The International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality early after heart transplantation (HT). The International Consortium on PGD is a multicenter collaboration dedicated to identifying the clinical risk factors for PGD in the contemporary era of HT. The objectives of the current report were (1) to assess the incidence of severe PGD in an international cohort; (2) to evaluate the performance of the most strongly validated PGD risk tool, the RADIAL score, in a contemporary cohort; and (3) to redefine clinical risk factors for severe PGD in the current era of HT. METHODS: This is a retrospective, observational study of consecutive adult HT recipients between 2010 and 2020 in 10 centers in the United States, Canada and Europe. Patients with severe PGD were compared to those without severe PGD (comprising those with no, mild and moderate PGD). The RADIAL score was calculated for each transplant recipient. The discriminatory power of the RADIAL score was evaluated using receiver operating characteristic (ROC) analysis, and its calibration was assessed by plotting the percentage of PGD predicted vs that which was observed. To identify clinical risk factors associated with severe PGD, we performed multivariable mixed-effects logistic regression modeling to account for among-center variability. RESULTS: A total of 2746 patients have been enrolled in the registry to date, including 2015 (73.4%) from North America, and 731 (26.6%) from Europe; 215 participants (7.8%) met the criteria for severe PGD. There was an increase in the incidence of severe PGD over the study period (P value for trend by difference sign test = 0.004). The Kaplan-Meier estimate for 1-year survival was 75.7% (95% CI 69.4-80.9%) in patients with severe PGD as compared to 94.4% (95% CI 93.5-95.2%) in those without severe PGD (log-rank P value < 0.001). The RADIAL score performed poorly in our contemporary cohort and was not associated with severe PGD; it had an AUC of 0.53 (95% CI 0.48-0.58). In the multivariable regression model, acute preoperative dialysis (OR 2.41, 95% CI 1.31-4.43), durable left ventricular assist device support (OR 1.77, 95% CI 1.13-2.77), and total ischemic time (OR 1.20 for each additional hour, 95% CI 1.02-1.41) were associated with an increased risk of severe PGD. CONCLUSIONS: Our consortium has identified an increasing incidence of PGD in the modern transplant era. We identified contemporary risk factors for this early post-transplant complication, which confers a high mortality risk. These results may enable the identification of patients at high risk for developing severe PGD in order to inform peri-transplant donor and recipient management practices.

Perfusion Cardiac Magnetic Resonance Imaging as a Rule-Out Test for Cardiac Allograft Vasculopathy.

Cardiac allograft vasculopathy (CAV) is a leading cause of mortality after heart transplantation. Noninvasive imaging techniques used in CAV evaluation have important limitations. In a cross-sectional study, we investigated perfusion cardiac magnetic resonance (CMR) imaging to determine an optimal myocardial perfusion reserve index (MPR) cutoff for detecting CAV using receiver operating characteristic curve analysis. We evaluated CMR performance using sensitivity, specificity and likelihood ratio analysis. We included 29 patients (mean 5 ± 4 years after transplant) scheduled for coronary angiography with intravascular ultrasound (IVUS) who completed CMR. CAV was defined as maximal intimal thickness (MIT) >0.5 mm by IVUS of the left anterior descending artery. CAV was evident in 19 patients (70%) on IVUS (mean MIT 0.82 ± 0.42 mm). MPR was significantly lower in patients with MIT ≥0.50 mm (1.35 ± 0.23 vs. 1.71 ± 0.45, p = 0.013). There was moderate inverse correlation between MPR and MIT (r = -0.36, p = 0.075). The optimal MPR cutoff ≤1.68 for predicting CAV showed sensitivity of 100%, specificity of 63%, a negative predictive value of 100%, a positive predictive value of 86% and a positive likelihood ratio of 2.7. An MPR ≤1.68 has high negative predictive value, suggesting its potential as a test to rule out CAV.

A survey of current practice for antibody-mediated rejection in heart transplantation.

No evidence based management guidelines exist for antibody mediated rejection (AMR) in heart transplantation. The International Society for Heart and Lung Transplantation (ISHLT) recently introduced standardized pathologic based diagnostic criteria for AMR (pAMR 0-3). We evaluated international practice for the management of AMR focusing on pAMR grade, donor specific antibody (DSA) and allograft function. On-line survey data were analyzed from 184 ISHLT members (physicians-78%, surgeons-20%). The majority were from adult-transplant (84%), medium-large volume centres (transplants/year: 10-25, 61%; 25-50, 19%) across North America (60%) and Europe (26%). Irrespective of pAMR grade and DSA, 83-90% treated a drop in ejection fraction (EF≤45% or >25% decrease). In the presence of stable EF, an increasing number elected treatment for progressively severe pAMR grade (p<0.001) and for accompanying DSA (p<0.05, pAMR 1-3). Intravenous steroid was the most commonly used therapy followed by intravenous immunoglobulin (IVIG) or plasmapheresis, rituximab and thymoglobulin. Plasmapheresis and rituximab were favored for positive versus negative DSA (p<0.05). Using a threshold of ≥70% consensus among respondents, treatment for AMR may be considered for a drop in EF, asymptomatic pAMR 3 or asymptomatic pAMR 2 with DSA. Combination steroid, IVIG and plasmapheresis are suggested as initial therapies.

Association between hemodynamics in the common carotid artery and severity of carotid atherosclerosis in patients with essential hypertension.

