Quantitative flow ratio computed from invasive coronary angiography as a predictor for cardiac allograft vasculopathy after cardiac transplant.

Cardiac allograft vasculopathy (CAV) is a significant determinant of long-term survival in heart transplant recipients. Standard CAV screening typically utilizes invasive coronary angiography (ICA). Quantitative flow ratio (QFR) is a computational method for functional testing of coronary stenosis, and may add diagnostic value to ICA in assessing CAV. Consecutive subjects who received heart transplantation and underwent two separate routine coronary angiograms between January 2013 and April 2016 were enrolled. Coronary angiograms and IVUS were performed per local protocol at 1, 2, 3 and 5 years post-transplant. QFR was calculated offline. CAV was assessed semi-quantitively based on coronary angiogram results. Twenty-two patients were enrolled. Mean time from transplant to first included ICA was 2.1 years. QFR in at least 1 coronary vessel was interpretable in 19/22 (86%) of initial ICA (QFR1). QFR1 correlated well with the CAV score derived from the second ICA (CAV2) with a clustering of CAV at lower QFR values. In a receiver-operating characteristic (ROC) analysis, an optimal QFR threshold of 0.88 yielded 0.94 sensitivity and 0.67 specificity (AUC of 0.79) for at least non-obstructive subsequent CAV. Initial angiographically and intravascular ultrasound derived CAV severity poorly predicted subsequent CAV severity. QFR derived from invasive coronary angiography predicts subsequent development of CAV more accurately than angiography and intravascular ultrasound. This novel method of coronary flow assessment in recipients of heart transplantation may be useful to diagnose and predict subsequent CAV development.

Induction of Endotoxin Tolerance Delays Acute Rejection in a Hindlimb Transplantation Model in Rats.

BACKGROUND: Acute rejection is seen in 85 percent of composite vascular allogeneic transplants despite long-term immunosuppression. Recently, it was reported that the induction of endotoxin tolerance prolonged heart allograft survival in mice. However, it produced side effects in all the animals secondary to the inflammatory reaction. Galactomannan has shown endotoxin tolerance without this side effect in vitro. The authors hypothesized that galactomannan-induced endotoxin tolerance delays acute rejection in vascular allogeneic transplantation without the side effects produced by lipopolysaccharide. METHODS: Twenty-four rat hindlimb transplants were divided into four groups according to the preconditioning received: control, lipopolysaccharide (0.16 ml/kg), galactomannan 72 hours before (galactomannan-72) (8 ml/kg), and galactomannan 24 hours before (galactomannan-24) (8 ml/kg). Median acute rejection time, weight loss, and diarrheal episodes were monitored. Blood samples were collected at 0, 7, 21, 30, 45, and 60 days. Plasma cytokines (i.e., tumor necrosis factor alpha, interferon gamma), peripheral chimerism, and lymphocyte percentages were analyzed. RESULTS: Median allograft survival was 40 days (range, 40 to 44 days) in the control group, 68 days (range, 61 to 71 days) in the lipopolysaccharide group, and 70 days (range, 69 to 73 days) in both galactomannan groups (p = 0.001). Weight loss was higher in the lipopolysaccharide group (p < 0.001), as was the 83.3 percent rate of diarrheal episodes (control, 0 percent, p = 0.015; galactomannan-72, 0 percent, p = 0.015; and galactomannan-24, 16.7 percent, p = 0.02). Preconditioned rats had higher peripheral blood chimerism (lipopolysaccharide, 2.30 ± 0.13 percent; galactomannan-72, 2.63 ±1.46 percent; and galactomannan-24, 2.47 ± 0.19 percent) compared to the control group (2.06 ± 0.36 percent) (lipopolysaccharide, p = 0.04; galactomannan-72, p = 0.002; and galactomannan-24, p = 0.002). CONCLUSIONS: Induction of endotoxin tolerance delays acute rejection in the rat hindlimb transplantation model. Galactomannan preconditioning has no lipopolysaccharide side effects and was equally effective in delaying acute rejection. CLINICAL RELEVANCE STATEMENT: The contributions of this experimental work are very incipient. Although the use of galactomannan in clinical practice requires more studies to assess its safety, there is no doubt that immunomodulation may be one of the responses that solve the problem of long-term immunosuppression.

