Risk of early, intermediate, and late rejection following heart transplantation: Trends over the past 25 years and relation to changes in medical management. Tertiary center experience: The Sheba Heart Transplantation Registry

Katz, Miriam; Freimark, Dov; Raichlin, Eugenia; Har-Zahav, Yedael; Arad, Michael; Kassif, Yigal; Peled, Amir; Asher, Elad; Elian, Dan; Kogan, Alexander; Nir, Shlomo; Ofek, Efrat; Lavee, Jacob; Goldenberg, Ilan; Peled, Yael

doi:10.1111/ctr.13063

Cited by 9 publications

(5 citation statements)

References 21 publications

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“…In both pediatric and adult HT recipients, the frequency of ACR is most common in the first‐year post transplantation and declines with time 43,44 . This is consistent with our results that demonstrate ACR almost exclusively occurring in the pretransition period closer to the time of HT, with a drastic reduction of rates in the post‐transition period 3,45 . AMR can occur at any time in the post‐transplant period and in our cohort, rates of AMR were similar in both the pre‐ and post‐transition period 46 .…”

Section: Discussionsupporting

confidence: 91%

“…43,44 This is consistent with our results that demonstrate ACR almost exclusively occurring in the pretransition period closer to the time of HT, with a drastic reduction of rates in the post-transition period. 3,45 AMR can occur at any time in the post-transplant period and in our cohort, rates of AMR were similar in both the pre-and post-transition period. 46 Additionally, less invasive and novel techniques to detect rejection, such as cell-free DNA and advanced imaging, are becoming increasingly more utilized in adult HT programs.…”

Section: Rejection and Graft Failuresupporting

confidence: 55%

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Long‐term outcomes for pediatric heart transplant recipients transitioning to adult care teams

Donald,

Oren,

DeFilippis

et al. 2024

Clinical Transplantation

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BackgroundThere are limited data evaluating the success of a structured transition plan specifically for pediatric heart transplant (HT) recipients following their transfer of care to an adult specialist. We sought to identify risk factors for poor adherence, graft failure, and mortality following the transfer of care to adult HT care teams.MethodsWe retrospectively reviewed all patients who underwent transition from the pediatric to adult HT program at our center between January 2011 and June 2021. Demographic characteristics, comorbid conditions, and psychosocial history were collected at the time of HT, the time of transition, and the most recent follow‐up. Adverse events including mortality, graft rejection, infection, and renal function were also captured before and after the transition.ResultsSeventy‐two patients were identified (54.1% male, 54.2% Caucasian). Mean age at the time of transition was 23 years after a median of 11.6 years in the pediatric program. The use of calcineurin inhibitors was associated with reduced mortality (HR .04, 95% CI .0–.6, p = .015), while prior psychiatric hospitalization (HR 45.3, 95% CI, 6.144–333.9, p = .0001) was associated with increased mortality following transition. Medication nonadherence and young age at the time of transition were markers for high‐risk individuals prior to the transition of care.ConclusionsTransition of HT recipients from a pediatric program to an adult program occurs during a vulnerable time of emerging adulthood, and we have identified risk factors for mortality following transition. Development of a formalized transition plan with a large multidisciplinary team with focused attention on high‐risk patients, including those with psychiatric comorbidities, may favorably influence outcomes.

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Section: Discussionsupporting

confidence: 91%

Section: Rejection and Graft Failuresupporting

confidence: 55%

Long‐term outcomes for pediatric heart transplant recipients transitioning to adult care teams

Donald,

Oren,

DeFilippis

et al. 2024

Clinical Transplantation

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“…Currently, heart transplantation is considered the most effective method of treating heart failure and improving the patient’s quality of life. However, the use of heart transplant has some limitations, such as: the risk of organ rejection and the small number of donors [ 2 ]. Regenerative medicine, which has been developing in recent years, might turn out to be one of the methods that will improve the effectiveness of heart failure treatment.…”