BACKGROUND: Carotid intima-media thickness (IMT) and plaque burden evaluated by B-mode ultrasound have been used as relevant indicators for carotid atherosclerosis. This study was aimed to investigate the relationship between hemodynamic parameters in the common carotid artery (CCA) and the severity of carotid atherosclerosis in untreated hypertensive patients. METHODS: Carotid IMT and plaque burden were evaluated in bilateral CCA, bifurcations, external and internal carotid arteries using duplex ultrasound in 80 untreated hypertensive patients. The patients were divided into four groups according to plaque burden. Hemodynamic parameters of CCA, including peak and mean circumferential wall tension (CWT), tensile stress (TS), wall shear stress (WSS), and Young's elastic modulus (YEM), were calculated after measurements of internal diameter (ID), IMT, and peak and mean flow velocities of CCA. Arterial stiffness was also assessed using the brachial-ankle pulse wave velocity (baPWV). RESULTS: Age, pulse pressure, creatinine, carotid IMT, and mean TS were shown to have significant differences among the four plaque groups (P < 0.05). Peak CWT and peak TS were also shown to have marginal differences. In univariate analysis, the peak and mean CWT and TS were significantly correlated with plaque score. Stepwise multiple regression analysis showed that carotid IMT, age, and peak CWT were independently associated with plaque score. CONCLUSIONS: These results suggest that the CWT and TS of the CCA are associated with the severity of carotid atherosclerosis in untreated hypertensive patients. Hence, the hemodynamics of vessels may contribute to the plaque burden of low-resistance arteries.

Association of carotid hemodynamics with risk of coronary heart disease in a Taiwanese population with essential hypertension.

BACKGROUND: The resistive index (RI) of the carotid artery is a hemodynamic parameter that depends on the degree of vascular resistance in hypertensive patients. The pulsatility index (PI) of the carotid artery was shown to be associated with microangiopathy in diabetic patients. In contrast to carotid intima-media thickness (IMT), no study has yet applied the carotid RI and PI to estimate coronary heart disease (CHD) risk. METHODS: Framingham risk scores (FRS) were determined for 62 patients (32 women; mean age 65 years (range 35-83)) with essential hypertension. Duplex sonography of the common carotid artery (CCA) was performed, with determination of RI, PI, and IMT. RESULTS: The mean FRS of all patients was 14.3% (range 1-30%), the mean IMT value of CCA was 0.89 +/- 0.23 mm, the mean RI was 0.71 +/- 0.07, and the mean PI was 1.46 +/- 0.39. FRS was found to have highly significant correlations with RI and PI (r = 0.47, P < 0.001 and r = 0.45, P < 0.001, respectively). The correlation between FRS and IMT was also significant (r = 0.41, P = 0.001). Multiple stepwise regression analysis showed that RI was an independent determinant of the risk of CHD. CONCLUSIONS: Although RI indirectly reflected the atherosclerotic process, the correlation between RI and CHD risk was comparable to the well-known correlation between cardiovascular event and carotid IMT. Hence, carotid RI can be used as a tool for risk stratification in Taiwanese patients with essential hypertension.

Fluorochrome and flow cytometry to monitor microorganisms in treated hospital wastewater.

Flow cytometry with a fluorescent technique (FCM/FL), epifluorescence microscopy with a fluorescent technique (EFM/FL), and a culture method were used and compared to study the microorganism population profiles in wastewater treatment. In the two non-culture methods (FCM/FL and EFM/FL), four fluorescent dyes [acridine orange (AO), 4',6-diamino-2-phenylindole dihydrochloride (DAPI), propidium iodide (PI), and YOPRO-1] were used to determine the total concentration and viability of microorganisms in the wastewater samples. Results showed that the total cell concentrations (both the bacteria and fungi) determined by using the non-culture-based methods were 18 to 67 times higher than those by the culture method (p = 0.036): the total cell concentration ranged from 1.10 x 10(7) to 2.44 x 10(8) cells/mL determined by both FCM and EFM with AO-staining method, and from 1.02 x 10(7) to 2.00 x 10(8) cells/mL by EFM with DAPI-staining method, whereas the culturable concentration of bacteria and fungi ranged from 0 to 3.22 x 10(6) CFU/mL and from 0 to 4.13 x 10(5) CFU/mL, respectively. No difference in total concentrations between dyes (AO and DAPI) and methods (FCM and EFM) were observed. By using EFM method, the microorganism viability ranged from 0.24 to 0.86 with PI staining and from 0.09 to 0.74 with YOPRO-1 staining. In the FCM analysis, the microorganism viability ranged from 0.23 to 0.87 with PI staining and from 0.18 to 0.73 with YOPRO-1 staining. In addition, the cultivability of microorganism ranged from 0 to 0.105 by the culture method. The total concentrations and viabilities of microorganisms were highly underestimated by the culture method. Results also showed that the viabilities determined by using either EFM/FL or FCM/FL were significantly higher than the cultivabilities. In addition, significant difference in viability between PI and YOPRO-1 for both EFM and FCM analysis was observed. However, the difference in viability between EFM and FCM depended on dyes. In regard to the difference between bacteria and fungi, significant difference in total concentration, viability, and cultivability was observed. In conclusion, the EFM/FL and FCM/FL methods can effectively assess total concentration and viability of microorganisms in environmental samples.