Non-invasive Imaging in the Evaluation of Cardiac Allograft Vasculopathy in Heart Transplantation: A Systematic Review.

Cardiac allograft vasculopathy (CAV) is the leading cause of long-term graft dysfunction in patients with heart transplantation and is linked with significant morbidity and mortality. Currently, the gold standard for diagnosing CAV is coronary imaging with intravascular ultrasound during traditional invasive coronary angiography. Invasive imaging, however, carries increased procedural risk and expense to patients in addition to requiring an experienced interventionalist. With the improvements in non-invasive cardiac imaging modalities such as transthoracic echocardiography, computed tomography, magnetic resonance imaging and positron emission tomography, an alternative non-invasive imaging approach for the early detection of CAV may be feasible. In this systematic review, we explored the literature to investigate the utility of non-invasive imaging in diagnosis of CAV in >3000 patients across 49 studies. We also discuss the strengths and weaknesses for each imaging modality. Overall, all 4 imaging modalities show good to excellent accuracy for identifying CAV with significant variations across studies. Majority of the studies compared non-invasive imaging with invasive coronary angiography without intravascular imaging. In summary, non-invasive imaging modalities offer an alternative approach to invasive coronary imaging for CAV. Future studies should investigate longitudinal non-invasive protocols in low-risk patients after heart transplantation.

Aggravation of fibrin deposition and microthrombus formation within the graft during kidney transplantation.

In kidney transplantation, microthrombi and fibrin deposition may lead to local perfusion disorders and subsequently poor initial graft function. Microthrombi are often regarded as donor-derived. However, the incidence, time of development, and potential difference between living donor kidneys (LDK) and deceased donor kidneys(DDK), remains unclear. Two open-needle biopsies, taken at preimplantation and after reperfusion, were obtained from 17 LDK and 28 DDK transplanted between 2005 and 2008. Paraffin-embedded sections were immunohistochemically stained with anti-fibrinogen antibody. Fibrin deposition intensity in peritubular capillaries(PTC) and glomeruli was categorized as negative, weak, moderate or strong and the number of microthrombi/mm2 was quantified. Reperfusion biopsies showed more fibrin deposition (20% to 100% moderate/strong, p < 0.001) and more microthrombi/mm2 (0.97 ± 1.12 vs. 0.28 ± 0.53, p < 0.01) than preimplantation biopsies. In addition, more microthrombi/mm2 (0.38 ± 0.61 vs. 0.09 ± 0.22, p = 0.02) and stronger fibrin intensity in glomeruli (28% vs. 0%, p < 0.01) and PTC (14% vs. 0%, p = 0.02) were observed in preimplantation DDK than LDK biopsies. After reperfusion, microthrombi/mm2 were comparable (p = 0.23) for LDK (0.09 ± 0.22 to 0.76 ± 0.49, p = 0.03) and DDK (0.38 ± 0.61 to 0.90 ± 1.11, p = 0.07). Upon reperfusion, there is an aggravation of microthrombus formation and fibrin deposition within the graft. The prominent increase of microthrombi in LDK indicates that they are not merely donor-derived.

Inflammation Determines the Capacity of Allogenic Endothelial Cells to Regulate Human Treg Expansion.

