Donor-Specific Cell-Free DNA qPCR Quantification as a Noninvasive Accurate Biomarker for Early Rejection Detection in Liver Transplantation.

(1) Background: Graft-cell-free DNA (cfDNA) in the circulation of liver transplant recipients has been proposed as a noninvasive biomarker of organ rejection. The aim of this study was to detect donor-specific cfDNA (ds-cfDNA) in the recipient's serum after either liver damage or rejection using a qPCR-based method. (2) Methods: We proposed a qPCR method based on the amplification of 10 specific insertion-deletion (InDel) polymorphisms to detect donor-specific circulating DNA diluted in the recipient cfDNA. ds-cfDNA from 67 patients was evaluated during the first month post-transplantation. (3) Results: Graft rejection in the first month post-transplantation was reported in 13 patients. Patients without liver complications showed a transitory increase in ds-cfDNA levels at transplantation. Patients with rejection showed significant differences in ds-cfDNA increase over basal levels at both the rejection time point and several days before rejection. Receiver operator characteristic (ROC) analysis showed that ds-cfDNA levels discriminated rejection, with an AUC of 0.96. Maximizing both sensitivity and specificity, a threshold cutoff of 8.6% provided an estimated positive and negative predictive value of 99% and 60%, respectively. (4) Conclusions: These results suggest that ds-cfDNA may be a useful marker of graft integrity in liver transplant patients to screen for rejection and liver damage.

Right Ventricular Assist Devices After Heart Transplantation.

BACKGROUND: Severe right ventricular failure (RVF) has a significant incidence among cardiac transplant patients. It is a serious complication and an independent risk factor for postoperative mortality. In this setting, ventricular assist devices (VADs) must be considered if conservative medical management fails. This study sought to examine our series of patients with early RVF after heart transplantation requiring VAD support. METHOD: We analyzed consecutive, adult heart transplant recipients at a third level intensive care unit who underwent transplantation from January 2011 to March 2019 requiring post-transplant mechanical circulatory support for RVF. Demographic characteristics, clinical data, complications, and survival rates were collected. RESULTS: Ten patients were included. Median age was 50 years (range, 31.7-57). Eight patients (80%) were male. The most frequent indication for heart transplantation was ischemic heart disease (4 patients) followed by dilated cardiomyopathy and congenital heart disease (2 patients). Preoperative pulmonary hypertension was present in 6 patients. Three patients required a VAD before transplant. Whole survival rate was 60%. After heart transplantation, 7 patients required renal replacement therapy, 2 patients suffered a hemorrhagic stroke, and 5 patients needed a tracheostomy for long-term ventilation. CONCLUSION: Patients who develop RVF after transplantation have an increased incidence of complications and high mortality after surgery. VADs could be implanted immediately after heart transplantation in high-risk patients.

Transplantation in Congenital Heart Disease: A Challenge.

BACKGROUND: Heart failure is the leading cause of death in grown-up congenital heart disease patients (GUCH). Although heart transplantation (OHT) remains the gold standard in end-stage heart failure, the ratio of GUCH patients undergoing this procedure remains low. OBJECTIVE: Describe the cohort of GUCH patients undergoing heart transplantation at a third-level hospital. METHODS: A retrospective review of GUCH patients undergoing OHT between 1997 and 2019 was conducted at a single tertiary university hospital. We included different preoperative (demographic and clinical data, cardiac catheterization data from the last routine hemodynamic monitoring) and postoperative variables (complications, survival). RESULTS: Fourteen patients were enrolled. The median age was 25.5 years (range, 20.7-32.2). Eight patients (57.1%) were male. The median preoperative left ventricular ejection fraction was 37% (range, 22.5%-55%). As for preoperative hemodynamic evaluation, the median for the mean arterial pulmonary pressure was 19 mm Hg (range, 12-22.5), for the capillary wedge pressure was 16 mm Hg (range, 13.5-19.5), and for pulmonary vascular resistance was 1.83 Wood units (range, 1-4). After OHT, 6 patients (42.9%) suffered an infection, the most common of which was respiratory (3 out of 6). Four patients (28.6%) needed renal replacement therapy, and 4 patients (28.6%) presented liver failure. Four patients (28.6%) developed graft failure, thus requiring mechanical support with extracorporeal membrane oxygenation during a median of 6 days (range, 1-17.5). Survival rate of patients under extracorporeal membrane oxygenation was 50%, and overall survival rate was 78.6%. CONCLUSION: OHT represents a good option for GUCH patients, with good overall survival rates.

Donor-specific circulating cell free DNA as a noninvasive biomarker of graft injury in heart transplantation.

BACKGROUND: Considerable effort has been exerted to develop noninvasive diagnostic biomarkers that might replace or reduce the need to perform endomyocardial biopsies. In this context, graft DNA circulating on transplant recipients has been proposed as a potential biomarker of organ rejection or cellular graft injury. METHODS: We propose a digital PCR (dPCR) method based on the amplification of ten specific InDels sufficiently sensitive to detect small amounts of specific donor circulating DNA diluted on the host cell free DNA (cfDNA). We obtained 23 informative mismatches from 30 host and donor organ biopsy pairs. RESULTS: Patients without heart-related complications showed a high increase in the specific genomic marker levels during the first 24 h after transplantation that dropped to the basal levels on days 3-4 post-surgery. In contrast, patients with complications presented a significantly lagged decay pattern from day one after transplantation. A specific donor cfDNA increase was detected in one patient two days before rejection diagnosis, diminishing the basal levels after successful immunotherapy. A cfDNA increase was also observed during graft injury due to heart damage. CONCLUSION: These results suggest that cfDNA monitoring of transplanted patients may be a useful tool to detect and probably anticipate graft rejection.