Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study.

INTRODUCTION: As the adult Fontan population with Fontan associated liver disease continues to increase, more patients are being referred for transplantation, including combined heart and liver transplantation. METHODS: We report updated mortality and morbidity outcomes after combined heart and liver transplant in a retrospective cohort series of 40 patients (age 14 to 49 years) with Fontan circulation across two centers from 2006-2022. RESULTS: The 30-day, 1-year, 5-year and 10-year survival rate was 90%, 80%, 73% and 73% respectively. Sixty percent of patients met a composite comorbidity of needing either post-transplant mechanical circulatory support, renal replacement therapy or tracheostomy. Cardiopulmonary bypass time > 283 min (4.7 h) and meeting the composite comorbidity were associated with mortality by Kaplan Meier analysis. CONCLUSION: Further study to mitigate early mortality and the above comorbidities as well as the high risk of bleeding and vasoplegia in this patient population is warranted.

Multicenter study of universal prophylaxis versus pre-emptive therapy for patients at intermediate risk (R+) for CMV following heart transplantation.

INTRODUCTION: Heart transplant (HT) recipients with prior exposure to cytomegalovirus (CMV R+) are considered intermediate risk for CMV-related complications. Consensus guidelines allow for either universal prophylaxis (UP) or preemptive therapy (PET) (serial CMV testing) approaches to CMV prevention in such patients. Whether an optimal approach to mitigate CMV related risks exists in this setting remains uncertain. We therefore assessed the utility of PET as compared to UP in CMV R+ HT recipients. METHODS: Retrospective analysis of all CMV R+ HT recipients from 6 U.S. centers between 2010 and 2018 was performed. The primary outcome was the development of CMV DNAemia or end-organ disease resulting in the initiation/escalation of anti-CMV therapy. The secondary outcome was CMV-related hospitalization. Additional outcomes included incidence of acute cellular rejection (ACR) ≥ grade 2R, death, cardiac allograft vasculopathy (CAV), and leukopenia. RESULTS: Of 563 CMV R+ HT recipients, 344 (61.1%) received UP. PET was associated with increased risk for the primary (adjusted HR 3.95, 95% CI: 2.65-5.88, p < .001) and secondary (adjusted HR 3.19, 95% CI: 1.47-6.94, p = .004) outcomes, and with increased ACR ≥ grade 2R (PET 59.4% vs. UP 34.4%, p < .001). Incidence of detectable CAV was similar at 1 year (PET 8.2% vs. UP 9.5%, p = .698). UP was associated with increased incidence of leukopenia within 6 months post-HT (PET 34.7% vs. UP 43.6%, p = .036). CONCLUSION: The use of a PET CMV prophylaxis strategy in intermediate risk HT recipients associated with increased risk of CMV infection and CMV-related hospitalization, and may associate with worse post-HT graft outcomes.

Tracking the Temporal Footprint Effect of Thermonociception and Denervation on the Brain's Pain Matrix: fMRI and BOLD Study in Rats.

Objective: Pain constitutes an essential alarm for preserving the organism's integrity. Damage to the nervous system produces a pathological condition known as neuropathic pain. Purpose: Blood oxygenation level-dependent (BOLD) and functional magnetic resonance imaging (fMRI) have been widely used to map neuroanatomy and the active regions of interest (ROI) of nociceptive processing. Our study explored the brain's BOLD response in rats after thermal noxious stimulation, immediately after sciatic nerve damage and during 75 minutes after surgical lesion of the sciatic nerve. Methods: Nine male Wistar rats were tested; the experiments were performed on a 7-Tesla /21-cm Varian Agilent system. This approach allowed, for the first time, to measure in vivo the BOLD changes in brain regions involved with the pain process: cingulated (ACC), somatosensory (S1), and insular cortices (IC), as well as thalamus (Th) and ventral tegmental area (VTA) related with acute thermal pain and during the early stages of sciatic denervation that produce neuropathic pain. Results: During thermonociception scan, all subjects showed BOLD activation in the ROIs determined as ACC, S1, Th, IC and VTA. After denervation, these regions continued to show activation with a slow decrement in intensity for the duration of the experiment. The results suggest that these brain structures are overactive during the genesis of neuropathic pain. Conclusion: The study shows for the first time continuous activation of the pain matrix following an acute thermal nociceptive stimulus followed by neuropathic damage. These results have given insight into the early stages of the development of neuropathic pain in vivo.

Diagnosis and management of cardiac allograft vasculopathy.

One of the main causes of death beyond the first year after heart transplantation is cardiac allograft vasculopathy (CAV). This review summarises the current understanding of its complex pathophysiology, detection and treatment, including the available data on non-invasive imaging modalities used for screening and diagnosis. A better understanding of this entity is crucial to improving the long-term outcomes of the growing population of patients with a heart transplant.

Immune benefit of combined heart and liver transplantation.

PURPOSE OF REVIEW: Understanding the mechanisms involved in immune protection provided by a hepatic allograft is imperative as further therapies for highly sensitized patients could be developed and thus expanding the donor pool and improving outcomes. RECENT FINDINGS: The clinical data from immune protection comes mainly from combined liver and kidney transplants with excellent results in overall survival and also that of the allograft. This phenomenon has also been observed in dual liver transplants with heart, lung, skin and intestines, albeit with less data. In heart transplant recipients, the liver allograft has proven to be protective even in cases of highly sensitized patients with at least equal survival and rejection outcomes to recipients of heart alone. Although not fully understood, the mechanisms for immune benefit proposed are extensive at different levels of the hepatic immune system. Some of these mechanisms include chimerism, T-cell deletion, the presence of peripheral regulatory T cells and donor-specific antibody neutralization. SUMMARY: Combined heart and liver transplantation is an infrequent but growing procedure due to increasing need in the adult congenital heart disease and cardiac amyloid populations. Given the ever expanding need for heart transplantation, understanding immunological phenomena that could expand the donor pool could, subsequently, increase the number of transplants.

Acute myocarditis following high-dose interleukin-2 treatment.

We describe the case of a 49-year-old woman with metastatic renal carcinoma receiving treatment with high-dose interleukin-2 (IL-2) who developed acutely progressive dyspnea on exertion and an elevated troponin level. Cardiac magnetic resonance imaging (CMR) was used to establish the diagnosis of IL-2-associated cardiotoxicity, differentiating myocarditis from acute coronary syndrome (ACS) and preventing an unnecessary invasive coronary angiogram. .