During allotransplantation, the endothelium acts as semi-professional antigen-presenting cells with the ability to activate proliferation and to promote differentiation of CD4+-T subsets. These abilities are dependent on the luminal expression of HLA class II antigens by microvascular endothelial cells, which is regulated by inflammatory cytokines. The upregulation of HLA-DR and HLA-DQ during rejection implies significant intragraft inflammation. Furthermore, the microvascular inflammation is an independent determinant for renal allograft failure. In this study, the potential of inflammation to modify endothelial regulation of peripheral CD4+ Treg cells was examined. Microvascular endothelial cells were exposed to pro-inflammatory cytokines for varying durations before co-culture with PBMC from non-HLA matched donors. Proliferation and expansion of CD4+Treg and soluble factor secretion was determined. Early interactions were detected by phosphorylation of Akt. Video microscopy was used to examine spatial and temporal endothelial-CD4+T interactions. Highly inflammatory conditions led to increased endothelial expression of HLA-DR, the adhesion molecule ICAM-1, the costimulatory molecule PD-L1 and de novo expression of HLA-DQ. Treg differentiation was impaired by exposure of endothelial cells to a high level of inflammation. Neither IL-6, IL-2 nor TGFß were implicated in reducing Treg numbers. High PD-L1 expression interfered with early endothelial cell interactions with CD4+T lymphocytes and led to modified TCR signaling. Blocking endothelial PD-L1 resulted in a partial restoration of Treg. The allogenic endothelial cell-mediated expansion of Treg depends on a critical threshold of inflammation. Manipulation of the PD-L1/PD-1 pathway or endothelial activation post-transplantation may promote or interfere with this intrinsic mechanism of allospecific Treg expansion.

Surgical Angiogenesis of Decellularized Nerve Allografts Improves Early Functional Recovery in a Rat Sciatic Nerve Defect Model.

BACKGROUND: Surgical angiogenesis applied to nerve grafts has been suggested to enhance nerve regeneration after nerve injury. The authors hypothesized that surgical angiogenesis to decellularized nerve allografts would improve functional recovery in a rat sciatic nerve defect model. METHODS: Sixty Lewis rats were divided in three groups of 20 animals each. Unilateral sciatic nerve defects were repaired with (1) autografts, (2) decellularized allografts, and (3) decellularized allografts wrapped with a superficial inferior epigastric artery fascial flap to add surgical angiogenesis. Twelve and 16 weeks after surgery, nerve regeneration was assessed using functional, electrophysiologic, histologic, and immunofluorescence analyses. Ultrasonography was used during the survival period to noninvasively evaluate muscle atrophy and reinnervation by measuring cross-sectional muscle area. RESULTS: Surgical angiogenesis of allografts demonstrated significantly improved isometric tetanic force recovery at 12 weeks, compared to allograft alone, which normalized between groups at 16 weeks. Cross-sectional muscle areas showed no differences between groups. Electrophysiology showed superiority of autografts at both time points. No differences were found in histologic analysis, besides a significantly inferior N ratio in allografts at 12 weeks. Immunofluorescent expression of CD34, indicating vascularity, was significantly enhanced in the superficial inferior epigastric artery fascial group compared to allografts at 12 weeks, with highest expression at 16 weeks compared to all groups. CONCLUSION: Surgical angiogenesis with an adipofascial flap to the nerve allograft increases vascularity in the nerve graft, with subsequent improvement of early muscle force recovery, comparable to autografts.

The Transition to Microsurgical Technique for Hepatic Artery Reconstruction in Pediatric Liver Transplantation.

BACKGROUND: Hepatic artery thrombosis represents a potentially fatal complication following liver transplantation. Rates of hepatic artery thrombosis are significantly higher in children, with mortality reported up to 80 percent. Microsurgical anastomosis has been shown to decrease the rate of hepatic artery thrombosis and now represents the standard of care at the authors' institution. In this article, the authors present the largest study of its type directly comparing rates of hepatic artery thrombosis with and without microsurgical reconstruction of the hepatic artery. METHODS: All pediatric patients who underwent primary orthotopic liver transplantation between 1989 and 2018 were included. Patients were divided into two cohorts: standard anastomosis with loupes, and microsurgical anastomosis under the operating microscope. The authors' primary outcome was the rate of hepatic artery thrombosis. Secondary outcomes were graft survival, patient survival, retransplantation rate, requirement for intraoperative blood products, and length of stay. RESULTS: Two hundred thirty-one children met criteria for inclusion. One hundred eighty cases were performed with loupe magnification and 51 cases were performed under the microscope. The hepatic artery thrombosis rate was lower, but not significantly so (p = 0.114), in the microsurgical group [n = 1 (2.0 percent)] compared with the standard cohort [n = 15 (8.3 percent)]. Survival analysis revealed a significant increase in graft survival with microsurgical anastomosis (p = 0.020), but not patient survival (p = 0.196). The retransplantation rate was significantly lower with microsurgical anastomosis (p = 0.021). CONCLUSIONS: Microsurgical anastomosis was associated with a clinically important decrease in hepatic artery thrombosis compared with standard loupe anastomosis. The graft survival rate was significantly higher in the microsurgical cohort, with a reduced retransplantation rate at 1 year. On this basis, the authors recommend microsurgical hepatic artery anastomosis in cases of pediatric liver transplantation. . CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Early critical cortical infarction by anti-angiotensin II type 1 receptor antibody: A case report and literature review.