Section: Introductionmentioning

confidence: 99%

Study of Stem Cells Influence on Cardiac Cells Cultured with a Cyanide-P-Trifluoromethoxyphenylhydrazone in Organ-on-a-Chip System

et al. 2021

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Regenerative medicine and stem cells could prove to be an effective solution to the problem of treating heart failure caused by ischemic heart disease. However, further studies on the understanding of the processes which occur during the regeneration of damaged tissue are needed. Microfluidic systems, which provide conditions similar to in vivo, could be useful tools for the development of new therapies using stem cells. We investigated how mesenchymal stem cells (MSCs) affect the metabolic activity of cardiac cells (rat cardiomyoblasts and human cardiomyocytes) incubated with a potent uncoupler of mitochondrial oxidative phosphorylation under microfluidic conditions. A cyanide p-trifluoromethoxyphenylhydrazone (FCCP) was used to mimic disfunctions of mitochondria of cardiac cells. The study was performed in a microfluidic system integrated with nanofiber mats made of poly-l-lactid acid (PLLA) or polyurethane (PU). The microsystem geometry allows four different cell cultures to be conducted under different conditions (which we called: normal, abnormal—as both a mono- and co-culture). Metabolic activity of the cells, based on the bioluminescence assay, was assessed in the culture’s performed in the microsystem. It was proved that stem cells increased metabolic activity of cardiac cells maintained with FCCP.

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“…1 Nevertheless, 13% to 30% of heart transplant recipients experience acute allograft rejection within the first year after transplantation, 1 and it remains as one of the leading causes of mortality. 2,3 Although immune-mediated reaction is the key initiation process, several studies have presented the association among acute allograft rejection, myocyte damage, microscopic architectural distortion, and development of microvasculopathy and cardiac allograft vasculopathy in epicardial coronary arteries. [3][4][5][6][7] Despite continued efforts to develop noninvasive imaging tools, 8 there are limited modalities to detect acute allograft rejection before myocytes are damaged.…”

mentioning

confidence: 99%

Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation

Lee

Choi

et al. 2021

Circulation

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Background: Acute cellular rejection is a major determinant of mortality and re-transplantation after heart transplantation. We sought to evaluate prognostic implications of coronary microcirculatory dysfunction assessed by index of microcirculatory resistance (IMR) for risk of acute cellular rejection after heart transplantation. Methods: The current study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiologic assessment 1 month after transplantation. IMR is microcirculatory resistance under maximal hyperemia. By measuring hyperemic mean transit time using 3 injections (4 mL each) of room-temperature saline under maximal hyperemia, IMR was calculated as hyperemic distal coronary pressure × hyperemic mean transit time. The primary endpoint was biopsy-proven acute cellular rejection of grade ≥2R during 2 years of follow-up after transplantation and was compared using multivariable Cox proportional hazard regression according to IMR. The incremental prognostic value of IMR, in addition to the model with clinical factors, was evaluated by comparison of c-index, net reclassification index (NRI), and integrated discrimination index (IDI). Results: Mean age of recipients was 51.2±13.1 years (81.2% male), and cumulative incidence of acute cellular rejection was 19.0% at 2 years. Patients with acute cellular rejection had significantly higher IMR values at 1 month than those without acute cellular rejection (23.1±8.6 vs. 16.8±11.1, P=0.002). IMR was significantly associated with the risk of acute cellular rejection (per 5-unit increase: adjusted HR 1.18, 95% CI 1.04-1.34, P=0.011) and the optimal cut-off value of IMR to predict acute cellular rejection was 15. Patients with IMR≥15 showed significantly higher risk of acute cellular rejection than those with IMR<15 (34.4% vs. 3.8%, adjusted HR 15.3, 95% CI 3.6-65.7, P<0.001). Addition of IMR to clinical variables showed significantly higher discriminant and reclassification ability for risk of acute cellular rejection (C-index 0.87 vs. 0.74, P<0.001; NRI 1.05, P<0.001, IDI 0.20, P<0.001). Conclusions: Coronary microcirculatory dysfunction assessed by IMR measured early after heart transplantation showed significant association with the risk of acute cellular rejection. In addition to surveillance endomyocardial biopsy, early stratification using IMR could be a clinically useful tool to identify patients at higher risk of future acute cellular rejection after heart transplantation. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02798731

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Risk of early, intermediate, and late rejection following heart transplantation: Trends over the past 25 years and relation to changes in medical management. Tertiary center experience: The Sheba Heart Transplantation Registry

Abstract: Major rejection rates following HT have significantly declined over the past 2 decades even after adjustment for changes in immunosuppressive therapies, suggesting that other factors may also play a role in the improved outcomes of HT recipients.

Cited by 9 publications

References 21 publications

Long‐term outcomes for pediatric heart transplant recipients transitioning to adult care teams

Long‐term outcomes for pediatric heart transplant recipients transitioning to adult care teams

Study of Stem Cells Influence on Cardiac Cells Cultured with a Cyanide-P-Trifluoromethoxyphenylhydrazone in Organ-on-a-Chip System

Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation

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