Late Graft Dysfunction After Lung Transplantation?

(904) - Are Highly Sensitized Recipients at Increased Risk for Early or Late Graft Dysfunction After Lung Transplantation?

(1138) - Interatrial Shunt: A “Hole in Time” to Delay Cardiac Retransplantation in Late Graft Dysfunction

(1138) - Interatrial Shunt: A “Hole in Time” to Delay Cardiac Retransplantation in Late Graft Dysfunction

Enhancing the Prediction of Cardiac Allograft Vasculopathy Using Intravascular Ultrasound and Machine Learning: A Proof of Concept.

Cardiac allograft vasculopathy (CAV) is the leading cause of late graft dysfunction in heart transplantation. Building on previous unsupervised learning models, we sought to identify CAV clusters using serial maximal intimal thickness and baseline clinical risk factors to predict the development of early CAV. This is a single-center retrospective study including adult heart transplantation recipients. A latent class mixed-effects model was used to identify patient clusters with similar trajectories of maximal intimal thickness posttransplant and pretransplant covariates associated with each cluster. Among 186 heart transplantation recipients, we identified 4 patient phenotypes: very low, low, moderate, and high risk. The 5-year risk (95% CI) of the International Society for Heart and Lung Transplantation-defined CAV in the high, moderate, low, and very low risk groups was 49.1% (35.2%-68.5%), 23.4% (13.3%-41.2%), 5.0% (1.3%-19.6%), and 0%, respectively. Only patients in the moderate to high risk cluster developed the International Society for Heart and Lung Transplantation CAV 2-3 at 5 years (P=0.02). Of the 4 groups, the low risk group had significantly younger female recipients, shorter ischemic time, and younger female donors compared with the high risk group. We identified 4 clusters characterized by distinct maximal intimal thickness trajectories. These clusters were shown to discriminate against the development of angiographic CAV. This approach allows for the personalization of surveillance and CAV-directed treatment before the development of angiographically apparent disease.

De Novo Autoimmune Hepatitis After Liver Transplantation: Natural History and Diagnosis

De novo autoimmune hepatitis (dnAIH) refers to autoimmune hepatitis manifesting in post-liver transplant patients for whom liver transplant was performed for pathologies other than autoimmune hepatitis. dnAIH, also called plasma cell-rich hepatitis though rare, is a form of graft rejection and is one of the causes of late graft dysfunction. This paper reviews the literature on the subject, focusing on the treatment and outcomes of dnAIH in both pediatric and adult populations. Diagnosis of dnAIH relies on serological and histological examinations however dnAIH should not be ruled out in seronegative patients.

Impact of donor-specific anti-HLA antibody on cardiac hemodynamics and graft function 3 years after pediatric heart transplantation: First results from the CTOTC-09 multi-institutional study

The aim of this study (CTOTC-09) was to assess the impact of “preformed” (at transplant) donor-specific anti-HLA antibody (DSA) and first year newly detected DSA (ndDSA) on allograft function at 3 years after pediatric heart transplantation (PHTx). We enrolled children listed at 9 North American centers. The primary end point was pulmonary capillary wedge pressure (PCWP) at 3 years posttransplant. Of 407 enrolled subjects, 370 achieved PHTx (mean age, 7.7 years; 57% male). Pre-PHTx sensitization status was nonsensitized (n = 163, 44%), sensitized/no DSA (n = 115, 31%), sensitized/DSA (n = 87, 24%), and insufficient DSA data (n = 5, 1%); 131 (35%) subjects developed ndDSA. Subjects with any DSA had comparable PCWP at 3 years to those with no DSA. There were also no significant differences overall between the 2 groups for other invasive hemodynamic measurements, systolic graft function by echocardiography, and serum brain natriuretic peptide concentration. However, in the multivariable analysis, persistent first-year DSA was a risk factor for 3-year abnormal graft function. Graft and patient survival did not differ between groups. In summary, overall, DSA status was not associated with worse allograft function or inferior patient and graft survival at 3 years, but persistent first-year DSA was a risk factor for late graft dysfunction.

Microcirculatory Disease in Patients after Heart Transplantation.