RATIONALE: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been demonstrated to increase the risk of antibody-mediated rejection. We report a case of AT1R-Ab mediated rejection which caused early critical cortical infarction. PATIENT CONCERNS: A 52-year-old man with end-stage kidney disease underwent preemptive kidney transplantation (KT) from his wife. He had no immunologic risk except ABO incompatibility. Proper desensitization treatment were applied prior to KT. On postoperative day 1, he showed stable clinical course with adequate urine output, but there was no decrease in serum creatinine level and imaging studies showed hypoperfusion in the transplanted kidney. DIAGNOSES: Allograft biopsy revealed total cortical infarction with severe necrotizing vasculitis, but the medullary area was preserved. Serum AT1R-Ab concentration was elevated from 10.9 U/mL before KT to 19.1 U/mL on 7 days after KT. INTERVENTIONS: He was treated with plasmapheresis, intravenous immunoglobulin, rituximab, high-dose methylprednisolone, and bortezomib. OUTCOMES: The treatment showed a partial response, and he was discharged with 7.3 mg/dL creatinine level. At 4 months, his creatinine plateaued at 5.5 mg/dL and AT1R-Ab decreased to 3.6 U/mL. LESSONS: This case highlights the risk of early active antibody-mediated rejection by preformed AT1R-Ab, suggesting its ability to exhibit atypical histopathologic findings, such as total cortical infarction.

Evaluation of cardiac allograft vasculopathy by positron emission tomography.

Cardiac allograft vasculopathy (CAV) remains one of the most important late occurring complications in heart transplant (HT) recipients significantly effecting graft survival. Recently, there has been tremendous focus on the development of effective and safe non-invasive diagnostic strategies for the diagnosis of CAV employing a wide range of imaging technologies. During the past decade multiple studies have been published using positron emission tomography (PET) myocardial perfusion imaging, establishing the value of PET myocardial blood flow quantification for the evaluation of CAV. These independent investigations demonstrate that PET can be successfully used to establish the diagnosis of CAV, can be utilized for prognostication and may be used for serial monitoring of HT recipients. In addition, molecular imaging techniques have started to emerge as new tools to enhance our knowledge to better understand the pathophysiology of CAV.

Splenic Artery Transposition for Arterial Reconstruction in Living Donor Liver Transplantation.

PURPOSE: In living donor liver transplantation, poor compatibility of the recipient hepatic artery remains a technical challenge. Here, we analyzed our 14 years of experience with extra-anatomic hepatic artery reconstruction. METHODS: Between July 2004 and December 2018, there were 1063 liver transplantations at our center. All patients with an extra-anatomic hepatic artery reconstruction were identified. The gastroduodenal artery and the transposed splenic artery were the primary options for extra-anatomic arterial reconstruction. Patient characteristics, operative data, and post-transplant outcome were reviewed retrospectively. RESULTS: There were 22 patients with extra-anatomic hepatic artery reconstruction, 6 with gastroduodenal artery, and 16 with splenic artery. There were 2 major complications: 1 patient underwent early reoperation due to bleeding from the splenic artery trunk and another had an iatrogenic injury to the transposed splenic artery during conversion hepaticojejunostomy. Both were treated successfully with surgery. One patient died perioperatively due to sepsis. The 1- and 3-year graft survival rates of these 16 patients were 93.7% and 87.5%. CONCLUSION: If the hepatic arteries are not suitable for anastomosis, then we consider the gastroduodenal artery and the splenic artery to be the conduits of choice for extra-anatomic arterial reconstruction. The transposed splenic artery is very consistent, easily accessible, and offers adequate length and diameter for successful arterial anastomosis.