Although the treatment and prognosis of patients after heart transplantation have significantly improved, late graft dysfunction remains a critical problem. Two main subtypes of late graft dysfunction are currently described: acute allograft rejection and cardiac allograft vasculopathy, and microvascular dysfunction appears to be the first stage of both. Studies revealed that coronary microcirculation dysfunction, assessed by invasive methods in the early post-transplant period, correlates with a higher risk of late graft dysfunction and death during long-term follow-up. The index of microcirculatory resistance, measured early after heart transplantation, might identify the patients at higher risk of acute cellular rejection and major adverse cardiovascular events. It may also allow optimization and enhancement of post-transplantation management. Moreover, cardiac allograft vasculopathy is an independent prognostic factor for transplant rejection and survival rate. The studies showed that the index of microcirculatory resistance correlates with anatomic changes and reflects the deteriorating physiology of the epicardial arteries. In conclusion, invasive assessment of the coronary microcirculation, including the measurement of the microcirculatory resistance index, is a promising approach to predict graft dysfunction, especially the acute allograft rejection subtype, during the first year after heart transplantation. However, further advanced studies are needed to fully grasp the importance of microcirculatory dysfunction in patients after heart transplantation.

Asymptomatic Allograft Fibrosis in Pediatric Liver Transplantation: Potential Clinical Implications.

Asymptomatic Allograft Fibrosis in Pediatric Liver Transplantation: Potential Clinical Implications.

(354) De Novo Donor Specific Antibodies and Late Graft Dysfunction: Another Reason to Treat Before the Damage is Done?

(354) De Novo Donor Specific Antibodies and Late Graft Dysfunction: Another Reason to Treat Before the Damage is Done?

Donor substance use and lung transplantation: A single center experience

BackgroundLung transplantation (LT) demand outpaces supply. Consequently, extended criteria for donor selection are used, resulting in LT from donors with a history of substance use (SU). The aim of this study is to assess the association between donor SU and short-term LT outcomes. MethodsWe obtained recipient and donor data for LTs performed between January 2014 to January 2019 from electronic health records and the United Network for Organ Sharing (UNOS) database. We defined SU as cigarette/e-cigarette smoking, illicit SU (cannabis, cocaine, opioids, amphetamines), or heavy alcohol use (2+ alcoholic drinks per day). Our primary outcome was late high-grade primary graft dysfunction (PGD), which we defined as grade 2-3 PGD between 48-72 hours post-LT. Secondary outcomes included mechanical ventilation (MV) hours, intensive care unit (ICU) length of stay (LOS), hospital LOS, number of bronchoscopies, cumulative acute rejection (CAR) score in the first year after LT, and overall survival (OS). ResultsA total of 352 LTs were included in this study. On multivariable regression, we found that any donor cigarette smoking was associated with increased odds of late high grade PGD (p=0.021), while any donor cannabis use was associated with reduced odds of late high grade PGD (p=0.002). There was no association between any donor SU and secondary outcomes. ConclusionsDonor cigarette use was associated with higher risk for PGD. Our findings may suggest a history of donor cannabis use and other illicit SU are not associated with PGD or worse OS.

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.

Our Continued Experience With Using Watchpat® (itamar Medical, Ltd.), Home Sleep Testing For The Diagnosis Of Sleep Apnea In Heart Failure And Orthotopic Heart Transplant Patients.

<h3>Introduction</h3> Untreated sleep disorders are well known to significantly increase risk of coronary artery disease (CAD), hypertension (HTN), obesity, diabetes (DM), anxiety and depression. Despite maximal medical therapy, approximately 50% of patients with heart failure (HF) have moderate-to-severe sleep apnea (SA). Moreover, obstructive sleep apnea (OSA) has also been described in cardiac transplant recipients (OHT) as a significant risk factor for late graft dysfunction, thus screening and diagnosis is critical^. Access to in-lab polysomnography (PSG) has been limited throughout the pandemic leading to more reliance on home sleep testing. WatchPAT® Home Sleep Testing (WPHST) has been validated to accurately detect both obstructive as well as central sleep apnea (CSA) in the general population yet there is limited data to date that support its use in advanced HF/OHT patients. <h3>Objective</h3> Herein we describe our prospective utilization of WPHST highlighting differences in sleep apnea patterns in our HF and OHT population. <h3>Methods</h3> This is a single center, prospective, observational analysis, beginning February 22, 2020 through April 7, 2021. 50 consecutive patients that screened positive on the STOP-BANG® sleep apnea screen questionnaire were consented and assigned to WPHST and analyzed for comorbidities, and SA patterns and severity. <h3>Results</h3> Of the 50 patients enrolled, 48 patients (n=38 HF and n=10 OHT) were included in the analysis (1 failed study in each arm). Baseline characteristics were equivalent; mean age of 60 years, BMI 28.6 kg/m2, and 75% were male. A high prevalence of co-morbid conditions included CAD 52%, DM 50% and HTN 98%, (fig 1). Central/Mixed Sleep apnea accounted for 10.4% of the total cohort. Apnea Hypopnea Index (AHI) was significantly greater in the HF patient cohort vs OHT (p=0.02). However, no statistical differences were noted in nocturnal 02 sat (p=0.49). REM% was lower in the OHT compared to the HF cohort (p=0.049). <h3>Conclusion</h3> : In this limited prospective study AHI was significantly higher in the HF cohort compared to OHT. More importantly, WPHST has contributed to greater access to sleep diagnostics for high-risk patient populations throughout the pandemic. Continued work on short- and long-term outcomes is warranted.

Histological changes associated with early and late renal allograft dysfunction in a large three-center transplant program in Iraq

Introduction: Transplantation is the sole viable option for the long-term survival of patients with end-stage renal disease (ESRD) in low-resourced countries. Objectives: To report the histopathological characteristics of kidney graft dysfunction in a large transplant program of a developing country. Patients and Methods: Renal transplant biopsies were analyzed by the Banff 2017 classification and subdivided into early (≤1 year) or late (&gt;1 year) post-engraftment periods during the 12 months of 2019. Results: Here, 290 satisfactory graft biopsies were obtained on 290 patients for graft failure and/ or proteinuria. The median age of the recipient was 39 years (interquartile range 28-47), where 77% were male and 5.5% had been previously transplanted and 84% of donors were unrelated. Histological diagnosis was as follow; acute T-cell mediated rejection (A-TCMR; 23.1%), acute tubular necrosis (ATN; 14.8%), interstitial fibrosis and tubular atrophy (IFTA; 11.4%), recurrent or de novo kidney disease (R/DKD; 8.6%), transplant glomerulopathy (TG; 7.6%), calcineurin inhibitor toxicity (CNI; 6.9%), and active antibody-mediated rejection (A-AMR; 8.6%). Early graft dysfunctions were A-TCMR (29%) and ATN (22.4%). Late graft dysfunction included IF/TA, (20.2%), TG (20.2%), R/DRD (17%), and A-TCMR (9.5%). C4d+AMR was equally represented in early (5.6%) and late (6.3%) biopsies. Conclusion: A-TCMR was the most common cause of early graft dysfunction and was replaced by chronic conditions as the cause of 57.8% of late graft biopsies. The causes of graft dysfunction are not remarkably different from the west and TG will be a major cause of late graft failure in Iraq.

A comparative histological analysis of early and late graft dysfunction in different time zones following living donor liver transplantation.

Liver biopsy plays a crucial role in evaluating allograft dysfunction. Comprehensive analysis of the histological spectrum of complications, particularly rejection, in different time zones is lacking. To evaluate the histological spectrum of rejection, in four time zones, in a large Living donor liver transplant series. Retrospective analysis of 313 biopsies for the last 10 years of living donor liver transplantation (LDLT) recipients. 123 of which had rejection as diagnosis, were redistributed in four time zones [1-early (<3), 2-intermediate (3-6), 3 and 4-late (6-12 and > 12) months] and were assessed for sixteen histological parameters. Biopsies in time zone 1 (26.5%), 2 (20.7%), 3 (24.6%), and 4 (28.1%)] were nearly equal. Multiple coexistent complications existed in 12% of the cases. Rejection diagnosed in time zone groups: 1 = 22 (17.9%), 2 = 27 (22%), 3 = 36 (29.3%), and 4 = 38 (30.9%). Portal inflammation mixed type (P < 0.000), portal vein (P = 0.001) and hepatic vein endothelialitis (P < 0.000), portal eosinophils (P = 0.001), and lymphocytic bile duct damage (P = 0.01) were most pronounced in group 1. Perivenulitis without hepatic vein endothelialitis was observed (P = 0.03) in groups 3, whereas bile duct atypia (P = 0.01) and duct loss (P < 0.000) were observed in group 4. Multiple episodes of rejection displayed significant association with central perivenulitis (P = 0.002) and bile duct loss (P < 0.001). Histological analysis in large series of LDLT recipients highlights the spectrum of complications in different time zones. Late acute and chronic rejection occurred as early as 3 months posttransplant. Central perivenulitis and bile duct atrophy were associated with repeated episodes of rejection and deterioration.

Liver transplant biopsy interpretation: Diagnostic considerations and conundrums.