Predictive Model of Ureteral Obstruction of Allograft Kidney Following Living Donor Kidney Transplantation.

BACKGROUND: Ureteral obstruction is one of the most frequent urologic complications of kidney transplantation. This study aimed to analyze independent factors that contribute to ureteral obstruction following kidney transplantation and develop predictive models form those factors. METHODS: As many as 545 kidney transplantations were analyzed. Patients underwent transplantation between January 2014 and December 2018. Logistic regression analysis was used to develop the predictive model. Both donor and recipient demographic characteristics and operative parameters were analyzed and presented. RESULTS: There were 37 (6.8%) subjects who developed ureteral obstruction. The independent risk factors for ureteral obstruction were multiple allograft renal arteries, older donor ages (>38 years), and older recipient age (>60 years). From the receiver operating characteristic (ROC) curve analysis, the area under the ROC curve of the predictive model was 0.843 (P < .001). Subjects with >2 renal allograft arteries, recipient age >60 years, and donor age >38 years had 83.8% probability of developing ureteral stenosis after kidney transplantation. CONCLUSION: Donor age, recipient age, and multiple renal arteries were independent risk factors of graft ureteral obstruction. Probability of developing ureteral obstruction should be considered pre-operatively in our population, using the proposed predictive model.

Hypothermic machine perfusion can safely prolong cold ischemia time in deceased donor kidney transplantation. A retrospective analysis on postoperative morbidity and graft function.

In deceased donor kidney transplantation (KT), a prolonged cold ischemia time (CIT) is a negative prognostic factor for KT outcome, and the efficacy of hypothermic machine perfusion (HMP) in prolonging CIT without any additional hazard is highly debated. We conducted a retrospective study on a cohort of 154 single graft deceased donor KTs, in which a delayed HMP, after a preliminary period of static cold storage (SCS), was used to prolong CIT for logistic reasons. Primary outcomes were postoperative complications as well as 1 year graft survival and function. 73 cases (47.4%) were managed with HMP and planned KT, while 81 (52.6%) with SCS and urgent KT. The median CIT in HMP group and SCS group was 29 hour:57 minutes [27-31 hour:45 minutes] and 11 hour:25 minutes [9-14 hour:30 minutes], respectively (P < .001). The period of SCS in the HMP group was significantly shorter than in the SCS group (10 vs. 11 hour:25 minutes, P = .02) as well as the prevalence of expanded criteria donors was significantly higher (43.8% vs. 18.5%, P < .01). After propensity score matching for these two baseline characteristics, the HMP and SCS groups showed comparable outcomes in terms of delayed graft function, vascular, and urologic complications, infections, and episodes of graft rejection. At 1 year follow-up, serum creatinine levels were comparable between the groups. Therefore, the use of HMP to prolong the CIT and convert KT into a planned procedure seemed to have an adequate safety profile, with outcomes comparable to KT managed as an urgent procedure and a CIT nearly three time shorter.

Liver transplantation in patients with portal vein thrombosis: A strategic road map throughout management.

BACKGROUND: Liver transplantation in the setting of portal vein thrombosis is an intricate issue that occasionally necessitates extraordinary procedures for portal flow restoration. However, to date, there is no consensus on a persistent management strategy, particularly with extensive forms. This work aims to introduce our experience-based surgical management algorithm for portal vein thrombosis during liver transplantation and to clarify some of the debatable circumstances associated with this problematic issue. METHODS: Between 2006 and 2019, 494 adults underwent liver transplantation at our institute. Ninety patients had preoperative portal vein thrombosis, and 79 patients underwent living donor liver transplantation. Our algorithm trichotomized the management plan into 3 pathways based on portal vein thrombosis grade. The surgical procedures implemented included thrombectomy, interposition vein grafts, jump grafts from the superior mesenteric vein, jump grafts from a collateral and renoportal anastomosis in 56, 13, 11, 4, and 2 patients, respectively. Four patients with mural thrombi did not require any special intervention. RESULTS: Thirteen patients experienced posttransplant portal vein complications. They all proved to have a patent portal vein by the end of follow-up regardless of the management modality. No significant survival difference was observed between cohorts with versus without portal vein thrombosis. The early graft loss rate was significantly higher with advanced grades (P = .048) as well as technically demanding procedures (P = .032). CONCLUSION: A stepwise broad-minded strategy should always be adopted when approaching advanced portal vein thrombosis during liver transplantation. An industrious preoperative evaluation should always be carried out to locate the ideal reliable source for portal flow restoration.