Liver transplantation is now a well-established therapeutic strategy for irreversible acute and chronic liver diseases. There is a broad spectrum of complications encountered in early and late period after transplantation and these contribute to significant morbidity and mortality. Distinguishing among these complications often requires interpretation of allograft biopsies. Histology is the gold standard for the diagnosis of rejection. However, interpretation of these biopsies is quite challenging due to the atypical and complex histomorphology. Multiple simultaneous insults, effects of immunosuppression (IMS), de novo complications, and presentations distinct from non-transplant setting are a few cardinal concerns. Awareness of the time period of occurrence of various complications, the most characteristic histological features or patterns, and distinguishing features between various complications are crucial. The management can be completely divergent; hence, recognition of dominant problem and interpretation in appropriate clinical context is much needed. This review focuses on histopathology of major complications accountable for early and late graft dysfunction. Tabulation of clinico-pathological features to distinguish various complications helps to solve the conundrums and arrive at the correct diagnosis.

The effects of donor-specific antibody characteristics on cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) causes late graft dysfunction and post-transplant mortality. Currently, the effects of different donor-specific antibodies (DSA) on the severity of CAV remain unclear. We evaluated 526 adult heart transplant recipients at a single center between January 2010 and August 2015. Subjects were divided into those with DSA (n = 142) and those without DSA (n = 384, control). The DSA group was stratified into persistent DSA (n = 34), transient DSA (n = 105), 1:8 dilution DSA (n = 45), complement-binding (C1q) DSA (n = 36), Class I DSA (n = 37), and Class II DSA (n = 105). The primary outcome was the incidence of moderate-to-severe CAV (CAV 2/3) at 5-year follow-up. Subjects with persistent DSA, 1:8 dilution DSA, and C1q DSA had higher incidence of CAV 2/3 compared the control group (17.6%, 13.3%, and 16.7% vs. 3.1%, respectively; P≤ .001). The incidence of CAV 2/3 between subjects with transient DSA and the control group was similar (2.8% vs. 3.1%; P = .888). Subjects with Class II DSA also had higher incidence of CAV 2/3 (7.6% vs. 3.1%; P = .039). DSA that are persistent, 1:8 dilution positive, C1q positive, and Class II are associated with more severe grades of CAV. These DSA characteristics may prognosticate disease and warrant consideration for treatment.

Prediction of late allograft dysfunction following liver transplantation by immunological blood biomarkers

BackgroundAn accelerated course of hepatic fibrosis may occur in liver transplantation (LT) patients despite normal or slightly abnormal liver blood tests. AimTo identify screening tools based on blood biomarkers to predict late allograft dysfunction in LT recipients. Methods174 LT recipients were enrolled. Liver biopsy, liver functional tests, cytokine quantitation in serum, as well as soluble MHC class I polypeptide-related sequence A and B (sMICA/sMICB) and soluble UL16 binding protein 2 (sULBP2) were performed. ResultsPatients with late graft dysfunction had a significantly higher donor age, lower albumin level, higher alanine (ALT) and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bilirubin and alkaline phosphatase (ALP), higher sMICA, sULBP2, higher interleukin (IL) 6, interferon γ and lower IL10 in serum as compared to recipients without allograft dysfunction. In order to provide a better statistical accuracy for discriminating 5-year allograft dysfunction from other less progressive subtype of allograft injury, we established a predictive model, based on 7 parameters (serum ALP, ALT, AST, GGT, sMICA, IL6 and albumin) which provided an Area Under the Receiver Operating Characteristics (AUROC) curve of 0.905. ConclusionsBlood-based biomarkers can significantly improve prediction of late liver allograft outcome in LT patients. The new developed score comprising serum parameters, with an excellent AUROC, can be reliably used for diagnosing late allograft dysfunction in transplanted patients.

Donor Substance Abuse is Not Associated with Late High-Grade Primary Graft Dysfunction (PGD) in Lung Transplant