Normal Pancreas Graft Appearance in Magnetic Resonance Diffusion Tensor Imaging (DTI).

BACKGROUND The main purpose of diagnostic imaging after pancreas transplantation is to exclude potential complications. As long as standard anatomical imaging such as sonography, contrast-enhanced computed tomography, and magnetic resonance imaging (MRI) are sufficient to display macroscopic vasculature, early changes within the graft caused by insufficient microperfusion will not be displayed for evaluation. MATERIAL AND METHODS Patients with pancreas allograft function in good condition were included in the study. No specific preparation was demanded before the MRI examination. The results of MRI were correlated with Igls criteria. It was a preliminary study to examine diffusion tensor imaging (DTI) value and safety in pancreas transplantation. RESULTS Our results indicated that higher fractional anisotropy (FA) values of the graft's head were associated with delayed graft function and insulin intake. We also compared grafts' images in early and late periods and found differences in T1 signal intensity values. DTI is a reliable noninvasive tool, requiring no contrast agent, to assess graft microstructure in correlation with its function, with FA values showing the most consistent results. By Igls criteria, no graft failure, 76% had optimal function, 10% had good function, and 14% had marginal function. CONCLUSIONS Our results suggest that DTI can be safely used in patients after pancreas transplantation and is advantageous in detecting early as well as late postoperative complications such as intra-abdominal fluid collection, malperfusion, and ischemia of the graft. Our findings correspond with clinical condition and Igls criteria. DTI is free of ionizing agents and is safe for kidney grafts.

Peripheral Donor-specific Antibodies Are Associated With Histology and Cellular Subtypes in Protocol Liver Biopsies of Pediatric Recipients.

BACKGROUND: The cellular infiltrate in protocol liver biopsies (PB) following pediatric liver transplantation remains mostly uncharacterized, yet there is increasing concern about the role of inflammation and fibrosis in long-term liver allografts. We aimed to define cell types in PB and to analyze their relationship with donor-specific antibodies (DSA) and histological phenotype. METHODS: PB were performed at least 1 year after transplantation. We identified 4 phenotypes: normal, fibrosis, inflammation, inflammation with fibrosis. Cell types were counted after immunostaining for CD3, CD4, CD8, CD68, CD20, MUM1, and FoxP3. RESULTS: Forty-four patients underwent 1 PB between 2000 and 2015. Eleven percent (5/44) of PB displayed normal histology, 13.6% (6/44) fibrosis, 34.1% (15/44) inflammation, and 40.9% (18/44) inflammation and fibrosis. The main cell types in the portal tracts and lobules were CD3+ and CD68+ cells. Frequency of de novo DSA was 63% (27/44). The presence of CD8+ cells in the lobules was associated with fibrosis. Inflammation and fibrosis in PB were associated with the presence of circulating de novo DSA, number of de novo DSA, and C1q binding activity when compared to other phenotypes. CONCLUSIONS: T cells (CD3+) and macrophages (CD68+) were the most prevalent cell-types in PB. In the presence of inflammation, portal tracts were enriched in CD3+, CD20+ but displayed fewer CD68+. This coincided with the presence and number of de novo DSA. How these cellular and humoral actors interact is unclear, but peripheral DSA may be a marker of immune cellular activity in the seemingly quiescent allograft.

Vessel Fractional Flow Reserve and Graft Vasculopathy in Heart Transplant Recipients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the Achilles' heel of long-term survival after heart transplantation (HTx). The severity and extent of CAV is graded with conventional coronary angiography (COR) which has several limitations. Recently, vessel fractional flow reserve (vFFR) derived from COR has emerged as a diagnostic computational tool to quantify the functional severity of coronary artery disease. PURPOSE: The present study assessed the usefulness of vFFR to detect CAV in HTx recipients. METHODS: In HTx patients referred for annual check-up, undergoing surveillance COR, the extent of CAV was graded according to the criteria proposed by the international society of heart and lung transplantation (ISHLT). In addition, three-dimensional coronary geometries were constructed from COR to calculate pressure losses using vFFR. RESULTS: In 65 HTx patients with a mean age of 53.7 ± 10.1 years, 8.5 years (IQR 1.90, 15.2) years after HTx, a total number of 173 vessels (59 LAD, 61 LCX, and 53 RCA) were analyzed. The mean vFFR was 0.84 ± 0.15 and median was 0.88 (IQR 0.79, 0.94). A vFFR ≤ 0.80 was present in 24 patients (48 vessels). HTx patients with a history of ischemic cardiomyopathy (ICMP) had numerically lower vFFR as compared to those with non-ICMP (0.70 ± 0.22 vs. 0.79 ± 0.13, p = 0.06). The use of vFFR reclassified 31.9% of patients compared to the anatomical ISHLT criteria. Despite a CAV score of 0, a pathological vFFR ≤ 0.80 was detected in 8 patients (34.8%). CONCLUSION: The impairment in epicardial conductance assessed by vFFR in a subgroup of patients without CAV according to standard ISHLT criteria suggests the presence of a diffuse vasculopathy undetectable by conventional angiography. Therefore, we speculate that vFFR may be useful in risk stratification after HTx.

Tailored classification of portal vein thrombosis for liver transplantation: Focus on strategies for portal vein inflow reconstruction.

Portal vein thrombosis (PVT) is currently not considered a contraindication for liver transplantation (LT), but diffuse or complicated PVT remains a major surgical challenge. Here, we review the prevalence, natural course and current grading systems of PVT and propose a tailored classification of PVT in the setting of LT. PVT in liver transplant recipients is classified into three types, corresponding to three portal reconstruction strategies: Anatomical, physiological and non-physiological. Type I PVT can be removed via low dissection of the portal vein (PV) or thrombectomy; porto-portal anastomosis is then performed with or without an interposed vascular graft. Physiological reconstruction used for type II PVT includes vascular interposition between mesenteric veins and PV, collateral-PV and splenic vein-PV anastomosis. Non-physiological reconstruction used for type III PVT includes cavoportal hemitransposition, renoportal anastomosis, portal vein arterialization and multivisceral transplantation. All portal reconstruction techniques were reviewed. This tailored classification system stratifies PVT patients by surgical complexity, risk of postoperative complications and long-term survival. We advocate using the tailored classification for PVT grading before LT, which will urge transplant surgeons to make a better preoperative planning and pay more attention to all potential strategies for portal reconstruction. Further verification in a large-sample cohort study is needed.

The pharmaceutical management of cardiac allograft vasculopathy after heart transplantation.

INTRODUCTION: Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival after heart transplantation. Its peculiar pathophysiology involves multifactorial pathways including immune-mediated and metabolic risk factors, which are associated with the development of specific pathological lesions. The often diffuse and chronic nature of the disease reduces the effectiveness of revascularization procedures, and pharmacological prevention of the disease is the sole therapeutic approach with some proven efficacy. AREAS COVERED: In this article, after briefly outlining the risk factors for CAV, the authors revise the potential pharmacological approaches that may reduce the burden of CAV. While several therapies have shown convincing efficacy in terms of CAV prevention diagnosed by coronary imaging, very few have been reported to improve prognosis with any meaningful level of evidence. EXPERT OPINION: The authors believe that a customizable approach is necessary for clinical practice given the currently available evidence. Furthermore, it is important, in the future, to address the glaring therapeutic gap of an effective treatment against donor-specific antibodies, whose effect on endothelial injury is currently one of the major mechanisms of CAV development and for which no pharmacological treatment is currently available.