<h3>Purpose</h3> The donor pool for lung transplantation (LT) may be expanded by procuring from donors with substance abuse (SA) history. Scant data exists on the early course of recipients of these lungs. We assessed the association between donor SA and perioperative outcomes. <h3>Methods</h3> We reviewed LTs at our center from Jan. 2014-Jan. 2019 and donor data from the United Network for Organ Sharing. SA was defined as reported use of illicit substances (cannabis, cocaine, amphetamines, opioids)/tobacco 1+ times/month or positive post-mortem screen, or consumption of 2+ alcoholic drinks/day. The primary outcome was late high-grade PGD due to its risk for chronic lung allograft dysfunction (CLAD). Late high-grade PGD was defined as PGD 2-3 at 48-72 hours. Secondary outcomes were ventilator hours (VH), initial intensive care unit (ICU) hours, initial hospital length of stay (LOS), 30-day mortality, and first year FEV1% predicted trends. <h3>Results</h3> 350 LT patients were included in this study. 198/350 (57%) patients received SA donor lungs, while 152/350 (43%) patients received non-SA donor lungs. 82/198 (42%) in the SA donor group developed late high-grade PGD vs. 61/152 (42%) in the non-SA donor group. On multivariable logistic regression (Figure 1), late high-grade PGD was not associated with donor SA (OR 1.11, 95% CI 0.67-1.85, p=0.687). Bivariate comparison found no association between donor SA and VH, ICU hours, and LOS. 30-day survival was 98.99% (n=196) in the SA donor group vs. 98.68% (n=150) in the non-SA donor group. The log rank test detected no difference in 30-day survival between the groups (p=0.789). An estimating equation model and analysis found no evidence that donor SA had an effect on FEV1% predicted over time (p=0.907). <h3>Conclusion</h3> Donor SA does not impact risk for late high-grade PGD, perioperative outcomes, 30-day survival, or first-year FEV1% predicted. Lungs from donors with history of SA may be considered for use in transplant to help reduce waitlist mortality.

The Effects of Donor-Specific Antibody Characteristics on Cardiac Allograft Vasculopathy

Purpose Cardiac allograft vasculopathy (CAV) is a major cause of late graft dysfunction and mortality after heart transplantation. The pathophysiology of CAV consists of a complex interplay between donor risk factors, recipient comorbidities, and immune-mediated processes. Despite many studies showing a correlation between donor-specific antibodies (DSA) and CAV, the effects of different DSA types on the severity of CAV remains elusive. This study investigates the characteristics of DSA amongst different CAV severity groups. Methods We evaluated 526 adult heart transplant recipients at a single tertiary medical center between January 2010 and August 2015. Subjects were screened for DSA at the time of transplant, 1 month, 3 months, 6 months, 1 year, and then annually thereafter. CAV screening was performed with annual angiography. Subjects were divided into those with DSA (n= 143) and those without DSA (control group, n =383). Subjects with DSA were further categorized into those with persistent DSA (n=34), transient DSA (n=106), 1:8 dilution positive DSA (n=45), complement-binding (C1q) DSA (n=36), Class I DSA (n=36), and Class II DSA (n=106). The mean duration of follow up was 3.6 years. The outcomes are the incidence of CAV based on the ISHLT grading scale. Results Subjects with persistent DSA were found to have higher incidence of moderate-to-severe CAV (CAV2/3) compared the control group (p= Subjects with 1:8 dilution positive DSA and C1q positive DSA also had a higher incidence of CAV2/3 when compared those without DSA (p=0.001, p= Conclusion DSA that are persistent, 1:8 dilution positive, C1q positive, and Class II are associated with more severe grades of CAV. Given CAV2/3 is linked with higher mortality post-transplantation, these DSA characteristics may serve as prognostic markers of disease and may warrant consideration for treatment.

Comparison of short-term outcomes with and without induction therapy in low-risk renal transplant recipients.

With low rates of rejection with current immunosuppression consisting of steroids, mycophenolic acid and tacrolimus, the question arises whether induction offers any additional benefit in low-risk renal transplant recipients. This study evaluated outcomes with and without induction in low-risk renal transplant recipients. A prospective observational study in which 100 low-risk renal transplant recipients were included and divided into two groups - one that received induction (IND) and another that did not (NO IND). They were followed for 1.5 years. Three endpoints were compared - efficacy of induction, patient and graft survival, and adverse effects. Incidence of rejection in early posttransplant period did not differ (4% NO IND vs. 6% IND; P = 0.171). Rejection as cause of late graft dysfunction was seen in 16% in IND vs. 20% NO IND; (P = 0.603). No difference in serum creatinine at end of 1.5 years was seen. Graft survival was also similar. Relapsing and recurrent urinary tract infections (46% IND vs. 16% NO IND; P = 0.09), hospitalization requiring infections (76%IND vs. 64% NO IND; P = 0.119 NS) were more common in IND. Cytomegalovirus infection affected only IND (6% vs. none; P = 0.07). Patient survival at 1.5 years was comparable (94% IND vs. 96% NO IND; P = 0.646). The study showed comparable results between IND and NO IND with however an increased incidence of infections and hospitalizations in the IND group. The use of induction may be avoided in low-risk renal transplant 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.